What is the rate determining step in the Hajos-Parrish-Eder-Sauer-Wiechert reaction (reaction 1)? This basic question of the mechanism for the first example of the use of proline as a catalyst remains unanswered, though a recent paper by Meyer and Houk¹ does moves us forward.

Their ¹³C kinetic isotope effect study revealed that only the nucleophilic ketone (the carboyl of the butyl chain) experiences any significant effect, with a value of about 1.03. B3LYP/6-31G(d,p) computations of the three transition states shown below were performed for both the gas phase and solution using IEF-PCM. Calculations of the transition state for the formation of the C-C bond (TS3) predicts no kinetic isotope effect, indicating that it is not the rate limiting step, in conflict with previous² suggestions. The transition states for the formation of the carbinolamine (TS1) and formation of the iminium (TS2) both predict an isotope effect comparable with experiment. TS1 is about 3 kcal mol^-1 higher in energy than TS2. The authors conclude that a step prior to formation of the C-C is the rate limiting step of the Hajos-Parrish-Eder-Sauer-Wiechert reaction, but cannot discern between the two possibilities examined.

References

(1) Zhu, H.; Clemente, F. R.; Houk, K. N.; Meyer, M. P., "Rate Limiting Step Precedes C-C Bond Formation in the Archetypical Proline-Catalyzed Intramolecular Aldol Reaction," J. Am. Chem. Soc., 2009, 131, 1632-1633, DOI: 10.1021/ja806672y.

(2) Clemente, F. R.; Houk, K. N., "Computational Evidence for the Enamine
Mechanism of Intramolecular Aldol Reactions Catalyzed by Proline," Angew. Chem. Int. Ed., 2004, 43, 5766-5768, DOI: 10.1002/anie.200460916.

InChIs

2-methyl-2-(3-oxobutyl)cyclopentane-1,3-dione:
InChI=1/C10H14O3/c1-7(11)5-6-10(2)8(12)3-4-9(10)13/h3-6H2,1-2H3
InChIKey=OZBYSCPBJGAYMQ-UHFFFAOYAW

(3aS,7aS)-3a-hydroxy-7a-methyl-3,4,6,7-tetrahydro-2H-indene-1,5-dione:
InChI=1/C10H14O3/c1-9-4-2-7(11)6-10(9,13)5-3-8(9)12/h13H,2-6H2,1H3/t9-,10+/m1/s1
InChIKey=PUHCDQVSBDIJTM-ZJUUUORDBA

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

Concern about the use of DFT for general use in organic chemistry remains high; see my previous posts (1, 2, 3). Houk has now examined the reaction enthalpies of ten simple Diels-Alder reactions using a variety of functionals in the search for the root cause of the problem(s).¹

The ten reactions are listed in Scheme 1, and involve cyclic and acyclic dienes and either ethylene or acetylene as the dienophile. Table 1 lists the minimum and maximum deviation of the DFT enthalpies relative to the CBS-QB3 enthalpies (which are in excellent accord with experiment). Clearly, all of the DFT methods perform poorly, with significant errors in these simple reaction energies. The exception is the MO6-2X functional, whose errors are only slightly larger than that found with the SCS-MP2 method. Use of a larger basis set (6-311+G(2df,2p)) reduced errors only a small amount.

Table 1. Maximum, minimum and mean deviation of reaction enthalpies (kcal mol^-1) for the reactions in Scheme 1 using the 6-31+G(d,p) basis set.¹

In order to discern where the problem originates, they next explore the changes that occur in the Diels-Alder reaction: two π bonds are transformed into one σ and one π bond and the conjugation of the diene is lost, leading to (proto)branching in the product. Reactions 1-3 are used to assess the energy consequence of converting a π bond into a σ bond, creating a protobranch, and the loss of conjugation, respectively.

The energies of these reactions were then evaluated with the various functionals. It is only with the conversion of the π bond into a σ bond that they find a significant discrepancy between the DFT estimates and the CBS-QB3 estimate. DFT methods overestimate the energy for the π → σ exchange, by typically around 5 kcal mol^-1, but it can be much worse. Relying on cancellation of errors to save the day for DFT will not work when these types of bond changes are involved. Once again, the user of DFT is severely cautioned!

