Reaction selectivity in the synthesis of paeoveitol

Diels-Alder Steven Bachrach 02 Aug 2016 No Comments

Xu, Liu, Xu, Gao, and Zhao report a very efficient synthesis of paeoveitol 1 by the [4+2]-cycloaddition of paeveitol D 2 with the o-quinone methide 3.1 What is interesting here is the selectivity of this reaction. In principle the cyloadditon can give four products (2 different regioisomeric additions along with endo/exo selectivity) and it could also proceed via a Michael addition.

They performed PCM(CH2Cl2)/M06-2x/6-311+G(d,p) computations on the reaction of 2 with 3 and located two different transition states for the Michael addition and the four cycloaddition transition states. The lowest energy Michael and cycloaddition transition states are shown in Figure 1. The barrier for the cycloaddition is 17.6 kcal mol-1, 2.5 kcal mol-1 below that of the Michael addition. The barriers for the other cycloaddition paths are at more than 10 kcal mol-1 above the one shown. This cycloaddition TS is favored by a strong intermolecular hydrogen bond and by π-π-stacking. In agreement with experiment, it is the transition state that leads to the observed product.

Michael TS
(20.1)

[4+2] TS
(17.6)

Figure 1. Optimized geometries of the lowest energy TSs for the Michael and [4+2]cycloaddtion routes. Barrier heights (kcal mol-1) are listed in parenthesis.

References

(1) Xu, L.; Liu, F.; Xu, L.-W.; Gao, Z.; Zhao, Y.-M. "A Total Synthesis of Paeoveitol," Org. Lett. 2016, ASAP, DOI: 10.1021/acs.orglett.6b01736.

paeoveitol 1: InChI=1S/C21H24O3/c1-5-21-10-14-6-11(2)17(22)8-15(14)13(4)20(21)24-19-7-12(3)18(23)9-16(19)21/h6-9,13,20,22-23H,5,10H2,1-4H3/t13-,20-,21-/m1/s1
InChIKey=LCLFTLPUJXVULB-OBVPDXSSSA-N

paeveitol D 2: InChI=1S/C9H10O2/c1-3-7-5-8(10)6(2)4-9(7)11/h3-5,10H,1-2H3/b7-3+
InChIKey=KWDDAFOCZGDLEG-XVNBXDOJSA-N

3: InChI=1S/C9H10O2/c1-3-7-5-8(10)6(2)4-9(7)11/h3-5,10H,1-2H3/b7-3+
InChIKey=KWDDAFOCZGDLEG-XVNBXDOJSA-N

Dehydro-Diels-Alder Reactions

benzynes &Cramer &Diels-Alder &Houk Steven Bachrach 25 Jul 2016 No Comments

I have been delinquent in writing about the dehydro-Diels-Alder reactions, but really can’t put it off any further. These sets of reactions really deserve a fuller analysis than I am going to summarize here, but this post will provide a good jumping off point for anyone interested in further investigation.

So the Diels-Alder reaction is among the most famous and most important reactions in organic chemistry. The reaction creates a 6-member ring and sets up to four stereocenters. In the past couple of years many chemists have expressed interest in the variant where the four-carbon component is more highly unsaturated, i.e. enyne or diyne. I will summarize the results of three recent computational papers dealing with the reaction of a diyne with an yne.

The first paper is by Skraba-Joiner, Johnson, and Agarwal.1 They discuss, among a number of interesting pericyclic reactions, the intramolecular Diels-Alder reaction of triyne 1 to give 2. They examined a concerted and stepwise pathway at (U)M05-2X/6-311+G(d,p) and find the concerted to be favored by 6.0 kcal mol-1. CCSD(T) using these geometries increases the difference to 8.2 kcal mol-1. The T1 diagnostic is fairly large for both the concerted and stepwise transition states, so they also performed CCSD(T)/CBS computations, which had much lower T1 values. The concerted TS remained favorable, but by only 2.7 kcal mol-1.

