Practical and Scalable Synthesis of Borylated Heterocycles Using Bench-Stable Precursors of Metal-Free Lewis Pair Catalysts

Abstract

A practical and scalable metal-free catalytic method for the borylation and borylative dearomatization of heteroarenes has been developed. This synthetic method uses inexpensive and conveniently synthesizable bench-stable precatalysts of the form 1-NHR2-2-BF3-C6H4, commercially and synthetically accessible heteroarenes as substrates, and pinacolborane as borylation reagent. Preparation of several borylated heterocycles in 2 and 50 grams was achieved under solvent-free conditions without the use of Schlenk techniques or a glove box. A kilogram-scale borylation of one of the heteroarene substrates was also achieved using this cost-effective green methodology to exemplify the fact that our methodology can be conveniently implemented in fine chemical industries.

Application of Mutualism in Organic Synthetic Chemistry: Mutually Promoted C−H Functionalization of Indole and Reduction of Quinoline

“…In recent years, the selective functionalization (i. e. borylation or silylation) of C−H bond in N‐ heterocylic aromatics such as indoles has attracted intense attention due to their wide applications in synthesis, [1–3] medicinal chemistry [4,5] and materials sciences [6,7] . Different synthetic strategies have been developed to accomplish this goal by metal [8–23] or metal‐free catalysts [24–35] . Among them, potent boron Lewis acid tris(pentafluorophenyl)borane, B(C 6 F 5 ) 3 , have demonstrated its powerful capability in the C−H borylation (silylation) of indoles [36–39] .…”

Element‐Ligand Cooperativity with p‐Block Elements

“…The latter transformation is, for example, manifested in the borylation of pyrroles, indoles, thiophenes, and furans, employing 16 as the catalyst and pinacol borane as the boron source (Figure b). Further catalyst optimizations resulted not only in increased activity but also in air‐ and moisture‐stable species for catalysis and in protocols suitable for reactions on the kilogram scale . The Repo group reported the ability of 16 to act as a borylation agent for olefinic substrates …”

Boron Lewis Pair Mediated C–H Activation and Borylation

“…While transition metal catalysts usually borylate at the C2 of indoles, this metal-free catalytic system borylate at the C3 position. [67] Scheme 20 Selected examples of scale up for the C-H borylation by X and comparison with Ir catalysis.…”

“…While transition metal catalysts usually borylate C2 of indoles, this metal-free catalytic system borylates at C3. 67 In an attempt to make these C-H borylation catalysts more sustainable, Fontaine and co-workers also developed FLP borylation catalysts on polymeric supports (Scheme 21). 68 These consisted of alkylammonium trifluoroborate functionalized polystyrene, Pip 40, NEt 2 41, and NMe 2 42.…”