References

(1) Pieniazek, S. N.; Clemente, F. R.; Houk, K. N., "Sources of Error in DFT Computations of C-C Bond Formation Thermochemistries: π → σ Transformations and Error Cancellation by DFT Methods," Angew. Chem. Int. Ed. 2008, 47, 7746-7749, DOI: 10.1002/anie.200801843

Cyclization of enediynes is thoroughly discussed in Chapter 3.3 of my book. The reaction that started all the excitement is the C₁-C₆ cyclization (the Bergman cyclization, Reaction 1). Meyers and Saito then proposed the alternative C₂-C₇ cyclization (Reaction 2), and a variant on this, the Schmittel cyclization (Reaction 3) followed soon thereafter. Now, Pascal completes the theme with a report on the C₁-C₅ cyclization (Reaction 4).¹

Pascal begins with the assumption that terminal aryl substitution on the enediyne will both (a) inhibit the C₁-C₆ cyclization due to steric interactions and (b) the C₁-C₅ cyclization should be enhanced due to stabilization of the radical by the neighboring aryl group. He computed the activation energies of a series of analogues, some of which are listed in Table 1. The transition state structures are shown in Figure 1 for 1b and 1c. Phenyl substitution does accomplish both suggestions: the activation barrier for the Bergman cyclization increases by 4 kcal mol^-1, while the barrier for the C₁-C₅ cyclization is lowered by nearly 6 kcal mol^-1. Further substitution of the phenyl ring by either chloro or methyl groups brings the barriers into near degeneracy.

Table 1. RBLYP/6-31G(d) Activation energies (kcal mol^-1) for
competing cyclization reactions of substituted enediynes.¹

C1-C5 TS of 1b	C1-C6 TS of 1b
C1-C5 TS of 1c	C1-C6 TS of 1c

Figure 1. RBLYP/6-31G(d) optimized geometries of the C₁-C₅ and C₁-C₆ transition states for 1b and 1c.¹

The di-substituted enediynes were examined next. The C₁-C₅ and C₁-C₆ transition states for the phenyl (2a) analogue are shown in Figure 2, and the activation energies for it and the 2,4,6-trichlorophenyl (2b) analogue are listed in Table 1. With BLYP, the C₁-C₅ cyclization is favored by a significant amount over the Bergman cyclization. This may be an overestimation as the BCCD(T)/cc-pVDZ//-BLYP/6-31G(d) computations predict the opposite energy ordering.

C1-C5 TS of 2a

C1-C2 TS of 2a

Figure 1. RBLYP/6-31G(d) optimized geometries of the C₁-C₅ and C₁-C₆ transition states for 2a.¹

Pascal synthesized 2b and subjected it to thermolysis. Only indenes were obtained, indicative of the C₁-C₅ cyclization occurring in total preference over the C₁-C₆ pathway. The presence of 1,4-cyclohexadiene does improve the yields, suggestive that the transfer hydrogenation mechanism may be operative. However, when the reaction is done in the absence of 1,4-cyclohexadiene and at lower temperature (180 °C), the C₁-C₅ cyclization is still observed and no Bergman cyclization is seen. It appears that C₁-C₅ cyclization of enediynes is a viable reaction.

References

(1) Vavilala, C.; Byrne, N.; Kraml, C. M.; Ho, D. M.; Pascal, R. A., "Thermal C¹-C⁵ Diradical Cyclization of Enediynes," J. Am. Chem. Soc. 2008, 130, 13549-13551, DOI: 10.1021/ja803413f.