In the same special issue of the Journal of Organic Chemistry, Cramer, Hoye, and Kuwata examined a reaction closely related to what Johnson examined above.2 They looked at the reaction taking 3 into 4 via both experiments and computations. The M06-2x/6-311+G(d,p) geometries for the concerted and first TS along the stepwise path (with R1=R2=H) are shown in Figure 1. Evaluating the energies at SMD(o-dichlorobenzene)/B3LYP-D3BJ/6-311+G-(d,p)//M06-2X/6-311+G(d,p) find in this case (along with all of the other R1/R2 variants they examined) that the stepwise path has a lower barrier than the concerted path. In the case where R1=R2=H, the stepwise path is favored by 6.0 kcal mol-1. Additionally, these stepwise barriers are in reasonable agreement with the experimentally-derived barriers.

Concerted TS

Stepwise TS

Figure 1. M06-2x/6-311+G(d,p) optimized geometries of the concerted and stepwise TSs for the reaction of 3H going to 4H.

It should be pointed out that the wavefunctions for the concerted TSs were all found to be unstable with regard to a restricted to unrestricted relaxation. Given this problem, they also performed a CASPT2 energy evaluation of the concerted and stepwise transition states for the case R1=R2=H. CASPT2 finds the stepwise barrier to be 3.7 kcal mol-1 lower than the concerted barrier.

The last paper comes from the Houk lab, and examines the simplest set of intermolecular dehdro-Diels-Alder reactions.3 I will focus here on the most unsaturated analogue, the reaction of 1,3-butadiyne 5 with ethyne to give benzyne 6.

The concreted and stepwise transition states for this reaction (at (U)M06-2X/6-311+G(d,p)) are shown in Figure 2. The concerted barrier is 36.0 kcal moml-1 while the stepwise barrier is slightly lower: 35.2 kcal mol-1. The distortion energy for the concerted reaction is large (43.2 kcal mol-1) due mostly to angle changes in the diyne. Its interaction energy is -7.2 kcal mol-1, similar to the interaction energy in other similar Diels-Alder reactions. In contrast, the distortion energy for the stepwise pathway is 27.5 kcal mol-1, but the interaction energy is +7.7 kcal mol-1. These values are very similar to the distortion and interaction energy of the related (but less saturated DA reactions).

Concerted TS

Stepwise TS

Figure 2. (U)M06-2X/6-311+G(d,p) optimized concerted and stepwise TS for the reaction of 1,3-diyne with ethyne.

Molecular dynamics trajectories for both the concerted and stepwise paths reveal interesting differences. The concerted trajectories show an oscillatory behaviour of bending the angles at the C2 and C3 carbons prior to the TS, and then near synchronous formation of the new C-C bonds. The trajectories initiated at the stepwise TS show no systematic motion. Once the bond is formed, the biradical exhibits a long lifetime, on the order of picoseconds, much longer than the trajectory runs.

These three studies indicate the nature of the dehydro Diels-Alder reaction is very sensitive to reaction conditions, substituents, solvation, and all other manner of effects and will likely prove an area of interest for some time. It should keep a number of computational chemists busy for some time!

References

(1) Skraba-Joiner, S. L.; Johnson, R. P.; Agarwal, J. "Dehydropericyclic Reactions: Symmetry-Controlled Routes to Strained Reactive Intermediates," J. Org. Chem. 2015, 80, 11779-11787, DOI: 10.1021/acs.joc.5b01488.

(2) Marell, D. J.; Furan, L. R.; Woods, B. P.; Lei, X.; Bendelsmith, A. J.; Cramer, C. J.; Hoye, T. R.; Kuwata, K. T. "Mechanism of the Intramolecular Hexadehydro-Diels–Alder Reaction," J. Org. Chem. 2015, 80, 11744-11754, DOI: 10.1021/acs.joc.5b01356.

(3) Yu, P.; Yang, Z.; Liang, Y.; Hong, X.; Li, Y.; Houk, K. N. "Distortion-Controlled Reactivity and Molecular Dynamics of Dehydro-Diels–Alder Reactions," J. Am. Chem. Soc. 2016, 138, 8247-8252, DOI: 10.1021/jacs.6b04113.

