Base-free palladium-catalyzed borylation of enol carboxylates and further reactivity toward deboronation and cross-coupling

A series of base-free Pd-catalyzed borylation procedures are reported for a number of alkenyl carboxylates, with pivalates generally outperforming their acetate counterparts. High-throughput experimentation was used to discover and optimize these reactions using in situ generated catalyst systems. Mechanistic studies identified C–O oxidative addition to Pd(0) as the turnover-limiting step, with a variety of rates observed depending on substrate structure. One exemplar oxidative addition complex was isolated and fully characterized, including by X-ray crystallography. This complex undergoes rapid and complete reaction with excess B₂Pin₂ at room temperature, confirming that no exogeneous base is required for transmetallation with the Pd(II) pivalate intermediate. Notably, gamma-lactone and lactam substrates lead to unstable alkenyl pinacol boronates, which undergo protodeboronation under acidic and basic aqueous conditions. Optimization of this protodeboronation resulted in a mild, two-step reduction of the C–O bond, achieving net-deoxygenation while leaving the alkene intact. In contrast, use of an alternative tetraalkoxydiboron source – B₂EPin₂ – was successful in catalysis, and offered improved stability of the resulting organoboron species. This enables further reactivity, such as cross-coupling, without competing protodeboronation.