Squarate desymmetrisation-ozonolysis as an approach to β-substituted-α-ketosuccinates and squalestatin synthesis

[摘要] Silylated tertiary alcohols from 1,2-addition of alkyllithiums to dialkyl squarates undergo alkene ozonolysis to give beta-substituted-alpha-keto-beta-(silyloxy)succinates. With 3-(triethylsilyloxy)butyllithium the methodology was applied to the 2,8-dioxabicyclo[3.2.1]octane core of the squalestatins. Enantioselective 1,2-addition to di-tert-butyl squarate using butyllithium or diethylzinc/Ti(iPrO)(4) in the presence of chiral ligands (such as bisoxazolines or camphorsulfonamides, respectively) gave the corresponding tertiary alcohols in up to 67.5:32.5 er. (C) 2019 Elsevier Ltd. All rights reserved.

[发布日期] 2019-12-13

[关键词] Squarate;Ozonolysis;Succinate;Organolithium;Organozinc;Squalestatin