Natural Product Synthesis by Intramolecular Alkylidene Carbene C−H Insertion

Abstract

Direct functionalization of unactivated C−H bonds is of increasing importance in organic synthesis. Of the many methods that have been developed, intramolecular alkylidene C−H insertion, proceeding with retention of absolute configuration, is among the most versatile. This Review explores all examples of the use of intramolecular alkylidene C−H insertion in natural product synthesis.

Alkylidene Carbene from Silyl Vinyl Iodide Provides Mechanistic Insights on Trimethylenemethane Diyl-Mediated Tandem Cyclizations

“…Alkylidene carbenes are reactive intermediates that have received tremendous interest from the organic chemistry community. − In situ generated alkylidene carbenes have been widely used as key intermediates in chemical transformations, such as alkyne synthesis via 1,2-migration and 1,5 C–H insertion. , Alkylidene carbenes have also been used as a precursor of trimethylenemethane (TMM) diyls via intramolecular cyclopropanation with an alkene moiety (Scheme A)…”

“…1−3 In situ generated alkylidene carbenes have been widely used as key intermediates in chemical transformations, such as alkyne synthesis via 1,2-migration 2 and 1,5 C−H insertion. 1,4 Alkylidene carbenes have also been used as a precursor of trimethylenemethane (TMM) diyls via intramolecular cyclopropanation with an alkene moiety (Scheme 1A). 5 The chemistry of TMM diyls have been thoroughly investigated by several research groups, including those of Dowd, Kobrich, and Berson.…”