Diastereoselective Diels−Alder Reactions of <i>N</i>-Sulfonyl-1-aza-1,3-butadienes with Optically Active Enol Ethers: An Asymmetric Variant of the 1-Azadiene Diels−Alder Reaction

The first detailed study of a room-temperature asymmetric Diels−Alder reaction of N-sulfonyl-1-aza-1,3-butadienes is reported enlisting a series of 19 enol ethers bearing chiral auxiliaries, with many providing highly diastereoselective (endo and facial diastereoselection) reactions, largely the result of an exquisitely organized [4+2] cycloaddition transition state. Three new, readily accessible, and previously unexplored auxiliaries rationally emerged from the studies and provide remarkable selectivities (two of these give 49:1 endo:exo and 48:1 facial selectivity) that promise to be useful in systems beyond those detailed.本研究首次针对N-磺酰基-1-氮杂-1,3-丁二烯的室温不对称狄尔斯-阿尔德（Diels−Alder）反应展开系统性详细探究，选用了一系列共计19种携带手性助剂（chiral auxiliaries）的烯醇醚（enol ethers）作为反应底物。其中多数底物均可实现高非对映选择性（内型选择性与面选择性）转化，该效果主要源于高度有序的[4+2]环加成（[4+2] cycloaddition）过渡态（transition state）。本研究通过理性设计开发出三种全新、易于制备且此前未被探索的手性助剂，它们展现出极为突出的选择性：其中两种助剂分别可实现49:1的内型/外型比与48:1的面选择性，其应用潜力有望拓展至本次研究涉及体系之外的更多反应场景中。