Enantioselective organo-cascade catalysis
Enantioselective organo-cascade catalysis
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DOI：
10.1021/ja055545d
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发表时间：
2005-11-02
影响因子：
15
通讯作者：
MacMillan, DWC
中科院分区：
文献类型：
--
作者：
Huang, Y;Walji, AM;MacMillan, DWC
基于生物合成的生化蓝图，一种新的有机催化策略为级联催化提供了新的实验室方法。以咪唑烷酮为基础的催化循环，涉及到胺和烯胺的活化，已经成功地结合起来，允许大量的亲核试剂（呋喃、噻吩、吲哚、丁烯内酯、氢化物源、叔胺内酯等价物）和亲电试剂（氟化和氯化试剂）与一系列α、β-不饱和醛进行顺序加成。这些新的级联催化方案允许发明以前未知的对映选择性转化，包括在三取代烯烃上不对称催化加成HF元素。重要的是，这些多米诺骨牌催化方案可以由单一咪唑烷酮催化剂或使用循环特异性胺催化剂介导。在后一种情况下，级联催化途径可以很容易地通过明智地选择胺催化剂的对映体系列来提供所需的非映体和对映体选择性结果。将多个不对称有机催化事件组合成一个序列的主要好处是在第二个诱导周期中对映体富集的内在要求，正如在整个研究中获得的对映体选择性（所有情况下的ee≥99%）所证明的那样。
A new strategy for organocatalysis based on the biochemical blueprints of biosynthesis has enabled a new laboratory approach to cascade catalysis. Imidazolidinone-based catalytic cycles, involving iminium and enamine activation, have been successfully combined to allow a large diversity of nucleophiles (furans, thiophenes, indoles, butenolides, hydride sources, tertiary amino lactone equivalents) and electrophiles (fluorinating and chlorinating reagents) to undergo sequential addition with a wide array of α,β-unsaturated aldehydes. These new cascade catalysis protocols allow the invention of enantioselective transformations that were previously unknown, including the asymmetric catalytic addition of the elements of HF across a trisubstituted olefin. Importantly, these domino catalysis protocols can be mediated by a single imidazolidinone catalyst or using cycle-specific amine catalysts. In the latter case, cascade catalysis pathways can be readily modulated to provide a required diastereo- and enantioselective outcome via the judicious selection of the enantiomeric series of the amine catalysts. A central benefit of combining multiple asymmetric organocatalytic events into one sequence is the intrinsic requirement for enantioenrichment in the second induction cycle, as demonstrated by the enantioselectivities obtained throughout this study (≥99% ee in all cases).