Luo Xingjie, Jiang Zhiyu, Yang Siqun, Ren Xiaoyu, Wang Tianli
Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University, 29 Wangjiang Road, 610064, Chengdu, P. R. China.
Beijing National Laboratory for Molecular Sciences, 100190, Beijing, P. R. China.
Chemistry. 2024 Jul 5;30(38):e202401325. doi: 10.1002/chem.202401325. Epub 2024 Jun 18.
Chiral secondary alcohols, serving as essential structural motifs, hold significant potential for diverse applications. The exploration of effective synthetic strategies toward these compounds is both attractive and challenging. Herein, we present an asymmetric oxa-Michael reaction involving aliphatic alcohols as nucleophiles and β-fluoroalkyl vinylsulfones catalyzed by bifunctional phosphonium salt (BPS), achieving high yields and excellent enantioselectivities (up to 98 % yield and 98 % ee). Additionally, a sequential process including asymmetric oxa-Michael and debenzylation, facilitated by BPS/Lewis acid cooperation, was revealed for synthesizing diverse chiral secondary alcohol compounds in high yields (81-88 %) with consistent stereoselectivities. Furthermore, mechanistic explorations and subsequent results unveiled that the enantioselectivity originates from hydrogen-bonding and ion-pair interactions between the BPS catalyst and the substrates.
手性仲醇作为重要的结构基序,在多种应用中具有巨大潜力。探索针对这些化合物的有效合成策略既具有吸引力又具有挑战性。在此,我们报道了一种不对称氧杂 - 迈克尔反应,该反应以脂肪醇作为亲核试剂,β - 氟烷基乙烯基砜为底物,由双功能鏻盐(BPS)催化,可实现高产率和优异的对映选择性(产率高达98%,对映体过量值高达98%)。此外,还揭示了一种由BPS/路易斯酸协同促进的包括不对称氧杂 - 迈克尔反应和脱苄基反应的连续过程,可用于高产率(81 - 88%)且立体选择性一致地合成多种手性仲醇化合物。此外,机理探索及后续结果表明,对映选择性源于BPS催化剂与底物之间的氢键和离子对相互作用。