Direct Access to Carbenoids from Alkyl and α-Acyloxy Halide`s for Boron Homologations: Method Development and Mechanistic Insights
Year: 2026
Type: preprint
Abstract: Despite the widespread utility of carbenoids in boron homologations, practical challenges in accessing unstabilized gem-halometal carbenoids limit their broader synthetic application.A major bottleneck is the historical reliance on gem-dihalide precursors, which restricts the accessible substrate scope.Bypassing gem-dihalides via direct deprotonation of unactivated alkyl halides offers an ideal but historically elusive alternative due to competing base-mediated elimination and substitution reactions.Here we introduce a straightforward deprotonation/boron homologation protocol for both alkyl and α-acyloxy halides using hindered amide bases (over 50 examples).The method was effective for both primary and secondary alkyl halide substrates, tolerating a wide range of functional groups including base-sensitive moieties.The α-acyloxy boronic esters, generated via an efficient aldehyde addition and homologation sequence, readily undergo diverse downstream substitutions with Grignard and organolithium nucleophiles.Finally, combining DFT-based natural bond orbital analysis with statistical modeling of the resulting descriptors, we establish that the energy of the σ(C-H) natural bond orbital predicts the site of deprotonation across every substrate examined, and we trace this selectivity to the interplay of increased scharacter and reduced steric (Pauli) repulsion at the C-H bond geminal to the halogen.
Source: ChemRxiv
Institutions: Texas A&M University, University of Pennsylvania
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7223168291