Reductive Generation of Anionic C1 Carbenoid Species Attached to Organosulfur Functional Groups

The generation of heteroatom-substituted C1 carbenoids is highly challenging due to their extreme instability and electronic perturbations. We report the reductive lithiation of organosulfur chloromethyl precursors using lithium naphthalenide (LiNp) under flow microreactor conditions. This method enables the flash generation of sulfur-containing lithium carbenoids, which were efficiently trapped with a wide range of electrophiles to afford functionalized organosulfur compounds. Spatially resolved optimization revealed that reaction efficiency critically depends on millisecond-scale residence times and temperature control, allowing selective generation while suppressing decomposition. The protocol tolerated diverse electrophiles, including carbonyls, isocyanates, and organometalloids, and subsequent selective deprotection of sulfur substituents further expanded synthetic utility. Comparative studies demonstrated the unique reactivity of sulfur versus oxygen or nitrogen analogues, highlighting the distinctive redox properties of organosulfur substituents.