Computational Investigation of the Mechanism of Addition of Singlet Carbenes to Bicyclobutanes

Abstract

Singlet carbenes are known to react with bicyclobutanes to yield 1,4-diene products, as in the addition of dichlorocarbene to bicyclobutane to yield 1,1-dichloro-1,4-pentadiene. At least two mechanisms have been proposed to explain this unusual reaction: (1) a concerted process and (2) a stepwise process involving a zwitterionic intermediate. Ab initio electronic structure calculations have been performed in order to help distinguish between these two mechanistic possibilities. In the parent system, the concerted pathway and the corresponding transition structure are readily located. On the other hand, the hypothesized zwitterionic intermediate does not correspond to a minimum at most levels of theory, even in the presence of a polar medium representing the solvent. Instead, this structure corresponds to a transition state or, at best, an extremely shallow minimum. The two pathways--one unambiguously concerted, the other possibly leading through an extremely shallow minimum (intermediate)--have very similar barriers and are expected to be competitive. In the substituted 1,2,2-trimethylbicyclobutane system, five regioisomeric concerted pathways exist and lead to four different diene products. Two of these pathways lie well below the others in energy, and they alone are expected to play a significant role at ordinary temperatures. Of these two pathways, the one calculated to have the slightly lower barrier leads to the only product that is reported experimentally. In addition, a sixth geometry of approach exists, leading over a transition structure of comparable energy to a shallow minimum that corresponds to a zwitterionic intermediate. The calculated potential energy surface suggests that the reaction can proceed through this intermediate both to the observed diene product and to one of the other isomers. It therefore appears that the concerted and stepwise mechanisms are competitive in the substituted system. Taken together, the calculated pathways and barriers do not adequately account for the very pronounced regioselectivity observed experimentally; only modest regioselectivity would be predicted at best. Examination of a calculated potential energy surface defined over two relevant internal coordinates sheds further light on the reaction and suggests that the experimentally observed regioselectivity might derive in considerable part from dynamic effects.

Synthesis and Applications of Polysubstituted Bicyclo[1.1.0]butanes

“…The stereochemistry of the deuterium atom in 16 appears to support exclusive fragmentation of 17 , as fragmentation of 18 (Path D) should generate stereoisomer 19 , and an unequal ratio of 15 and 16 , which was not observed. An alternative concerted pathway may also be possible, in which 2y directly fragments to dienes 15 and 16 (Path E) . These observations provide the first experimental support for previous computational work on dichlorocarbene insertion in analogous systems, which considered both stepwise and concerted routes, albeit these authors noted the distinct behaviors of dichloro- and difluorocarbene …”

“…An alternative concerted pathway may also be possible, in which 2y directly fragments to dienes 15 and 16 (Path E) . These observations provide the first experimental support for previous computational work on dichlorocarbene insertion in analogous systems, which considered both stepwise and concerted routes, albeit these authors noted the distinct behaviors of dichloro- and difluorocarbene …”

Computational methods for contemporary carbene chemistry

“…It was also found that activated, i.e., acidic CH bonds preferably undergo insertion due to significantly lower than usual activation barriers, which were also evaluated with the B3LYP functional. An addition reaction of dichlorocarbene, namely, that with 1,2,2‐trimethylbicyclobutene ( 13 ) giving open‐chain 1,1‐dichloro‐3,3,4‐trimethylpenta‐1,4‐diene, was computationally studied by Rablen et al101 with the goal of deciphering the exact mechanism, for which multiple propositions based on experimental studies had been made before. The addition of singlet dichlorocarbene was modeled at the HF/6‐31G( d ), B3LYP/6‐31G( d ), QCISD(T)/6‐31G( d ), and CCSD(T)/6‐31G( d ) levels of theory.…”

Dynamic control of dichlorocarbene addition to cyclopropene

“…[3] The energetics of the CCl 2 -cyclopropene systemthat is, a near-negligible barrier to addition (<2 kcal/mol), substantial exothermicity (ΔH = −65 to −78 kcal/mol to form 2; ΔH = −83 to −106 kcal/mol to form 5), and post-TS branching of the reaction pathsled us to propose that CCl 2 addition to cyclopropene, and therefore the experimental product ratio, is controlled by nonstatistical reaction dynamics. [3] Previous instances of a single TS leading to multiple products [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] on a potential energy surface containing a plateau [20][21][22][23][24][25][26][27] have been attributed to dynamic control [28][29][30][31][32][33] of these reactions as well.…”