Asymmetric phase-transfer catalysis by quaternary ammonium ions derived from Cinchona-alkaloid analogs containing 1,1'-binaphthalene moieties

Abstract

The synthesis and catalytic properties of a new type of enantioselective phase-transfer catalysts, incorporating both the quinuclidinemethanol fragment of Cinchona alkaloids and a 1,1'-binaphthalene moiety, are described. Catalyst (+)-(aS,3R,4S,8R,9S)-4 with the quinuclidine fragment attached to C(7') in the major groove of the 1,1'-binaphthalene residue was predicted by computer modeling to be an efficient enantioselective catalyst for the unsymmetric alkylation of 6,7-dichloro-5-methoxy-2-phenylindanone (1; Scheme 1, Fig. 1). Its synthesis involved the selective oxidative cross- coupling of two differently substituted naphthalen-2-ols to afford the asymmetrically substituted 1,1'-binaphthalene derivative (±)-17 in high yield (Scheme 3). Chromatographic optical resolution via formation of diastereoisomeric camphorsulfonyl esters and functional-group manipulation gave access to the 7-bromo-1,1'-binaphthalene derivative (-)-(aS)-11 (Scheme 4). Nucleophilic addition of lithiated (-)-(aS)-11 to the quinuclidine Weinreb amide (+)-(3R,4S,8R)-8 afforded the two ketones (aS,3R,4S,8R)-27 and (aS,3R,4S,8S)-28 as an inseparable mixture of diastereoisomers (Scheme 6). Stereoselective reduction of this mixture with DIBAL-H (diisobutylaluminum hydride; preferred formation of the C(8)-C(9) erythro-pair of diastereoisomers with 18% de) or with NaBH4 (preferred formation of the threo-pair of diastereoisomers with 50% de) afforded the four separable diastereoisomers (+)-(aS,3R,4S,8S,9S)-29, (+)-(aS,3R,4S,8R,9R)-30, (-)- (aS,3R,4S,8S,9R)-31, and (+)-(aS,3R,4S,8R,9S)-32 (Scheme 6). A detailed conformational analysis, combining 1H-NMR spectroscopy and molecular- mechanics computations, revealed that the four diastereoisomers displayed distinctly different conformational preferences (Figs. 2 and 3). These novel Cinchona-alkaloid analogs were quaternized to give (+)-(aS,3R,4S,8R,9S)-4, (+)-(aS,3R,4S,8S,9S)-5, (+)-(aS,3R,4S,8R,9R)-6, and (-)-(aS,3R,4S,8S,9R)-7 (Scheme 7) which were tested as phase-transfer agents in the asymmetric allylation of phenylindanone 1. Without any optimization work, (+)- (aS,3R,4S,8R,9S)-4 was found to catalyze the allylation of 1 yielding the predicted enantiomer (+)-(S)-3b in 32% ee. The three diastereoisomeric catalysts (+)-5, (+)-6, and (-)-7 gave access to lower enantioselectivities (6 to 22% ee's), which could be rationalized by computer modeling (Fig. 4).