## Tuesday, September 30, 2014

### Why Bistetracenes Are Much Less Reactive Than Pentacenes in Diels–Alder Reactions with Fullerenes

Cao, Y.; Liang, Y.; Zhang, L.; Osuna, S.; Hoyt, A.-L. M.; Briseno, A. L.; Houk, K. N. J. Am. Chem. Soc. 2014, 136, 10743-10751
Contributed by Steven Bachrach.
Reposted from Computational Organic Chemistry with permission

Diels-Alder reaction involving fullerenes have been known for some time. They occur across the [6,6] double bond of C60, the one between two fused 6-member rings. Houk and Briseno report on the Diels-Alder reaction of C60 with pentacene 1 and bistetracene 2 and compare their computations with experiments.1

Pentacene and bistetracene ring numbering convention

Computations were performed for the reaction of 1 and 2 with C60 at M06-2x/6-31G(d)//M062x-3-21G*. The reaction can occur with the dienophile being either ring 1, 2, or 3 of pentacene and ring 1, 2, 3, or 4 of bistetracene. They located TSs and products for all of these possibilities. Select TSs and products are shown in Figure 1.

For the reaction of 1a, the lowest energy TS is for the reaction at the central ring (ring 3), and the resulting product is the lowest energy product. The transition state (PT_TS3) is shown in Figure 1. This TS has the least distortion energy of the three possibilities, because reacting at this central ring destroys the least amount of aromaticity of pentacene. For the reaction of 1b, the lowest barrier is again for reaction of ring 3 (through TMSPT_TS3). However, the product from the reaction with ring 2 (TMSPT_P2) is lower in free energy than TMSPT­_P3, likely caused by steric interactions with the silyl substituents. This actually matches up with experiments which indicate that an analogue of TMSPT_P2 is the kinetic product butTMSPT_P3 is the thermodynamic product.
 PT_TS3 TMSPT_­TS3 TMSPT_P2 TMSPT_P3 BT_TS2 BT_P2
Figure 1. M06-2x/3-21G* optimized geometries.
(Once again a reminder that clicking on any of these structures will launch JMol and you’ll be able to visualize and manipulate this structure in 3-D.)

The computations involving the Diels-Alder reaction of C60 with either 2a or 2b come to the same conclusion. In both cases, the lowest barrier is for the reaction at ring 2, and the product of the reaction at this same ring is the only one that is endoergonic. The geometries of BT_TS2 and BT_P2 are shown in Figure 1. More importantly, the barrier for the Diels-Alder reaction involving 2a and 2b are at least 6 kcal mol-1 higher than the barriers for the reaction of 1a and 1b, in complete agreement with experiments that show little reaction involving analogues of 2b with C60, while analogues of 1b are reasonably rapid.

### References

(1) Cao, Y.; Liang, Y.; Zhang, L.; Osuna, S.; Hoyt, A.-L. M.; Briseno, A. L.; Houk, K. N. "Why Bistetracenes Are Much Less Reactive Than Pentacenes in Diels–Alder Reactions with Fullerenes," J. Am. Chem. Soc.2014136, 10743-10751, DOI: 10.1021/ja505240e.

## Saturday, September 27, 2014

### A General Quantum Mechanically Derived Force Field (QMDFF) for Molecules and Condensed Phase Simulations

Stefan Grimme J. Chem. Theory Comput. 2014, ASAP
Contributed by +Jan Jensen

Stefan Grimme has develop a black-box approach by which a molecule-specific polarizable force field that can be automatically generated from the equilibrium geometry, Hessian, atomic partial charges and covalent bond orders computed with standard quantum mechanical methods.  In addition to the molecule-specific parameters there are 47 fixed parameters (listed in the paper) that were parameterized by separate QM calculations and cover all elements up to Radon.

