Chemodivergent Organolanthanide Catalyzed C-H a-Mono-1 Borylation of Azines

Abstract

C-H activation and functionalization of pyridinoid azines is a key transformation forthe synthesis of many natural products, pharmaceuticals, and materials. Reflecting the azinyl nitrogen lone-pair steric repulsion, tendency to irreversibly bind to metal ion catalysts, and the electron-deficient nature of pyridine, C-H functionalization at the important a-position remains challenging. Thus, the development of earth abundant catalysts for the a-selective mono-functionalization of azines is a crucial hurdle for modern chemical synthesis. Here, the selective organolanthanide catalyzed a-mono-borylation of a diverse series of pyridines is reported, affording a valuable precursor for cross-coupling reactions. Experimental and theoretical mechanistic evidence support the formation of a C-H activated η2-lanthanide-azine complex, followed by intermolecular a-mono-borylation via σ-bond metathesis. Notably, varying the lanthanide identity and substrate electronics promotes chemodivergence of the catalytic selectivity: smaller/more electrophilic lanthanide3+ ions and electron-rich substrates favor selective a-C-H functionalization, whereas larger/less electrophilic lanthanide3+ 1 ions and electron poor substrates favor selective B-N bond-forming 1,2-dearomatization. Such organolanthanide series catalytic chemodivergence is, to our knowledge, unprecedented.

Yttrium‐Catalyzed ortho‐Selective C−H Borylation of Pyridines with Pinacolborane

“…Although scandocene alkyl complex 1 was applicable for previous stoichiometric borylation reaction, it only produced trace amounts of desired product 9 a under catalytic conditions (3 mol % catalyst loading, 60 °C, 6 h, Table 1, entry 1). Gratifyingly, Y complex 2 selectively afforded 9 a in 92 % yield under the same conditions (Table 1, entry 2), and no other isomer was observed, e.g., hydroboration product 9 a′ [13] . A characteristic 1 H NMR resonance at δ =4.47 ppm attributed to H 2 was also detected.…”

Chemodivergent Organolanthanide-Catalyzed C–H α-Mono-Borylation of Pyridines

“…To date, the majority of documented organolanthanide-mediated α-pyridine activation has come at the expense of synthetically restrictive blocking groups and/or additives to assist turnover. − After the initial disclosure of this work and while this full account was nearing completion, a synthetically focused communication by Xu et al appeared, reporting an analogous pyridine α-borylation methodology using primarily organo-Y catalysts and additional late-stage functionalizations . This laboratory previously reported the highly 1,2-selective and atom-efficient B–N bond-forming pyridine dearomatization using an organolanthanum (Cp* 2 La-) catalyst (Figure c) .…”