dJ-DP4 and iJ-DP4: including coupling constants

I have written quite a number of posts on using quantum mechanics computations to predict NMR spectra that can aid in identifying chemical structure. Perhaps the most robust technique is Goodman’s DP4 method (post), which has seen some recent revisions (updated DP4, DP4+). I have also posted on the use of computed coupling constants (posts).

Grimblat, Gavín, Daranas and Sarotti have now combined these two approaches, using computed ¹H and ¹³C chemical shifts and ³J_HH coupling constants with the DP4 framework to predict chemical structure.¹

They describe two different approaches to incorporate coupling constants:

• dJ-DP4 (direct method) incorporates the coupling constants into a new probability function, using the coupling constants in an analogous way as chemical shifts. This requires explicit computation of all chemical shifts and ³J_HH coupling constants for all low-energy conformations.
• iJ-DP4 (indirect method) uses the experimental coupling constants to set conformational constraints thereby reducing the number of total conformations that need be sampled. Thus, large values of the coupling constant (³J_HH > 8 Hz) selects conformations with coplanar hydrogens, while small values (³J_HH < 4 Hz) selects conformations with perpendicular hydrogens. Other values are ignored. Typically, only one or two coupling constants are used to select the viable conformations.

The authors test these two variants on 69 molecules. The original DP4 method predicted the correct stereoisomer for 75% of the examples, while dJ-DP4 correct identifies 96% of the cases. As a test of the indirect method, they examined marilzabicycloallenes A and B (1 and 2). DP4 predicts the correct stereoisomer with only 3.1% (1) or <0.1% (2) probability. dJ-DP4 predicts the correct isomer for 1 with 99.9% probability and 97.6% probability for 2. The advantage of iJ-DP4 is that using one coupling constant reduces the number of conformations that must be computed by 84%, yet maintains a probability of getting the correct assignment at 99.2% or better. Using two coupling constants to constrain conformations means that only 7% of all of the conformations need to be samples, and the predictive power is maintained.

1

2

Both of these new methods clearly deserve further application.

References

1. Grimblat, N.; Gavín, J. A.; Hernández Daranas, A.; Sarotti, A. M., “Combining the Power of J Coupling and DP4 Analysis on Stereochemical Assignments: The J-DP4 Methods.” Org. Letters 2019, 21, 4003-4007, DOI: 10.1021/acs.orglett.9b01193.

InChIs

1: InChI=1S/C15H21Br2ClO4/c1-8-15(20)14-6-10(17)12(19)7-11(18)13(22-14)5-9(21-8)3-2-4-16/h3-4,8-15,19-20H,5-7H2,1H3/t2-,8-,9+,10-,11+,12+,13+,14+,15-/m0/s1
InChIKey=APNVVMOUATXTFG-NTSAAJDMSA-N

2: InChI=1S/C15H21Br2ClO4/c1-8-15(20)14-6-10(17)12(19)7-11(18)13(22-14)5-9(21-8)3-2-4-16/h3-4,8-15,19-20H,5-7H2,1H3/t2-,8-,9-,10-,11+,12+,13+,14+,15-/m0/s1
InChIKey=APNVVMOUATXTFG-SSBNIETDSA-N

from Computational Organic Chemistry https://ift.tt/2YbmMYC

I have written quite a number of posts on using quantum mechanics computations to predict NMR spectra that can aid in identifying chemical structure. Perhaps the most robust technique is Goodman’s DP4 method (post), which has seen some recent revisions (updated DP4, DP4+). I have also posted on the use of computed coupling constants (posts).

Grimblat, Gavín, Daranas and Sarotti have now combined these two approaches, using computed ¹H and ¹³C chemical shifts and ³J_HH coupling constants with the DP4 framework to predict chemical structure.¹

They describe two different approaches to incorporate coupling constants:

• dJ-DP4 (direct method) incorporates the coupling constants into a new probability function, using the coupling constants in an analogous way as chemical shifts. This requires explicit computation of all chemical shifts and ³J_HH coupling constants for all low-energy conformations.
• iJ-DP4 (indirect method) uses the experimental coupling constants to set conformational constraints thereby reducing the number of total conformations that need be sampled. Thus, large values of the coupling constant (³J_HH > 8 Hz) selects conformations with coplanar hydrogens, while small values (³J_HH < 4 Hz) selects conformations with perpendicular hydrogens. Other values are ignored. Typically, only one or two coupling constants are used to select the viable conformations.

The authors test these two variants on 69 molecules. The original DP4 method predicted the correct stereoisomer for 75% of the examples, while dJ-DP4 correct identifies 96% of the cases. As a test of the indirect method, they examined marilzabicycloallenes A and B (1 and 2). DP4 predicts the correct stereoisomer with only 3.1% (1) or <0.1% (2) probability. dJ-DP4 predicts the correct isomer for 1 with 99.9% probability and 97.6% probability for 2. The advantage of iJ-DP4 is that using one coupling constant reduces the number of conformations that must be computed by 84%, yet maintains a probability of getting the correct assignment at 99.2% or better. Using two coupling constants to constrain conformations means that only 7% of all of the conformations need to be samples, and the predictive power is maintained.

1

2

Both of these new methods clearly deserve further application.

References

1. Grimblat, N.; Gavín, J. A.; Hernández Daranas, A.; Sarotti, A. M., “Combining the Power of J Coupling and DP4 Analysis on Stereochemical Assignments: The J-DP4 Methods.” Org. Letters 2019, 21, 4003-4007, DOI: 10.1021/acs.orglett.9b01193.

InChIs

1: InChI=1S/C15H21Br2ClO4/c1-8-15(20)14-6-10(17)12(19)7-11(18)13(22-14)5-9(21-8)3-2-4-16/h3-4,8-15,19-20H,5-7H2,1H3/t2-,8-,9+,10-,11+,12+,13+,14+,15-/m0/s1
InChIKey=APNVVMOUATXTFG-NTSAAJDMSA-N

2: InChI=1S/C15H21Br2ClO4/c1-8-15(20)14-6-10(17)12(19)7-11(18)13(22-14)5-9(21-8)3-2-4-16/h3-4,8-15,19-20H,5-7H2,1H3/t2-,8-,9-,10-,11+,12+,13+,14+,15-/m0/s1
InChIKey=APNVVMOUATXTFG-SSBNIETDSA-N

from Computational Organic Chemistry https://ift.tt/2YbmMYC

Using vibrational frequencies to identify stereoisomers

Can vibrational spectroscopy be used to identify stereoisomers? Medel, Stelbrink, and Suhm have examined the vibrational spectra of (+)- and (-)-α-pinene, (±)-1, in the presence of four different chiral terpenes 2-5.¹ They recorded gas phase spectra by thermal expansion of a chiral α-pinene with each chiral terpene.

For the complex of 4 with (+)-1 or (-)-1 and 5 with (+)-1 or (-)-1, the OH vibrational frequency is identical for the two different stereoisomers. However, the OH vibrational frequencies differ by 2 cm^-1 with 3, and the complex of 3/(+)-1 displays two different OH stretches that differ by 11 cm^-1. And in the case of the complex of α-pinene with 2, the OH vibrational frequencies of the two different stereoisomers differ by 11 cm^-1!

The B3LYP-D3(BJ)/def2-TZVP optimized geometry of the 2/(+)-1 and 2/(-)-1 complexes are shown in Figure 2, and some subtle differences in sterics and dispersion give rise to the different vibrational frequencies.

2/(+)-1

2/(-)-1

Figure 2. B3LYP-D3(BJ)/def2-TZVP optimized geometry of the 2/(+)-1 and 2/(-)-1

Of interest to readers of this blog will be the DFT study of these complexes. The authors used three different well-known methods – B3LYP-D3(BJ)/def2-TZVP, M06-2x/def2-TZVP, and ωB97X-D/def2-TZVP – to compute structures and (most importantly) predict the vibrational frequencies. Interestingly, M06-2x/def2-TZVP and ωB97X-D/ def2-TZVP both failed to predict the vibrational frequency difference between the complexes with the two stereoisomers of α-pinene. However, B3LYP-D3(BJ)/def2-TZVP performed extremely well, with a mean average error (MAE) of only 1.9 cm^-1 for the four different terpenes. Using this functional and the larger may-cc-pvtz basis set reduced the MAE to 1.5 cm^-1 with the largest error of only 2.5 cm^-1.

As the authors note, these complexes provide some fertile ground for further experimental and computational study and benchmarking.

Reference

1. Medel, R.; Stelbrink, C.; Suhm, M. A., “Vibrational Signatures of Chirality Recognition Between α-Pinene and Alcohols for Theory Benchmarking.” Angew. Chem. Int. Ed. 2019, 58, 8177-8181, DOI: 10.1002/anie.201901687.

InChIs

(-)-1, (-)-α-pinene: InChI=1S/C10H16/c1-7-4-5-8-6-9(7)10(8,2)3/h4,8-9H,5-6H2,1-3H3/t8-,9-/m0/s1
InChIKey=GRWFGVWFFZKLTI-IUCAKERBSA-N

(+)-1, (-)-α-pinene: InChI=1S/C10H16/c1-7-4-5-8-6-9(7)10(8,2)3/h4,8-9H,5-6H2,1-3H3/t8-,9-/m1/s1
InChIKey=GRWFGVWFFZKLTI-RKDXNWHRSA-N

2, (-)borneol: InChI=1S/C10H18O/c1-9(2)7-4-5-10(9,3)8(11)6-7/h7-8,11H,4-6H2,1-3H3/t7-,8+,10+/m0/s1
InChiKey=DTGKSKDOIYIVQL-QXFUBDJGSA-N

3, (+)-fenchol: InChI=1S/C10H18O/c1-9(2)7-4-5-10(3,6-7)8(9)11/h7-8,11H,4-6H2,1-3H3/t7-,8-,10+/m0/s1
InChIKey=IAIHUHQCLTYTSF-OYNCUSHFSA-N

4, (-1)-isopinocampheol: InChI=1S/C10H18O/c1-6-8-4-7(5-9(6)11)10(8,2)3/h6-9,11H,4-5H2,1-3H3/t6-,7+,8-,9-/m1/s1
InChIKey=REPVLJRCJUVQFA-BZNPZCIMSA-N

5, (1S)-1-phenylethanol: InChI=1S/C8H10O/c1-7(9)8-5-3-2-4-6-8/h2-7,9H,1H3/t7-/m0/s1
InChIKey=WAPNOHKVXSQRPX-ZETCQYMHSA-N

from Computational Organic Chemistry http://bit.ly/2KzOsCC

Can vibrational spectroscopy be used to identify stereoisomers? Medel, Stelbrink, and Suhm have examined the vibrational spectra of (+)- and (-)-α-pinene, (±)-1, in the presence of four different chiral terpenes 2-5.¹ They recorded gas phase spectra by thermal expansion of a chiral α-pinene with each chiral terpene.

For the complex of 4 with (+)-1 or (-)-1 and 5 with (+)-1 or (-)-1, the OH vibrational frequency is identical for the two different stereoisomers. However, the OH vibrational frequencies differ by 2 cm^-1 with 3, and the complex of 3/(+)-1 displays two different OH stretches that differ by 11 cm^-1. And in the case of the complex of α-pinene with 2, the OH vibrational frequencies of the two different stereoisomers differ by 11 cm^-1!

The B3LYP-D3(BJ)/def2-TZVP optimized geometry of the 2/(+)-1 and 2/(-)-1 complexes are shown in Figure 2, and some subtle differences in sterics and dispersion give rise to the different vibrational frequencies.

