A rational approach to catalytic enantioselective enolate alkylation using a structurally rigidified and defined chiral quaternary ammonium salt under phase transfer conditions
A rational approach to catalytic enantioselective enolate alkylation using a structurally rigidified and defined chiral quaternary ammonium salt under phase transfer conditions
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DOI：
10.1021/ja973174y
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发表时间：
1997-12-17
影响因子：
15
通讯作者：
Noe, MC
中科院分区：
文献类型：
--
作者：
Corey, EJ;Xu, F;Noe, MC
在相转移条件下离子对介导的反应（相转移催化，PTC）自引入以来在有机合成中越来越有用。1然而，除了少数涉及使用金鸡纳生物碱衍生季铵盐外，还没有成功的应用于催化不对称合成。其中最突出的是在PTC下使用N-（对三氟甲基）苄基溴化辛choninium氢氧化钠配合物甲基化6,7 -二氯-5-甲氧基-2-苯基-1-吲哚酮，形成(S)- r -甲基化的吲哚酮，对映体过量92% （ee）。值得注意的是，用n-苄基辛choninium离子-氢氧化钠PTC体系烷基化甘氨酸叔丁基二苯甲酮席夫碱（范围为5:1 -2.5:1）的对映选择性更为温和。这些病例中对映选择性偏倚的原因尚不清楚。本文介绍了一项研究计划的初步结果，旨在确定PTC中对映体选择性的机理和几何因素，并合理设计基于金鸡纳生物碱体系的高效新型相转移催化剂。我们关注于碳催化不对称烷基化的发展，因为这是目前最迫切需要的合成方法之一。我们的做法可以简单地概括。如果金鸡纳生物碱季盐的桥头堡氮位于四面体的中心，则相转移催化剂的结构应提供立体筛选，以防止反离子接近该四面体的三个面，而第四个面应足够开放，以使底物反离子与N+紧密接触。在范德华相互作用的附近也应该有一个结合面。金鸡纳生物碱的季铵盐是理想的，因为带电荷的桥接氮的一个四面体面被环系统本身完全阻断。此外，近年来的研究也阐明了OsO4在生物碱催化烯烃二羟基化反应中对映体选择性的根本原因。特别重要的是发现9-蒽基甲基（anth）基团与桥头堡氮导联的连接
Ion-pair-mediated reactions under phase transfer conditions (phase transfer catalysis, PTC) have been increasingly useful in organic synthesis since their introduction. 1 However, there have been no successful applications to catalytic asymmetric synthesis, 1d except for a few involving the use of cinchonaalkaloid-derived quaternary ammonium salts. The most outstanding of these is the methylation of 6, 7-dichloro-5-methoxy-2-phenyl-1-indanone using N-(p-trifluoromethyl) benzylcinchoninium bromide sodium hydroxide complex under PTC to form (S)-R-methylated indanone in 92% enantiomeric excess (ee). 2 Noteworthy, but more modest enantioselectivities have been reported for the alkylation of tert-butyl glycinatebenzophenone Schiff base (range of 5: 1-2.5: 1) using the N-benzylcinchoninium ion-sodium hydroxide PTC system. 3 The reasons for the enantioselective bias in these cases have been unclear. In this paper, we present the initial results of a research program aimed at the determination of the mechanistic and geometrical factors responsible for enantioselectivity in PTC and the rational design of highly effective new phase transfer catalysts based on the cinchona alkaloid system. We have focused on the development of catalytic asymmetric alkylation at carbon because this is one of the most urgently needed synthetic methods.Our approach may be summarized simply. If the bridgehead nitrogen of a cinchona alkaloid quaternary salt is taken to be at the center of a tetrahedron, the phase transfer catalyst should be structured so as to provide steric screening which prevents close approach of the counterion to three of the faces of this tetrahedron, while the fourth face should be sufficiently open to allow close contact between the substrate counterion and N+. There should also be a nearby binding surface for attractive van der Waals interaction. Quaternary ammonium salts of cinchona alkaloids are ideal because one of the tetrahedron faces about the charged bridged nitrogen is totally blocked by the ring system itself. In addition, recent studies4 have elucidated the fundamental reasons for enantioselectivity in the biscinchona-alkaloid-catalyzed dihydroxylation of olefins by OsO4. Especially relevant was the finding that the attachment of the 9-anthracenylmethyl (anth) group to a bridgehead nitrogen leads