InChIs

1: InChI=1S/C9H8/c1-3-5-7-9-8-6-4-2/h1-2H,5,7,9H2
InChIKey=IYZAZSVBWMMSLQ-UHFFFAOYSA-N

2: InChI=1S/C9H8/c1-2-5-9-7-3-6-8(9)4-1/h1,4H,3,6-7H2
InChIKey=PZJMTUKDGZUDBH-UHFFFAOYSA-N

3H: InChI=1S/C8H4O2/c1-3-5-6-7-10-8(9)4-2/h1-2H,7H2
InChIKey=MGXDIFXPYGGQLF-UHFFFAOYSA-N

4H: InChI=1S/C10H8O4/c1-6(11)14-8-2-3-9-7(4-8)5-13-10(9)12/h2-4H,5H2,1H3
InChIKey=GEFLHLNIKGXWCA-UHFFFAOYSA-N

5: InChI=1S/C4H2/c1-3-4-2/h1-2H
InChIKey=LLCSWKVOHICRDD-UHFFFAOYSA-N

6: InChI=1S/C6H4/c1-2-4-6-5-3-1/h1-4H
InChIKey=KLYCPFXDDDMZNQ-UHFFFAOYSA-N

Identifying the n→π* interaction

Uncategorized Steven Bachrach 18 Jul 2016 1 Comment

The weak n→π* interaction has been proposed to explain some conformational structure. Singh, Mishra, Sharma, and Das have now provided the first spectroscopic evidence of this interactions.1 They examined the structure of phenylformate 1. This compound can exist as two conformational isomers, having the carbonyl oxygen pointing towards (cis) or away (trans) from the phenyl ring. They optimized the structures of these two conformers at M05-2X/aug-cc-pVDZ and find that the cis isomer is lower in energy by 1.32 kcal mol-1. Unfortunately, the authors do not provide the structures of these isomers, but since they are so small, I reoptimized them at ωB97XD/6-311g(d) and they are displayed in Figure 1. At this computational level, the cis isomer is lower in enthalpy than the trans isomer by 1.35 kcal mol-1.

1cis

1trans

Figure 1. ωB97XD/6-311g(d) optimized structures of the cis and trans conformations of 1.

One-color resonant 2-photon ionization (1C-R2PI) spectroscopy followed by UV-VIS hole burning spectroscopy identified two isomers of 1, one present in greater amount that the other. The IR spectra of the dominant isomer showed a carbonyl stretch at 1766 cm-1, in nice agreement with the predicted frequency of 1cis (1770 cm-1). The carbonyl stretch for the minor isomer is at 1797 cm-1, again in nice agreement with the computed frequency for 1trans (1800 cm-1). The cis isomer has the lower carbonyl frequency due to partial donation of the carbonyl oxygen electrons to the π* orbital of the phenyl ring.

References

(1) Singh, S. K.; Mishra, K. K.; Sharma, N.; Das, A. "Direct Spectroscopic Evidence for an n→π* Interaction," Angew. Chem. Int. Ed. 2016, 55, 7801-7805, DOI: 10.1002/anie.201511925.

InChIs

1: InChI=1S/C7H6O2/c8-6-9-7-4-2-1-3-5-7/h1-6H
InChIKey=GEOWCLRLLWTHDN-UHFFFAOYSA-N

Changes to the blog

Uncategorized Steven Bachrach 11 Jul 2016 5 Comments

I have been posting regularly on this blog for over nine years, beginning in July 2007. I have used this blog as a way to keep my book Computational Organic Chemistry current for its readers. I have also used it as a way for me to keep current with the literature.

It has been a terrific adventure for me, but an important change will be taking place in my life that will have an impact on the blog. Starting on August 1, 2016 I will become the Dean of the School of Science at Monmouth University in West Long Branch, NJ. (See the announcement.) I am extraordinarily excited to take on the challenges of leading the School. I suspect that my duties as Dean will keep me from finding the time to post as often as I have been for this past years. I will try to occasionally write a post as I intend to keep connected to the computational chemistry community. I have a few posts backlogged but expect a more infrequent posting schedule come August.

I fully intend to maintain the blog so that past posts remain accessible.

I want to thank all of the readers of this blog, those who read me through the Computational Chemistry Highlights blog, and especially those of you who have posted comments.

Redox switching

Aromaticity Steven Bachrach 06 Jul 2016 No Comments

In searching for a redox switch, Matsuda, Ishikawa and co-workers1 landed on 13,14-picenedione 1, which could, at least in principle, be reduced by reacting with H2 to form the diol 2. The back reaction could then occur via the reaction with oxygen gas.

