Ｎ，Ｎ‐ジアルキルノルエフェドリンおよびピロリジニルメタノール誘導体を不斉触媒・配位子に用いる不斉合成

Abstract

A series of N, N-dialkylnorephedrines and pyrrolidinylmethanol derivatives are synthesized as chiral catalysts and as chiral ligands for the highly enantioselective 1, 2- and conjugate additions of organozinc reagents to aldehydes, ketones, phosphinylimines and α, β-unsaturated ketones. N, N-Dibutylnorephedrine (DBNE) and diphenyl (1-methylpyrrolidin-2-yl) methanol (DPMPM) are used as chiral catalysts in the enantioselective addition of dialkylzincs to aldehydes (up to 100% ee). Chiral thiophosphoramidate and N-benzyl-N-methylephedrinium halides are also enantioselective catalysts. Polystyrene and silica gel (and alumina) supported N-alkylnorephedrines with or without a spacer are used as heterogeneous chiral catalysts. Chiral compounds prepared include sec- alcohols, furylalcohols, alkynylalcohols, allylalcohols, β-hydroxynitrile, fluorine- containing alcohols, deuterated alcohols, γ-hydroxyketones, pyridylalkylalcohols, diols, hydroxyaldehyde, γ- and δ-hydroxyesters, butyro-and δ- valerolactones. Enantioselective Reformatsky reaction with aldehydes and ketones using DPMPM and N, N-diallylnorephedrine affords chiral β-sec-, and β-t-hydroxyesters, respectively. Enantioselective alkylation of aldehydes using DBNE is applied to the synthesis of chiral alkylphthalides, (+) -Iepicidin A, and a precursor of tacalcitol. Diastereodivergent alkylations of α or β-chiral aldehydes are achieved by using the appropriate enantiomer of DBNE or DPMPM. Self-replication and auto-multiplication of chiral zinc alkoxides of pyridylalkylalcohols and diols as asymmetric autocatalysts is described. Enantioselective and/or diastereoselective alkylation of diphenylphosphinylimine affords chiral amine. Chiral nickel complex with DBNE catalyzes the enantioselective conjugate addition of dialkylzincs to α, β-unsaturated ketones.