Nondynamic kinetic resolution of configurationally stable biaryl lactones by reduction with oxazaborolidine-activated borane: AM1 studies and experimental verification

The complete mechanistic course of the atroposelective ring opening of a la ctone-bridged biaryl, dinaphth[2,1-c:1',2'-e]oxepin-3-(5H)-one (3), with a chiral oxazaborolidine-BH3 complex was calculated using the semiempirical A M1 method. The first hydride transfer to the activated carbonyl function of the adduct complexes was elaborated to be the selectivity-determining step in the postulated five-step mechanism. The calculated enantioselectivity i s in good accordance with the experimental results, so that related calcula tions were performed on the atroposelective ring opening of a sterically st rongly hindered and therefore also configurationally stable six-membered bi aryl lactone, 1,3-di-tert-butyl-6H-benzo[b]naphtho[1,2-d]pyran-6-one (6f). These calculations predicted a highly (M)-selective reduction of 6f(k(M)/k( P) = 358 at -78 degrees C), which, after the smooth preparation of 6f by in tramolecular biaryl coupling in high yields, was fully confirmed experiment ally (k(M)/k(P) > 200 at -78 degrees C). Isolation of the intermediate hydr oxy aldehyde (M)-14 at the beginning of the reaction with the same enantiom eric excess as found for the corresponding alcohol (M)-7f conclusively show ed the first hydride transfer step to determine the selectivity of this pro cess. The good agreement of computationally predicted and experimentally co nfirmed values proves the suitability of the AM1 method for mechanistic stu dies on even such complex reactions and opens a most efficient overall synt hesis of sterically highly hindered biaryls, in excellent chemical (for the ring closure) and optical (for the ring cleavage) yields and for any desir ed axial configuration.