They first optimized the geometries of both compounds at B3PW91/6-311+G(2d), and these geometries are shown in Figure 1. TD-DFT computations then predicted that 1 would be yellow (maximum absorption at 412nm) and 2 would be colorless (maximum absorption at 378nm). Furthermore, 1 should have no fluorescence while 2 should fluoresce at 464nm and be blue.

1

2

Figure 1. B3PW91/6-311+G(2d) optimized geometries of 1 and 2.

Of particular note is that the geometry of 1 is twisted, with the O-C-C-O dihedral angle being 34.9°, while there is essentially no such twisting in 2 (its O-C-C-O dihedral angle is 0.7°). The twisting in 1 manifests in antiaromatic character of the central ring, with NICS(0)=+13.2ppm, while the central ring of 2 is aromatic, with NICS(0)=-10.0. The redox properties therefore reflect the change in the aromatic character.

They next synthesized 2 and reduced it with hydrogen gas to 1. The x-ray crystal structure of 1 shows a twisted structure (O-C-C-O dihedral of 28.87°). As predicted, 1 is yellow and 2 is colorless, and 1 has no fluorescence while 2 fluoresces blue.

References

(1) Urakawa, K.; Sumimoto, M.; Arisawa, M.; Matsuda, M.; Ishikawa, H. "Redox Switching of Orthoquinone-Containing Aromatic Compounds with Hydrogen and Oxygen Gas," Angew. Chem. Int. Ed. 2016, 55, 7432-7436, DOI: 10.1002/anie.201601906.

InChIs

1: InChI=1S/C22H12O2/c23-21-19-15-7-3-1-5-13(15)9-11-17(19)18-12-10-14-6-2-4-8-16(14)20(18)22(21)24/h1-12H
InChIKey=ASVNSCAISPNPGI-UHFFFAOYSA-N

2: InChI=InChI=1S/C22H14O2/c23-21-19-15-7-3-1-5-13(15)9-11-17(19)18-12-10-14-6-2-4-8-16(14)20(18)22(21)24/h1-12,23-24H
InChIKey=KZHNWJFXGDGIDE-UHFFFAOYSA-N

Predicting chemical structure using DP4+

NMR Steven Bachrach 20 Jun 2016 1 Comment

Structure determination has been greatly facilitated by the use of computed NMR spectra to compare with experimental spectra. Perhaps the best method for doing this is the DP4 procedure developed by Smith and Goodman.1 (I have a previous post on their paper.) The basic idea is that if you have an experimental NMR spectrum and a number of potential structures, the computed spectra for each possibility are ranked by a statistical treatment based on the Student t-test.

Grimblat, Zanardi, and Sarotti question a couple of the assumptions embedded within the DP4 method, and offer a revision that they call DP4+.2 The two assumptions are (1) that the chemical shifts are computed at B3LYP/6-31G**//MMFF and (2) that the chemical shifts are scaled and then utilized in the analysis.

To test these assumptions, they examine a set of 72 organic compounds comprising 1219 13C shifts and 1123 1H shifts. They optimized the structures at B3LYP/6-31G* and computed the chemical shifts of these compounds using the B3LYP and mPW1PW91 functionals with 6 basis sets (6-31G*, 6-31G**, 6-31+G**, 6-311G*, 6-311G**, and 6-311+G**). With all of the combinations, the standard deviation of both the proton and carbon chemical shifts were significantly smaller than with the originally proposed method.

With regards to the second assumption, they define a new probability functions that multiplies the error using scaled chemical shifts with the error using unscaled chemical shifts, and this they call DP4+. Again with all of the computational methods, the DP4+ prediction outperforms the DP4 prediction.

As a test case, they looked at cryptomoscatone D1 and D2 (1), for which the structures were determined with traditional methods. DP4 predicts that both cryptomoscatone D1 and D2 are structure 1d. However, DP4+ correctly predicts that cryptomoscatone D1 is 1b and cryptomoscatone D2 is 1a.

Lin and Tagliatatela-Scafati have reported the use of DP4+ to aid in the structure determination of plakdiepoxide 2.3 ROESY NMR could not provide definitive judgement of the stereochemical relationship about the bond between the two epoxide rings. They computed a number of conformers of the model compounds 2a and 2b at B3LYP/6-31G(d). The computed chemical shifts were then used with the DP4+ procedure to determine that the structure has the stereochemistry of 2b.