2/(+)-1

2/(-)-1

Figure 2. B3LYP-D3(BJ)/def2-TZVP optimized geometry of the 2/(+)-1 and 2/(-)-1

Of interest to readers of this blog will be the DFT study of these complexes. The authors used three different well-known methods – B3LYP-D3(BJ)/def2-TZVP, M06-2x/def2-TZVP, and ωB97X-D/def2-TZVP – to compute structures and (most importantly) predict the vibrational frequencies. Interestingly, M06-2x/def2-TZVP and ωB97X-D/ def2-TZVP both failed to predict the vibrational frequency difference between the complexes with the two stereoisomers of α-pinene. However, B3LYP-D3(BJ)/def2-TZVP performed extremely well, with a mean average error (MAE) of only 1.9 cm^-1 for the four different terpenes. Using this functional and the larger may-cc-pvtz basis set reduced the MAE to 1.5 cm^-1 with the largest error of only 2.5 cm^-1.

As the authors note, these complexes provide some fertile ground for further experimental and computational study and benchmarking.

Reference

1. Medel, R.; Stelbrink, C.; Suhm, M. A., “Vibrational Signatures of Chirality Recognition Between α-Pinene and Alcohols for Theory Benchmarking.” Angew. Chem. Int. Ed. 2019, 58, 8177-8181, DOI: 10.1002/anie.201901687.

InChIs

(-)-1, (-)-α-pinene: InChI=1S/C10H16/c1-7-4-5-8-6-9(7)10(8,2)3/h4,8-9H,5-6H2,1-3H3/t8-,9-/m0/s1
InChIKey=GRWFGVWFFZKLTI-IUCAKERBSA-N

(+)-1, (-)-α-pinene: InChI=1S/C10H16/c1-7-4-5-8-6-9(7)10(8,2)3/h4,8-9H,5-6H2,1-3H3/t8-,9-/m1/s1
InChIKey=GRWFGVWFFZKLTI-RKDXNWHRSA-N

2, (-)borneol: InChI=1S/C10H18O/c1-9(2)7-4-5-10(9,3)8(11)6-7/h7-8,11H,4-6H2,1-3H3/t7-,8+,10+/m0/s1
InChiKey=DTGKSKDOIYIVQL-QXFUBDJGSA-N

3, (+)-fenchol: InChI=1S/C10H18O/c1-9(2)7-4-5-10(3,6-7)8(9)11/h7-8,11H,4-6H2,1-3H3/t7-,8-,10+/m0/s1
InChIKey=IAIHUHQCLTYTSF-OYNCUSHFSA-N

4, (-1)-isopinocampheol: InChI=1S/C10H18O/c1-6-8-4-7(5-9(6)11)10(8,2)3/h6-9,11H,4-5H2,1-3H3/t6-,7+,8-,9-/m1/s1
InChIKey=REPVLJRCJUVQFA-BZNPZCIMSA-N

5, (1S)-1-phenylethanol: InChI=1S/C8H10O/c1-7(9)8-5-3-2-4-6-8/h2-7,9H,1H3/t7-/m0/s1
InChIKey=WAPNOHKVXSQRPX-ZETCQYMHSA-N

from Computational Organic Chemistry http://bit.ly/2KzOsCC

Trispericyclic transition state

A major topic of this blog has been the growing body of studies that demonstrate that dynamic effects can control reaction products (see these posts). Often these examples crop up with valley ridge inflection points. Another cause can be bispericyclic transition states, first discovered by Caramello et al for the dimerization of cyclopentadiene.¹ The Houk group now reports on the first trispericyclic transition state.²

Using ωB97X-D/6-31G(d), they examined the reaction of the tropone derivative 1 with dimethylfulvene 2. Three possible products can arrive from different pericyclic reactions: 3, the [4+6] product; 4, the [6+4] product; and 5, the [8+2] product. The thermodynamic product is predicted to be 5, but it is only 1.2 kcal mol^-1 lower in energy than 4 and 6.2 kcal mol^-1 lower than 3.

They identified one transition state originating from the reactants TS1. Hypothesizing that it would be trispericyclic, they performed a molecular dynamics study with trajectories starting from TS1. They ran a total of 142 trajectories, and 87% led to 3, 3% led to 4, and 3% led to 5. This demonstrates the unusual nature of TS1 and the dynamic effects on this reaction surface.

TS1
TS2	TS3

Figure 1. ωB97X-D/6-31G(d) optimized geometries of TS1-TS3.

Additionally, there are two different Cope rearrangements (through TS2 and TS3) that convert 3 into 4 and 5. Some trajectories can pass from TS1 and then directly through either TS2 or TS3 and these give rise to products 4 and 5. In other words, some trajectories will pass from a trispericyclic transition state and then through a bispericyclic transition state before ending in product.

References

1. Caramella, P.; Quadrelli, P.; Toma, L., “An Unexpected Bispericyclic Transition Structure Leading to 4+2 and 2+4 Cycloadducts in the Endo Dimerization of Cyclopentadiene.” J. Am. Chem. Soc. 2002, 124, 1130-1131, DOI: 10.1021/ja016622h

2. Xue, X.-S.; Jamieson, C. S.; Garcia-Borràs, M.; Dong, X.; Yang, Z.; Houk, K. N., “Ambimodal Trispericyclic Transition State and Dynamic Control of Periselectivity.” J. Am. Chem. Soc. 2019, 141, 1217-1221, DOI: 10.1021/jacs.8b12674.

InChIs

1: InChI=1S/C10H6N2/c11-7-10(8-12)9-5-3-1-2-4-6-9/h1-6H
InChIKey=KAWLLELUFONBGI-UHFFFAOYSA-N

2: InChI=1S/C8H10/c1-7(2)8-5-3-4-6-8/h3-6H,1-2H3
InChIKey=WXACXMWYHXOSIX-UHFFFAOYSA-N

3: InChI=1S/C18H16N2/c1-11(2)17-15-7-8-16(17)14-6-4-3-5-13(15)18(14)12(9-19)10-20/h3-8,13-16H,1-2H3
InChIKey=DRPXVBLNTKGMTB-UHFFFAOYSA-N

4: InChI=1S/C18H16N2/c1-18(2)13-6-8-14(12(10-19)11-20)15(9-7-13)16-4-3-5-17(16)18/h3-9,13,15-16H,1-2H3
InChIKey=FSIPGNLAWKVXDD-UHFFFAOYSA-N

5: InChI=1S/C18H16N2/c1-12(2)13-8-9-16-17(13)14-6-4-3-5-7-15(14)18(16,10-19)11-20/h3-9,14,16-17H,1-2H3/t14?,16-,17-/m1/s1
InChIKey=SYLWEGLODFLARZ-VNCLPFQGSA-N

from Computational Organic Chemistry http://bit.ly/2I8mltF

A major topic of this blog has been the growing body of studies that demonstrate that dynamic effects can control reaction products (see these posts). Often these examples crop up with valley ridge inflection points. Another cause can be bispericyclic transition states, first discovered by Caramello et al for the dimerization of cyclopentadiene.¹ The Houk group now reports on the first trispericyclic transition state.²

Using ωB97X-D/6-31G(d), they examined the reaction of the tropone derivative 1 with dimethylfulvene 2. Three possible products can arrive from different pericyclic reactions: 3, the [4+6] product; 4, the [6+4] product; and 5, the [8+2] product. The thermodynamic product is predicted to be 5, but it is only 1.2 kcal mol^-1 lower in energy than 4 and 6.2 kcal mol^-1 lower than 3.

They identified one transition state originating from the reactants TS1. Hypothesizing that it would be trispericyclic, they performed a molecular dynamics study with trajectories starting from TS1. They ran a total of 142 trajectories, and 87% led to 3, 3% led to 4, and 3% led to 5. This demonstrates the unusual nature of TS1 and the dynamic effects on this reaction surface.

TS1
TS2	TS3

Figure 1. ωB97X-D/6-31G(d) optimized geometries of TS1-TS3.

Additionally, there are two different Cope rearrangements (through TS2 and TS3) that convert 3 into 4 and 5. Some trajectories can pass from TS1 and then directly through either TS2 or TS3 and these give rise to products 4 and 5. In other words, some trajectories will pass from a trispericyclic transition state and then through a bispericyclic transition state before ending in product.

References

1. Caramella, P.; Quadrelli, P.; Toma, L., “An Unexpected Bispericyclic Transition Structure Leading to 4+2 and 2+4 Cycloadducts in the Endo Dimerization of Cyclopentadiene.” J. Am. Chem. Soc. 2002, 124, 1130-1131, DOI: 10.1021/ja016622h

2. Xue, X.-S.; Jamieson, C. S.; Garcia-Borràs, M.; Dong, X.; Yang, Z.; Houk, K. N., “Ambimodal Trispericyclic Transition State and Dynamic Control of Periselectivity.” J. Am. Chem. Soc. 2019, 141, 1217-1221, DOI: 10.1021/jacs.8b12674.

InChIs

1: InChI=1S/C10H6N2/c11-7-10(8-12)9-5-3-1-2-4-6-9/h1-6H
InChIKey=KAWLLELUFONBGI-UHFFFAOYSA-N

2: InChI=1S/C8H10/c1-7(2)8-5-3-4-6-8/h3-6H,1-2H3
InChIKey=WXACXMWYHXOSIX-UHFFFAOYSA-N

3: InChI=1S/C18H16N2/c1-11(2)17-15-7-8-16(17)14-6-4-3-5-13(15)18(14)12(9-19)10-20/h3-8,13-16H,1-2H3
InChIKey=DRPXVBLNTKGMTB-UHFFFAOYSA-N

4: InChI=1S/C18H16N2/c1-18(2)13-6-8-14(12(10-19)11-20)15(9-7-13)16-4-3-5-17(16)18/h3-9,13,15-16H,1-2H3
InChIKey=FSIPGNLAWKVXDD-UHFFFAOYSA-N

5: InChI=1S/C18H16N2/c1-12(2)13-8-9-16-17(13)14-6-4-3-5-7-15(14)18(16,10-19)11-20/h3-9,14,16-17H,1-2H3/t14?,16-,17-/m1/s1
InChIKey=SYLWEGLODFLARZ-VNCLPFQGSA-N

from Computational Organic Chemistry http://bit.ly/2I8mltF

Planar ring in a nano-Saturn

For the past twelve years, I have avoided posting on any of my own papers, but I will stoop to some shameless promotion to mention my latest paper,¹ since it touches on some themes I have discussed in the past.

Back in 2011, Iwamoto, et al. prepared the complex of C₆₀ 1 surrounded by [10]cycloparaphenylene 2 to make the Saturn-like system 3.² Just last year, Yamamoto, et al prepared the Nano-Saturn 5a as the complex of 1 with the macrocycle 4a.³ The principle idea driving their synthesis was to utilize a ring that is flatter than 2. The structures of 3 and 5b (made with the parent macrocycle 4b) are shown in side view in Figure 1, and clearly seen is the achievement of the flatter ring.

3

5b

7

Figure 1. Computed structures of 3, 5, and 7.

However, the encompassing ring is not flat, with dihedral angles between the anthrenyl groups of 35°. This twisting is due to the steric interactions of the ortho-ortho’ hydrogens. A few years ago, my undergraduate student David Stück and I suggested that selective substitution of a nitrogen for one of the C-H groups would remove the steric interaction,⁴ leading to a planar poly-aryl system, such as making twisted biphenyl into the planar 2-(2-pyridyl)-pyridine (Scheme 1)

Scheme 1.

Following this idea leads to four symmetrical nitrogen-substituted analogues of 4b; and I’ll mention just one of them here, 6.

As expected, 6 is perfectly flat. The ring remains flat even when complexed with 1 (as per B3LYP-D3(BJ)/6-31G(d) computations), see the structure of 7 in Figure 1.

I also examined the complex of the flat macrocycle 6 (and its isomers) with a [5,5]-nanotube, 7. The tube bends over to create better dispersion interaction with the ring, which also become somewhat non-planar to accommodate the tube. Though not mentioned in the paper, I like to refer to 7 as Beyoncene, in tribute to All the Single Ladies.

Figure 2. Computed structure of 7.

My sister is a graphic designer and she made this terrific image for this work:

References

1. Bachrach, S. M., “Planar rings in nano-Saturns and related complexes.” Chem. Commun. 2019, 55, 3650-3653, DOI: 10.1039/C9CC01234F.

