Base-free palladium-catalyzed borylation of enol carboxylates and further reactivity toward deboronation and cross-coupling
Date
2025
Authors
Gaube, Gregory
Miller, Douglas L.
McCallum, Rowan A.
Nahiane Pipaón Fernández
Leitch, David C.
Journal Title
Journal ISSN
Volume Title
Publisher
Tetrahedron
Abstract
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.
Description
Keywords
borylation, cross-coupling, C–O activation, palladium catalysis, deoxygenation, high-throughput experimentation
Citation
Gaube, G., Miller, D. L., McCallum, R. A., Fernández, N. P., & Leitch, D. C. (2025). Base-free palladium-catalyzed borylation of enol carboxylates and further reactivity toward deboronation and cross-coupling. Tetrahedron, 182, 134682. https://doi.org/10.1016/j.tet.2025.134682