InChIs

1a: InChI=1/C10H6/c1-3-9-7-5-6-8-10(9)4-2/h1-2,5-8H
InChIKey=CBYDUPRWILCUIC-UHFFFAOYAY

1b: InChI=1/C16H10/c1-2-15-10-6-7-11-16(15)13-12-14-8-4-3-5-9-14/h1,3-11H
InChIKey=FFEGFMOHMPSHTK-UHFFFAOYAQ

1c: InChI=1/C16H8Cl2/c1-2-12-6-3-4-7-13(12)10-11-14-15(17)8-5-9-16(14)18/h1,3-9H
InChIKey=ZQRAACNBGPDESE-UHFFFAOYAV

1d: InChI=1/C18H14/c1-4-16-10-5-6-11-17(16)12-13-18-14(2)8-7-9-15(18)3/h1,5-11H,2-3H3
InChIKey=XGUCEMJKUJLOHZ-UHFFFAOYAZ

2a: InChI=1/C22H14/c1-3-9-19(10-4-1)15-17-21-13-7-8-14-22(21)18-16-20-11-5-2-6-12-20/h1-14H
InChIKey=XOJSMLDMLXWRMT-UHFFFAOYAD

2b: InChI=1/C22H8Cl6/c23-15-9-19(25)17(20(26)10-15)7-5-13-3-1-2-4-14(13)6-8-18-21(27)11-16(24)12-22(18)28/h1-4,9-12H
InChIKey=FNGRRGHMCFPDDG-UHFFFAOYAU

While catalysis of many pericyclic reactions have been reported, until now there have been no reports of a catalyzed electrocylization. Bergman, Trauner and coworkers have now identified the use of an aluminum Lewis Acid to catalyze a 6e^– electrocyclization.¹

They start off by noting that electron withdrawing groups on the C₂ position of a triene lowers the barrier of the electrocylization. So they model the carbomethoxy substituted hexatriene (1a-d) with a proton attached to the carbonyl oxygen as the Lewis acid at B3LYP/6-31G**. Table 1 presents the barrier for the four possible isomeric reactions. Only in the case where the substituent is in the 2 position is there a significant reduction in the activation barrier: 10 kcal mol^-1.

Table 1. B3LYP/6-31G** activation barriers (kcal mol^-1) for the catalyzed (H⁺) and uncatalyzed electrocylication reaction of carbomethoxy-substituted hexatrienes.

With these calculations as a guide, they synthesized compounds 3 and 5 and used Me₂AlCl as the catalysts. In both cases, significant rate enhancement was observed. The thermodynamic parameters for these electrocylizations are given in Table 2. The aluminum catalyst acts primarily to lower the enthalpic barrier, as predicted by the DFT computations. The effect is not as dramatic as for the computations due likely to a much greater charge dispersal in over the aluminum catalyst (as opposed to the tiny proton in the computations) and the omission of solvent from the calculations.

Table 2. Experimental thermodynamic parameters for the electrocylcization of 3 and 5.

References

(1) Bishop, L. M.; Barbarow, J. E.; Bergman, R. G.; Trauner, D., "Catalysis of 6π Electrocyclizations," Angew. Chem. Int. Ed. 2008, 47, 8100-8103, DOI: 10.1002/anie.200803336

InChIs

1a: InChI=1/C8H10O2/c1-3-4-5-6-7-8(9)10-2/h3-7H,1H2,2H3/b5-4-,7-6+
InChIKey=INMLJEKOJCNLTL-SCFJQAPRBY

1b: InChI=1/C8H10O2/c1-3-4-5-6-7-8(9)10-2/h3-7H,1H2,2H3/b5-4-,7-6-
InChIKey=INMLJEKOJCNLTL-RZSVFLSABV

1c: InChI=1/C8H10O2/c1-4-5-6-7(2)8(9)10-3/h4-6H,1-2H2,3H3/b6-5-
InChIKey=QALYADPPGKOFPQ-WAYWQWQTBX

1d: InChI=1/C8H10O2/c1-4-6-7(5-2)8(9)10-3/h4-6H,1-2H2,3H3/b7-6+
InChIKey=BRDQFYBEWWPLFX-VOTSOKGWBR

