The origins of stereoselectivity in asymmetric reductions with boranes based on (+)-α-pinene—II. The geometries of competing transition-states and the nature of the reaction. A semiempirical study

Abstract

In the first paper from this series we pointed out that the stereoselectivity in the reduction of benzaldehyde with B- alkyl-9-BBN reagents greatly depends on the borane reagent conformations. The AM1 calculations show that the stereoselectivity in the reduction of acetophenone with a series of B- Ipc-BYX reagents is also controlled by the borane conformations. It appears that this control is imposed early along the reaction coordinate, during generation of the first rather than the second of the two new transition-state's stereogenic centers, i.e. during B-sp 2 → B-sp 3, rather than C-sp 2 → C-sp 3 process. The calculated enantiomeric excesses were generally in good agreement with the experimentally observed ones: B-XY=9-BBN, (S): 99 vs. 87%; X=Cl, Y=Me, (S): 13% vs. 14.5%; Et, (S): 44% vs. 33%; i-Pr, (S): 84% vs. 81; Cyp, (S): 85% vs. 84%; Ipc, (S): 99% vs. 98%; t-Bu, (R): 97% vs. 96%; Thx, (R): 99% vs. 83%. The reversal of absolute configuration in the reductions with B- t-Bu-IpcBCl and B-Thx-IpcBCl is a logical consequence of the reaction mechanism. Unlike in the simple nucleophilic additions to carbonyl group from the Felkin-Anh model, where the stereoselectivity is controlled by the developing steric interactions only on the single reactive prostereogenic center provided by the substrate, it appears that in the borane reductions the stereoselectivity is mainly controlled by analogous steric interactions developing on the prostereogenic boron center in the reagent.