When gem-Diborylalkanes Meet Carboxylic Acids and Their Derivatives: Enolate/Enamine Chemistry beyond Conventional Reactivity.

ConspectusThe booming progress of organoboron chemistry has unleashed a profound revolution in the field of synthetic chemistry. Among emerging organoboron reagents, gem-diborylalkanes stand out as uniquely versatile platforms that unlock unconventional reaction pathways through activation of their dual boryl groups. The empty p orbitals of adjacent the boryl groups not only allow generation of α-boryl carbanionic intermediates but also enable precise selectivity controls, allowing chemists to navigate a previously inaccessible chemical space.In this Account, we summarize our systematic exploration of gem-diborylalkanes as multiple nucleophiles in reactions with carboxylic acid derivatives as multiple electrophiles, revealing boron enolate/enamine intermediates as linchpins for efficient functional group interconversions.Our journey began with a breakthrough in the direct deoxygenative enolization of carboxylic acids using gem-diborylalkanes. In that work, carboxylic acids participated in the enolization reaction as an acyl source for the first time. Electrophilic capture of the resulting boron enolates enables dual functionalization of gem-diborylalkanes to yield various α-functionalized ketones. Expanding this paradigm to amide systems, we discovered that amide activation follows distinct mechanistic divergences. While tertiary amides undergo B-N elimination to generate enol species, primary/secondary amides and lactams preferentially undergo B-O elimination to form enamine intermediates. This result provides a strategic blueprint for synthesizing α-functionalized ketones, enamides, and cyclic amines from common amides through substrate-controlled chemoselectivity. Revisiting the reaction of lithiated gem-diborylalkanes with carboxylic esters, we developed an enolate-O trapping strategy that revolutionized alkyne synthesis. Reaction of lithiated gem-diborylalkanes with esters generates α-boryl boron enolates, which upon α,β-[B-O] elimination with a novel trapping reagent produce alkynes with high efficiency. The versatility of this method extends to the precision synthesis of 13C-labeled alkynes using isotopically labeled gem-diborylmethane. Pursuing the chemistry of lithiated gem-diborylalkanes with nitriles, we achieved a remarkable atom swap in the triple bond through α-boryl enamine intermediates. The reaction cascade between lithiated gem-diborylalkanes and nitriles, mediated by tert-butyl nitrite (TBN) as a N-deleting reagent, accomplishes an efficient swap of N-to-C bonds within triple bonds. This "atom transposition" strategy expands the synthetic toolbox for accessing functionalized alkynes from readily available nitriles.Through these case studies, we demonstrate how a systematic investigation of boron effects can rewrite textbook synthesis. The developed methodologies not only solve long-standing synthetic challenges in functional group interconversion but also establish gem-diboryl chemistry as a conceptual framework for designing novel bond-forming processes. We anticipate that this Account will stimulate broad applications of gem-diborylalkane reagents in catalysis, materials science, and bioactive molecule synthesis.