2. Iwamoto, T.; Watanabe, Y.; Sadahiro, T.; Haino, T.; Yamago, S., “Size-Selective Encapsulation of C₆₀ by [10]Cycloparaphenylene: Formation of the Shortest Fullerene-Peapod.” Angew. Chem. Int. Ed. 2011, 50, 8342-8344, DOI: 10.1002/anie.201102302

3. Yamamoto, Y.; Tsurumaki, E.; Wakamatsu, K.; Toyota, S., “Nano-Saturn: Experimental Evidence of Complex Formation of an Anthracene Cyclic Ring with C60.” Angew. Chem. Int. Ed. 2018 , 57, 8199-8202, DOI: 10.1002/anie.201804430.

4. Bachrach, S. M.; Stück, D., “DFT Study of Cycloparaphenylenes and Heteroatom-Substituted Nanohoops.” J. Org. Chem. 2010, 75, 6595-6604, DOI: 10.1021/jo101371m

InChIs

4b: InChI=1S/C84H48/c1-13-61-25-62-15-3-51-33-75(62)43-73(61)31-49(1)50-2-14-63-26-64-16-4-52(34-76(64)44-74(63)32-50)54-6-18-66-28-68-20-8-56(38-80(68)46-78(66)36-54)58-10-22-70-30-72-24-12-60(42-84(72)48-82(70)40-58)59-11-23-71-29-69-21-9-57(39-81(69)47-83(71)41-59)55-7-19-67-27-65-17-5-53(51)35-77(65)45-79(67)37-55/h1-48H
InChIKey=ZYXXLAYETADMDM-UHFFFAOYSA-N

6: InChI=1S/C72H36N12/c1-2-38-14-44-20-45-25-67(73-31-50(45)13-37(1)44)57-9-4-39-15-51-32-74-68(26-46(51)21-61(39)80-57)58-10-5-40-16-52-33-75-69(27-47(52)22-62(40)81-58)59-11-6-41-17-53-34-76-70(28-48(53)23-63(41)82-59)60-12-7-42-18-54-35-77-71(29-49(54)24-64(42)83-60)72-78-36-55-19-43-3-8-56(38)79-65(43)30-66(55)84-72/h1-36H
InChIKey=NSSCKPFBHGOOIJ-UHFFFAOYSA-N

from Computational Organic Chemistry https://ift.tt/2FBuV1R

For the past twelve years, I have avoided posting on any of my own papers, but I will stoop to some shameless promotion to mention my latest paper,¹ since it touches on some themes I have discussed in the past.

Back in 2011, Iwamoto, et al. prepared the complex of C₆₀ 1 surrounded by [10]cycloparaphenylene 2 to make the Saturn-like system 3.² Just last year, Yamamoto, et al prepared the Nano-Saturn 5a as the complex of 1 with the macrocycle 4a.³ The principle idea driving their synthesis was to utilize a ring that is flatter than 2. The structures of 3 and 5b (made with the parent macrocycle 4b) are shown in side view in Figure 1, and clearly seen is the achievement of the flatter ring.

3

5b

7

Figure 1. Computed structures of 3, 5, and 7.

However, the encompassing ring is not flat, with dihedral angles between the anthrenyl groups of 35°. This twisting is due to the steric interactions of the ortho-ortho’ hydrogens. A few years ago, my undergraduate student David Stück and I suggested that selective substitution of a nitrogen for one of the C-H groups would remove the steric interaction,⁴ leading to a planar poly-aryl system, such as making twisted biphenyl into the planar 2-(2-pyridyl)-pyridine (Scheme 1)

Scheme 1.

Following this idea leads to four symmetrical nitrogen-substituted analogues of 4b; and I’ll mention just one of them here, 6.

As expected, 6 is perfectly flat. The ring remains flat even when complexed with 1 (as per B3LYP-D3(BJ)/6-31G(d) computations), see the structure of 7 in Figure 1.

I also examined the complex of the flat macrocycle 6 (and its isomers) with a [5,5]-nanotube, 7. The tube bends over to create better dispersion interaction with the ring, which also become somewhat non-planar to accommodate the tube. Though not mentioned in the paper, I like to refer to 7 as Beyoncene, in tribute to All the Single Ladies.

Figure 2. Computed structure of 7.

My sister is a graphic designer and she made this terrific image for this work:

References

1. Bachrach, S. M., “Planar rings in nano-Saturns and related complexes.” Chem. Commun. 2019, 55, 3650-3653, DOI: 10.1039/C9CC01234F.

2. Iwamoto, T.; Watanabe, Y.; Sadahiro, T.; Haino, T.; Yamago, S., “Size-Selective Encapsulation of C₆₀ by [10]Cycloparaphenylene: Formation of the Shortest Fullerene-Peapod.” Angew. Chem. Int. Ed. 2011, 50, 8342-8344, DOI: 10.1002/anie.201102302

3. Yamamoto, Y.; Tsurumaki, E.; Wakamatsu, K.; Toyota, S., “Nano-Saturn: Experimental Evidence of Complex Formation of an Anthracene Cyclic Ring with C60.” Angew. Chem. Int. Ed. 2018 , 57, 8199-8202, DOI: 10.1002/anie.201804430.

4. Bachrach, S. M.; Stück, D., “DFT Study of Cycloparaphenylenes and Heteroatom-Substituted Nanohoops.” J. Org. Chem. 2010, 75, 6595-6604, DOI: 10.1021/jo101371m

InChIs

4b: InChI=1S/C84H48/c1-13-61-25-62-15-3-51-33-75(62)43-73(61)31-49(1)50-2-14-63-26-64-16-4-52(34-76(64)44-74(63)32-50)54-6-18-66-28-68-20-8-56(38-80(68)46-78(66)36-54)58-10-22-70-30-72-24-12-60(42-84(72)48-82(70)40-58)59-11-23-71-29-69-21-9-57(39-81(69)47-83(71)41-59)55-7-19-67-27-65-17-5-53(51)35-77(65)45-79(67)37-55/h1-48H
InChIKey=ZYXXLAYETADMDM-UHFFFAOYSA-N

6: InChI=1S/C72H36N12/c1-2-38-14-44-20-45-25-67(73-31-50(45)13-37(1)44)57-9-4-39-15-51-32-74-68(26-46(51)21-61(39)80-57)58-10-5-40-16-52-33-75-69(27-47(52)22-62(40)81-58)59-11-6-41-17-53-34-76-70(28-48(53)23-63(41)82-59)60-12-7-42-18-54-35-77-71(29-49(54)24-64(42)83-60)72-78-36-55-19-43-3-8-56(38)79-65(43)30-66(55)84-72/h1-36H
InChIKey=NSSCKPFBHGOOIJ-UHFFFAOYSA-N

from Computational Organic Chemistry https://ift.tt/2FBuV1R

More DFT benchmarking

Selecting the appropriate density functional for one’s molecular system at hand is often a very confounding problem, especially for non-expert or first-time users of computational chemistry. The DFT zoo is vast and confusing, and perhaps what makes the situation worse is that there is no lack of benchmarking studies. For example, I have made more than 30 posts on benchmark studies, and I made no attempt to be comprehensive over the past dozen years!

One such benchmark study that I missed was presented by Mardirossian and Head-Gordon in 2017.¹ They evaluated 200 density functional using the MGCDB84 database, a combination of data from a number of different groups. They make a series of recommendations for local GGA, local meta-GGA, hybrid GGA, and hybrid meta-GGA functionals. And when pressed to choose just one functional overall, they opt for ωB97M-V, a range-separated hybrid meta-GGA with VV10 nonlocal correlation.

Georigk and Mehta² just recently offer a review of the density functional zoo. Leaning heavily on benchmark studies using the GMTKN55³ database, they report a number of observations. Of no surprise to readers of this blog, their main conclusion is that accounting for London dispersion is essential, usually through some type of correction like those proposed by Grimme.

These authors also note the general disparity between the most accurate, best performing functional per the benchmark studies and the results of the DFT poll conducted for many years by Swart, Bickelhaupt and Duran. It is somewhat remarkable that PBE or PBE0 have topped the poll for many years, despite the fact that many newer functionals perform better. As always, when choosing a functional caveat emptor.

References

1.  Mardirossian, N.; Head-Gordon, M., “Thirty years of density functional theory in computational chemistry: an overview and extensive assessment of 200 density functionals.” Mol. Phys. 2017, 115, 2315-2372, DOI: 10.1080/00268976.2017.1333644.

2. Goerigk, L.; Mehta, N., “A Trip to the Density Functional Theory Zoo: Warnings and Recommendations for the User.” Aust. J. Chem. 2019, ASAP, DOI: 10.1071/CH19023.

3. Goerigk, L.; Hansen, A.; Bauer, C.; Ehrlich, S.; Najibi, A.; Grimme, S., “A look at the density functional theory zoo with the advanced GMTKN55 database for general main group thermochemistry, kinetics and noncovalent interactions.” Phys. Chem. Chem. Phys. 2017, 19, 32184-32215, DOI: 10.1039/C7CP04913G.

from Computational Organic Chemistry https://ift.tt/2HpXW2F

Selecting the appropriate density functional for one’s molecular system at hand is often a very confounding problem, especially for non-expert or first-time users of computational chemistry. The DFT zoo is vast and confusing, and perhaps what makes the situation worse is that there is no lack of benchmarking studies. For example, I have made more than 30 posts on benchmark studies, and I made no attempt to be comprehensive over the past dozen years!

One such benchmark study that I missed was presented by Mardirossian and Head-Gordon in 2017.¹ They evaluated 200 density functional using the MGCDB84 database, a combination of data from a number of different groups. They make a series of recommendations for local GGA, local meta-GGA, hybrid GGA, and hybrid meta-GGA functionals. And when pressed to choose just one functional overall, they opt for ωB97M-V, a range-separated hybrid meta-GGA with VV10 nonlocal correlation.

Georigk and Mehta² just recently offer a review of the density functional zoo. Leaning heavily on benchmark studies using the GMTKN55³ database, they report a number of observations. Of no surprise to readers of this blog, their main conclusion is that accounting for London dispersion is essential, usually through some type of correction like those proposed by Grimme.

These authors also note the general disparity between the most accurate, best performing functional per the benchmark studies and the results of the DFT poll conducted for many years by Swart, Bickelhaupt and Duran. It is somewhat remarkable that PBE or PBE0 have topped the poll for many years, despite the fact that many newer functionals perform better. As always, when choosing a functional caveat emptor.

References

1.  Mardirossian, N.; Head-Gordon, M., “Thirty years of density functional theory in computational chemistry: an overview and extensive assessment of 200 density functionals.” Mol. Phys. 2017, 115, 2315-2372, DOI: 10.1080/00268976.2017.1333644.

2. Goerigk, L.; Mehta, N., “A Trip to the Density Functional Theory Zoo: Warnings and Recommendations for the User.” Aust. J. Chem. 2019, ASAP, DOI: 10.1071/CH19023.

3. Goerigk, L.; Hansen, A.; Bauer, C.; Ehrlich, S.; Najibi, A.; Grimme, S., “A look at the density functional theory zoo with the advanced GMTKN55 database for general main group thermochemistry, kinetics and noncovalent interactions.” Phys. Chem. Chem. Phys. 2017, 19, 32184-32215, DOI: 10.1039/C7CP04913G.

from Computational Organic Chemistry https://ift.tt/2HpXW2F

dodecaphenyltetracene

The Pascal group has synthesized dodecaphenyltetracene 1.¹

While this paper has little computational work, it is of interest to readers of this blog since I have discussed many aspect of aromaticity. This new tetracene is notable for its large twisting along the tetracene axis: about 97° in the x-ray structure. I have optimized the structure of 1 at B3LYP-D3(BJ)/6-311G(d) and its structure is shown in Figure 1. It is twisted by about 94°. The computed and x-ray structures are quite similar, as seen in Figure 2. Here the x-ray structure is shown with red balls, the computed structure with gray balls, and hydrogens have been removed for clarity.

