Nondynamic Kinetic Resolution of Configurationally Stable Biaryl Lactones by Reduction with Oxazaborolidine-Activated Borane:  AM1 Studies and Experimental Verification

Abstract

The complete mechanistic course of the atroposelective ring opening of a lactone-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 AM1 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 is in good accordance with the experimental results, so that related calculations were performed on the atroposelective ring opening of a sterically strongly hindered and therefore also configurationally stable six-membered biaryl 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 (kM/kP = 358 at -78 degrees C), which, after the smooth preparation of 6f by intramolecular biaryl coupling in high yields, was fully confirmed experimentally (kM/kP > 200 at -78 degrees C). Isolation of the intermediate hydroxy aldehyde (M)-14 at the beginning of the reaction with the same enantiomeric excess as found for the corresponding alcohol (M)-7f conclusively showed the first hydride transfer step to determine the selectivity of this process. The good agreement of computationally predicted and experimentally confirmed values proves the suitability of the AM1 method for mechanistic studies on even such complex reactions and opens a most efficient overall synthesis of sterically highly hindered biaryls, in excellent chemical (for the ring closure) and optical (for the ring cleavage) yields and for any desired axial configuration.

The Lactone Concept: An Efficient Pathway to Axially Chiral Natural Products and Useful Reagents

“…Figure 6), WHUW-butyl substituted, 6-membered lactone I can be cleaved highly atropo-enantioselectively (k rel > 200) to give enantiomerically pure 0-I and 3-I, 82 again in the sense of a non-dynamic kinetic resolution (Scheme 18). 81 By contrast, as seen before (cf. Schemes 8 and 13), the less hindered representatives of constitute substrates for G\QDPLF kinetic resolutions.…”

“…78 Further attempts to optimize this promising reaction are in progress. 80,81 The remaining unreacted 3-configured lactone 3-, which shows a very high enantiomeric purity, can be converted into the stereochemically homogeneous corresponding 3-diol (e.g. just by LAH reduction), or it can be racemized thermally and is then again submitted to the kinetic deracemization -another very efficient technique of stereoselective biaryl synthesis.…”

13C NMR spectral data and molecular descriptors to predict the antioxidant activity of flavonoids

“…The molecules were subjected to geometry optimization and conformational analysis (systematic analysis with dihedral angle rotated every 30°). The semi-empirical quantum chemical method used was AM1 (Austin Model1) (Dewar et al, 1985(Dewar et al, , 1990, which is suitable for this analysis (Bringmann et al, 2000), despite the existence of more recent methods, and the root mean square (RMS) gradient value of 0.001 kcal/mol was used as the termination condition. Energy minimized molecules were saved as MDL MolFiles for computing various molecular descriptors using DRAGON Professional version 5.4 (Dragon, 2010).…”

The B–H–B bridging interaction in B-substituted oxazaborolidine–borane complexes: a theoretical study

“…Linney et al [28] investigated model oxazaborolidine-borane complex within the HF, MP2, and AM1 approximations. Moreover, theoretical studies on the mechanism of reduction of ketones were carried out using the semiempirical MNDO [29] and AM1 [30,31] methods as well as within the ab initio techniques and the density functional theory (DFT) [32][33][34]. Reduction of oxime ethers [35] and imines [36] has been the subject of detailed analyses using DFT.…”