Reductive transformations of nitroarenes catalyzed by P(III)/P(V)=O redox cycling

Abstract

Nitroaromatics are widely available synthetic building blocks which present a strategical opportunity to serve as direct precursors to nitrogen-containing molecules of increasing complexity and worth through reductive/deoxygenative methods. Trivalent phosphorus compounds are valuable stoichiometric reagents for a range of reductive O-atom transfer reactions involving the conversion of R₃P[superscript III] to R₃P[superscript V]=O (including nitroarene deoxygenation), but can suffer from instability, pyrophoricity, and difficulty of removal during purification for both the phosphine and the generated phosphine oxide. Having the ability to start with a bench-stable phosphine oxide--which most often is regarded as a waste by-product--and repeatedly generate an active phosphine species in situ for catalytic reaction chemistry is a motivating concept with potentially practical benefits. With the incorporation of a hydrosilane reductant, it is demonstrated that a small-ring cyclic phosphine oxide can be quickly reduced in situ to catalyze the intramolecular cyclization of o-functionalized nitrobenzene derivatives to produce nitrogen-containing heterocycles (2H-indazoles, 2H-benzotriazoles, carbazoles, indoles, and benzimidazoles), as well as the intermolecular C-N cross coupling of nitroarenes with boronic acids through exhaustive nitro deoxygenation via P[superscript III]/P[superscript V]=O catalysis. The work herein not only describes the discovery of new organocatalytic methods founded on the use of a designer, small-ring phosphine oxide (pre)catalyst (1,2,2,3,4,4-hexamethylphosphetane 1-oxide) for the reductive transformations of nitroarenes, but also details investigations into the reaction mechanism for both reductive cyclization and C-N coupling reactions.