Urea- and thiourea-substituted cinchona alkaloid derivatives as highly efficient bifunctional organocatalysts for the asymmetric addition of malonate to nitroalkenes: Inversion of configuration at C9 dramatically improves catalyst performance
Urea- and thiourea-substituted cinchona alkaloid derivatives as highly efficient bifunctional organocatalysts for the asymmetric addition of malonate to nitroalkenes: Inversion of configuration at C9 dramatically improves catalyst performance
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DOI：
10.1002/anie.200501721
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发表时间：
2005-01-01
影响因子：
16.6
通讯作者：
Connon, SJ
中科院分区：
文献类型：
--
作者：
McCooey, SH;Connon, SJ
受到酶催化的高效、优雅和选择性的启发，设计能够有效和对映选择性地促进碳-碳键形成过程的有机分子是一项艰巨的挑战，目前受到相当多的关注在这种情况下，最难在合成系统中设计的基本酶催化能力之一是双功能；即催化剂利用Lewis/Brønsted酸性官能团和Lewis/Brønsted碱性官能团协同作用，同时激活反应中亲核和亲电组分的能力。20多年前，Wynberg和Hiemstra报道金鸡纳生物碱是一种高效的双功能有机催化剂（尽管只有中等选择性），用于噻吩衍生物在环己酮上的1,4加成，并提出了催化剂参与硫醇的去质子化（通过基喹啉生物碱氮原子）和由1，4加成步骤（通过与催化剂的羟基部分形成氢键）。[4-6]
Inspired by the efficiency, elegance, and selectivity of enzymatic catalysis, the design of organic molecules capable of the efficient and enantioselective promotion of carbon–carbon bond-forming processes is a formidable challenge which is currently receiving considerable attention.[1] In this context, one of the fundamental enzymatic catalyst competencies that is most difficult to engineer in synthetic systems is bifunctionality; that is, the ability of a catalyst to employ Lewis/Brønsted acidic and Lewis/Brønsted basic functionality synergistically to bring about the activation of both the nucleophilic and electrophilic components of a reaction simultaneously.[2]Over 20 years ago, Wynberg and Hiemstra [3] reported that cinchona alkaloids were efficient (albeit only moderately selective) bifunctional organocatalysts for the 1, 4-addition of thiophenol derivatives to cyclohexenones, and proposed catalyst participation in the deprotonation of the thiol (through the basic quinuclidine alkaloid nitrogen atom) and in the stabilization of the enolate resulting from the 1, 4-addition step (through hydrogen bonding with the hydroxy moiety of the catalyst).[4–6]