One of the key challenges for any FF parameterization is the parameterization of the torsions (and any inversions) which can be a difficult to automate.  Grimme solves this by automatically extracting all relevant four atom fragments (CABD) including first-shell substituents on atoms C and D, adding H atoms where needed, and performing a 360$^\circ$ energy scan using modified extended Hückel calculations. The resulting PES is fit to the usual $cos$ functional form.  The extended Hückel calculations are modified to avoid double counting 1,4 interaction also included in the non-bonded part of the FF.

So what can you use the QMDFF for?  Well, for example, you can perform a QM calculation on a single conformation of a flexible molecule and use the resulting QMDFF to map out the conformational PES.  A similar calculation on a single solvent molecule allows you to explicitly solvate the molecule.  Similarly, one can search for the lowest energy conformation (and compute frequencies!) of host-guest complexes based on QM calculations on the host and guest.  For very large systems some kind of fragmentation scheme is required.

Finally, the QMDFF also allows for bonds to be broken (but not formed) so it can also be used to predict mass spectra using Grimme's QCEIMS method, which I highlighted earlier.  Since bonds cannot be formed, QMDFF is not a reactive FF like ReaxFF, but it is interesting to think about how one could make it in to one.

## Thursday, September 25, 2014

### Perspective: Fifty years of density-functional theory in chemical physics

Becke, A. D. J. Chem. Phys. 2014, 140, 18A301
Contributed by Steven Bachrach.
Reposted from Computational Organic Chemistry with permission

The Journal of Chemical Physics has produced a Special Topics issue on Advances in Density Functional Theory. I want to call to your attention the Perspective article by Becke titled “Perspective: Fifty years of density-functional theory in chemical physics”.1 Becke writes a personal account of the history of DFT and makes a number of interesting points and observations. He rightly notes that DFT is exact and we should more properly refer to our actual implementations as Density Functional Approximations (DFA). He also notes that use of the term ab initio as a synonym for wavefunction theory is inappropriate as DFT is just asab initio as HF and post-HF theories.

A common perception about DFT (well, DFA) is that there is no way to systematically improve functionals. Becke exposes a true underlying logic that has driven much of DFA development.

Lastly, Becke is discouraged by the more recent developments that have included virtual orbitals, such as double hybrid methods. His approach is that true DFT is occupied orbitals only (for which he pointedly does not want to adopt the acronym OOO), and that developments that include the virtual orbitals might toll the “death knell” for DFT.

For those interested in a pretty accessible account of the history of DFT, Becke’s Perspective is an excellent place to get started.

### References

(1) Becke, A. D. "Perspective: Fifty years of density-functional theory in chemical physics," J. Chem. Phys.2014140, 18A301 DOI: 10.1063/1.4869598.

### A Quantum Mechanical “Jack in the Box”: Rapid Rearrangement of a Tetrahedryl-Tetrahedrane via Heavy Atom Tunneling

Kozuch, S.  Org. Lett., 2014, 16, 4102-4105
Contributed by Steven Bachrach.
Reposted from Computational Organic Chemistry with permission

1 is notable for its very short central C-C bond, computed at B1B95/6-31G(d) to be only 1.30 Å. Also notable is that 1 can rearrange to the carbene 2 with a release of considerable energy (ΔE=-105.4 kcal mol-1). Nonetheless, the barrier for this rearrangement is 6.7 kcal mol-1 suggesting that 1 might be stable and isolable at low temperatures. (See this previous post for more discussion on this rearrangement, including interactive molecules.)
Kozuch has now examined this rearrangement in more detail, to see if 1 is really stable.1 The issue he raises is the role of quantum mechanical tunneling – since the distance that the carbon atoms need to move in reaching the TS is rather small, perhaps heavy atom tunneling might manifest. In the absence of tunneling, conventional variation transition state theory (CVT) predicts that the half-life of 1 is 170 s at 75 K, and longer still at even lower temperatures. However, the situation is radically different when tunneling is included. Accounting for tunneling using the small curvature tunneling (SCT) approximation predicts a half-life of 1.6 x 10-3 s at 75 K and only a minimally longer half-life of 4.6 x 10-3s at 10 K. Thus, Kozuch concludes that 1 is not stable at any temperature! One should thus be cautious in applying the term “stable” to a compound that might be quite strained and susceptible to tunneling.

