Zhang Yulong, Guo Huichuang, Wu Qian, Bi Xiaojing, Shi Enxue, Xiao Junhua
State Key Laboratory of NBC Protection for Civilian Beijing 102205 P. R. China
RSC Adv. 2023 May 11;13(20):13511-13515. doi: 10.1039/d3ra02430j. eCollection 2023 May 2.
α,β-Unsaturated esters are key structural motifs widely distributed in various biologically active molecules, and their /-stereoselective synthesis has always been considered highly attractive in organic synthesis. Herein, we present a >99% ()-stereoselective one-pot synthetic approach towards β-phosphoroxylated α,β-unsaturated esters a mild trimethylamine-catalyzed 1,3-hydrogen migration of the corresponding unconjugated intermediates derived from the solvent-free Perkow reaction between low-cost 4-chloroacetoacetates and phosphites. Versatile β,β-disubstituted ()-α,β-unsaturated esters were thus afforded with full ()-stereoretentivity by cleavage of the phosphoenol linkage Negishi cross-coupling. Moreover, a stereoretentive ()-rich mixture of a α,β-unsaturated ester derived from 2-chloroacetoacetate was obtained and both isomers were easily afforded in one operation.
α,β-不饱和酯是广泛分布于各种生物活性分子中的关键结构基序,其立体选择性合成在有机合成中一直备受关注。在此,我们报道了一种对β-磷酰氧基化α,β-不饱和酯具有>99%立体选择性的一锅法合成方法——一种温和的三甲胺催化的1,3-氢迁移反应,该反应涉及由低成本的4-氯乙酰乙酸酯与亚磷酸酯在无溶剂Perkow反应中衍生出的相应非共轭中间体。通过磷烯醇键的裂解——根岸交叉偶联反应,从而以完全的立体保持性得到了通用的β,β-二取代()-α,β-不饱和酯。此外,还获得了一种由2-氯乙酰乙酸酯衍生的α,β-不饱和酯的富含()-异构体的立体保持混合物,并且两种异构体可在一次操作中轻松获得。