Catalytic, Asymmetric Michael-Aldol Annulations via a Stereodivergent/Stereoconvergent Path Operating under Curtin-Hammett Control.
Catalytic, Asymmetric Michael-Aldol Annulations via a Stereodivergent/Stereoconvergent Path Operating under Curtin-Hammett Control.
复制标题
在科廷-哈米特控制下通过立体发散/立体会聚路径进行催化、不对称迈克尔-羟醛环化。
DOI：
10.1021/jacs.3c03373
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发表时间：
2023
影响因子：
15
通讯作者：
Johnson,JeffreyS
中科院分区：
文献类型：
--
作者：
Giordano,MitchellT;Kitzinger,KatelynM;deJesúsCruz,Pedro;Liu,Shubin;Johnson,JeffreyS
一种双官能团亚胺磷烷催化合成密集官能化环己醇的方法在三取代亲电烯烃和γ-硝基酮之间的Michael/Aldol多米诺反应中建立了五个连续的立体中心(非对映选择性高达>；20：1，对映选择性高达>；99：1)。机械论研究表明，在最初的非对映发散Michael加成反应之后，立体收敛是通过动力学控制的环化来实现的。环化过程中的非对映收敛是Curtin-Hammett动力学的结果，这一发现与以前在类似系统中报道的结晶驱动的立体收敛形成了对比。尽管立体控制机制发生了变化，但操作属性仍然具有吸引力，在过滤反应混合物后，结晶产物通常以分析纯的形式分离出来。
A bifunctional iminophosphorane (BIMP)-catalyzed method for the synthesis of densely functionalized cyclohexanols establishes five contiguous stereocenters (diastereoselection up to >20:1, enantioselectivity up to >99:1) in a Michael/aldol domino reaction between trisubstituted electrophilic alkenes and γ-nitroketones. Mechanistic studies suggest a scenario in which stereoconvergency is achieved by kinetically controlled cyclization after the initial diastereodivergent Michael addition. Diastereoconvergency during cyclization is shown to result from Curtin–Hammett kinetics, a finding that contrasts the crystallization-driven stereoconvergency previously reported in similar systems. Despite the change in the stereocontrol mechanism, the operational attributes remain attractive, with the crystalline products typically isolated in analytically pure form upon filtration of the reaction mixture.