化学
二苯甲酮
催化作用
亚胺
衍生化
有机化学
对映体药物
酰胺
磺胺
路易斯酸
水解
组合化学
对映选择合成
高效液相色谱法
作者
John Jin Lim,David C. Leitch
标识
DOI:10.1021/acs.oprd.8b00133
摘要
Benzophenone imine was found to be an effective ammonia surrogate for the selective preparation of primary 1,2-amino alcohols from epoxides, including enantiopure epichlorohydrin, in the presence of catalytic Y(OTf)3. High-throughput screening of 48 Lewis acids quickly identified Y(OTf)3 as an effective mediator of the addition reaction under mild conditions. Following acidic hydrolysis, the primary amino alcohol salt is revealed and partitions into the aqueous solution, while the benzophenone byproduct is easily removed by simple extraction with ethyl acetate. These ammonium salts can be directly Boc-protected or further derivatized without isolation to form benzamides and sulfonamides under Schotten–Baumann-type conditions in up to 79% isolated yield over three steps. This methodology has been used to prepare key intermediates for the synthesis of PRMT5 inhibitors with high enantiopurity as well as numerous other amide and sulfonamide derivatives.
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