Marcos Suero

1. Introduction Click to copy section linkSection link copied! Scaffold hopping is a widely used optimization strategy in medicinal chemistry in which the core framework of a lead compound is modified while preserving the key pharmacophoric features. (1−4) As defined by Sun et al., (3) scaffold hopping is classified into four major categories: heterocycle replacements, ring opening or closure, peptidomimetics, and topology-based hopping.

Rh(II)-carbynoids, a class of Rh(II)-carbenes substituted with a leaving group at the carbene carbon atom, have emerged as key species in the catalytic transfer of monovalent cationic carbon units (:+C–R) (Figure 1A). (1) Our group pioneered their catalytic generation using diazo hypervalent iodine reagents, and we demonstrated that our Rh(II)-carbynoids can behave as a Rh(II)-carbene and undergo [2 + 1] cycloadditions with alkenes and alkynes.

Rh-catalysed single-carbon insertion to 1,3-dienes† Herein, we report the first catalytic single-carbon insertion to 1,3-dienes with Rh(II)-carbynoids. The skeletal editing process is based on the catalytic generation of a Rh-carbynoid that promotes the insertion of a cationic monovalent carbon unit (:+C–R) into the C(sp2)–C(sp2) bond of the 1,3-diene, leading to a pentadienyl cation.