Diversity-oriented libraries from benzylic boronic esters via a Pd-catalyzed matteson reaction of arylboronic acids
Kane A. C. Bastick, Allan. J. B. Watson EaStCHEM, University of St Andrews, UK
The rapid construction of small molecule libraries under mild conditions is a core facet of pharmaceutical research in both academic and industrial settings. 1 Approaches to the construction of classical organoboron linchpins, widely utilized in Suzuki–Miyaura and Chan–Lam couplings, typically require the use of stoichiometric organometallic reagents. 2 We have recently disclosed an alternative conceptual approach to the Matteson homologation by using a halomethyl boronic ester as a highly reactive surrogate carbenoid. 3 Under Pd catalysis, this reagent undergoes facile oxidative addition to generate bench stable benzylic Bpin esters that are commercially limited due to the instability of the requisite boronic acid intermediate generated during conventional methodologies. With over 40 examples in hand, we demonstrate the synthetic utility of these C(sp 3 )–B products in a variety of Pd and Cu– mediated protocols to assemble a diverse library of compounds bearing pharmaceutically desirable functional groups. Current limitations of the catalytic homologation are discussed.
References 1. W. R. J. D. Galloway, A. Isidro-Llobet, D. R. Spring, Nat . Commun . 2010, 1 , 1–13. 2. A. J. J. Lennox, G. C. Lloyd-Jones, Chem . Soc . Rev . 2014, 43 , 412–443.3. 3. K. A. C. Bastick, A. J. B. Watson, ACS Catal. 2023, 13 , 7013−7018.
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© The Author(s), 2023
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