2a: InChI=1/C8H10O2/c1-10-8(9)7-5-3-2-4-6-7/h2-5>,7H,6H2,1H3
InChIKey=LUFUPKXCMNRVLT-UHFFFAOYAU

2c: InChI=1/C8H10O2/c1-10-8(9)7-5-3-2-4-6-7/h2-3,5H,4,6H2,1H3
InChIKey=KPYYGHDMWKXJCE-UHFFFAOYAC

2d: InChI=1/C8H10O2/c1-10-8(9)7-5-3-2-4-6-7/h3,5-6H,2,4H2,1H3
InChIKey=YCTXQIVXFOMZCV-UHFFFAOYAU

3: InChI=1/C17H20O2/c1-5-16(17(18)19-4)14(3)11-13(2)12-15-9-7-6-8-10-15/h5-12H,1-4H3/b13-12+,14-11-,16-5-
InChIKey=DPBZDJWWRAWHQX-USTKDYFJBV

4: InChI=1/C17H20O2/c1-11-10-12(2)16(17(18)19-4)13(3)15(11)14-8-6-5-7-9-14/h5-10,13,15H,1-4H3/t13-,15-/m1/s1
InChIKey=JFBDOBRQORXZEY-UKRRQHHQBP

5: InChI=1/C16H16O/c1-13(12-14-6-3-2-4-7-14)10-11-15-8-5-9-16(15)17/h2-4,6-8,10-12H,5,9H2,1H3/b11-10-,13-12+
InChIKey=OAQIPONHGIZOBU-JPYSRSMKBG

6: InChI=1/C16H16O/c1-11-7-8-13-14(9-10-15(13)17)16(11)12-5-3-2-4-6-12/h2-8,14,16H,9-10H2,1H3/t14-,16-/m0/s1
InChIKey=MJUGKTLVECDOOO-HOCLYGCPBO

Schaefer and Allen have applied their focal point method to the question of the benzylic effect in the S_N2 reaction.¹ S_N2 reactions are accelerated when the attack occurs at the benzylic carbon, a well-known phenomenon yet the reason for this remains unclear. The standard textbook-like argument has been that the negative charge built up in the S_N2 transition state can be delocalized into the phenyl ring. However, solution phase Hammett studies are often U-shaped, indicating that both electron donating and withdrawing group accelerate the substitution reaction. (This is usually argued as indicative of a mechanism change from S_N2 to S_N1.)

The focal point method involves a series of very large computations where both basis set size and degree of electron correlation are systematically increased, allowing for an extrapolation to essentially infinite basis set and complete correlation energy. The energy of the transition state (relative to separated reactants) for four simple S_N2 reactions evaluated with the focal point method are listed in Table 1. The barrier for the benzylic substitutions is lower than for the methyl cases, indicative of the benzylic effect.

Table 1. Energy (kcal mol^-1) of the transition state relative to reactants.¹

To answer the question of why the benzylic substitution reactions are faster, they examined the charge distribution evaluated at B3LYP/DZP++. As seen in Table 1, this method does not accurately reproduce the activation barriers, but the errors are not terrible, and the trends are correct.

In Figure 1 are the geometries of the transition states for the reaction of fluoride with methylflouride or benzylfluoride. The NBO atomic charges show that the phenyl ring acquired very little negative charge at the transition state. Rather, the electric potential at the carbon under attack is much more revealing. The potential is significantly more positive for the benzylic carbon than the methyl carbon in both the reactant and transition states.

VC = -405.156 V	VC = -404.379 V

Figure 1. MP2/DZP++ transition states for the reaction of fluoride with methylfluoride and benzylflouride. NBO charges on F and C and the electrostatic potential in Volts.¹

They next examined the reaction of fluoride with a series of para-substituted benzylfluorides. The relation between the Hammet σ constants and the activation energy is fair (r = 0.971). But the relation between the electrostatic potential at the benzylic carbon (in either the reactant or transition state) with the activation energy is excellent (r = 0.994 or 0.998). Thus, they argue that it is the increased electrostatic potential at the benzylic carbon that accounts for the increased rate of the S_N2 reaction.

References

(1) Galabov, B.; Nikolova, V.; Wilke, J. J.; Schaefer III, H. F.; Allen, W. D., "Origin of the S_N2 Benzylic Effect," J. Am. Chem. Soc., 2008, 130, 9887-9896, DOI: 10.1021/ja802246y.

