Ti(III)-Catalyzed Anti-Markovnikov Reduction of Epoxides with Borohydride.

We have developed a Ti catalyst that carries out the anti-Markovnikov reduction of a wide range of epoxides; [BH] is used as both the electron and the hydrogen atom source. It requires only mild conditions and accommodates a broad range of epoxide substrates. The Ti catalyst is readily available and is environmentally friendly.

Hydrogen Atom Transfer (HAT)-Mediated Remote Desaturation Enabled by Fe/Cr-H Cooperative Catalysis.

An iron/chromium system (Fe(OAc), CpCr(CO)H) catalyzes the preparation of β,γ- or -unsaturated amides from 1,4,2-dioxazol-5-ones. An acyl nitrenoid iron complex seems likely to be responsible for C-H activation. A cascade of three H• transfer steps appears to be involved: (i) the abstraction of H• from a remote C-H bond by the nitrenoid N, (ii) the transfer of H• from Cr to N, and (iii) the abstraction of H• from a radical substituent by the Cr•.

Cooperative Fe/Co-Catalyzed Remote Desaturation for the Synthesis of Unsaturated Amide Derivatives.

Unsaturated amides represent common functional groups found in natural products and bioactive molecules and serve as versatile synthetic building blocks. Here, we report an iron(II)/cobalt(II) dual catalytic system for the syntheses of distally unsaturated amide derivatives. The transformation proceeds through an iron nitrenoid-mediated 1,5-hydrogen atom transfer (1,5-HAT) mechanism.

Kinetics of H· Transfer from CpCr(CO)H to Various Enamides: Application to Construction of Pyrrolidines.

The rate constants () have been determined at 27 °C for H· (D·) transfer from CpCr(CO)H(D) to the C=C bonds of various enamides. This process leads to the formation of α-amino radicals. Vinyl enamides with -alkyl and -phenyl substituents have proven to be good H· acceptors, with rate constants close to those of styrene and methyl methacrylate.

Isomerization of Aziridines to Allyl Amines via Titanium and Chromium Cooperative Catalysis.

A Ti/Cr cooperative catalyst isomerizes aziridines to allyl amines under mild conditions. The reaction tolerates a broad range of aziridines with various nitrogen substituents. The titanium catalyst is most successful in opening 1,2-disubstituted aziridines, forming radical intermediates in a highly regioselective manner.

Generation of α-Boryl Radicals by H Transfer and their Use in Cycloisomerizations.

Carbon-centered radicals can be stabilized by delocalization of their spin density into the vacant p orbital of a boron substituent. α-Vinyl boronates, in particular pinacol (Bpin) derivatives, are excellent hydrogen atom acceptors. Under H , in the presence of a cobaloxime catalyst, they generate α-boryl radicals; these species can undergo 5-exo radical cyclizations if appropriate double bond acceptors are present, leading to densely functionalized heterocycles with tertiary substituents on Bpin.

Highly Selective Hydrogenation of C═C Bonds Catalyzed by a Rhodium Hydride.

Under mild conditions (room temperature, 80 psi of H) Cp*Rh(2-(2-pyridyl)phenyl)H catalyzes the selective hydrogenation of the C═C bond in α,β-unsaturated carbonyl compounds, including natural product precursors with bulky substituents in the β position and substrates possessing an array of additional functional groups. It also catalyzes the hydrogenation of many isolated double bonds. Mechanistic studies reveal that no radical intermediates are involved, and the catalyst appears to be homogeneous, thereby affording important complementarity to existing protocols for similar hydrogenation processes.

Catalytic Cycloisomerization onto a Carbonyl Oxygen.

We have found that terminal -vinylindoles bearing cycloalkanone substituents are excellent hydrogen atom acceptors, generating α-aminyl radicals with a variety of catalysts (Co(II)/H or Co(III)Cl precatalysts with silane reductants). These radicals can be converted to internal vinylindoles but eventually add to the oxygen of the cycloalkanone substituents. These cyclizations eventually furnish a densely functionalized dihydrofuran (a net cycloisomerization).

