I missed this when it came out, but Quast, Sander and Borden have made the very interesting non-Kekule diradical 1.¹

³1

The EPR spectra shows the characteristic six-line signal, with zero-field splitting parameters consistent with related triplet diradicals. The Curie-Weiss plot is linear from 4.6 to 22.9 K. These data suggest a triplet ground state. CASSCF(14,14)/6-31G* computations indicate that the triplet lies 8.5 kcal mol^-1 below the singlet. The optimized triplet geometry is shown in Figure 1. The triplet ground state is consistent with the Borden-Davidson rules for radicals.²

31

Figure 1. CASSCF(14,14)/6-31G* optimized structure of triplet 1.

References

(1) Quast, H.; Nudling, W.; Klemm, G.; Kirschfeld, A.; Neuhaus, P.; Sander, W.; Hrovat, D. A.; Borden, W. T., "A Perimidine-Derived Non-Kekule Triplet Diradical," J. Org. Chem. 2008, 73, 4956-4961, DOI: 10.1021/jo800589y.

(2) Borden, W. T.; Davidson, E. R., "Effects of electron repulsion in conjugated hydrocarbon diradicals," J. Am. Chem. Soc. 1977, 99, 4587-4594, DOI: 10.1021/ja00456a010.

InChIs

1: InChI=1/C20H27N3/c1-19(2,3)13-8-12-9-14(20(4,5)6)11-16-17(12)15(10-13)22-18(21-7)23-16/h8-11H,1-7H3,(H2,21,22,23)/f/h22-23H
InChIKey=XAKUHDACNAUAAB-PDJAEHLQCL

Organic catalysis is a major topic of Chapter 5 of my book. The use of iminium ions as a catalyst and to provide stereoselection, pioneered by MacMillan,¹ was not discussed in the book.

Macmillan had proposed that the iminium 2 formed of imidazolinone 1 and (E)-3-phenylprop-2-enal has conformation A. This conformation blocks access to one face of the alkene and directs, for example, dienophiles to the opposite face. Houk found that conformer B is lower in energy at B3LYP/6-31G(d).²

Now Tomkinson³ has produced a study that convincingly shows that 2 exists as conformer B. An x-ray structure shows this conformation in the solid state. Proton NMR shows that the methyl group signals are interpretable only as coming from B. Finally, SCS-MP2/aug-cc-pVTZ//BHandH/6-31+G(d,p) (see Figure 1) computations show that B is 1.2 kcal mol^-1 more stable than A in the gas phase, and PCM computations indicate that this gap is reduced by less then 0.5 kcal mol^-1 in methanol or acetonitrile.

Conformation B provides little steric hindrance at the β-carbon of the iminium ion, explaining its poor stereoselectivity in conjugate additions.

A

B

Figure 1. BHandH/6-31+G(d,p) optimized structures of conformers A and B of 2.

References

(1) Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C., "New Strategies for Organic Catalysis: The First Highly Enantioselective Organocatalytic Diels-Alder Reaction," J. Am. Chem. Soc., 2000, 122, 4243-4244, DOI: 10.1021/ja000092s.

(2) Gordillo, R.; Houk, K. N., "Origins of Stereoselectivity in Diels-Alder Cycloadditions Catalyzed by Chiral Imidazolidinones," J. Am. Chem. Soc., 2006, 128, 3543-3553, DOI: 10.1021/ja0525859.

(3) Brazier, J. B.; Evans, G.; Gibbs, T. J. K.; Coles, S. J.; Hursthouse, M. B.; Platts,
J. A.; Tomkinson, N. C. O., "Solution Phase, Solid State, and Theoretical Investigations on the MacMillan Imidazolidinone," Org. Lett., 2009, 11, 133-136, DOI: 10.1021/ol802512y.

InChIs

1: InChI=1/C13H18N2O/c1-13(2)14-11(12(16)15(13)3)9-10-7-5-4-6-8-10/h4-8,11,14H,9H2,1-3H3/t11-/m0/s1
InChIKey=UACYWOJLWBDSHG-NSHDSACABQ

2: InChI=1/C22H25N2O/c1-22(2)23(3)21(25)20(17-19-13-8-5-9-14-19)24(22)16-10-15-18-11-6-4-7-12-18/h4-16,20H,17H2,1-3H3/q+1/b15-10+,24-16+/t20-/m0/s1
InChIKey=ZPEHVNACGWTABV-BYFMJTDEBT

Here’s a nice example of the application of computed solvation energies in non-aqueous studies. Cramer and Truhlar have employed their latest SM8 technique, which is parameterized for organic solvents and for water, to estimate solvation energies in olive oil.¹ Now you may wonder why solvation in olive oil of all things? But the partitioning of molecules between water and olive oil has been shown to be a good predictor of lipophilicity and therefore bioavailability of drugs! The model works reasonably well in reproducing experimental solvation energies and partition coefficients. They do make the case that fluorine substitution which appears to improve solubility in organics,originates not to more favorable solvation in organic solvents (like olive oil) but rather that fluorine substitution dramatically decreases solubility in water.