(As an aside, Kozuch also notes that 2 can rearrange into 3 and this rearrangement also has a very short half-life on the order of milliseconds at cryogenic temperatures. The structure of 3 is shown in Figure 1.)
Figure 1. B1B95/6-31G(d) optimized structure of 3.

### References

1) Kozuch, S. “A Quantum Mechanical “Jack in the Box”: Rapid Rearrangement of a Tetrahedryl-Tetrahedrane via Heavy Atom Tunneling,” Org. Lett., 201416, 4102-4105, DOI: 10.1021/ol5017977.

### InChIs

1: InChI=1S/C14H12/c1-2-8-11-5-3-9-7(1)10(9)4-6-12(8,11)14(8,11)13(7,9)10/h1-6H2
InChIKey=LNBZAENQMFDBJW-UHFFFAOYSA-N
2: InChI=1S/C14H12/c1-3-11-12-4-2-9-7-8(1,9)10(9)5-6-13(11,12)14(10,11)12/h1-6H2
InChIKey=UKVODHRLGFPZPT-UHFFFAOYSA-N
3: InChI=1S/C14H12/c1-2-10-8-12(10)4-3-11-7-9(1,11)13(11)5-6-14(10,12)13/h1-6H2
InChIKey=AATRYSJRWFKWAY-UHFFFAOYSA-N

## Tuesday, September 16, 2014

### Fullerene Van der Waals Oligomers as Electron Traps

Shubina, T. E.; Sharapa, D. I.; Schubert, C.; Zahn, D.; Halik, M.; Keller, P. A.; Pyne, S. G.; Jennepalli, S.; Guldi, D. M.; Clark, T. J. Am. Chem. Soc. 2014, 136, 10890-10893
Contributed by Steven Bachrach.
Reposted from Computational Organic Chemistry with permission

Clark and co-workers have examined small fullerene clusters for their ability to capture electrons.1 They first looked at the fullerene dimer, comparing the electron affinity of the dimer having a C-C bond between the two cages (about 1.6-1.7 Å between the two cages) 1 and where the two cages are interacting only through van der Waals attractions (around 2.6 Å) 2. The structures and their radical anions were computed at RI-BP86/TZV. The structures of the two radical anions are shown in Figure 1. Interestingly, the radical anion of 2 is actually lower in energy that the radical anion of 1. Comparisons with some other methods are discussed, including a CASSPT2(5,4)/ANO-L-VDZ, computation, that support this result.
 1 2 3 4
Figure 1. RI-BP86/TZV optimized geometries of the radical anions of 1-4.
(Be sure to click on these images to be able to manipulate these structures in 3-D!)

This suggests that the added electron is being held between the cages, in an interstitial region. That suggested looking at the trimer and tetramer structures 3 and 4. The radical anions of these two oligomers are also shown in Figure 1. These oligomers show electron affinities of 1 eV greater than for fullerene itself, along with the ability to stabilize the dianion and even the trianion, what the authors call “deep electron traps”.

### References

(1) Shubina, T. E.; Sharapa, D. I.; Schubert, C.; Zahn, D.; Halik, M.; Keller, P. A.; Pyne, S. G.; Jennepalli, S.; Guldi, D. M.; Clark, T. "Fullerene Van der Waals Oligomers as Electron Traps," J. Am. Chem. Soc. 2014,136, 10890-10893, DOI: 10.1021/ja505949m.