H· Transfer-Initiated Synthesis of -Lactams: Interpretation of Cycloisomerization and Hydrogenation Ratios.

A cobaloxime/H system used to synthesize valuable -lactams from acrylamide molecules is described. In addition to cycloisomerized lactams, linear hydrogenated products were also observed. The amounts of the hydrogenation product were observed to correlate with the bulk of the substituent on the acrylamide nitrogen.

TEMPO-Mediated Catalysis of the Sterically Hindered Hydrogen Atom Transfer Reaction between (CPh)Cr(CO)H and a Trityl Radical.

We have demonstrated the ability of TEMPO to catalyze H· transfer from (CPh)Cr(CO)H to a trityl radical (tris( p- tert-butylphenyl)methyl radical). We have measured the rate constant and activation parameters for the direct reaction, and for each step in the catalytic process: H· transfer from (CPh)Cr(CO)H to TEMPO and H· transfer from TEMPO-H to the trityl radical. We have compared the measured rate constants with the differences in bond strength, and with the changes in the Global Electrophilicity Index determined with high accuracy for each radical using state of the art quantum chemical methods.

Insertion of Isonitriles into the M-C Bonds of Group 4 Dialkyl Complexes.

The 2,3-dimethylbutadiene complexes of Group 4 metals with constrained geometry (cg) ligands have been prepared and found to adopt a supine orientation with σ,π bonding. Treatment of cgTi(2,3-dimethylbutadiene) (1-Ti) with BuNC leads to the formation of a titana-aziridine (3) with a coordinated cyclopentenimine that arises from the formal [4+1] addition of the diene to the isonitrile. In contrast, the reactions of cgZr(2,3-dimethylbutadiene) (1-Zr) or cgHf(2,3-dimethylbutadiene) (1-Hf) with 2 equiv of BuNC or XyNC proceeded in a more sophisticated manner to yield unsymmetrical 2,5-diazametallacyclopentane derivatives (4, 6-Zr, and 6-Hf) or symmetrical 2,5-diazametallacyclopentene complexes (7-Zr and 7-Hf).

Catalysis of Radical Cyclizations from Alkyl Iodides under H: Evidence for Electron Transfer from [CpV(CO)H].

Radical cyclizations are most often achieved with BuSnH in the presence of a radical initiator, but environmental considerations demand that alternative reagents be developed-ones that can serve as a synthetic equivalent to the hydrogen atom. We have revisited [CpV(CO)H], a known replacement for BuSnH, and found that it can be used catalytically under H in the presence of a base. We have carried out tin-free catalytic radical cyclizations of alkyl iodide substrates.

Cationic Copper Hydride Clusters Arising from Oxidation of (PhP)CuH.

Transfer of the first electron from (PhP)CuH to Cp*Fe is fast (k > 10 L·mol·s). Transfer of a second electron to the same oxidant has a much lower thermodynamic driving force and is considerably slower, with k = 9.29(4) × 10 L·mol·s.

Radical Isomerization and Cycloisomerization Initiated by H• Transfer.

Under H2 pressure, Co(II)(dmgBF2)2L2 (L = H2O, THF) generates a low concentration of an H• donor. Transfer of the H• onto an olefin gives a radical that can either (1) transfer an H• back to the metal, generating an isomerized olefin, or (2) add intramolecularly to a double bond, generating a cyclized radical. Transfer of an H• back to the metal from the cyclized radical results in a cycloisomerization.

Transition-Metal Hydride Radical Cations.

Transition-metal hydride radical cations (TMHRCs) are involved in a variety of chemical and biochemical reactions, making a more thorough understanding of their properties essential for explaining observed reactivity and for the eventual development of new applications. Generally, these species may be treated as the ones formed by one-electron oxidation of diamagnetic analogues that are neutral or cationic. Despite the importance of TMHRCs, the generally sensitive nature of these complexes has hindered their development.