There remains still new territory to explore even with such well-known reactions as the Claisen rearrangement. Jacobsen reports a catalyzed Claisen rearrangement where the catalyst is urea-based.¹ Catalyst 1 produces modest to very reasonable % conversion in a series of simple Claisen rearrangements, as shown in Table 1.

Table 1. Claisen Rearrangements

With the chiral catalyst 2, the Claisen rearrangement is both catalyzed and proceeds with large enantiomeric excess, as shown in the representative example Reaction 1.

Jacobsen and Uyeda also reported the transition state for a model Claisen rearrangement catalyzed by a model guanidinium ion (Reaction 2) computed at B3LYP/6-31G(d). I have reproduced this calculation and the calculations for the both the catalyzed and uncatalyzed rearrangements, shown in Figure 1. In email communication with Dr. Jacobsen, I was able to confirm these energies against their own unpublished results.

Uncatalyzed Reaction 2
Reactant: 0.0	TS: 25.73
Product 1: -11.04	Product 2: -13.69
Catalyzed Reaction 2
Reactant: 0.0	TS: 21.09
Product 1: -12.36	Product 2: -12.80

Figure 1. B3LYP/6-31G(d) optimized structures of the critical points of uncatalyzed and catalyzed Reaction 2. Relative energies in kcal mol^-1.

The structures show the beneficial hydrogen bonds between the guanidinium anion and the carbonyl oxygens (or the ether oxygen of the reactant). In progressing from the transition state, both reactions first gives Product 1. This product conformer can than rotate to give the lower energy conformer Product 2. The activation energy of the catalyzed reaction is 4.64 kcal mol^-1 lower than for the uncatalyzed reaction, demonstrating the benefit of the complexation in the transition state.

I want to thank Dr. Jacobsen and his graduate student Chris Uyeda for sharing their computational results with me for the preparation of this blog post.

References

(1) Uyeda, C.; Jacobsen, E. N., "Enantioselective Claisen Rearrangements with a Hydrogen-Bond Donor Catalyst," J. Am. Chem. Soc., 2008, 130, 9228-9229, DOI: 10.1021/ja803370x.

What happens when anions are sequentially solvated with more and more water? In an interesting study by Chesnovsky, Gerber and coworkers, the answer is proton transfer!¹ They examined the conjugate base of aniline (C₆H₅NH^–, 1) using both PES and MP2/DZP computations. The PES spectrum of 1 shows two strong peaks. When this anion is then coordinates with one or two water molecules, C₆H₅NH^–)^.(H₂O) or (C₆H₅NH^–)^.(H₂O)₂, the peaks shifts to higher energy but the general shape remains unchanged. When three or more water molecules are coordinated to 1, the PE spectra totally changes, becoming broad and relatively featureless.

What accounts for this different PES? The authors posit that the PES of these larger clusters resembles that of hydrated OH^– clusters. Optimization of (C₆H₅NH^–)^.(H₂O) or (C₆H₅NH^–)^.(H₂O)₂
gave structures of the waters hydrogen bonded to the nitrogen anion. However, optimization of the (C₆H₅NH^–)^.(H₂O)₃ gave in fact a cluster of the form (C₆H₅NH₂)^.(HO^–)^.(H₂O)₂. The two lowest energy structures are shown in Figure 1. The structures correspond to the transfer of one proton from water to the anilinide anion to give aniline associated with hydroxide and two water molecules.

Rel E: 0.0

Rel E: 0.10 eV

Figure 1. B3LYP/6-31+G(d) optimized structures of
the C₆H₅NH₂)^.(HO^–)^.(H₂O)₂ clusters.

(Note: Once again the authors have failed to include the computed structures as part of the supporting information and so I have reoptimized the structures but at a lower, computationally more tractable level. Hopefully, authors, editors and reviewers will standardize this practice and include such materials in all papers in the very near future!)

