Bifunctional Iminophosphorane Catalyzed Enantioselective Sulfa-Michael Addition to Unactivated α-Substituted Acrylate Esters
Bifunctional Iminophosphorane Catalyzed Enantioselective Sulfa-Michael Addition to Unactivated α-Substituted Acrylate Esters
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DOI：
10.1021/jacs.5b10226
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发表时间：
2015-12-30
影响因子：
15
通讯作者：
Dixon, Darren J.
中科院分区：
文献类型：
--
作者：
Farley, Alistair J. M.;Sandford, Christopher;Dixon, Darren J.
描述了在温和条件下双功能亚磷烷有机催化剂催化下，烷基硫醇在非活化α -取代丙烯酸酯上的高对乙酰氨基磺酸加成反应。催化剂的亚磷烷部分的强Bronsted碱度为烷基硫醇亲核试剂提供了必要的活化，而位于中心硫脲氢键供体两侧的两个叔亮氨酸残基在瞬态烯酸酯中间体的质子化过程中具有很高的对映面选择性。该反应的范围很广，涉及烷基硫醇、酯部分和α、β -不饱和酯的α -取代基，提供了极好的磺胺- michael加合物收率（高达99%）和对映选择性（高达96% ee），并且可以在低至0.05 mol %的催化剂负载下放大。
The highly enantioselective sulfa-Michael addition of alkyl thiols to unactivated alpha-substituted acrylate esters catalyzed by a bifunctional iminophosphorane organocatalyst under mild conditions is described. The strong Bronsted basicity of the iminophosphorane moiety of the catalyst provides the necessary activation of the alkyl thiol pro-nucleophile, while the two tert-leucine residues flanking a central thiourea hydrogen-bond donor facilitate high enantiofacial selectivity in the protonation of the transient enolate intermediate. The reaction is broad in scope with respect to the alkyl thiol, the ester moiety, and the alpha-substituent of the alpha,beta-unsaturated ester, affords sulfa-Michael adducts in excellent yields (up to >99%) and enantioselectivities (up to 96% ee), and is amenable to decagram scale-up using catalyst loadings as low as 0.05 mol %.