Carbon–Carbon Bond-Forming Reactions of α-Thioaryl Carbonyl Compounds for the Synthesis of Complex Heterocyclic Molecules

Strategies for the formation of carbon–carbon
bonds from
the α-thioaryl carbonyl products of substituted lactams are
described. Although direct functionalization is possible, a two step
process of oxidation and magnesium-sulfoxide exchange has proven optimal.
The oxidation step results in the formation of two diastereomers that
exhibit markedly different levels of stability toward elimination,
which is rationalized on the basis of quantum mechanical calculations
and X-ray crystallography. Treatment of the sulfoxide with i-PrMgCl results in the formation of a magnesium enolate
that will undergo an intramolecular Michael addition reaction to form
two new stereogenic centers. The relationship between the substitution
patterns of the sulfoxide substrate and the efficiency of the magnesium
exchange reaction are also described.

本研究报道了以取代内酰胺的α-硫芳基羰基产物为起始原料构建碳-碳键的策略。尽管可采用直接官能化路径，但经实验验证，氧化-镁亚砜交换两步法为最优方案。氧化步骤会生成两种非对映异构体，二者在消除反应中的稳定性差异显著，该现象可通过量子力学计算与X射线晶体学分析得到合理解释。将亚砜与异丙基氯化镁（i-PrMgCl）反应，可得到镁烯醇盐中间体，该中间体可发生分子内迈克尔加成反应，生成两个新的手性中心。本研究同时阐述了亚砜底物的取代模式与镁交换反应效率之间的构效关系。