Figure 1. B3LYP-D3(BJ)/6-311G(d) optimized structure of 1.

Figure 2. Comparison of the x-ray (red) and computed (gray) structures of 1. (Hydrogens omitted for clarity.)

The authors note that this molecule is chiral, having near D₂ symmetry. (The optimized structure has D₂ symmetry.) They performed AM1 computations to estimate a very low barrier for racemization of only 17.3 kcal mol^-1, leading to a half-life of less than one second at RT.

A notable aspect of the molecule is that aromaticity can adapt to significant twisting yet retain aromatic character. For example, the molecule is stable even surviving boiling off of chloroform (61 °C) to form crystals and the majority of the C-C bonds in the tetracene portion have distances typical of aromatic systems (~1.4 Å).

References

1) Xiao, Y.; Mague, J. T.; Schmehl, R. H.; Haque, F. M.; Pascal Jr., R. A., “Dodecaphenyltetracene.” Angew. Chem. Int. Ed. 2019, 58, 2831-2833, DOI: 10.1002/anie.201812418.

InChIs

1: InChI=1S/C90H60/c1-13-37-61(38-14-1)73-74(62-39-15-2-16-40-62)78(66-47-23-6-24-48-66)86-82(70-55-31-10-32-56-70)90-84(72-59-35-12-36-60-72)88-80(68-51-27-8-28-52-68)76(64-43-19-4-20-44-64)75(63-41-17-3-18-42-63)79(67-49-25-7-26-50-67)87(88)83(71-57-33-11-34-58-71)89(90)81(69-53-29-9-30-54-69)85(86)77(73)65-45-21-5-22-46-65/h1-60H
InChIKey=NJQABVWYMCSFNE-UHFFFAOYSA-N

from Computational Organic Chemistry https://ift.tt/2Spp3vB

The Pascal group has synthesized dodecaphenyltetracene 1.¹

While this paper has little computational work, it is of interest to readers of this blog since I have discussed many aspect of aromaticity. This new tetracene is notable for its large twisting along the tetracene axis: about 97° in the x-ray structure. I have optimized the structure of 1 at B3LYP-D3(BJ)/6-311G(d) and its structure is shown in Figure 1. It is twisted by about 94°. The computed and x-ray structures are quite similar, as seen in Figure 2. Here the x-ray structure is shown with red balls, the computed structure with gray balls, and hydrogens have been removed for clarity.

Figure 1. B3LYP-D3(BJ)/6-311G(d) optimized structure of 1.

Figure 2. Comparison of the x-ray (red) and computed (gray) structures of 1. (Hydrogens omitted for clarity.)

The authors note that this molecule is chiral, having near D₂ symmetry. (The optimized structure has D₂ symmetry.) They performed AM1 computations to estimate a very low barrier for racemization of only 17.3 kcal mol^-1, leading to a half-life of less than one second at RT.

A notable aspect of the molecule is that aromaticity can adapt to significant twisting yet retain aromatic character. For example, the molecule is stable even surviving boiling off of chloroform (61 °C) to form crystals and the majority of the C-C bonds in the tetracene portion have distances typical of aromatic systems (~1.4 Å).

References

1) Xiao, Y.; Mague, J. T.; Schmehl, R. H.; Haque, F. M.; Pascal Jr., R. A., “Dodecaphenyltetracene.” Angew. Chem. Int. Ed. 2019, 58, 2831-2833, DOI: 10.1002/anie.201812418.

InChIs

1: InChI=1S/C90H60/c1-13-37-61(38-14-1)73-74(62-39-15-2-16-40-62)78(66-47-23-6-24-48-66)86-82(70-55-31-10-32-56-70)90-84(72-59-35-12-36-60-72)88-80(68-51-27-8-28-52-68)76(64-43-19-4-20-44-64)75(63-41-17-3-18-42-63)79(67-49-25-7-26-50-67)87(88)83(71-57-33-11-34-58-71)89(90)81(69-53-29-9-30-54-69)85(86)77(73)65-45-21-5-22-46-65/h1-60H
InChIKey=NJQABVWYMCSFNE-UHFFFAOYSA-N

from Computational Organic Chemistry https://ift.tt/2Spp3vB

Very long C-C bond

Electrocycic reactions of cethrene derivatives

C18 carbomers

Interesting 18 π-electron systems involving cyclooctadecanonenetriyne rings have been synthesized and examined by computations.¹ The mono-, di- and tri-C₁₈
ring compounds 1, 2, and 3 were prepared and the x-ray structure of 2 was obtained. The B3PW91/6-31G(d,p) optimized geometries of 1-3 and of the tetra ring 4 are shown in Figure 1.

1

2

3

4

Figure 1. B3PW91/6-31G(d,p) optimized geometries of 1-4.

Since the rings are composed of 18 π-electrons in the π-system perpendicular to the nearly planar ring, the natural question is to wonder if the ring is aromatic. The authors computed NICS(0) and NICS(1) values at the center of the C₁₈ rings. For all four compounds, both the NICS(0) and NICS(1) values are negative, ranging from -12.4 to -14.9 ppm, indicating that the rings are aromatic.

References

1) Chongwei, Z.; Albert, P.; Carine, D.; Brice, K.; Alix, S.; Valérie, M.; Remi, C., "Carbo‐biphenyls and Carbo‐terphenyls: Oligo(phenylene ethynylene) Ring Carbo‐mers." Angew. Chem. Int. Ed. 2018, 57, 5640-5644, DOI: 10.1002/anie.201713411.

InChIs

1: InChI=1S/C58H54/c1-3-5-7-9-11-17-27-49-37-41-55(51-29-19-13-20-30-51)45-47-57(53-33-23-15-24-34-53)43-39-50(28-18-12-10-8-6-4-2)40-44-58(54-35-25-16-26-36-54)48-46-56(42-38-49)52-31-21-14-22-32-52/h13-16,19-26,29-36H,3-12,17-18,27-28H2,1-2H3
InChIKey=KWXYBTWOEJBCQD-UHFFFAOYSA-N

2: InChI=1S/C102H74/c1-3-5-7-9-11-21-39-83-59-67-95(87-41-23-13-24-42-87)75-79-99(91-49-31-17-32-50-91)71-63-85(64-72-100(92-51-33-18-34-52-92)80-76-96(68-60-83)88-43-25-14-26-44-88)57-58-86-65-73-101(93-53-35-19-36-54-93)81-77-97(89-45-27-15-28-46-89)69-61-84(40-22-12-10-8-6-4-2)62-70-98(90-47-29-16-30-48-90)78-82-102(74-66-86)94-55-37-20-38-56-94/h13-20,23-38,41-56H,3-12,21-22,39-40H2,1-2H3
InChIKey=HHRPTZGYBIHFOL-UHFFFAOYSA-N

3: InChI=1S/C146H94/c1-3-5-7-9-11-25-51-117-81-93-135(123-53-27-13-28-54-123)105-109-139(127-61-35-17-36-62-127)97-85-119(86-98-140(128-63-37-18-38-64-128)110-106-136(94-82-117)124-55-29-14-30-56-124)77-79-121-89-101-143(131-69-43-21-44-70-131)113-115-145(133-73-47-23-48-74-133)103-91-122(92-104-146(134-75-49-24-50-76-134)116-114-144(102-90-121)132-71-45-22-46-72-132)80-78-120-87-99-141(129-65-39-19-40-66-129)111-107-137(125-57-31-15-32-58-125)95-83-118(52-26-12-10-8-6-4-2)84-96-138(126-59-33-16-34-60-126)108-112-142(100-88-120)130-67-41-20-42-68-130/h13-24,27-50,53-76H,3-12,25-26,51-52H2,1-2H3
InChIKey=WCBXPLIBHKYESX-UHFFFAOYSA-N

4: InChI=1S/C190H114/c1-3-5-7-9-11-29-63-151-103-119-175(159-65-31-13-32-66-159)135-139-179(163-73-39-17-40-74-163)123-107-153(108-124-180(164-75-41-18-42-76-164)140-136-176(120-104-151)160-67-33-14-34-68-160)97-99-155-111-127-183(167-81-47-21-48-82-167)143-147-187(171-89-55-25-56-90-171)131-115-157(116-132-188(172-91-57-26-58-92-172)148-144-184(128-112-155)168-83-49-22-50-84-168)101-102-158-117-133-189(173-93-59-27-60-94-173)149-145-185(169-85-51-23-52-86-169)129-113-156(114-130-186(170-87-53-24-54-88-170)146-150-190(134-118-158)174-95-61-28-62-96-174)100-98-154-109-125-181(165-77-43-19-44-78-165)141-137-177(161-69-35-15-36-70-161)121-105-152(64-30-12-10-8-6-4-2)106-122-178(162-71-37-16-38-72-162)138-142-182(126-110-154)166-79-45-20-46-80-166/h13-28,31-62,65-96H,3-12,29-30,63-64H2,1-2H3
InChIKey=LLVPDVPZEIYJGN-UHFFFAOYSA-N

from Computational Organic Chemistry https://ift.tt/2z9xeW5

Interesting 18 π-electron systems involving cyclooctadecanonenetriyne rings have been synthesized and examined by computations.¹ The mono-, di- and tri-C₁₈
ring compounds 1, 2, and 3 were prepared and the x-ray structure of 2 was obtained. The B3PW91/6-31G(d,p) optimized geometries of 1-3 and of the tetra ring 4 are shown in Figure 1.

1

2

3

4

Figure 1. B3PW91/6-31G(d,p) optimized geometries of 1-4.

Since the rings are composed of 18 π-electrons in the π-system perpendicular to the nearly planar ring, the natural question is to wonder if the ring is aromatic. The authors computed NICS(0) and NICS(1) values at the center of the C₁₈ rings. For all four compounds, both the NICS(0) and NICS(1) values are negative, ranging from -12.4 to -14.9 ppm, indicating that the rings are aromatic.

References

1) Chongwei, Z.; Albert, P.; Carine, D.; Brice, K.; Alix, S.; Valérie, M.; Remi, C., "Carbo‐biphenyls and Carbo‐terphenyls: Oligo(phenylene ethynylene) Ring Carbo‐mers." Angew. Chem. Int. Ed. 2018, 57, 5640-5644, DOI: 10.1002/anie.201713411.

