61st Annual Report on Research 2016

Bicyclo[3.2.0]hept-2-ene (1) undergoes thermal isomerization to norbornene (2) in the gas phase (Scheme 1).  This rearrangement has served as a historical exemplar of a [1,3] sigmatropic carbon migration.  Competitive isomerization and fragmentation processes at temperatures in excess of 300 ^oC convert 1 to its isomer 2 or directly to fragments cyclopentadiene and ethylene (Scheme 1).^1,2  Determination of an accurate rate constant k₁₃ for the [1,3] rearrangement of 1-to-2 and the associated Arrhenius parameters is complicated by the observation that 2 experiences facile Diels-Alder cycloreversion (retro Diels-Alder reaction) to cyclopentadiene and ethylene.  Despite the large experimental error in activation parameters for the [1,3] process, Cock and Frey conclude that the activation parameters for the sum (k₁₃ + k_f) are close to the expected values 'if both processes have a biradical mechanism' and therefore that 'a two-step pathway is competitive.'

         Scheme 1. Thermal Reactions of Bicyclo[3.2.0]hept-2-ene (1)

In a dramatic reversal of this mechanistic rationale, Woodward and Hoffmann declared emphatically that exo-7-d-endo-6-acetoxybicyclo[3.2.0]hept-2-ene 'undergoes a concerted symmetry-allowed suprafacial [1,3] shift, with inversion at the migrating center, É at 307 °C.' ³ According to the Woodward-Hoffmann rules, suprafacial migration with inversion of configuration (si) is privileged as orbital-symmetry allowed and suprafacial migration with retention of configuration (sr) is orbital-symmetry forbidden.  The mechanistic debate about whether the [1,3] sigmatropic rearrangement is concerted or stepwise has therefore primarily focused on stereochemical outcomes in cases where the migrating center, C-7 of bicyclo[3.2.0]hept-2-ene, carries a substituent to enable differentiation between the si and sr products.  Thus, si/sr ratios have been cited as a measure of the degree of orbital symmetry control in [1,3] sigmatropic rearrangements.

Our current mechanistic analysis is that [1,3] sigmatropic rearrangements traverse short-lived diradical transition structures residing on a shallow energy surface.⁷  The mixed stereochemical results that have often converged toward a value of unity have effectively subverted alternative mechanistic interpretations such as competing orbital symmetry-allowed (si) and orbital symmetry-forbidden (sr) pathways⁸ or competing concerted (si) and diradical (si/sr) mechanisms.⁹  The potential however for a short-lived nonequilibrated diradical intermediate to partition between inversion and retention modes¹⁰ deserves more critical examination.

The higher stereoselectivity observed for exo-7-methylbicyclo[3.2.0]hept-2-ene (3)² versus that of deuterium-labeled 1 suggests that either steric factors or the moment of inertia about the C6-C7 bond might well influence the stereoselectivity of the [1,3] migration.  It is this proposition that allowed us to reconsider our earlier assumption that all exo-7-alkylbicyclo[3.2.0]hept-2-enes would yield comparable results both kinetically and stereochemically.

The thermal reactions of the exo-7-alkylbicyclo[3.2.0]hept-2-enes were followed at 275 ^oC in the gas phase.  The relative order of importance of kinetic processes is k₁₃ > k_f  (Table 1) although the k₁₃/k_f  ratio decreases as the alkyl group increases in size.

Capillary GC analysis provided relative concentration versus reaction time data for the reactants and for all isomeric products. A mixture of each exo- and endo-5-alkylnorbornene pair was also heated at 275 ^oC in order to obtain rates of the respective Diels-Alder cycloreversions.  The rates of retro Diels-Alder reactions for all exo-5-alkylnorbornenes were comparable as were those for the endo-5-alkylnorbornenes.  In all cases the reactivity of the endo-5-alkylnorbornenes exceeded that of the corresponding exo-5-alkylnorbornenes by a factor greater than 2 (Table 2).  

Table 1.  Rate Constants and Exit Channels for

                exo-7-Alkylbicyclo[3.2.0]hept-2-enes

Table 2.  Rates of Retro Diels-Alder Reactions for

exo- (k_1,RDA) and endo- (k_2,RDA)-7-Alkylbicyclo[3.2.0]hept-2-enes

Our preliminary thermal studies suggest that changing the alkyl group on the migrating carbon C-7 has little impact on reaction rates but results in a correlation between the stereoselectivity of the [1,3] sigmatropic rearrangements of exo-7-alkylbicyclo-[3.2.0]hept-2-enes and the mass of the C-7 substituent.  A linear relationship is also evident but less well-defined when the si/sr ratio is plotted versus either the respective Charton or Taft steric parameters.  Currently, thermal reactions of other exo-7-alkylbicyclo[3.2.0]hept-2-enes are underway so we can extend this analysis to more analogs.

Katie Kidder, one of two F&M undergraduates support by PRF funds in the summer of 2016 conducted experimental synthetic work in my lab and also engaged in a computational study of some of the hydrocarbon reactants and products relevant to this current investigation.  Prof. Alex Davis, who has been mentoring Katie in theoretical chemistry, has added a new dimension to our research by coupling computational and experimental analysis. Because Katie intends to pursue a Ph.D. in computational chemistry, this has and will continue to be an excellent research experience for her.  We believe that the inclusion of computational analyses with our experimental data in a future publication will enhance the value of the research.  Should these efforts be productive, Prof. Davis and I might well establish a permanent research collaboration.

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