A small ring phosphacycle (1,2,2,3,4,4-hexamethylphosphetane) is found to catalyze deoxygenative N-N bond-forming Cadogan heterocyclization of o-nitrobenzaldimines, o-nitroazobenzenes and related substrates in the presence of hydrosilane terminal reductant. The reaction provides a chemoselective catalytic synthesis of 2H-indazoles, 2H-benzotriazoles, and related fused heterocyclic systems with good functional group compatibility. On the basis of both stoichiometric and catalytic mechanistic experiments, the reaction is proposed to proceed via catalytic PIII/PV=O cycling, where DFT modelling suggests a turnover limiting (3+1) cheletropic addition between the phosphetane catalyst and nitroarene substrate. Strain/distortion analysis of the (3+1) transition structure highlights the controlling role of frontier orbital effects underpinning the catalytic performance of the phosphetane.
A main group-catalyzed method for the synthesis of aryl- and heteroarylamines by intermolecular C–N coupling is reported. The method employs a small-ring organophosphorus-based catalyst (1,2,2,3,4,4-hexamethylphosphetane) and a terminal hydrosilane reductant (phenylsilane) to drive reductive intermolecular coupling of nitro(hetero)arenes with boronic acids. Applications to the construction of both Csp2–N (from arylboronic acids) and Csp3–N bonds (from alkylboronic acids) are demonstrated; the reaction is stereospecific with respect to Csp3–N bond formation. The method constitutes a new route from readily available building blocks to valuable nitrogen-containing products with complementarity in both scope and chemoselectivity to existing catalytic C–N coupling methods.
A small-ring phosphacycloalkane (1,2,2,3,4,4-hexamethylphosphetane, 3) catalyzes intramolecular C–N bond forming heterocyclization of o-nitrobiaryl and –styrenyl derivatives in the presence of a hydrosilane terminal reductant. The method provides scalable access to diverse carbazole and indole compounds under operationally trivial homogeneous organocatalytic conditions, as demonstrated by 17 examples conducted on one-gram scale. In situ NMR reaction monitoring studies support a mechanism involving catalytic PIII/PV=O cycling, where tricoordinate phosphorus compound 3 represents the catalytic resting state. For the catalytic con-version of o-nitrobiphenyl to carbazole, the kinetic reaction order was determined for phosphetane catalyst 3 (first order), substrate (first order), and phenylsilane (zeroth order). For differentially 5-substituted 2-nitrobiphenyls, the transformation is accelerated by electron–withdrawing substituents (Hammett factor ρ = +1.5), consistent with the accrual of negative charge on the nitro substrate in the rate-determining step. DFT modeling of the turnover-limiting deoxygenation event implicates a rate-determining (3+1) cheletropic addition between the phosphetane catalyst 3 and 2-nitrobiphenyl substrate to form an unobserved pentacoordinate spiro-bicyclic dioxazaphosphetane, which decomposes via (2+2) cycloreversion giving one equivalent of phosphetane P-oxide 3•[O] and 2-nitrosobiphenyl. Experimental and computational investigations into the C–N bond forming event suggest the involvement of an oxazaphosphirane (2+1) adduct between 3 and 2-nitrosobiphenyl, which evolves through loss of phosphetane P-oxide 3•[O] to give the observed carbazole product via C–H insertion in a nitrene-like fashion.
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.
An organocatalytic method for the modular synthesis of diverse N‐aryl and N‐alkyl azaheterocycles (indoles, oxindoles, benzimidazoles, and quinoxalinediones) is reported. The method employs a small‐ring organophosphorus‐based catalyst (1,2,2,3,4,4‐hexamethylphosphetane P‐oxide) and a hydrosilane reductant to drive the conversion of ortho‐functionalized nitroarenes into azaheterocycles through sequential intermolecular reductive C−N cross coupling with boronic acids, followed by intramolecular cyclization. This method enables the rapid construction of azaheterocycles from readily available building blocks, including a regiospecific approach to N‐substituted benzimidazoles and quinoxalinediones.
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