InChIs

1: InChI=1S/C58H54/c1-3-5-7-9-11-17-27-49-37-41-55(51-29-19-13-20-30-51)45-47-57(53-33-23-15-24-34-53)43-39-50(28-18-12-10-8-6-4-2)40-44-58(54-35-25-16-26-36-54)48-46-56(42-38-49)52-31-21-14-22-32-52/h13-16,19-26,29-36H,3-12,17-18,27-28H2,1-2H3
InChIKey=KWXYBTWOEJBCQD-UHFFFAOYSA-N

2: InChI=1S/C102H74/c1-3-5-7-9-11-21-39-83-59-67-95(87-41-23-13-24-42-87)75-79-99(91-49-31-17-32-50-91)71-63-85(64-72-100(92-51-33-18-34-52-92)80-76-96(68-60-83)88-43-25-14-26-44-88)57-58-86-65-73-101(93-53-35-19-36-54-93)81-77-97(89-45-27-15-28-46-89)69-61-84(40-22-12-10-8-6-4-2)62-70-98(90-47-29-16-30-48-90)78-82-102(74-66-86)94-55-37-20-38-56-94/h13-20,23-38,41-56H,3-12,21-22,39-40H2,1-2H3
InChIKey=HHRPTZGYBIHFOL-UHFFFAOYSA-N

3: InChI=1S/C146H94/c1-3-5-7-9-11-25-51-117-81-93-135(123-53-27-13-28-54-123)105-109-139(127-61-35-17-36-62-127)97-85-119(86-98-140(128-63-37-18-38-64-128)110-106-136(94-82-117)124-55-29-14-30-56-124)77-79-121-89-101-143(131-69-43-21-44-70-131)113-115-145(133-73-47-23-48-74-133)103-91-122(92-104-146(134-75-49-24-50-76-134)116-114-144(102-90-121)132-71-45-22-46-72-132)80-78-120-87-99-141(129-65-39-19-40-66-129)111-107-137(125-57-31-15-32-58-125)95-83-118(52-26-12-10-8-6-4-2)84-96-138(126-59-33-16-34-60-126)108-112-142(100-88-120)130-67-41-20-42-68-130/h13-24,27-50,53-76H,3-12,25-26,51-52H2,1-2H3
InChIKey=WCBXPLIBHKYESX-UHFFFAOYSA-N

4: InChI=1S/C190H114/c1-3-5-7-9-11-29-63-151-103-119-175(159-65-31-13-32-66-159)135-139-179(163-73-39-17-40-74-163)123-107-153(108-124-180(164-75-41-18-42-76-164)140-136-176(120-104-151)160-67-33-14-34-68-160)97-99-155-111-127-183(167-81-47-21-48-82-167)143-147-187(171-89-55-25-56-90-171)131-115-157(116-132-188(172-91-57-26-58-92-172)148-144-184(128-112-155)168-83-49-22-50-84-168)101-102-158-117-133-189(173-93-59-27-60-94-173)149-145-185(169-85-51-23-52-86-169)129-113-156(114-130-186(170-87-53-24-54-88-170)146-150-190(134-118-158)174-95-61-28-62-96-174)100-98-154-109-125-181(165-77-43-19-44-78-165)141-137-177(161-69-35-15-36-70-161)121-105-152(64-30-12-10-8-6-4-2)106-122-178(162-71-37-16-38-72-162)138-142-182(126-110-154)166-79-45-20-46-80-166/h13-28,31-62,65-96H,3-12,29-30,63-64H2,1-2H3
InChIKey=LLVPDVPZEIYJGN-UHFFFAOYSA-N

from Computational Organic Chemistry https://ift.tt/2z9xeW5

Dynamics in the C-H insertion reaction of vinyl cations

A recent paper by Papov, Shao, Bagdasarian, Benton, Zou, Yang, Houk, and Nelson uncovers a vinyl cation insertion reaction that once again involves dynamic effects.¹

They find that vinyl triflates and cyclic vinyl triflates will react with [Ph₃C]⁺[HCB₁₁Cl₁₁]^– and triethylsilane to generate vinyl cations that can then be trapped through a C-H insertion reaction. For example, cyclohexenyl triflate 1 reacts in a cyclohexane solvent to give the insertion product 2.

The reactions of isomers 3 and 4 give different ratios of the two products 5 and 6. In both cases, the cyclohexyl is trapped predominantly at the site of the triflate substituent. This means that the mechanism cannot involve a cyclohexene intermediate, since then the two ratios should be identical.

They performed molecular dynamic trajectory analysis at the M062X/6-311+G(d,p) level, starting with the two transition states leading from 3 (TS3) and 4 (TS4), the only transition states located for the insertion reaction. The structures of these TSs are shown in Figure 1.

TS3

TS4

Figure 1. M062X/6-311+G(d,p) optimized geometries of TS3 and TS4.

The trajectories end up in two product basins associated with 5 and 6 starting with either TS3 or TS4. Thus, these transition states are ambimodal, and typical of reactions where dynamic effects dominate. For the reaction of 3, the majority of the trajectories starting at TS3 end up as 5, consistent with the experiments. Similarly, for the trajectories that start at TS4, the majority end up as 6, consistent with experiments.

Once again, we see that relatively simple organic reactions do not follow simple reaction mechanisms, that a single transition state leads to two different products and the product distributions are dependent on reaction dynamics. This may not be too surprising for the vinyl cation insertions given the many examples provide by the Tantillo group of cation rearrangements that are controlled by reaction dynamics (see for examples, this post and this post).

References

1. Popov, S.; Shao, B.; Bagdasarian, A. L.; Benton, T. R.; Zou, L.; Yang, Z.; Houk, K. N.; Nelson, H. M., "Teaching an old carbocation new tricks: Intermolecular C–H insertion reactions of vinyl cations." Science 2018, 361, 381-387, DOI: 10.1126/science.aat5440.

InChIs

1: InChI=1S/C7H10F3O3S/c8-7(9,10)14(11,12,13)6-4-2-1-3-5-6/h4H,1-3,5H2,(H,11,12,13)
InChIKey=CMPVYBNXADJVOM-UHFFFAOYSA-N

2: InChI<=1S/C12H22/c1-3-7-11(8-4-1)12-9-5-2-6-10-12/h11-12H,1-10H2
InChIKey=WVIIMZNLDWSIRH-UHFFFAOYSA-N

3: InChI=1S/C9H14F3O3S/c1-8(2)5-3-7(4-6-8)16(13,14,15)9(10,11)12/h3H,4-6H2,1-2H3,(H,13,14,15)
InChIKey=XDWBLRRAHKBZJR-UHFFFAOYSA-N

4: InChI=1S/C9H14F3O3S/c1-8(2)5-3-4-7(6-8)16(13,14,15)9(10,11)12/h4H,3,5-6H2,1-2H3,(H,13,14,15)
InChIKey=YHVCPSRICQJFDT-UHFFFAOYSA-N

5: InChI=1S/C14H26/c1-14(2)10-8-13(9-11-14)12-6-4-3-5-7-12/h12-13H,3-11H2,1-2H3
InChIKey=BZQBWUOXOYWYJC-UHFFFAOYSA-N

6: InChI=1S/C14H26/c1-14(2)10-6-9-13(11-14)12-7-4-3-5-8-12/h12-13H,3-11H2,1-2H3
InChIKey=AENMAOBTECURBO-UHFFFAOYSA-N

from Computational Organic Chemistry https://ift.tt/2OLUIJX

A recent paper by Papov, Shao, Bagdasarian, Benton, Zou, Yang, Houk, and Nelson uncovers a vinyl cation insertion reaction that once again involves dynamic effects.¹

They find that vinyl triflates and cyclic vinyl triflates will react with [Ph₃C]⁺[HCB₁₁Cl₁₁]^– and triethylsilane to generate vinyl cations that can then be trapped through a C-H insertion reaction. For example, cyclohexenyl triflate 1 reacts in a cyclohexane solvent to give the insertion product 2.

The reactions of isomers 3 and 4 give different ratios of the two products 5 and 6. In both cases, the cyclohexyl is trapped predominantly at the site of the triflate substituent. This means that the mechanism cannot involve a cyclohexene intermediate, since then the two ratios should be identical.

They performed molecular dynamic trajectory analysis at the M062X/6-311+G(d,p) level, starting with the two transition states leading from 3 (TS3) and 4 (TS4), the only transition states located for the insertion reaction. The structures of these TSs are shown in Figure 1.

TS3

TS4

Figure 1. M062X/6-311+G(d,p) optimized geometries of TS3 and TS4.

The trajectories end up in two product basins associated with 5 and 6 starting with either TS3 or TS4. Thus, these transition states are ambimodal, and typical of reactions where dynamic effects dominate. For the reaction of 3, the majority of the trajectories starting at TS3 end up as 5, consistent with the experiments. Similarly, for the trajectories that start at TS4, the majority end up as 6, consistent with experiments.

Once again, we see that relatively simple organic reactions do not follow simple reaction mechanisms, that a single transition state leads to two different products and the product distributions are dependent on reaction dynamics. This may not be too surprising for the vinyl cation insertions given the many examples provide by the Tantillo group of cation rearrangements that are controlled by reaction dynamics (see for examples, this post and this post).

References

1. Popov, S.; Shao, B.; Bagdasarian, A. L.; Benton, T. R.; Zou, L.; Yang, Z.; Houk, K. N.; Nelson, H. M., "Teaching an old carbocation new tricks: Intermolecular C–H insertion reactions of vinyl cations." Science 2018, 361, 381-387, DOI: 10.1126/science.aat5440.

InChIs

1: InChI=1S/C7H10F3O3S/c8-7(9,10)14(11,12,13)6-4-2-1-3-5-6/h4H,1-3,5H2,(H,11,12,13)
InChIKey=CMPVYBNXADJVOM-UHFFFAOYSA-N

2: InChI<=1S/C12H22/c1-3-7-11(8-4-1)12-9-5-2-6-10-12/h11-12H,1-10H2
InChIKey=WVIIMZNLDWSIRH-UHFFFAOYSA-N

3: InChI=1S/C9H14F3O3S/c1-8(2)5-3-7(4-6-8)16(13,14,15)9(10,11)12/h3H,4-6H2,1-2H3,(H,13,14,15)
InChIKey=XDWBLRRAHKBZJR-UHFFFAOYSA-N

4: InChI=1S/C9H14F3O3S/c1-8(2)5-3-4-7(6-8)16(13,14,15)9(10,11)12/h4H,3,5-6H2,1-2H3,(H,13,14,15)
InChIKey=YHVCPSRICQJFDT-UHFFFAOYSA-N

5: InChI=1S/C14H26/c1-14(2)10-8-13(9-11-14)12-6-4-3-5-7-12/h12-13H,3-11H2,1-2H3
InChIKey=BZQBWUOXOYWYJC-UHFFFAOYSA-N

6: InChI=1S/C14H26/c1-14(2)10-6-9-13(11-14)12-7-4-3-5-8-12/h12-13H,3-11H2,1-2H3
InChIKey=AENMAOBTECURBO-UHFFFAOYSA-N

from Computational Organic Chemistry https://ift.tt/2OLUIJX

Curved Aromatic molecules – 4 new examples

I have recently been interested in curved aromatic systems – see my own paper on double helicenes.¹ In this post, I cover four recent papers that discuss non-planar aromatic molecules.

The first paper² discusses the warped aromatic 1 built off of the scaffold of depleiadene 3. The crystal structure of 1 shows the molecule to be a saddle with near C_2v symmetry. B3LYP/6-31G computations indicate that the saddle isomer is 10.5 kcal mol^-1 more stable than the twisted isomer, and the barrier between them is 16.0 kcal mol^-1, with a twisted saddle intermediate as well.

The PES is significantly simpler for the structure lacking the t-butyl groups, 2. The B3LYP/6-31G PES of 2 has the saddle as the transition state interconverting mirror images of the twisted saddle isomer, and this barrier is only 1.8 kcal mol^-1. Figure 1 displays the twisted saddle and the saddle transition state. Clearly, the t-butyl groups significantly alter the flexibility of this C₈₆ aromatic surface. One should be somewhat concerned about the small basis set employed here, especially lacking polarization functions, and a functional that lacks dispersion correction. However, the computed geometry of 1 is quite similar to that of the x-ray structure.

2 twisted saddle (ground state)

2 saddle (transition state)

Figure 1. B3LYP/6-31G optimized geometries of the isomer of 2.

The second paper presents 4, a non-planar aromatic based on [8]circulene 6.³ (See this post for a general study of circulenes.) [8]circulene has a tub-shape, but is flexible and can undergo tub-to-tub inversion. The expanded aromatic 4 is found to have a twisted shape in the x-ray crystal structure. A simplified model 5 was computed at B3LYP/6-31G(d) and the twisted isomer is 4.1 kcal mol^-1 lower in energy than the saddle (tub) isomer (see Figure 2). The barrier for interconversion of the two isomers is only 6.2 kcal mol^-1, indicating a quite labile structure.

5 twisted 0.0

5 TS 6.2

5 saddle 4.1

Figure 2. B3LYP/6-31G(d) optimized geometries and relative energies (kcal mol^-1) of the isomers of 5.

The third paper presents a geodesic molecule based on 1,3,5-trisubstitued phenyl repeat units.⁴ The authors prepared 7, and its x-ray structure shows a saddle-shape. The NMR indicate a molecule that undergoes considerable conformational dynamics. To address this, they did some computations on the methyl analogue 8. The D_7h structure is 309 kcal mol^-1 above the local energy minimum structure, which is way too high to be accessed at room temperature. PM6 computations identified a TS only 0.6 kcal mol^-1 above the saddle ground state. (I performed a PM6 optimization starting from the x-ray structure, which is highly disordered, and the structure obtained is shown in Figure 3. Unfortunately, the authors did not report the optimized coordinates of any structure!)