References

(1) Smith, S. G.; Goodman, J. M. "Assigning Stereochemistry to Single Diastereoisomers by GIAO NMR Calculation: The DP4 Probability," J. Am. Chem. Soc. 2010, 132, 12946-12959, DOI: 10.1021/ja105035r.

(2) Grimblat, N.; Zanardi, M. M.; Sarotti, A. M. "Beyond DP4: an Improved Probability
for the Stereochemical Assignment of Isomeric Compounds using Quantum Chemical Calculations of NMR Shifts," J. Org. Chem. 2015, 80, 12526-12534, DOI: 10.1021/acs.joc.5b02396.

(3) Chianese, G.; Yu, H.-B.; Yang, F.; Sirignano, C.; Luciano, P.; Han, B.-N.; Khan, S.; Lin, H.-W.; Taglialatela-Scafati, O. "PPAR Modulating Polyketides from a Chinese Plakortis simplex and Clues on the Origin of Their Chemodiversity," J. Org. Chem. 2016, 81 (12), 5135–5143, DOI: 10.1021/acs.joc.6b00695.

InChIs

Cryptomoscatone D1: InChI=1S/C17H20O4/c18-14(10-9-13-5-2-1-3-6-13)11-15(19)12-16-7-4-8-17(20)21-16/h1-6,8-10,14-16,18-19H,7,11-12H2/b10-9+/t14-,15-,16-/m1/s1
InChIKey=GOQOIZFMLWZVMB-OUUZNBFFSA-N

Cryptomoscatone D2: InChI=1S/C17H20O4/c18-14(10-9-13-5-2-1-3-6-13)11-15(19)12-16-7-4-8-17(20)21-16/h1-6,8-10,14-16,18-19H,7,11-12H2/b10-9+/t14-,15+,16+/m0/s1
InChIKey=GOQOIZFMLWZVMB-GLBZDCTLSA-N

plakdiepoxide: InChI=1S/C18H32O4/c1-6-9-10-13(4)12-17(7-2)16(22-17)18(8-3)14(21-18)11-15(19)20-5/h13-14,16H,6-12H2,1-5H3/t13?,14-,16-,17+,18-/m0/s1
InChIKey=YZQCELNTSCPAPG-KSZMJELXSA-N

Mechanism of dimethyldioxirane oxidation

Houk Steven Bachrach 06 Jun 2016 No Comments

Dimethyldioxirane can oxidize alkanes to alcohols. The mechanism for the oxidation has been controversial, ranging from concerted, to radical intermediates to an H-abstraction—O-rebound mechanism. Yang, Yu, and Houk now offer a molecular dynamics examination of the reaction of dimethyldioxirane with isobutane.1

Gas–phase (U)B3LYP/6-311++G(d,p)//(U)B3LYP/6-31G(d) computations give critical points outlined in the reaction below. The structures of the transition states and the intermediate are shown in Figure 1.

TS1
26.6
(25.9)

INT
8.6
(9.3)

TS2
8.6
(-0.8)

Figure 1. (U)B3LYP/6-31G(d) optimized geometries of TS1, INT, and TS2. Relative free energies (kcal mol-1) in the gas (top) and solution (bottom) phases

The PES indicates a rebound mechanism, though in acetone solution phase, there was no transition state located for the second step; it appears to be barrierless. It should be noted that the size of the barrier is very small even in the gas phase. The energy given in Figure 1 is for the gas phase structure computed in solution.

Trajectories for both gas and solution phase were computed. For the gas phase, about 90% of the trajectories lead to separated radicals, but in an acetone about 90% of the trajectories lead directly to the alcohol, with only 10% leading to radicals. Even so, the acetone trajectories divide into two types, a dynamically concerted path where the time gap between the formation of the new C-O and O-H bonds is less than 60 fs, and a dynamically stepwise path where the time gap is greater than 60 fs, though for the trajectories that lead to product the gap is typically still less than 150 fs.

References

(1)  Yang, Z.; Yu, P.; Houk, K. N. "Molecular Dynamics of Dimethyldioxirane C–H Oxidation," J. Am. Chem. Soc. 2016, 138, 4237-4242, DOI: 10.1021/jacs.6b01028.

