Huang Yong, Walji Abbas M, Larsen Catharine H, MacMillan David W C
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
J Am Chem Soc. 2005 Nov 2;127(43):15051-3. doi: 10.1021/ja055545d.
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 alpha,beta-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).
一种基于生物合成生化蓝图的有机催化新策略，为级联催化带来了一种全新的实验室方法。基于咪唑烷酮的催化循环，涉及亚胺离子和烯胺活化，已成功结合，使多种亲核试剂（呋喃、噻吩、吲哚、丁烯内酯、氢化物源、叔氨基内酯等效物）和亲电试剂（氟化和氯化试剂）能够与多种α,β-不饱和醛进行顺序加成。这些新的级联催化方案实现了以前未知的对映选择性转化的发明，包括HF元素跨三取代烯烃的不对称催化加成。重要的是，这些多米诺催化方案可以由单一的咪唑烷酮催化剂介导，也可以使用特定循环的胺催化剂。在后一种情况下，通过明智地选择胺催化剂的对映体系列，可以很容易地调节级联催化途径，以提供所需的非对映和对映选择性结果。将多个不对称有机催化事件组合成一个序列的一个主要优点是，在第二个诱导循环中对映体富集的内在要求，本研究中获得的对映选择性证明了这一点（所有情况下ee值均≥99%）。