Figure 3. PM6 optimized structure of 8.

The fourth and last paper describes the aza-buckybowl 9.⁵ The x-ray crystal structure shows a curved bowl shape with C_s symmetry. NICS(0) values were computed for the parent molecule 10 B3LYP/6-31G(d). These values are shown in Scheme 1 and the geometry is shown in Figure 4. The 6-member rings that surround the azacylopentadienyl ring all have NICS(0) near zero, which suggests significant bond localization.

Scheme 1. NICS(0) values of 10

Figure 4. B3LYP/6-31G(d) optimized structure of 10.

Our understanding of what aromaticity really means is constantly being challenged!

References

1. Bachrach, S. M., "Double helicenes." Chem. Phys. Lett. 2016, 666, 13-18, DOI: 10.1016/j.cplett.2016.10.070.

2. Ho, P. S.; Kit, C. C.; Jiye, L.; Zhifeng, L.; Qian, M., "A Dipleiadiene-Embedded Aromatic Saddle Consisting
of 86 Carbon Atoms." Angew. Chem. Int. Ed. 2018, 57, 1581-1586, DOI: 10.1002/anie.201711437.

3. Yin, C. K.; Kit, C. C.; Zhifeng, L.; Qian, M., "A Twisted Nanographene Consisting of 96 Carbon Atoms." Angew. Chem. Int. Ed. 2017, 56, 9003-9007, DOI: 10.1002/anie.201703754.

4. Koki, I.; Jennie, L.; Ryo, K.; Sota, S.; Hiroyuki, I., "Fluctuating Carbonaceous Networks with a Persistent
Molecular Shape: A Saddle-Shaped Geodesic Framework of 1,3,5-Trisubstituted Benzene (Phenine)." Angew. Chem. Int. Ed. 2018, 57, 8555-8559, DOI: 10.1002/anie.201803984.

5. Yuki, T.; Shingo, I.; Kyoko, N., "A Hybrid of Corannulene and Azacorannulene: Synthesis of a Highly Curved Nitrogen-Containing Buckybowl." Angew. Chem. Int. Ed. 2018, 57, 9818-9822, DOI: 10.1002/anie.201805678.

InChIs

1: InChI=1S/C134H128/c1-123(2,3)57-37-65-66-38-58(124(4,5)6)42-70-74-46-62(128(16,17)18)50-82-94(74)110-106(90(66)70)105-89(65)69(41-57)73-45-61(127(13,14)15)49-81-93(73)109(105)119-113-97(81)85(131(25,26)27)53-77-78-54-87(133(31,32)33)99-83-51-63(129(19,20)21)47-75-71-43-59(125(7,8)9)39-67-68-40-60(126(10,11)12)44-72-76-48-64(130(22,23)24)52-84-96(76)112-108(92(68)72)107(91(67)71)111(95(75)83)121-115(99)103(78)118-104-80(56-88(134(34,35)36)100(84)116(104)122(112)121)79-55-86(132(28,29)30)98(82)114(120(110)119)102(79)117(118)101(77)113/h37-56H,1-36H3
InChIKey=GKUTUWMASUJSFD-UHFFFAOYSA-N

2: InChI=1S/C86H32/c1-9-33-34-10-2-14-38-42-18-6-22-46-50-26-30-55-56-32-28-52-48-24-8-20-44-40-16-4-12-36-35-11-3-15-39-43-19-7-23-47-51-27-31-54-53-29-25-49-45-21-5-17-41-37(13-1)57(33)73-74(58(34)38)78(62(42)46)84-70(50)66(55)81(65(53)69(49)83(84)77(73)61(41)45)82-67(54)71(51)85-79(63(43)47)75(59(35)39)76(60(36)40)80(64(44)48)86(85)72(52)68(56)82/h1-32H
InChIKey=MXCDWJZMTKLBDM-UHFFFAOYSA-N

3: InChI=1S/C18H12/c1-2-6-14-11-12-16-8-4-3-7-15-10-9-13(5-1)17(14)18(15)16/h1-12H
InChIKey=KVJJNMIHWIRGRP-UHFFFAOYSA-N

4: InChI=1S/C132H108O4/c1-125(2,3)53-29-65-66-30-54(126(4,5)6)34-70-74-38-58(130(16,17)18)42-78-86-46-82-63-51-91(135-27)92(136-28)52-64(63)84-48-88-80-44-60(132(22,23)24)40-76-72-36-56(128(10,11)12)32-68-67-31-55(127(7,8)9)35-71-75-39-59(131(19,20)21)43-79-87-47-83-62-50-90(134-26)89(133-25)49-61(62)81-45-85-77-41-57(129(13,14)15)37-73-69(33-53)93(65)109-110(94(66)70)114(98(74)78)122-106(86)118-103(82)104(84)120-108(88)124-116(100(76)80)112(96(68)72)111(95(67)71)115(99(75)79)123(124)107(87)119(120)102(83)101(81)117(118)105(85)121(122)113(109)97(73)77/h29-52H,1-28H3
InChIKey=ZLPRACZKLACDHX-UHFFFAOYSA-N

5: InChI=1S/C108H60O4/c1-37-13-49-50-14-38(2)18-54-58-22-42(6)26-62-70-30-66-47-35-75(111-11)76(112-12)36-48(47)68-32-72-64-28-44(8)24-60-56-20-40(4)16-52-51-15-39(3)19-55-59-23-43(7)27-63-71-31-67-46-34-74(110-10)73(109-9)33-45(46)65-29-69-61-25-41(5)21-57-53(17-37)77(49)93-94(78(50)54)98(82(58)62)106-90(70)102-87(66)88(68)104-92(72)108-100(84(60)64)96(80(52)56)95(79(51)55)99(83(59)63)107(108)91(71)103(104)86(67)85(65)101(102)89(69)105(106)97(93)81(57)61/h13-36H,1-12H3
InChIKey=ZSIVUKSPPZUSQL-UHFFFAOYSA-N

6: InChI=1S/C32H16/c1-2-18-5-6-20-9-11-22-13-15-24-16-14-23-12-10-21-8-7-19-4-3-17(1)25-26(18)28(20)30(22)32(24)31(23)29(21)27(19)25/h1-16H
InChIkey=BASWMOIVIHXTRC-UHFFFAOYSA-N

7: InChI=1S/C224H210/c1-211(2,3)197-99-169-85-183(113-197)184-86-170(100-198(114-184)212(4,5)6)157-66-149-67-158(79-157)172-88-187(117-200(102-172)214(10,11)12)188-90-174(104-202(118-188)216(16,17)18)161-70-151-71-162(81-161)176-92-191(121-204(106-176)218(22,23)24)193-95-179(109-207(123-193)221(31,32)33)165-74-153-75-166(83-165)180-96-195(125-208(110-180)222(34,35)36)196-98-182(112-210(126-196)224(40,41)42)168-77-154-76-167(84-168)181-97-194(124-209(111-181)223(37,38)39)192-94-178(108-206(122-192)220(28,29)30)164-73-152-72-163(82-164)177-93-190(120-205(107-177)219(25,26)27)189-91-175(105-203(119-189)217(19,20)21)160-69-150-68-159(80-160)173-89-186(116-201(103-173)215(13,14)15)185-87-171(101-199(115-185)213(7,8)9)156-65-148(64-155(169)78-156)141-50-127-43-128(51-141)130-45-132(55-143(150)53-130)134-47-136(59-145(152)57-134)138-49-140(63-147(154)61-138)139-48-137(60-146(153)62-139)135-46-133(56-144(151)58-135)131-44-129(127)52-142(149)54-131/h43-126H,1-42H3
InChIKey=ZDDKJXIESSWTIA-UHFFFAOYSA-N

8: InChI=1S/C182H126/c1-99-15-113-43-127(29-99)141-57-142-65-155(64-141)162-78-169-92-170(79-162)172-82-164-83-174(94-172)176-85-166-87-178(96-176)180-89-168-91-182(98-180)181-90-167-88-179(97-181)177-86-165-84-175(95-177)173-81-163(80-171(169)93-173)156-66-143(128-30-100(2)16-114(113)44-128)58-144(67-156)130-32-103(5)19-117(47-130)118-20-104(6)34-132(48-118)147-60-148(71-158(165)70-147)134-36-107(9)23-121(51-134)123-25-109(11)39-137(53-123)151-62-152(75-160(167)74-151)138-40-111(13)27-125(55-138)126-28-112(14)42-140(56-126)154-63-153(76-161(168)77-154)139-41-110(12)26-124(54-139)122-24-108(10)38-136(52-122)150-61-149(72-159(166)73-150)135-37-106(8)22-120(50-135)119-21-105(7)35-133(49-119)146-59-145(68-157(164)69-146)131-33-102(4)18-116(46-131)115-17-101(3)31-129(142)45-115/h15-98H,1-14H3
InChIKey=FJHGGHOTCCNJNI-UHFFFAOYSA-N

9: InChI=1S/C44H23N/c1-44(2,3)21-16-28-24-8-4-6-22-26-14-19-12-10-18-11-13-20-15-27-23-7-5-9-25-29(17-21)41(28)45-42(33(22)24)39-35(26)37-31(19)30(18)32(20)38(37)36(27)40(39)43(45)34(23)25/h4-17H,1-3H3
InChIKey=QHBWEZKXFSKCSM-UHFFFAOYSA-N

10: InChI=1S/C40H15N/c1-4-19-23-8-3-9-24-20-5-2-7-22-26-15-18-13-11-16-10-12-17-14-25-21(6-1)30(19)39-36-32(25)34-28(17)27(16)29(18)35(34)33(26)37(36)40(31(20)22)41(39)38(23)24/h1-15H
InChIKey=XWSUADIIRLXSBY-UHFFFAOYSA-N

from Computational Organic Chemistry https://ift.tt/2ONPjPp

I have recently been interested in curved aromatic systems – see my own paper on double helicenes.¹ In this post, I cover four recent papers that discuss non-planar aromatic molecules.

The first paper² discusses the warped aromatic 1 built off of the scaffold of depleiadene 3. The crystal structure of 1 shows the molecule to be a saddle with near C_2v symmetry. B3LYP/6-31G computations indicate that the saddle isomer is 10.5 kcal mol^-1 more stable than the twisted isomer, and the barrier between them is 16.0 kcal mol^-1, with a twisted saddle intermediate as well.

The PES is significantly simpler for the structure lacking the t-butyl groups, 2. The B3LYP/6-31G PES of 2 has the saddle as the transition state interconverting mirror images of the twisted saddle isomer, and this barrier is only 1.8 kcal mol^-1. Figure 1 displays the twisted saddle and the saddle transition state. Clearly, the t-butyl groups significantly alter the flexibility of this C₈₆ aromatic surface. One should be somewhat concerned about the small basis set employed here, especially lacking polarization functions, and a functional that lacks dispersion correction. However, the computed geometry of 1 is quite similar to that of the x-ray structure.

2 twisted saddle (ground state)

2 saddle (transition state)

Figure 1. B3LYP/6-31G optimized geometries of the isomer of 2.

The second paper presents 4, a non-planar aromatic based on [8]circulene 6.³ (See this post for a general study of circulenes.) [8]circulene has a tub-shape, but is flexible and can undergo tub-to-tub inversion. The expanded aromatic 4 is found to have a twisted shape in the x-ray crystal structure. A simplified model 5 was computed at B3LYP/6-31G(d) and the twisted isomer is 4.1 kcal mol^-1 lower in energy than the saddle (tub) isomer (see Figure 2). The barrier for interconversion of the two isomers is only 6.2 kcal mol^-1, indicating a quite labile structure.

5 twisted 0.0

5 TS 6.2

5 saddle 4.1

Figure 2. B3LYP/6-31G(d) optimized geometries and relative energies (kcal mol^-1) of the isomers of 5.