InChIs

Dimethyldioxirane: InChI=1S/C3H6O2/c1-3(2)4-5-3/h1-2H3
InChIKey=FFHWGQQFANVOHV-UHFFFAOYSA-N

Isobutane: InChI=1S/C4H10/c1-4(2)3/h4H,1-3H3
InChIKey=NNPPMTNAJDCUHE-UHFFFAOYSA-N

Diels-Alder reaction of buckybowls

Diels-Alder &fullerene Steven Bachrach 23 May 2016 No Comments

Fullerenes can undergo the Diels-Alder reaction with some specificity: the diene preferentially adds across the bond shared by two fused 6-member rings over the bond shared by the fused 6- and 5-member rings. Garcia-Rodeja and colleagues have examined the analogous Diels-Alder reaction of cyclopentadiene with five curved aromatic compounds, 1-5.1

The computations were performed at BP86-D3/def2-TZVPP//RI-BP86-D3/def2-SVP. Representative transition states for the addition of cyclopentadiene with 3 over the 6,6-bond and 5,6-bond are shown in Figure 1.

5,6-bond

6,6-bond

Figure 1. RI-BP86-D3/def2-SVP optimized transition states for the reaction of cyclopentadiene with 3.

For the reactions of cyclopentadiene with 2-5 the reactions with the 6,6-bond is both kinetically and thermodynamically favored, while with 1 the 6,6-bond is kinetically preffered and the 5,6-adduct is the thermodynamic product. As the molecules increase in size (from 1 to 5), the activation barrier decreases, and the barrier for the reaction with 5 is only 1.4 kcal mol-1larger than the barrier with C60. The reaction energy also becomes more exothermic with increasing size. There is a very good linear relationship between activation barrier and reaction energy.

Use of the distortion/interaction model indicates that the preference for the 6,6-regioselectivity come from better interaction energy than for the 5,6-reaction, and this seems to come about by better orbital overlap between the cyclopentadiene HOMO and the 6,6-LUMO of the buckybowl.

References

(1) García-Rodeja, Y.; Solà, M.; Bickelhaupt , F. M.; Fernández, I. "Reactivity and Selectivity of Bowl-Shaped Polycyclic Aromatic Hydrocarbons: Relationship to C60," Chem. Eur. J. 2016, 22, 1368-1378, DOI: <10.1002/chem.201502248.

InChIs

1: InChI=1S/C20H10/c1-2-12-5-6-14-9-10-15-8-7-13-4-3-11(1)16-17(12)19(14)20(15)18(13)16/h1-10H
InChIKey=VXRUJZQPKRBJKH-UHFFFAOYSA-N

2: InChIKey=ASIFYFRJNYNQLA-UHFFFAOYSA-N

3: InChI=1S/C26H12/c1-5-13-14-6-2-11-19-20-12-4-8-16-15-7-3-10-18-17(9-1)21(13)25(22(14)19)26(23(15)18)24(16)20/h1-12H
InChIKey=OUWFOTSXASFGQD-UHFFFAOYSA-N

4: InChI=1S/C30H12/c1-2-14-6-10-18-20-12-8-16-4-3-15-7-11-19-17-9-5-13(1)21-22(14)26(18)29(25(17)21)30-27(19)23(15)24(16)28(20)30/h1-12H
InChIKey=JEUCRZPADDQRKU-UHFFFAOYSA-N

5: InChI=1S/C36H12/c1-7-16-17-9-3-14-5-11-20-21-12-6-15-4-10-19-18-8-2-13(1)22-25(16)31-32(26(18)22)34-28(19)24(15)30(21)36(34)35-29(20)23(14)27(17)33(31)35/h1-12H
InChIKey=QMGQDOOJOCPYIA-UHFFFAOYSA-N

Benchmarking Platonic solids and related hydrocarbons

QM Method &Schreiner Steven Bachrach 10 May 2016 No Comments

Karton, Schreiner, and Martin have benchmarked the heats of formation of some Platonic Solids and related hydrocarbons.1 The molecules examined are tetrahedrane 1, cubane 2, dodecahedrane 3, trisprismane 4, pentaprismane 5, and octahedrane 6.

The optimized structures (B3LYP-D3BJ/def2-TZVPP) of these compounds are shown in Figure 1.

1

2

3

4

5

6

Figure 1. B3LYP-D3BJ/def2-TZVPP optimized geometries of 1-6.