### Transition State Analysis of Enantioselective Brønsted Base Catalysis Chiral Cyclopropenimines

Bandar, J. S.; Sauer, G. S.; Wulff, W. D.; Lambert, T. H.; Vetticatt, M. J. J. Am. Chem. Soc. 2014, 136, 10700-10707
Contributed by Steven Bachrach.
Reposted from Computational Organic Chemistry with permission

Computational techniques are gaining some traction in helping to understand enantioselective organocatalysis. I talk about a few examples in Chapter 6.3 of my book. Lambert and Vetticatt have now used computations to help understand the role of the catalyst 4 in the Michael addition shown in Scheme 1.1 This reaction proceeds with 99% yield and an ee of 98%.

Scheme 1.

13C kinetic isotope effect studies suggest that the rate determining step is the C-C bond formation (the Michael addition step) which follows the deprotonation of the imine 1 by the catalyst 4.
They performed ONIOM computations to search for transition states of this rate limiting step for the reaction in Scheme 1, using the full molecules. From this ONIOM search, the energies for all transition structures with 5 kcal mol-1 of the lowest energy structure were then obtained at B3LYP/6-31G*. The three lowest energy TS are shown in Figure 1. The two lowest energy structures lead to the major enantiomer, while the third lowest energy structure leads to the minor enantiomer. These energies lead to a prediction of an ee of 92%, in reasonable agreement with the experiment. The computed kinetic isotope effects are in nice agreement with experiment, supporting this step as the overall rate limiting step.
 TSs leading to the S isomer TS1(0.0) TS2(0.9) TS leading to the R isomer TS3(1.7)
Table 1. ONIOM optimized geometries of the three lowest energy TSs. Relative energy (kcal mol-1) in parenthesis.

Analysis of what factors are important in determining the ee is complicated and ultimately the authors are unable to provide a simple explanation. They properly note that
The observation that the major enantiomer (S) is formed from two very geometrically distinct transition structures … suggests that the prediction of enantioselectivity for other reactions … will require a full consideration of all possible transition state assemblies. (emphasis mine)
I agree with this sentiment, pessimistic as it may be. Answering this type of question is likely to remain very challenging for years to come.

### References

1) Bandar, J. S.; Sauer, G. S.; Wulff, W. D.; Lambert, T. H.; Vetticatt, M. J. "Transition State Analysis of Enantioselective Brønsted Base Catalysis Chiral Cyclopropenimines," J. Am. Chem. Soc. 2014136, 10700-10707, DOI: 10.1021/ja504532d.

### InChIs

1: InChI=1S/C20H23NO/c1-20(2,3)14-18(22)15-21-19(16-10-6-4-7-11-16)17-12-8-5-9-13-17/h4-13H,14-15H2,1-3H3
InChIKey=UZCWUGCTNCNJHI-UHFFFAOYSA-N
2: InChI=1S/C4H6O2/c1-3-4(5)6-2/h3H,1H2,2H3
InChIKey=BAPJBEWLBFYGME-UHFFFAOYSA-N
3: InChI=1S/C24H29NO3/c1-24(2,3)17-21(26)20(15-16-22(27)28-4)25-23(18-11-7-5-8-12-18)19-13-9-6-10-14-19/h5-14,20H,15-17H2,1-4H3/t20-/m0/s1
InChIKey=KTASCPHNNZODSX-FQEVSTJZSA-N
4: InChI=1S/C37H57N3/c1-2-30(28-29-18-8-3-9-19-29)38-35-36(39(31-20-10-4-11-21-31)32-22-12-5-13-23-32)37(35)40(33-24-14-6-15-25-33)34-26-16-7-17-27-34/h3,8-9,18-19,30-34H,2,4-7,10-17,20-28H2,1H3/t30-/m1/s1
InChIKey=GEHSIGXXLTVFFG-SSEXGKCCSA-N

