α-Substituted Organolithiums as Homologating Reagents in Synthesis

Carbenoids are organometallic reagents employed in organic synthesis in order to realize a homologation event via insertion of a reactive fragment featuring a precise substitution pattern. Homologation reaction refers to synthetic operations allowing the formation of a new carbonecarbon or carboneheteroatom bond through the addition of methylene unit (e.g. eCH2X, X ¼ Halogen, CN, OR). Functionalized methylene units (e.g. MCH2X, M ¼ metal, X ¼ halogen) act as nucleophilic synthons enabling the transfer of the CH2X unit into a proper electrophilic partner. The halogen(s) featuring the carbenoid can be included (or not) in the final compound, thus different outcomes can be identified. The inherent instabilityeoften constituting Achilles’ heel of these speciesebenefited from the use of Barbier-type conditions to prevent decomposition phenomena to unproductive carbenes. In this article the breakthroughs in homologation processes with these reagents are presented. Not only canonical processes are discussed, but also modern sequential transformations triggered by an initial homologative event. Most of the attention is devoted toein batcheoperations dealing with carbon- and heteroatom-centered electrophiles.