Reduction of Activated Alkenes by PIII /PV Redox Cycling Catalysis.
ABSTRACT: 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.
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: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 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: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:1. Oxygen-pulse experiments on antimycin-treated liver mitochondria from young rats in the absence of added substrates indicate the presence of an endogenous hydrogenated reductant on the oxygen side of the antimycin inhibition site. This reductant has been estimated to be present in a 20--50-fold molar excess over cytochrome aa3. Oxidation of the reductant by small bursts of electron flow to oxygen gives a ratio H+ translocated:O atoms taken up of 2.1 +/- 0.2. 2. The endogenous hydrogenated reductant competes with added ferrocyanide and with ascorbate/NNN'N'-tetramethyl-p-phenylenediamine as a source of reducing equivalents to oxygen. 3. When the contribution of endogenous substrate to H+ production is taken into account, there still remains some respiration-dependent H+ translocation consistent with a H+ pumping activity of cytochrome oxidase. The stoichiometry of this 'extra' H+ translocation is variable and depends on the rate of electron flow.
Project description:The hydrophosphorylation of phenylacetylene with di(aryl)phosphane oxides Ar2 P(O)H (Pudovik reaction) yields E/Z-isomer mixtures of phenylethenyl-di(aryl)phosphane oxides (1). Alkali and alkaline-earth metal di(aryl)phosphinites have been studied as catalysts for this reaction with increasing activity for the heavier s-block metals. The Pudovik reaction can only be mediated for di(aryl)phosphane oxides whereas P-bound alkyl and alcoholate substituents impede the P-H addition across alkynes. The demanding mesityl group favors the single-hydrophosphorylated products 1-Ar whereas smaller aryl substituents lead to the double-hydrophosphorylated products 2-Ar. Polar solvents are beneficial for an effective addition. Increasing concentration of the reactants and the catalyst accelerates the Pudovik reaction. Whereas Mes2 P(O)H does not form the bis-phosphorylated product 2-Mes, activation of an ortho-methyl group and cyclization occurs yielding 2-benzyl-1-mesityl-5,7-dimethyl-2,3-dihydrophosphindole 1-oxide (3).
Project description:Realizing the full potential of oxide-supported single-atom metal catalysts (SACs) is key to successfully bridge the gap between the fields of homogeneous and heterogeneous catalysis. Here we show that the one-pot combination of Ru1 /CeO2 and Rh1 /CeO2 SACs enables a highly selective olefin isomerization-hydrosilylation tandem process, hitherto restricted to molecular catalysts in solution. Individually, monoatomic Ru and Rh sites show a remarkable reaction specificity for olefin double-bond migration and anti-Markovnikov ?-olefin hydrosilylation, respectively. First-principles DFT calculations ascribe such selectivity to differences in the binding strength of the olefin substrate to the monoatomic metal centers. The single-pot cooperation of the two SACs allows the production of terminal organosilane compounds with high regio-selectivity (>95?%) even from industrially-relevant complex mixtures of terminal and internal olefins, alongside a straightforward catalyst recycling and reuse. These results demonstrate the significance of oxide-supported single-atom metal catalysts in tandem catalytic reactions, which are central for the intensification of chemical processes.
Project description:The asymmetric unit of the title co-crystal, 2,2'-thiodi-benzoic acid-tri-phenyl-phosphane oxide (1/2), C14H10O4S·2C18H15OP, comprises two mol-ecules of 2,2'-thiodi-benzoic acid [TDBA; systematic name: 2-[(2-carb-oxy-phen-yl)sulfan-yl]benzoic acid] and four mol-ecules of tri-phenyl-phosphane oxide [TPPO; systematic name: (di-phenyl-phosphor-yl)benzene]. The two TDBA mol-ecules are twisted about their di-sulfide bonds and exhibit dihedral angles of 74.40?(5) and 72.58?(5)° between the planes through the two SC6H4 residues. The carb-oxy-lic acid groups are tilted out of the planes of the rings to which they are attached forming a range of CO2/C6 dihedral angles of 19.87?(6)-60.43?(8)°. Minor conformational changes are exhibited in the TPPO mol-ecules with the range of dihedral angles between phenyl rings being -2.1?(1) to -62.8?(1)°. In the mol-ecular packing, each TDBA acid mol-ecule bridges two TPPO mol-ecules via hy-droxy-O-H?O(oxide) hydrogen bonds to form two three-mol-ecule aggregates. These are connected into a three-dimensional architecture by TPPO-C-H?O(oxide, carbon-yl) and TDBA-C-H?(oxide, carbon-yl) inter-actions. The importance of H?H, O?H/H?O and C?H/H?C contacts to the calculated Hirshfeld surfaces has been demonstrated. In terms of individual mol-ecules, O?H/H?O contacts are more important for the TDBA (ca 28%) than for the TPPO mol-ecules (ca 13%), as expected from the chemical composition of these species. Computational chemistry indicates the four independent hy-droxy-O-H?O(oxide) hydrogen bonds in the crystal impart about the same energy (ca 52?kJ?mol-1), with DTBA-phenyl-C-H?O(oxide) inter-actions being next most stabilizing (ca 40?kJ?mol-1).
Project description:The first plasma-assisted immobilization of an organocatalyst, namely a bifunctional phosphonium salt in an amorphous hydrogenated carbon coating, is reported. This method makes the requirement for prefunctionalized supports redundant. The immobilized catalyst was characterized by solid-state 13 C and 31 P?NMR spectroscopy, SEM, and energy-dispersive X-ray spectroscopy. The immobilized catalyst (1?mol?%) was employed in the synthesis of cyclic carbonates from epoxides and CO2 . Notably, the efficiency of the plasma-treated catalyst on SiO2 was higher than those of the SiO2 support impregnated with the catalyst and even the homogeneous counterpart. After optimization of the reaction conditions, 13 terminal and four internal epoxides were converted with CO2 to the respective cyclic carbonates in yields of up to 99?%. Furthermore, the possibility to recycle the immobilized catalyst was evaluated. Even though the catalyst could be reused, the yields gradually decreased from the third run. However, this is the first example of the recycling of a plasma-immobilized catalyst, which opens new possibilities in the recovery and reuse of catalysts.