## Thursday, September 4, 2014

### 8π-Electron Tautomeric Benziphthalocyanine: A Functional Near-Infrared Dye with Tunable Aromaticity

Toriumi, N.; Muranaka, A.; Hirano, K.; Yoshida, K.; Hashizume, D.; Uchiyama, M. Angew. Chem. Int. Ed. 2014, 53, 7814-7818
Contributed by Steven Bachrach.
Reposted from Computational Organic Chemistry with permission

Muranaka and Uchiyama have prepared an 18π-electron system that exhibits variable aromaticity in its tautomeric forms.1 The synthesized benziphthalacyanine 1 shows upfield resonances in the 1H NMR for the internal hydrogens: 1.89 ppm for the C-H proton and 4.67 ppm for the N-H proton. This indicates some weak diatropicity.

To address this interesting magnetic property, they reported B3LYP/6-31+G(d) computations on the model system 2 in its phenol 2p and quinoidal 2q tautomeric forms.

The optimized structures are shown in Figure 1. The phenol form 2p has NICS(0) and NICS(1) values of -6.77 and -6.04 ppm, respectively, indicating only modest aromaticity. However, the NICS values for the quinoidal from 2q are much more negative, -11.43 (NICS(0)) and -10.10 (NICS(1)) ppm, indicating a more significant aromatic character. The calculated chemical shift of the internal C-H is most telling: for 2q it is -4.55ppm but for 2p it is 0.97 ppm, in good agreement with experiment. Thus, 1 has an 18π-electron modestly aromatic periphery, with the phenol form dominant. There is no evidence of a 20π-electron periphery.
 2p 2q
Figure 1. B3LYP/6-31+G(d) optimized geometries of 2p and 2q.

(Note that the supporting materials have a missing carbon in 2q and I have made a guess at its proper location – so this is not quite the optimized structure! Once again, a statement about the quality of SI!)

### References

(1) Toriumi, N.; Muranaka, A.; Hirano, K.; Yoshida, K.; Hashizume, D.; Uchiyama, M. "18π-Electron Tautomeric Benziphthalocyanine: A Functional Near-Infrared Dye with Tunable Aromaticity," Angew. Chem. Int. Ed. 201453, 7814-7818, DOI: 10.1002/anie.201404020.

### InChIs

1: InChI=1S/C108H125N7O2/c1-57(2)75-31-25-32-76(58(3)4)87(75)43-69-49-93-95(51-71(69)45-89-79(61(9)10)35-27-36-80(89)62(11)12)105-111-103(93)109-99-55-100(102(117)56-101(99)116)110-104-94-50-70(44-88-77(59(5)6)33-26-34-78(88)60(7)8)72(46-90-81(63(13)14)37-28-38-82(90)64(15)16)52-96(94)106(112-104)114-108-98-54-74(48-92-85(67(21)22)41-30-42-86(92)68(23)24)73(53-97(98)107(113-105)115-108)47-91-83(65(17)18)39-29-40-84(91)66(19)20/h25-42,49-68,116-117H,43-48H2,1-24H3,(H,109,110,111,112,113,114,115)
InChIKey=LCYQUXHUTZWPDZ-UHFFFAOYSA-N

2p: InChI=1S/C30H17N7O2/c38-23-14-24(39)22-13-21(23)31-25-15-7-1-3-9-17(15)27(33-25)35-29-19-11-5-6-12-20(19)30(37-29)36-28-18-10-4-2-8-16(18)26(32-22)34-28/h1-14,38-39H,(H,31,32,33,34,35,36,37)
InChIKey=JBKUPBCBFUTSRM-UHFFFAOYSA-N

2q: InChI=1S/C30H17N7O2/c38-23-14-24(39)22-13-21(23)31-25-15-7-1-3-9-17(15)27(33-25)35-29-19-11-5-6-12-20(19)30(37-29)36-28-18-10-4-2-8-16(18)26(32-22)34-28/h1-14H,(H3,31,32,33,34,35,36,37,38,39)
InChIKey=PSSSGMKTDQVWLR-UHFFFAOYSA-N