Asymmetric Cascade Assembly of 1,2-Diaza-1,3-dienes and α,β‑Unsaturated Aldehydes via Dienamine Activation

A cascade vinylogous 1,6-Michael addition/1,4-proton shift/aza-Michael addition/hemiaminal formation sequence of 1,2-diaza-1,3-dienes and β-substituted 2-butenals has been developed under the influence of dienamine activation of a chiral secondary amine. This method exhibits high regio- and chemoselectivity and provides an efficient and straightforward approach to bicyclic l,8-diazabicyclo[3.3.0]­octane skeletons with a tetrasubstituted stereogenic center with fair to excellent enantioselectivity.在手性二级胺的烯胺活化作用下，本研究开发了1,2-二氮杂-1,3-二烯（1,2-diaza-1,3-dienes）与β-取代2-丁烯醛的级联乙烯基型1,6-迈克尔加成（1,6-Michael addition）/1,4-质子转移（1,4-proton shift）/氮杂-迈克尔加成（aza-Michael addition）/半胺缩醛形成（hemiaminal formation）串联反应序列。该方法展现出优异的区域与化学选择性，可为构建带有四取代手性中心的双环1,8-二氮杂双环[3.3.0]辛烷（1,8-diazabicyclo[3.3.0]octane）骨架提供高效简洁的途径，且对映选择性从中等到优异。