Tetraalkylphosphonium Salts as Chiral Phase-Transfer Catalysts

Abstract

Significance: The C 2 -symmetric chiral quaternary tetraalkylphosphonium salt (S)-3 is employed as a phase-transfer catalyst (PTC) in asymmetric aminations of b-keto esters. In the presence of 3 mol% of (S)-3, 1.2 equivalents of di-tert-butyl azodicarboxylate and 1-5 equivalents of K 2 HPO 4 as the base, the corresponding amination products of cyclic five-membered b-keto esters are obtained in nearly quantitative yields and high enantioselectivities (er up to 97.5:2.5). This method is useful for the preparation of aldose reductase inhibitor AS-3201 (Ranirestat).Comment: The present work shows the first successful utilization of chiral quaternary tetraalkylphosphonium salts in phase-transfer catalysis for asymmetric amination of b-keto esters. Since the potential of chiral binaphthyl-modified quaternary tetraalkylammonium salts has been demonstrated by the same group during the last decade (see Reviews below), further applications of chiral phosphonium salts as PTCs can be expected. (S)-3 (3 mol%) t-BuO 2 CN NCO 2 t-Bu K 2 HPO 4 , toluene -20 °C, 14 h O CO 2 t-Bu N NHCO 2 t-Bu CO 2 t-Bu 2 99% yield, er = 95.5:4.5 N O CO 2 t-Bu N NHCO 2 t-Bu CO 2 t-Bu 5 O t-BuO O (S)-3 1 O CO 2 t-Bu N NHCO 2 t-Bu CO 2 t-Bu 4 99% yield, er = 97.5:2.5 99% yield, er = 96:4 SYNFACTS Contributors: Benjamin List, Saihu Liao Synfacts