The third paper presents a geodesic molecule based on 1,3,5-trisubstitued phenyl repeat units.⁴ The authors prepared 7, and its x-ray structure shows a saddle-shape. The NMR indicate a molecule that undergoes considerable conformational dynamics. To address this, they did some computations on the methyl analogue 8. The D_7h structure is 309 kcal mol^-1 above the local energy minimum structure, which is way too high to be accessed at room temperature. PM6 computations identified a TS only 0.6 kcal mol^-1 above the saddle ground state. (I performed a PM6 optimization starting from the x-ray structure, which is highly disordered, and the structure obtained is shown in Figure 3. Unfortunately, the authors did not report the optimized coordinates of any structure!)

Figure 3. PM6 optimized structure of 8.

The fourth and last paper describes the aza-buckybowl 9.⁵ The x-ray crystal structure shows a curved bowl shape with C_s symmetry. NICS(0) values were computed for the parent molecule 10 B3LYP/6-31G(d). These values are shown in Scheme 1 and the geometry is shown in Figure 4. The 6-member rings that surround the azacylopentadienyl ring all have NICS(0) near zero, which suggests significant bond localization.

Scheme 1. NICS(0) values of 10

Figure 4. B3LYP/6-31G(d) optimized structure of 10.

Our understanding of what aromaticity really means is constantly being challenged!

References

1. Bachrach, S. M., "Double helicenes." Chem. Phys. Lett. 2016, 666, 13-18, DOI: 10.1016/j.cplett.2016.10.070.

2. Ho, P. S.; Kit, C. C.; Jiye, L.; Zhifeng, L.; Qian, M., "A Dipleiadiene-Embedded Aromatic Saddle Consisting
of 86 Carbon Atoms." Angew. Chem. Int. Ed. 2018, 57, 1581-1586, DOI: 10.1002/anie.201711437.

3. Yin, C. K.; Kit, C. C.; Zhifeng, L.; Qian, M., "A Twisted Nanographene Consisting of 96 Carbon Atoms." Angew. Chem. Int. Ed. 2017, 56, 9003-9007, DOI: 10.1002/anie.201703754.

4. Koki, I.; Jennie, L.; Ryo, K.; Sota, S.; Hiroyuki, I., "Fluctuating Carbonaceous Networks with a Persistent
Molecular Shape: A Saddle-Shaped Geodesic Framework of 1,3,5-Trisubstituted Benzene (Phenine)." Angew. Chem. Int. Ed. 2018, 57, 8555-8559, DOI: 10.1002/anie.201803984.

5. Yuki, T.; Shingo, I.; Kyoko, N., "A Hybrid of Corannulene and Azacorannulene: Synthesis of a Highly Curved Nitrogen-Containing Buckybowl." Angew. Chem. Int. Ed. 2018, 57, 9818-9822, DOI: 10.1002/anie.201805678.

InChIs

1: InChI=1S/C134H128/c1-123(2,3)57-37-65-66-38-58(124(4,5)6)42-70-74-46-62(128(16,17)18)50-82-94(74)110-106(90(66)70)105-89(65)69(41-57)73-45-61(127(13,14)15)49-81-93(73)109(105)119-113-97(81)85(131(25,26)27)53-77-78-54-87(133(31,32)33)99-83-51-63(129(19,20)21)47-75-71-43-59(125(7,8)9)39-67-68-40-60(126(10,11)12)44-72-76-48-64(130(22,23)24)52-84-96(76)112-108(92(68)72)107(91(67)71)111(95(75)83)121-115(99)103(78)118-104-80(56-88(134(34,35)36)100(84)116(104)122(112)121)79-55-86(132(28,29)30)98(82)114(120(110)119)102(79)117(118)101(77)113/h37-56H,1-36H3
InChIKey=GKUTUWMASUJSFD-UHFFFAOYSA-N

2: InChI=1S/C86H32/c1-9-33-34-10-2-14-38-42-18-6-22-46-50-26-30-55-56-32-28-52-48-24-8-20-44-40-16-4-12-36-35-11-3-15-39-43-19-7-23-47-51-27-31-54-53-29-25-49-45-21-5-17-41-37(13-1)57(33)73-74(58(34)38)78(62(42)46)84-70(50)66(55)81(65(53)69(49)83(84)77(73)61(41)45)82-67(54)71(51)85-79(63(43)47)75(59(35)39)76(60(36)40)80(64(44)48)86(85)72(52)68(56)82/h1-32H
InChIKey=MXCDWJZMTKLBDM-UHFFFAOYSA-N

3: InChI=1S/C18H12/c1-2-6-14-11-12-16-8-4-3-7-15-10-9-13(5-1)17(14)18(15)16/h1-12H
InChIKey=KVJJNMIHWIRGRP-UHFFFAOYSA-N

4: InChI=1S/C132H108O4/c1-125(2,3)53-29-65-66-30-54(126(4,5)6)34-70-74-38-58(130(16,17)18)42-78-86-46-82-63-51-91(135-27)92(136-28)52-64(63)84-48-88-80-44-60(132(22,23)24)40-76-72-36-56(128(10,11)12)32-68-67-31-55(127(7,8)9)35-71-75-39-59(131(19,20)21)43-79-87-47-83-62-50-90(134-26)89(133-25)49-61(62)81-45-85-77-41-57(129(13,14)15)37-73-69(33-53)93(65)109-110(94(66)70)114(98(74)78)122-106(86)118-103(82)104(84)120-108(88)124-116(100(76)80)112(96(68)72)111(95(67)71)115(99(75)79)123(124)107(87)119(120)102(83)101(81)117(118)105(85)121(122)113(109)97(73)77/h29-52H,1-28H3
InChIKey=ZLPRACZKLACDHX-UHFFFAOYSA-N

5: InChI=1S/C108H60O4/c1-37-13-49-50-14-38(2)18-54-58-22-42(6)26-62-70-30-66-47-35-75(111-11)76(112-12)36-48(47)68-32-72-64-28-44(8)24-60-56-20-40(4)16-52-51-15-39(3)19-55-59-23-43(7)27-63-71-31-67-46-34-74(110-10)73(109-9)33-45(46)65-29-69-61-25-41(5)21-57-53(17-37)77(49)93-94(78(50)54)98(82(58)62)106-90(70)102-87(66)88(68)104-92(72)108-100(84(60)64)96(80(52)56)95(79(51)55)99(83(59)63)107(108)91(71)103(104)86(67)85(65)101(102)89(69)105(106)97(93)81(57)61/h13-36H,1-12H3
InChIKey=ZSIVUKSPPZUSQL-UHFFFAOYSA-N

6: InChI=1S/C32H16/c1-2-18-5-6-20-9-11-22-13-15-24-16-14-23-12-10-21-8-7-19-4-3-17(1)25-26(18)28(20)30(22)32(24)31(23)29(21)27(19)25/h1-16H
InChIkey=BASWMOIVIHXTRC-UHFFFAOYSA-N

7: InChI=1S/C224H210/c1-211(2,3)197-99-169-85-183(113-197)184-86-170(100-198(114-184)212(4,5)6)157-66-149-67-158(79-157)172-88-187(117-200(102-172)214(10,11)12)188-90-174(104-202(118-188)216(16,17)18)161-70-151-71-162(81-161)176-92-191(121-204(106-176)218(22,23)24)193-95-179(109-207(123-193)221(31,32)33)165-74-153-75-166(83-165)180-96-195(125-208(110-180)222(34,35)36)196-98-182(112-210(126-196)224(40,41)42)168-77-154-76-167(84-168)181-97-194(124-209(111-181)223(37,38)39)192-94-178(108-206(122-192)220(28,29)30)164-73-152-72-163(82-164)177-93-190(120-205(107-177)219(25,26)27)189-91-175(105-203(119-189)217(19,20)21)160-69-150-68-159(80-160)173-89-186(116-201(103-173)215(13,14)15)185-87-171(101-199(115-185)213(7,8)9)156-65-148(64-155(169)78-156)141-50-127-43-128(51-141)130-45-132(55-143(150)53-130)134-47-136(59-145(152)57-134)138-49-140(63-147(154)61-138)139-48-137(60-146(153)62-139)135-46-133(56-144(151)58-135)131-44-129(127)52-142(149)54-131/h43-126H,1-42H3
InChIKey=ZDDKJXIESSWTIA-UHFFFAOYSA-N

8: InChI=1S/C182H126/c1-99-15-113-43-127(29-99)141-57-142-65-155(64-141)162-78-169-92-170(79-162)172-82-164-83-174(94-172)176-85-166-87-178(96-176)180-89-168-91-182(98-180)181-90-167-88-179(97-181)177-86-165-84-175(95-177)173-81-163(80-171(169)93-173)156-66-143(128-30-100(2)16-114(113)44-128)58-144(67-156)130-32-103(5)19-117(47-130)118-20-104(6)34-132(48-118)147-60-148(71-158(165)70-147)134-36-107(9)23-121(51-134)123-25-109(11)39-137(53-123)151-62-152(75-160(167)74-151)138-40-111(13)27-125(55-138)126-28-112(14)42-140(56-126)154-63-153(76-161(168)77-154)139-41-110(12)26-124(54-139)122-24-108(10)38-136(52-122)150-61-149(72-159(166)73-150)135-37-106(8)22-120(50-135)119-21-105(7)35-133(49-119)146-59-145(68-157(164)69-146)131-33-102(4)18-116(46-131)115-17-101(3)31-129(142)45-115/h15-98H,1-14H3
InChIKey=FJHGGHOTCCNJNI-UHFFFAOYSA-N

9: InChI=1S/C44H23N/c1-44(2,3)21-16-28-24-8-4-6-22-26-14-19-12-10-18-11-13-20-15-27-23-7-5-9-25-29(17-21)41(28)45-42(33(22)24)39-35(26)37-31(19)30(18)32(20)38(37)36(27)40(39)43(45)34(23)25/h4-17H,1-3H3
InChIKey=QHBWEZKXFSKCSM-UHFFFAOYSA-N

10: InChI=1S/C40H15N/c1-4-19-23-8-3-9-24-20-5-2-7-22-26-15-18-13-11-16-10-12-17-14-25-21(6-1)30(19)39-36-32(25)34-28(17)27(16)29(18)35(34)33(26)37(36)40(31(20)22)41(39)38(23)24/h1-15H
InChIKey=XWSUADIIRLXSBY-UHFFFAOYSA-N

from Computational Organic Chemistry https://ift.tt/2ONPjPp

Dynamics in a terpene cation rearrangement

Sarpong and Tantillo have examined the acid-catalyzed Prins/semipinacol rearrangement of hydroxylated pinenes, such as Reaction 1.¹

Rxn 1

Interestingly, only the fenchone scaffold products, like 1, are observed and the camphor scaffold products, like 2, are not observed. Cation intermediates are likely, and this means that a primary alkyl shift is taking place in preference to a tertiary alkyl shift, see Scheme 1.

Scheme 1.

Primary alkyl shift

Tertiary alkyl shift

They proposed the following key steps in the reaction mechanism:

ωB97X-D/6-31+G(d,p) computations find a flat surface around cation intermediate 4: the TS leading to 5 and 6 are only 1.3 and 3.3 kcal mol^-1, respectively. Since these small barriers are quite susceptible to changes in basis set and functional, and since Tantillo has found many examples of post-transition state bifurcations in cation systems, the authors reasonably decided to conduct molecular dynamics trajectories originating at the TS connecting 3 and 4. The geometries of the critical points are shown in Figure 1.

The trajectory study shows all the usual characteristics of reactions that are under dynamic control. A third of the trajectories show recrossing of the barrier, typical of very flat surfaces. Nearly all of the remaining trajectories led to 5, with only 2 trajectories (~1%) leading to 6. The dynamics are understandable in terms of favoring the primary alkyl shift over the tertiary since a significantly smaller mass needs to move in the former case.