Though aniline is a stronger gas-phase acid than water (DPE(aniline) = 366.4 kcal mol^-1 and DPE(H₂O) = 390.3 kcal mol^-1), the reverse is true in solution (pK_a(aniline) = 27.3) and pK_a(water) = 15.7). As more water molecules are present, the preferential solvation of the hydroxide anion over C₆H₅NH^– results in the formation of hydroxide.

References

(1) Wolf, I.; Shapira, A.; Giniger, R.; Miller, Y.; Gerber, R. B.; Cheshnovsky, O., "Critical Size for Intracluster Proton Transfer from Water to an Anion," Angew. Chem. Int. Ed., 2008, DOI: 10.1002/anie.200800542

Bickelhaupt has reported a broad benchmark study of the prototype S_N2 and E2 reactions.¹ These are the reactions of ethyl fluoride with fluoride and ethyl chloride with chloride (Scheme A). The critical points were optimized at OLYP/TZ2P and then CCSD(T)/CBS energies are used as benchmark. A variety of different density functionals were then used to obtain single-point energies.

Scheme A

The relative energies of the transition states for the six different reactions are listed for some of the functionals in Table 1. (These are energies relative to separated reactants – and keep in mind that an ion dipole complex is formed between the reactants and the transition states – Bickelhaupt calls this a “reaction complex”.)

Table 1. Relative energies (kcal mol^-1) of the transition states for the six reactions shown in Scheme A.

There is a lot more data in this paper, along with a summary of the mean absolute errors in the overall and central barriers that mimics the data I show in Table 1. The trends are pretty clear. Generalized gradient approximation (GGA) functions – like BLYP, PW91, and PBE – dramatically underestimate the barriers. The hybrid functionals perform much better. The recently maligned B3LYP functional gets the correct trend and provides reasonable estimates of the barriers. Truhlar’s MO5-2X and MO6-2X functionals do very well in matching up the barrier heights along with getting the correct trends in the relative barriers. Simply looking for the functional with the lowest absolute error is not sufficient; BHandH and MO6-L have small errors but give a wrong trend in barriers, predicting that the S_N2 reaction is preferred over the E2 for the fluoride reaction.

Reference

(1) Bento, A. P.; Sola, M.; Bickelhaupt, F. M., "E2 and S_N2 Reactions of X^– + CH₃CH₂X (X = F, Cl); an ab Initio and DFT Benchmark Study," J. Chem. Theory Comput., 2008, 4, 929-940, DOI: 10.1021/ct700318e.

I concluded the subchapter on pseudopericyclic reaction (Chapter 3.4) with a discussion of the controversy concerning the nature of the electrocyclization of 7-azahepta-1,2,4,6-tetraene 1. Quickly summarizing form the book, based on which data one deems important, the reaction can be seen as either pericyclic or pseudopericyclic.

However, I offered David Birney’s opinion as perhaps the proper way to interpret this reaction. David suggested that the TS has both pericyclic and pseudopericyclic character. I wrote that “what we have is a continuum from pericyclic to pseudopericyclic character, analogous to the S_N1 to S_N2 continuum for nucleophilic substitution”.

Duncan has revisited this reaction,¹ employing both B3LYP and CASSCF(10,9) computations. He concludes that the reaction is “neither purely pericyclic nor pseudopericyclic” – just as Birney had indicated. Duncan does offer the possibility of a secondary orbital interaction involving the nitrogen lone pair. But it is nice to see confirmation of the interpretation that David originated for my book!

References

(1) Duncan, J. A.; Calkins, D. E. G.; Chavarha, M., "Secondary Orbital Effect in the Electrocyclic Ring Closure of 7-Azahepta-1,2,4,6-tetraene – A CASSCF Molecular Orbital Study,", J. Am. Chem. Soc., 2008, 130, 6740-6748, DOI: 10.1021/ja074402j.

InChIs

1: InChI=1/C6H7N/c1-2-3-4-5-6-7/h3-7H,1H2/b5-4-,7-6+
InChIKey=VCEMZTODUGWAPF-SCFJQAPRBS

2: InChI=1/C6H7N/c1-6-4-2-3-5-7-6/h2-5,7H,1H2
InChIKey=JGSLKNWXPRDWBA-UHFFFAOYAH