γ-hydroxy-α,β-alkenenitriles:: Chelation-controlled conjugate additions
γ-hydroxy-α,β-alkenenitriles:: Chelation-controlled conjugate additions
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DOI：
10.1021/jo0258150
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发表时间：
2002-08-23
影响因子：
3.6
通讯作者：
Steward, OW
中科院分区：
文献类型：
--
作者：
Fleming, FF;Wang, QZ;Steward, OW
将格氏试剂和有机锂试剂暂时锚定在 γ-羟基-α,β-烯烃腈上可促进与原本顽固的迈克尔受体的有效缀合物加成。顺序去质子化。添加适度过量的第二种格氏试剂可以有效地将烷基缀合递送至环状和无环烯腈。从机理上讲，除了需要从更具反应性的酯络合物进行烷基转移的更多取代的烯腈之外，所有的共轭加成都是通过烷基镁醇盐络合物进行的。合成上，螯合控制的共轭加成反应快速、立体选择性地组装取代的腈，在一次合成操作中安装多达两个新的立体中心。
Temporarily anchoring Grignard and organolithium reagents to gamma-hydroxy-alpha,beta-alkenenitriles promotes efficient conjugate additions to what are otherwise recalcitrant Michael acceptors. Sequential deprotonation. and addition of a modest excess of a second Grignard reagent allows effective conjugate delivery of alkyl groups to cyclic and acyclic alkenenitriles. Mechanistically, conjugate additions proceed through alkylmagnesium alkoxide complexes for all but the more substituted alkenenitriles that require alkyl transfers from the more reactive ate complexes. Synthetically, chelation-controlled conjugate additions rapidly, and stereoselectively, assemble substituted nitriles, installing up to two new stereocenters in a single synthetic operation.