Direct generation of oxygen-stabilized radicals by H• transfer from transition metal hydrides.

Transition-metal hydrides generate α-alkoxy radicals by H• transfer to enol ethers. We have measured the rate constant for transfer from CpCr(CO)3H to n-butyl vinyl ether and have examined the chemistry of radicals generated by such transfers. Radicals from appropriate substrates undergo 5-exo cyclization, with higher diastereoselectivity than the analogous all-carbon radicals.

The reaction of cobaloximes with hydrogen: products and thermodynamics.

A cobalt hydride has been proposed as an intermediate in many reactions of the Co(dmgBF2)2L2 system, but its observation has proven difficult. We have observed the UV-vis spectra of Co(dmgBF2)2L2 (1) in CH3CN under hydrogen pressures of up to 70 atm. A Co(I) compound (6a) with an exchangeable proton is eventually formed.

Dihydrogen activation by cobaloximes with various axial ligands.

We have investigated the effect of axial ligands on the ability of cobaloximes to catalyze the generation of transferable hydrogen atoms from hydrogen gas and have learned that the active catalyst contains one and only one axial ligand. We have, for example, shown that Co(dmgBF2)2 coordinates only one Ph3P and that the addition of additional Ph3P (beyond 1 equiv) to solvated Co(dmgBF2)2 does not affect its catalytic turnover for H• transfer from H2.

Kinetics and thermodynamics of H-/H•/H+ transfer from a rhodium(III) hydride.

The thermodynamics and kinetics of all three cleavage modes for Rh-H, the transfer of H(-), H(+), or H•, have been studied for the Rh(III) hydride complex Cp*Rh(2-(2-pyridyl)phenyl)H (1a). The thermodynamic hydricity, ΔG°H(-), for 1a has been measured (49.5(1) kcal/mol) by heterolytic cleavage of H2 with Et3N in CH3CN.

Effect of double-bond substituents on the rate of cyclization of α-carbomethoxyhex-5-enyl radicals.

Rate constants have been calculated, and compared with experimental results, for the cyclizations of 1-carbomethoxy-1-methyl-5-hexenyl radicals (2) with various substituents on C6. The calculations have been done by DFT at the B3LYP/6-311++G** level of theory. They show considerable interaction between C5 and the radical centers even in the ground state of all of the radicals 2.

Electron transfer from hexameric copper hydrides.

The octahedral core of 84-electron LCuH hexamers does not dissociate appreciably in solution, although their hydride ligands undergo rapid intramolecular rearrangement. The single-electron transfer proposed as an initial step in the reaction of these hexamers with certain substrates has been observed by stopped-flow techniques when [(Ph3P)CuH]6 is treated with a pyridinium cation. The same radical cation has been prepared by the oxidation of [(Ph3P)CuH]6 with Cp*2Fe(+) and its reversible formation observed by cyclic voltammetry; its UV-vis spectrum has been confirmed by spectroelectrochemistry.

Mechanisms by which alkynes react with CpCr(CO)3H. Application to radical cyclization.

The reaction of CpCr(CO)(3)H with activated alkynes in benzene has been examined. The kinetics of these reactions have been studied with various alkynes, along with the stereochemistry with which the alkynes are hydrogenated. The hydrogenation of phenyl acetylene and diphenyl acetylene with CpCr(CO)(3)H has been shown to occur by a hydrogen atom transfer (HAT) mechanism.

Evidence for formation of a Co-H bond from (H2O)2Co(dmgBF2)2 under H2: application to radical cyclizations.

Under H(2), the radical cyclization of appropriate dienes can be catalyzed by cobaloximes. H• can be abstracted from an intermediate (presumably a cobalt hydride) by trityl radicals (Ar(3)C•) or by TEMPO. The rate-determining step in these reactions is the uptake of H(2), which is second order in cobalt and first order in hydrogen; the third-order rate constant is 106(3) M(-2)·s(-1).