A Carbene Relay Strategy for Cascade Insertion Reactions

Abstract Insertion reactions that involve stabilized electrophilic metallocarbenes are of great importance for installing α‐heteroatoms to carbonyl compounds. Nevertheless, the limited availability of carbene precursors restricts the introduction of only a single heteroatom. In this report, we describe a new approach based on an I (III) /S (VI) reagent that promotes the cascade insertion of heteroatoms. This is achieved by sequentially generating two α‐heteroatom‐substituted metal carbenes in one reaction. We found that this mixed I (III) /S (VI) ylide reacts efficiently with a transition metal catalyst and an X−H bond (where X=O, N). This transformation leads to the sequential formation of a sulfoxonium‐ and an X‐substituted Rh‐carbenes, enabling further reactions with another Y−H bond. Remarkably, a wide range of symmetrical and unsymmetrical α,α‐ O , O ‐, α,α‐ O , N ‐, and α,α‐ N , N ‐subsituted ketones can be prepared under mild ambient conditions. In addition, we successfully demonstrated other cascades, such as CN/CN double amidation, C−H/C−S double insertion, and C−S/Y−H double insertion (where Y=S, N, O, C). Notably, the latter two cascades enabled the simultaneous installation of three functional groups to the α‐carbon of carbonyl compounds in a single step. These reactions demonstrate the versatility of our approach, allowing for the synthesis of ketones and esters with multiple α‐heteroatoms using a common precursor.