Driving Recursive Dehydration by PIII/PV Catalysis: Annulation of Amines and Carboxylic Acids by Sequential C-N and C-C Bond Formation.
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ABSTRACT:
SUBMITTER: Lecomte M
PROVIDER: S-EPMC6693942 | BioStudies | 2019-01-01
REPOSITORIES: biostudies
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Project description: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 main-group 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 PIII phosphetane 1 is kinetically fast under conditions of catalysis; (2) phosphetane 1 represents the catalytic resting state as observed by 31P NMR spectroscopy; (3) there are no long-lived nitroarene partial-reduction intermediates observable by 15N 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 rate-determining 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.
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Project description: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 1 g 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 conversion 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 ? = +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 1 equiv 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.
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Project description:A method for electrophilic sulfenylation by organophosphorus-catalyzed deoxygenative O-atom transfer from sulfonyl chlorides is reported. This C-S bond-forming reaction is catalyzed by a readily available small-ring phosphine (phosphetane) in conjunction with a hydrosilane terminal reductant to afford a general entry to sulfenyl electrophiles, including valuable trifluoromethyl, perfluoroalkyl, and heteroaryl derivatives that are otherwise difficult to access. Mechanistic investigations indicate that the twofold deoxygenation of the sulfonyl substrate proceeds by the intervention of an off-cycle resting state thiophosphonium ion. The catalytic method represents an operationally simple protocol using a stable phosphine oxide as a precatalyst and exhibits broad functional-group tolerance.
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Project description:The carbon-carbon double bond of unsaturated carbonyl compounds was readily reduced by using a phosphetane oxide catalyst in the presence of a simple organosilane as the terminal reductant and water as the hydrogen source. Quantitative hydrogenation was observed when 1.0?mol?% of a methyl-substituted phosphetane oxide was employed as the catalyst. The procedure is highly selective towards activated double bonds, tolerating a variety of functional groups that are usually prone to reduction. In total, 25 alkenes and two alkynes were hydrogenated to the corresponding alkanes in excellent yields of up to 99?%. Notably, less active poly(methylhydrosiloxane) could also be utilized as the terminal reductant. Mechanistic investigations revealed the phosphane as the catalyst resting state and a protonation/deprotonation sequence as the crucial step in the catalytic cycle.
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Project description:We report that a regioselective reductive transposition of primary allylic bromides is catalyzed by a biphilic organophosphorus (phosphetane) catalyst. Spectroscopic evidence supports the formation of a pentacoordinate (?(5)-P) hydridophosphorane as a key reactive intermediate. Kinetics experiments and computational modeling are consistent with a unimolecular decomposition of the ?(5)-P hydridophosphorane via a concerted cyclic transition structure that delivers the observed allylic transposition and completes a novel P(III)/P(V) redox catalytic cycle. These results broaden the growing repertoire of reactions catalyzed within the P(III)/P(V) redox couple and suggest additional opportunities for organophosphorus catalysis in a biphilic mode.
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