References

(1) Chamberlin, A. C.; Levitt, D. G.; Cramer, C. J.; Truhlar, D. G., "Modeling Free Energies of Solvation in Olive Oil," Mol. Pharmaceutics, 2008, 5, 1064-1079, DOI: 10.1021/mp800059u

Liu has provided the link between pure the prototype organic aromatic compound (benzene) and the prototype pure inorganic aromatic (borazine).¹ His group has prepared 1,2-dihydro1,2-azaborine 1. Dixon has performed computations to support the identification of the molecule. For example, the computed and experimental chemical shifts are in nice agreement (see Table 1). The B3LYP/DZVP2 optimized structure of 1 is shown in Figure 1.

Table 1. Computed^a and experimental chemical shifts (ppm) of 1.¹

^aB3LYP/Alhrichs-vTZP.

Figure 1. B3LYP/DZVP2 optimized structure of 1.¹

The computations support the notion that 1 is truly aromatic. Its NICS(1) value is -7.27 ppm, close that of benzene (-10.39 ppm), and much more negative that that of borazine (-3.01 ppm). Reactions 1 and 2 compare the stability of 1 to benzene. These indicate that the resonance stabilization energy of 1 is about 13 kcal mol^-1 less than that of benzene, whose RSE is about 34 kcal mol^-1. Liu and Dixon thus consider 1 to be an aromatic compound and one that helps create a sort of organic, mixed organic-inorganic and inorganic aromatic continuum.

References

(1) Marwitz, A. J. V.; Matus, M. H.; Zakharov, L. N.; Dixon, D. D.; Liu, S.-Y., "A Hybrid Organic/Inorganic Benzene," Angew. Chem. Int. Ed. 2009, 48, 973-977, DOI: 10.1002/anie.200805554

InChIs

1: InChI=1/C4H6BN/c1-2-4-6-5-3-1/h1-6H
InChIKey=OGZZEGWWYQKMSO-UHFFFAOYAN

The failure of DFT in dealing with some seemingly straightforward reactions (as discussed in these previous blog posts: A, B, C, D, E, F) has become a bit clearer. Brittain and co-workers have identified the culprit.¹ They examined twelve different reactions, involving neutral, radical, cations and anions:

R-Me + Me-H → R-H +Me-Me

R-Me + Me^. → R^. + Me-Me

R-Me + Me^– → R^– + Me-Me

R-Me + Me⁺ → R⁺ + Me-Me

where R is ethyl, i-propyl and t-butyl. They used a variety of different functionals, and benchmarked the energies against those found at CCSD(T)/cc-pVTZ. By systematically using different densities and different exchange and correlation components, DFT exchange is responsible for the poor performance – and it can be very poor: the error for the cation reaction with R=t-butyl is 12 kcal mol^-1 with B3LYP and 18 kcal mol^-1 with PBE. It should be noted that the maximum error with G3(MP2) and MP2 is 1.5 and 2.5 kcal mol^-1, respectively. These authors make three important conclusions: (a) that traditional ab initio methods are preferred, (b) that development of new functionals should target the exchange component, and (c) Truhlar’s highly parameterized functional MO5-2X works quite well (maximum error is 2.6 kcal mol^-1 – again for the cation t-butyl case) but the reason for its success is unknown.

References

(1) Brittain, D. R. B.; Lin, C. Y.; Gilbert, A. T. B.; Izgorodina, E. I.; Gill, P. M. W.; Coote, M. L., "The role of exchange in systematic DFT errors for some organic reactions," Phys. Chem. Chem. Phys. 2009, DOI: 10.1039/b818412g.

Here’s another great example of synthesis of highly strained compounds. Bertrand has prepared the substituted triafulvalene 1.¹ The compound is stable as a solid or in solution under inert gas. It does however react quickly with water, a remarkable addition of water across an alkene. This is understood in terms of a very high HOMO and a low LUMO, indicating a very reactive double bond. The UV/Vis corroborates this: its absorption is at 502nm, compared to 171nm of ethylene and 217nm of 1,3-butadiene. The B3LYP/6-31G(d) structure of the tetraphenyl derivative 2 is shown in Figure 1.