Using the W1-F12 and W2-F12 composite methods, the estimated the heats of formation of these hydrocarbons are listed in Table 1. Experimental values are available only for 2 and 3; the computed values are off by about 2 kcal mol-1, which the authors argue is just outside the error bars of the computations. They suggest that the experiments might need to be revisited.

Table 1. Heats of formation (kcal mol-1) of 1-6.

compound

ΔHf (comp)

ΔHf (expt)

1

128.57

 

2

144.78

142.7 ± 1.2

3

20.18

22.4 ± 1

4

132.84

 

5

119.42

 

6

63.08

 

They conclude with a comparison of strain energies computed using isogyric, isodesmic, and homodesmotic reactions with a variety of computational methods. Somewhat disappointingly, most DFT methods have appreciable errors compared with the W1-F12 results, and the errors vary depend on the chemical reaction employed. However, the double hybrid method DSD-PBEP86-D3BJ consistently reproduces the W1-F12 results.

References

(1)  Karton, A.; Schreiner, P. R.; Martin, J. M. L. "Heats of formation of platonic hydrocarbon cages by means of high-level thermochemical procedures," J. Comput. Chem. 2016, 37, 49-58, DOI: 10.1002/jcc.23963.

InChIs

1: InChI=1S/C4H4/c1-2-3(1)4(1)2/h1-4H
InChIKey=FJGIHZCEZAZPSP-UHFFFAOYSA-N

2: InChI=1S/C8H8/c1-2-5-3(1)7-4(1)6(2)8(5)7/h1-8H
InChIKey=TXWRERCHRDBNLG-UHFFFAOYSA-N

3: InChI=1S/C20H20/c1-2-5-7-3(1)9-10-4(1)8-6(2)12-11(5)17-13(7)15(9)19-16(10)14(8)18(12)20(17)19/h1-20H
InChIKey=OOHPORRAEMMMCX-UHFFFAOYSA-N

4: InChI=1S/C6H6/c1-2-3(1)6-4(1)5(2)6/h1-6H
InChIKey=RCJOMOPNGOSMJU-UHFFFAOYSA-N

5: InChI=1S/C10H10/c1-2-5-3(1)7-8-4(1)6(2)10(8)9(5)7/h1-10H
InChIKey=TXSUZIHPJIZTJT-UHFFFAOYSA-N

6: InChI=1S/C12H12/c1-2-4-6-5(11-7(1)10(4)11)3(1)9-8(2)12(6)9/h1-12H
InChIKey=DUDCBTWUEJEMGD-UHFFFAOYSA-N

Diels-Alder reactions of some arenes

Aromaticity &Diels-Alder &Houk Steven Bachrach 26 Apr 2016 No Comments

Houk has examined the Diels-Alder reaction involving ethene with benzene 1 and all of its aza-substituted isomers having four or fewer nitrogen atoms 2-11.1 The reactions were computed at M06-2X/6-311+G(d,p).

All of the possible Diels-Alder reactions were examined, and they can be classified in terms of whether two new C-C bonds are formed, one new C-C and one new C-N bond are formed, or two new C-N bonds are formed. Representative transition states of these three reaction types are shown in Figure 1, using the reaction of 7 with ethene.

Figure 1. M06-2X/6-311+G(d,p) optimized transition states for the Diels-Alders reactions of 7 with ethene.

A number of interesting trends are revealed. For a given type of reaction (as defined above), as more nitrogens are introduced into the ring, the activation energy decreases. Forming two C-C bonds has a lower barrier than forming a C-C and a C-N, which has a lower barrier than forming two C-N bonds. The activation barriers are linearly related to the aromaticity of the ring defined by either NICS(0) or aromatic stabilization energy, with the barrier decreasing with decreasing aromaticity. The barrier is also linearly related to the exothermicity of the reaction.

The activation barrier is also linearly related to the distortion energy. With increasing nitrogen substitution, the ring becomes less aromatic, and therefore more readily distorted from planarity to adopt the transition state structure.

References

(1) Yang, Y.-F.; Liang, Y.; Liu, F.; Houk, K. N. "Diels–Alder Reactivities of Benzene, Pyridine, and Di-, Tri-, and Tetrazines: The Roles of Geometrical Distortions and Orbital Interactions," J. Am. Chem. Soc. 2016, 138, 1660-1667, DOI: 10.1021/jacs.5b12054.

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