TS 3 → 4
4
TS 4 → 5	TS 4 → 6

Figure 1. ωB97X-D/6-31+G(d,p) optimized geometries.

This is yet another study that implicates dynamic effects in routine reactions, one of many I have discussed over the years.

References

1. Blümel, M.; Nagasawa, S.; Blackford, K.; Hare, S. R.; Tantillo, D. J.; Sarpong, R., "Rearrangement of Hydroxylated Pinene Derivatives to Fenchone-Type Frameworks: Computational Evidence for Dynamically-Controlled Selectivity." J. Am. Chem. Soc. 2018, 140, 9291-9298, DOI: 10.1021/jacs.8b05804.

InChIs

1: InChI=1S/C17H20O2/c1-16-9-12-8-13(16)14(11-6-4-3-5-7-11)19-10-17(12,2)15(16)18/h3-7,12-14H,8-10H2,1-2H3/t12?,13?,14-,16?,17?/m0/s1
InChIKey=LTTUIPPXEHHMJS-XWTIBIIYSA-N

2: InChI=1S/C17H20O2/c1-16-10-19-15(11-6-4-3-5-7-11)13-8-12(16)9-14(18)17(13,16)2/h3-7,12-13,15H,8-10H2,1-2H3/t12?,13?,15-,16?,17?/m0/s1
InChIKey=GCKIOHNLJYVWKL-CMESGNGWSA-N

from Computational Organic Chemistry https://ift.tt/2wYeDLK

Sarpong and Tantillo have examined the acid-catalyzed Prins/semipinacol rearrangement of hydroxylated pinenes, such as Reaction 1.¹

Rxn 1

Interestingly, only the fenchone scaffold products, like 1, are observed and the camphor scaffold products, like 2, are not observed. Cation intermediates are likely, and this means that a primary alkyl shift is taking place in preference to a tertiary alkyl shift, see Scheme 1.

Scheme 1.

Primary alkyl shift

Tertiary alkyl shift

They proposed the following key steps in the reaction mechanism:

ωB97X-D/6-31+G(d,p) computations find a flat surface around cation intermediate 4: the TS leading to 5 and 6 are only 1.3 and 3.3 kcal mol^-1, respectively. Since these small barriers are quite susceptible to changes in basis set and functional, and since Tantillo has found many examples of post-transition state bifurcations in cation systems, the authors reasonably decided to conduct molecular dynamics trajectories originating at the TS connecting 3 and 4. The geometries of the critical points are shown in Figure 1.

The trajectory study shows all the usual characteristics of reactions that are under dynamic control. A third of the trajectories show recrossing of the barrier, typical of very flat surfaces. Nearly all of the remaining trajectories led to 5, with only 2 trajectories (~1%) leading to 6. The dynamics are understandable in terms of favoring the primary alkyl shift over the tertiary since a significantly smaller mass needs to move in the former case.

TS 3 → 4
4
TS 4 → 5	TS 4 → 6

Figure 1. ωB97X-D/6-31+G(d,p) optimized geometries.

This is yet another study that implicates dynamic effects in routine reactions, one of many I have discussed over the years.

References

1. Blümel, M.; Nagasawa, S.; Blackford, K.; Hare, S. R.; Tantillo, D. J.; Sarpong, R., "Rearrangement of Hydroxylated Pinene Derivatives to Fenchone-Type Frameworks: Computational Evidence for Dynamically-Controlled Selectivity." J. Am. Chem. Soc. 2018, 140, 9291-9298, DOI: 10.1021/jacs.8b05804.

InChIs

1: InChI=1S/C17H20O2/c1-16-9-12-8-13(16)14(11-6-4-3-5-7-11)19-10-17(12,2)15(16)18/h3-7,12-14H,8-10H2,1-2H3/t12?,13?,14-,16?,17?/m0/s1
InChIKey=LTTUIPPXEHHMJS-XWTIBIIYSA-N

2: InChI=1S/C17H20O2/c1-16-10-19-15(11-6-4-3-5-7-11)13-8-12(16)9-14(18)17(13,16)2/h3-7,12-13,15H,8-10H2,1-2H3/t12?,13?,15-,16?,17?/m0/s1
InChIKey=GCKIOHNLJYVWKL-CMESGNGWSA-N

from Computational Organic Chemistry https://ift.tt/2wYeDLK

nano-Saturn

It never hurts to promote one’s science through clever names – think cubane, buckminsterfullerene, bullvalene, etc. Host-guest chemistry is not immune to this cliché too, and this post discusses the latest synthesis and computations of a nano-Saturn; nano-Saturns are a spherical guest molecule captured inside a ring host molecule. I discussed an example of this a number of years ago – the nano-Saturn comprised of C₆₀ fullerene surrounded by [10]cycloparaphenylene.

Yamamoto, Tsurumaki, Wakamatsu, and Toyota have prepared a nano-Saturn complex with the goal of making a flatter ring component.¹ The inner planet is modeled again by C₆₀ and the ring is the [24]circulene analogue 1. The x-ray crystal structure of this nano-Saturn complex is shown in Figure 1.

1: R = 2,4,6-tri-iso-propylphenyl
2: R = H

Figure 1. X-ray crystal structure of the nano-Saturn complex of 1 with C₆₀.

Variable temperature NMR experiments gave the binding values of ΔH = -18.1 ± 2.3 kJ mol^-1 and TΔS = 0.8 ± 2.2 kJ mol^-1 at 298 K. To gauge this binding energy, they computed the complex of C₆₀ with the parent compound 2 at B3LYP/6-1G(d)//M05-2X/6-31G(d), unfortunately without publishing the coordinates in the supporting materials. The computed binding enthalpy is ΔH = -50.6 kJ mol^-1, but this computation is for the gas phase. The computed structure shows close contacts of 0.29 nm between the fullerene and the C₉-proton of the anthracenyl groups, in excellent agreement with the x-ray structure. These weak C-H^…π interactions undoubtedly help stabilize the complex, especially given that the fullerene carries a very tiny Mulliken charge of +0.08 e.

References

1) Yuta, Y.; Eiji, T.; Kan, W.; Shinji, T., "Nano-Saturn: Experimental Evidence of Complex Formation of an Anthracene Cyclic Ring with C60." Angew. Chem. Int. Ed. 2018, 57, 8199-8202, DOI: 10.1002/anie.201804430.

InChIs

1: InChI=1S/C174H180/c1-91(2)121-78-150(97(13)14)164(151(79-121)98(15)16)163-90-128-71-139-70-127-59-109(37-38-120(127)77-162(139)163)110-39-49-140-129(60-110)72-130-61-111(40-50-141(130)165(140)170-152(99(17)18)80-122(92(3)4)81-153(170)100(19)20)112-41-51-142-131(62-112)73-132-63-113(42-52-143(132)166(142)171-154(101(21)22)82-123(93(5)6)83-155(171)102(23)24)114-43-53-144-133(64-114)74-134-65-115(44-54-145(134)167(144)172-156(103(25)26)84-124(94(7)8)85-157(172)104(27)28)116-45-55-146-135(66-116)75-136-67-117(46-56-147(136)168(146)173-158(105(29)30)86-125(95(9)10)87-159(173)106(31)32)118-47-57-148-137(68-118)76-138-69-119(128)48-58-149(138)169(148)174-160(107(33)34)88-126(96(11)12)89-161(174)108(35)36/h37-108H,1-36H3
InChIKey=AMDNULXMAMDTMX-UHFFFAOYSA-N

2: InChI=1S/C84H48/c1-13-61-25-62-15-3-51-33-75(62)43-73(61)31-49(1)50-2-14-63-26-64-16-4-52(34-76(64)44-74(63)32-50)54-6-18-66-28-68-20-8-56(38-80(68)46-78(66)36-54)58-10-22-70-30-72-24-12-60(42-84(72)48-82(70)40-58)59-11-23-71-29-69-21-9-57(39-81(69)47-83(71)41-59)55-7-19-67-27-65-17-5-53(51)35-77(65)45-79(67)37-55/h1-48H
InChIKey=ZYXXLAYETADMDM-UHFFFAOYSA-N

from Computational Organic Chemistry https://ift.tt/2LBo1Jz

It never hurts to promote one’s science through clever names – think cubane, buckminsterfullerene, bullvalene, etc. Host-guest chemistry is not immune to this cliché too, and this post discusses the latest synthesis and computations of a nano-Saturn; nano-Saturns are a spherical guest molecule captured inside a ring host molecule. I discussed an example of this a number of years ago – the nano-Saturn comprised of C₆₀ fullerene surrounded by [10]cycloparaphenylene.

Yamamoto, Tsurumaki, Wakamatsu, and Toyota have prepared a nano-Saturn complex with the goal of making a flatter ring component.¹ The inner planet is modeled again by C₆₀ and the ring is the [24]circulene analogue 1. The x-ray crystal structure of this nano-Saturn complex is shown in Figure 1.

1: R = 2,4,6-tri-iso-propylphenyl
2: R = H

Figure 1. X-ray crystal structure of the nano-Saturn complex of 1 with C₆₀.

Variable temperature NMR experiments gave the binding values of ΔH = -18.1 ± 2.3 kJ mol^-1 and TΔS = 0.8 ± 2.2 kJ mol^-1 at 298 K. To gauge this binding energy, they computed the complex of C₆₀ with the parent compound 2 at B3LYP/6-1G(d)//M05-2X/6-31G(d), unfortunately without publishing the coordinates in the supporting materials. The computed binding enthalpy is ΔH = -50.6 kJ mol^-1, but this computation is for the gas phase. The computed structure shows close contacts of 0.29 nm between the fullerene and the C₉-proton of the anthracenyl groups, in excellent agreement with the x-ray structure. These weak C-H^…π interactions undoubtedly help stabilize the complex, especially given that the fullerene carries a very tiny Mulliken charge of +0.08 e.

References

1) Yuta, Y.; Eiji, T.; Kan, W.; Shinji, T., "Nano-Saturn: Experimental Evidence of Complex Formation of an Anthracene Cyclic Ring with C60." Angew. Chem. Int. Ed. 2018, 57, 8199-8202, DOI: 10.1002/anie.201804430.

InChIs

1: InChI=1S/C174H180/c1-91(2)121-78-150(97(13)14)164(151(79-121)98(15)16)163-90-128-71-139-70-127-59-109(37-38-120(127)77-162(139)163)110-39-49-140-129(60-110)72-130-61-111(40-50-141(130)165(140)170-152(99(17)18)80-122(92(3)4)81-153(170)100(19)20)112-41-51-142-131(62-112)73-132-63-113(42-52-143(132)166(142)171-154(101(21)22)82-123(93(5)6)83-155(171)102(23)24)114-43-53-144-133(64-114)74-134-65-115(44-54-145(134)167(144)172-156(103(25)26)84-124(94(7)8)85-157(172)104(27)28)116-45-55-146-135(66-116)75-136-67-117(46-56-147(136)168(146)173-158(105(29)30)86-125(95(9)10)87-159(173)106(31)32)118-47-57-148-137(68-118)76-138-69-119(128)48-58-149(138)169(148)174-160(107(33)34)88-126(96(11)12)89-161(174)108(35)36/h37-108H,1-36H3
InChIKey=AMDNULXMAMDTMX-UHFFFAOYSA-N

2: InChI=1S/C84H48/c1-13-61-25-62-15-3-51-33-75(62)43-73(61)31-49(1)50-2-14-63-26-64-16-4-52(34-76(64)44-74(63)32-50)54-6-18-66-28-68-20-8-56(38-80(68)46-78(66)36-54)58-10-22-70-30-72-24-12-60(42-84(72)48-82(70)40-58)59-11-23-71-29-69-21-9-57(39-81(69)47-83(71)41-59)55-7-19-67-27-65-17-5-53(51)35-77(65)45-79(67)37-55/h1-48H
InChIKey=ZYXXLAYETADMDM-UHFFFAOYSA-N

from Computational Organic Chemistry https://ift.tt/2LBo1Jz