Stereoselective reductive debromination-cyclopropanation of 2-bromo-1-phenylethylidenemalononitrile and 2-bromo-1-β€-naphthylethylidenemalononitrile by coenzyme NADH model BNAH through chiral induction in cyclodextrins is reported. The matching between substrates and cyclodextrins, the substituent effect, and the effect of cyclodextrin concentration on the optical yields have been investigated. α§ 2001 Academic Press Coenzyme nicotinamide adenine dinucleotide (NADH) plays an important role in biological redox processes through the interconversion between a 1,4-dihydropyridine moiety and a pyridinium ion (1). Stereoselective reduction by NADH models has been a focus of interest. Since Ohnishi and Ohno (2) reported the first stereoselective reduction by a chiral 1,4-dihydropyridine derivative, numerous publications have appeared on stereospecific reduction using various NADH models (3,8).
Cyclodextrins are the most extensively investigated biomimetic models for enzymes. The hydrophobic character of their internal cavity enables cyclodextrins to form inclusion complexes with organic compounds (4) and to provide both a chiral receptor and reactive sites (5). For this reason, many investigators have used cyclodextrins as nanoreactors to induce regio-and enantioselectivity in a biomimetic system carried out in water ( 6).
1-Benzyl-1,4-dihydronicotinamide (BNAH) is an NADH model frequently employed in mechanistic studies. We have previously reported the reductive debromination-cyclopropanation of 2-bromo-1-phenylethylidenemalononitrile (BPM) and 2bromo-1-β€-naphthylethylidenemalononitrile (β€-BNM) with BNAH to give racemic 2-phenyl-1,1-cyclopropanedicarbonitrile (PCN) (7) and racemic 2-β€-naphthyl-1,1cyclopropanedicarbonitrile (β€-NCN)(8), respectively (Fig. 1). In this paper, we report on the stereoselective reduction of BPM andβ€-BNM through the chiral induction of β£-cyclodextrin (β£-CD), β€-cyclodextrin (β€-CD), β₯-cyclodextrin(β₯-CD), and hydroxypropyl-β€-cyclodextrin (hp-β€-CD) in a biomimetic system.