THE ORIGINS OF STEREOSELECTIVITY IN ASYMMETRIC REDUCTIONS WITH BORANES BASED ON (-ALPHA-PINENE .2. THE GEOMETRIES OF COMPETING TRANSITION-STATES AND THE NATURE OF THE REACTION - A SEMIEMPIRICAL STUDY())

In the first paper from this series we pointed out that the stereosele ctivity in the reduction of benzaldehyde with B-alkyl-9-BBN reagents g reatly depends on the borane reagent conformations. The AMI calculatio ns show that the stereoselectivity in the reduction of acetophenone wi th a series of B-lpc-BYX reagents is also controlled by the borane con formations. It appears that this control is imposed early along the re action coordinate, during generation of the first rather than the seco nd 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 calc ulated enantiomeric excesses were generally in good agreement with the experimentally observed ones: BXY=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 reduc tions 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 singl e reactive prostereogenic center provided by the substrate, it appears that in the borane reductions the stereoselectivity is mainly control led by analogous steric interactions developing on the prostereogenic boron center in the reagent. (C) 1997 Elsevier Science Ltd.