An Improved PIII/PV?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 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.
Project description: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.
Project description:The first intermolecular carbonyl arylations via transfer hydrogenative reductive coupling are described. Using rhodium catalysts modified by tBu2PMe, sodium formate-mediated reductive coupling of aryl iodides with aldehydes occurs in a chemoselective fashion in the presence of protic functional groups and lower halides. This work expands the emerging paradigm of transfer hydrogenative coupling as an alternative to pre-formed carbanions or metallic reductants in C?X addition.
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.
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.
Project description:A single ruthenium complex catalyzes two discrete transformations resulting in the net conversion of an acetylenic pyrrole and alcohols to products of carbonyl anti-(?-amino)allylation. An initial catalytic process enables isomerization of an alkyne to a kinetically more reactive allene. A second catalytic process promotes alcohol-to-allene hydrogen transfer to form an aldehyde-allylruthenium pair that engages in regio- and diastereoselective carbonyl addition. A related reductive coupling of aldehydes mediated by 2-propanol also is described. The present catalytic processes represent rare examples of the use of alkynes as nucleophilic allylmetal precursors.
Project description:Herein, we disclose Ru(II)-catalyzed regioselective distal C(sp2)-H arylation of quinoline N-oxide with arylboronic acids to 8-arylquinolines. In the developed method, the Ru(II)-catalyst shows dual activity, that is, distal C-H activation of quinoline N-oxides followed by in situ deoxygenation of arylated quinoline N-oxide in the same pot. The current catalytic method features use of Ru metal as the catalyst and arylboronic acids as the arylating source under mild reaction conditions. Use of the Rh(III)-catalyst in place of Ru(II) under the same conditions afforded 8-arylquinoline N-oxides with excellent regioselectivity. Furthermore, the developed Ru(II) catalytic system is also extended for the C(sp2)-H arylation of indolines, N-tert-butylbenzamide, and 6-(5H)-phenanthridinone. Formation of the quinoline N-oxide coordinated ruthenium adduct is found to be the key reaction intermediate, which has been characterized by single crystal X-ray diffraction and NMR spectroscopy.
Project description:A method for the annulation of amines and carboxylic acids to form pharmaceutically relevant azaheterocycles via organophosphorus PIII/PV redox catalysis is reported. The method employs a phosphetane catalyst together with a mild bromenium oxidant and terminal hydrosilane reductant to drive successive C-N and C-C bond-forming dehydration events via the serial action of a catalytic bromophosphonium intermediate. These results demonstrate the capacity of PIII/PV redox catalysis to enable iterative redox-neutral transformations in complement to the common reductive driving force of the PIII/PV couple.
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.
Project description:Natural availability of carbonyl groups offers reductive carbonyl coupling tremendous synthetic potential for efficient olefin synthesis, yet the catalytic carbonyl cross-coupling remains largely elusive. We report herein such a reaction, mediated by hydrazine under ruthenium(ii) catalysis. This method enables facile and selective cross-couplings of two unsymmetrical carbonyl compounds in either an intermolecular or intramolecular fashion. Moreover, this chemistry accommodates a variety of substrates, proceeds under mild reaction conditions with good functional group tolerance, and generates stoichiometric benign byproducts. Importantly, the coexistence of KO t Bu and bidentate phosphine dmpe is vital to this transformation.
Project description:A new methodology to form C(sp<sup>3</sup> )-C(sp<sup>2</sup> ) bonds by visible-light-driven intermolecular reductive ene-yne coupling has been successfully developed. The process relies on the ability of the Hantzsch ester to contribute in both SET and HAT processes through a unified cobalt and iridium catalytic system. This procedure avoids the use of stoichiometric amounts of reducing metallic reagents, which is translated into high functional-group tolerance and atom economy.