Systematic evaluation of 1,5-dienes bearing 3,3-electron-withdrawing groups and 4-methylation results in the discovery of a Cope rearrangement for Meldrum’s acid-containing substrates that have unexpectedly favorable kinetic and thermodynamic profiles. The protocol is quite general due to a concise and convergent synthesis from abundant starting materials. Furthermore, products with an embedded Meldrum’s acid moiety are prepared, which, in turn, can yield complex amides under neutral conditions. We have now expanded the scope of the reductive Cope rearrangement, which, via chemoselective reduction, can promote thermodynamically unfavorable [3,3] sigmatropic rearrangements of 3,3-dicyano-1,5-dienes to form reduced Cope rearrangement products. The Cope rearrangement is found to be stereospecific and can yield enantioenriched building blocks when chiral, nonracemic 1,3-disubstituted allylic electrophiles are utilized. We expand further the use of Cope rearrangements for the synthesis of highly valuable building blocks for complex- and drug-like molecular synthesis.

中文翻译：

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克服经典应付重排的动力学和热力学挑战

对带有3,3-吸电子基团和4-甲基化的1,5-二烯的系统评价导致发现了Meldrum含酸底物的Cope重排，该底物具有出乎意料的动力学和热力学特征。由于从丰富的起始原料中进行了简洁，收敛的合成，因此该协议非常通用。此外，制备了具有包埋的Meldrum酸部分的产物，其又可以在中性条件下产生复杂的酰胺。我们现在已经扩大了还原型Cope重排的范围，该还原性Cope重排通过化学选择性还原，可以促进3,3-二氰基-1,5-二烯的热力学不利的[3,3]σ重排，从而形成还原的Cope重排产物。发现当使用手性的，非外消旋的1，3-二取代的烯丙基亲电试剂时，Cope重排具有立体特异性，并且可以产生对映体富集的结构单元。我们进一步扩展了Cope重排的用途，以合成用于复杂和类药物分子合成的极有价值的构建基块。