An Improved P^III/P^V═O-Catalyzed Reductive C–N Coupling of Nitroaromatics and Boronic Acids by Mechanistic Differentiation of Rate- and Product-Determining Steps

Abstract

Experimental, spectroscopic, and computational studies are reported that provide an evidence-based mechanistic description of an intermolecular reductive C−N coupling of nitroarenes and arylboronic acids catalyzed by a redox-active maingroup catalyst (1,2,2,3,4,4-hexamethylphosphetane P-oxide, i.e., 1• [O]). The central observations include the following: (1) catalytic reduction of 1•[O] to P III phosphetane 1 is kinetically fast under conditions of catalysis; (2) phosphetane 1 represents the catalytic resting state as observed by 31 P NMR spectroscopy; (3) there are no long-lived nitroarene partial-reduction intermediates observable by 15 N NMR spectroscopy; (4) the reaction is sensitive to solvent dielectric, performing best in moderately polar solvents (viz. cyclopentylmethyl ether); and (5) the reaction is largely insensitive with respect to common hydrosilane reductants. On the basis of the foregoing studies, new modified catalytic conditions are described that expand the reaction scope and provide for mild temperatures (T ≥ 60 °C), low catalyst loadings (≥2 mol%), and innocuous terminal reductants (polymethylhydrosiloxane). DFT calculations define a two-stage deoxygenation sequence for the reductive C−N coupling. The initial deoxygenation involves a ratedetermining step that consists of a (3+1) cheletropic addition between the nitroarene substrate and phosphetane 1; energy decomposition techniques highlight the biphilic character of the phosphetane in this step. Although kinetically invisible, the second deoxygenation stage is implicated as the critical C−N product-forming event, in which a postulated oxazaphosphirane intermediate is diverted from arylnitrene dissociation toward heterolytic ring opening with the arylboronic acid; the resulting dipolar intermediate evolves by antiperiplanar 1,2-migration of the organoboron residue to nitrogen, resulting in displacement of 1•[O] and formation of the target C−N coupling product upon in situ hydrolysis. The method thus described constitutes a mechanistically well-defined and operationally robust main-group complement to the current workhorse transition-metal-based methods for catalytic intermolecular C−N coupling.

Light‐Promoted C–N Coupling of Aryl Halides with Nitroarenes

“…[11] Since the early report on nucleophilic C-N addition of aryl magnesium reagents to nitroarenes by the Knochel group, [12] the following pioneering studies from the Baran [13] and Hu [14] groups have successfully demonstrated that nitroarenes are valuable precursor to anilines in organic synthesis. [15] Of particular note is the recent seminal work on organophosphorus [16] and molybdenum [17] catalyzed coupling of nitroarenes with boronic acids, which provides a new, effective process for the C À N bond formation (Scheme 1 b). However, there has been no report on the more economic, direct amination of aryl halides with nitroarenes.…”

Pincer‐Type Ligand‐Assisted Catalysis and Small‐Molecule Activation by non‐VSEPR Main‐Group Compounds

“…In 2017, Radosevich group found out that 1,2,2,3,4,4‐hexamethylphosphetane ( 21a[O] ), catalyzed the deoxygenative N−N bond‐forming Cadogan heterocyclization of o‐nitrobenzaldimine, and its derivatives in the presence of hydrosilane terminal reductant (Scheme a) . A reductive intermolecular C−N coupling of boronic acids and nitroaromatics using common hydrosilane reductants was reported using 21a[O] as catalyst (Scheme b) . Extending the organophosphorus‐catalyzed C−N coupling approach, they have synthesized several azaheterocycles from the reactions of ortho‐functionalized nitroarenes and boronic acid (Scheme c).…”

Recent Progress on Reductive Coupling of Nitroarenes by Using Organosilanes as Convenient Reductants

“…Very recently, further conditions optimization and detailed mechanistic studies on this reaction were conducted by the same group. [34] The "second-generation" conditions with innocuous PMHS as reductant in cyclopentylmethyl ether (CPME) provides a general improvement in yield (Scheme 21). Notably, a variety of heterocyclic nitroarenes that are challenging under the previous conditions react smoothly with arylboronic acids under the new conditions.…”