Forming all-carbon quaternary stereogenic centres in acyclic systems from alkynes

摘要

The formation of all-carbon quaternary stereocentres in acyclic systems is one of the most difficult contemporary challenges in modern synthetic organic chemistry~(1,2). Particularly challenging is the preparation of all-carbon quaternary stereocentres in aldol adducts~3; this difficulty is problematic because the aldol reaction represents one of the most valuable chemical transformations in organic synthesis~4. The main problem that limits the formation of these stereocentres is the absence of an efficient method of preparing stereodefined trisubstituted enolates in acyclic systems~(5-8). Here we describe a different approach that involves the formation of two new stereogenic centres-including the all-carbon quaternary one-via a combined carbometalation-oxidation reaction of an organocuprate to give a stereodefined trisubstituted enolate. We use this method to generate a series of aldol and Mannich products from ynamides with excellent diastereomerk and enantiomeric ratios and moderate yields.%当今合成化学中所面临的最大挑战之一是，在非环系统中形成全碳第四系立体中心。本文作者介绍了一个化学变化，它涉及通过一种立体烯醇化物与一种有机铜酸盐之间所发生的“碳金属化一氧化”组合反应来生成两个新的立体中心，其中包括全碳第四系立体中心。该方法被用来以极好的非对映异构一对映异构比率和rn中等产率从ynarhides生成一系列羟醛和“曼尼希”产物。