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. Author manuscript; available in PMC: 2021 Mar 5.
Published in final edited form as: Trends Chem. 2020 Nov 4;3(1):72–73. doi: 10.1016/j.trechm.2020.10.001

Reductive Csp2–N Coupling by PIII/PV=O–Catalysis

Gen Li 1,†, Colet te Grotenhuis 1,†, Alexander T Radosevich 1,*
PMCID: PMC7935090  NIHMSID: NIHMS1666562  PMID: 33681749

Graphical Abstract

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ORIGIN

The preparation of (hetero)arylamines has been significantly advanced by developments in transition metal catalyzed Csp2–N coupling (e.g., Buchwald-Hartwig, Chan-Lam, and Ullmann couplings). As a complement to these strategies, our group recently demonstrated the reductive Csp2–N coupling of arylboronic acids and nitro compounds—initially nitro(hetero)arenes, and more recently nitromethane—by an organophosphorus-catalyzed method operating via PIII/PV=O redox cycling.

REACTION MECHANISM

The PIII/PV=O catalyzed reductive Csp2–N coupling method is predicated on a rapid reduction of the precatalyst phosphetane oxide 1·[O] to the corresponding phosphetane 1. Experimental kinetic (A) and spectroscopic (B) studies of the reaction of nitrobenzene and phenylboronic acid show that 1 is indeed the catalyst resting state, and that the overall two-fold reduction of the nitro substrate evolves via two distinct PIII/PV=O cycles. In the first cycle, a (3+1) cheletropic addition of nitrobenzene to phosphetane 1 gives cycloadduct Int-1 in an overall turnover limiting step (C). Int-1 undergoes a retro-(2+2) fragmentation to liberate nitrosobenzene (Int-2) and phosphetane oxide 1·[O], which is rapidly re-reduced to 1 by the hydrosilane reductant. In the second cycle, Int-2 undergoes facile (2+1) addition with PIII resting state 1 to provide oxazaphosphirane Int-3. Similar intermediates have been proposed in the literature previously, but we are the first to obtain spectroscopical data of this highly reactive intermediate (D). Int-3 serves as a product-determining branching point. In the absence of an arylboronic acid, Int-3 evolves with loss of 1·[O] to give an arylnitrene intermediate, as exemplified by the formation of carbazole from 2-nitrobiphenyl through Cadogan-type cyclization. However, in the presence of an arylboronic acid, oxazaphosphirane Int-3 is diverted to betaine Int-4, which undergoes 1,2-metallate rearrangement to form the desired Csp2–N bond and releases the product arylamine upon workup (E). Rapid deoxygenation of phosphetane oxide 1·[O] mediated by hydrosilane again closes the second deoxygenation cycle and regenerates the PIII phosphetane resting state 1.

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IMPORTANCE

The intermolecular reductive Csp2–N coupling of nitroarenes and boronic acids represents a practical and robust organophosphorus-catalyzed method complementary to established transition metal-based Csp2–N coupling techniques. The mechanism emphasizes the biphilic character of phosphetanes in catalytic reductive O-atom transfer via PIII/PV=O redox cycling, providing a framework for further catalyst design and ongoing reaction development in the Csp2–N coupling space.

LITERATURE

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