Diastereoselection in the Formation of Contiguous Quaternary Carbon Stereocenters by the Intramolecular Heck Reaction

The second in a series of two papers, this study examines the origins of diastereoselection in the second
ring closure of the highly diastereoselective double Heck cyclization of cyclohexenes 1 and 3 that form
contiguous quaternary stereocenters. Seven model substrates were synthesized and cyclized to examine
the structural features responsible for imparting diastereoselection in the second intramolecular Heck
reaction. These studies demonstrate that stereoselection in the formation of the second spirooxindole
ring results from the avoidance of steric interactions in the insertion step with the spirooxindole formed
in the first Heck cyclization. An axial substituent (carbonyl or arene) is required at the allylic position
for high levels of diastereoselection to be realized.

作为两篇系列论文的第二篇，本研究针对环己烯1与3的高非对映选择性双Heck环化反应（Double Heck Cyclization），探讨其第二次环合步骤的非对映选择性起源——该反应可生成连续的季碳立体中心。本研究合成了七种模型底物并开展环合实验，以探究第二次分子内Heck反应（Intramolecular Heck Reaction）中赋予非对映选择性的结构特征。研究表明，第二个螺羟吲哚环的立体选择性形成，源于在插入步骤中避免了与第一步Heck环化反应生成的螺羟吲哚之间的空间位阻相互作用。若要实现高非对映选择性，需在烯丙基位引入轴向取代基（羰基或芳烃）。