1

2

Figure 1. B3LYP/6-31G(d) optimized structure of 2.

References

(1) Kinjo, R.; Ishida, Y.; Donnadieu, B.; Bertrand, G., "Isolation of Bicyclopropenylidenes: Derivatives of the Smallest Member of the Fulvalene Family," Angew. Chem. Int. Ed. 2009, 48, 517-520, DOI: 10.1002/anie.200804372

InChIs

1: InChIKey=GJHAFFXCMBMUNM-DBFBYELTBP

2: InChIKey=WTGGHSXPMAHUNP-UHFFFAOYAY

Malonaldehyde 1 possesses a very short intramolecular hydrogen bond. Its potential energy surface has two local minima (the two mirror image hydrogen-bonded structures) separated by a C_2v transition state. Schaefer reports a high-level computational study for the search for even shorter hydrogen bonds that might even lead to a single well on the PES.¹

The hydrogen bond distance is characterized by the non-bonding separation between the two oxygen atoms. Table 1 shows the O^…O distance for a number of substituted malonaldehydes computed at B3LYP/DZP++. Electron withdrawing groups on C₂ reduce the O^..O distance (see trend in 1 → 4). Electron donating groups on C₁ and C₃ also reduce this distance (see 5 and 6). Bulky substituents on the terminal carbons also reduce the O^…O distance (see 7). Combining all of these substituent effects in 8 leads to the very short O^…O distance of 2.380 Å.

Table 1. Distance (Å) between the two oxygen atoms and the barrier for hydrogen transfer of substituted malonaldehydes .¹

^aFocal point energy. ^bFocal point energy and corrected for zero-point vibrational energy.

A shorter O^…O distance might imply a smaller barrier for hydrogen transfer between the two oxygens. The structures of 8 and the transition state for its hydrogen transfer are shown in Figure 1. The energies of a number of substituted malonaldehydes were computed using the focal point method, and the barriers for hydrogen transfer are listed in Table 1. There is a nice correlation between the O^…O distance and the barrier height. The barrier for 8 is quite small, suggesting that with some bulkier substituents, the barrier might vanish altogether, leaving only a symmetric structure. In fact, the barrier appears to vanish when zero-point vibrational energies are included.

8

8TS

Figure 1. B3LYP/DZP++ optimized geometries of 8 and the transition state for hydrogen transfer 8TS.¹

References

(1) Hargis, J. C.; Evangelista, F. A.; Ingels, J. B.; Schaefer, H. F., "Short Intramolecular Hydrogen Bonds: Derivatives of Malonaldehyde with Symmetrical Substituents," J. Am. Chem. Soc., 2008, 130, 17471-17478, DOI: 10.1021/ja8060672.

InChIs

1: InChI=1/C3H4O2/c4-2-1-3-5/h1-4H/b2-1-
InChIKey=GMSHJLUJOABYOM-UPHRSURJBI

2: InChI=1/C4H3NO2/c5-1-4(2-6)3-7/h2-3,6H/b4-2-
InChIKey=BHYIQMFSOGUTRT-RQOWECAXBC

3: InChI=1/C3H3NO4/c5-1-3(2-6)4(7)8/h1-2,5H/b3-1+
InChIKey=JBBHDCMVSJADCE-HNQUOIGGBS

4: InChI=1/C3H5BO2/c4-3(1-5)2-6/h1-2,5H,4H2/b3-1+
InChIKey=IQNKNZSFMBIPBI-HNQUOIGGBX

5: InChI=1/C3H6N2O2/c4-2(6)1-3(5)7/h1,6H,4H2,(H2,5,7)/b2-1-/f/h5H2
InChIKey=AOZIOAJNRYLOAH-KRHGAQEYDI

6: InChI=1/C5H8O4/c1-8-4(6)3-5(7)9-2/h3,6H,1-2H3/b4-3+
InChIKey=BYYYYPBUMVENKB-ONEGZZNKBI

7: InChI=1/C11H20O2/c1-10(2,3)8(12)7-9(13)11(4,5)6/h7,12H,1-6H3/b8-7-
InChIKey=SOZFXLUMSLXZFW-FPLPWBNLBX

8: InChI=1/C3H5N3O4/c4-2(7)1(3(5)8)6(9)10/h7H,4H2,(H2,5,8)/b2-1+/f/h5H2
InChIKey=IHYUFGCOUITNJP-CHFMFTGODK