Department of Chemistry, Dmitri Mendeleev Block, Indian Institute of Science Education and Research, Pune, India.
Org Biomol Chem. 2012 Oct 7;10(37):7536-44. doi: 10.1039/c2ob26007g. Epub 2012 Aug 13.
A Cu(I)-catalyzed α-oxyaldehyde-dibenzylamine-alkyne coupling reaction was delineated for the construction of α-oxyamines with excellent yields and diastereoselectivity. Crystal structure analysis and theoretical calculations were also supportive of the formation of syn-α-oxyamines as the major products. Application of the methodology addresses the synthesis of (+)-β-conhydrine along with analogs having two different diversity features. A ring size variation allows construction of piperidine and pyrrolidine rings while a variation of side arm functionality is achieved by complete regioselective opening of epoxide by different organocopper ylides (Gilman reagents). A lactam-Cu(I) complexation motif is proposed which allows an intramolecular attack of ylides at the terminal epoxy carbon via the six-membered cyclic transition state. The present work features the synthesis of (+)-β-conhydrine over eight steps in 26% yield and its seven analogs in 21-28% yields.
一种 Cu(I)催化的α-氧醛-二苄基胺-炔烃偶联反应被描绘出来，用于构建具有优异收率和非对映选择性的α-氧胺。晶体结构分析和理论计算也支持顺式-α-氧胺作为主要产物的形成。该方法学的应用解决了(+)-β-康因及其具有两种不同多样性特征的类似物的合成问题。环大小的变化允许构建哌啶和吡咯烷环，而通过不同的有机铜叶立德（吉尔曼试剂）完全区域选择性地开环，可以实现侧臂官能团的变化。提出了一个内酰胺-Cu(I)配合物的模体，该模体允许叶立德通过六元环状过渡态在末端环氧碳原子上进行分子内攻击。本工作以 26%的收率完成了(+)-β-康因的八步合成，并以 21-28%的收率完成了其七个类似物的合成。
