General Synthesis of Conformationally Constrained Noncanonical Amino Acids with C()-Rich Benzene Bioisosteres.

Recent years have seen novel modalities emerge for the treatment of human diseases resulting in an increase in beyond rule of 5 (bRo5) chemical matter. As a result, synthetic innovations aiming to enable rapid access to complex bRo5 molecular entities have become increasingly valuable for medicinal chemists' toolkits. Herein, we report the general synthesis of a new class of noncanonical amino acids (ncAA) with a cyclopropyl backbone to achieve conformational constraint and bearing C()-rich benzene bioisosteres.

Scaffold hopping by net photochemical carbon deletion of azaarenes.

Discovery chemists routinely identify purpose-tailored molecules through an iterative structural optimization approach, but the preparation of each successive candidate in a compound series can rarely be conducted in a manner matching their thought process. This is because many of the necessary chemical transformations required to modify compound cores in a straightforward fashion are not applicable in complex contexts. We report a method that addresses one facet of this problem by allowing chemists to hop directly between chemically distinct heteroaromatic scaffolds.

Thermodynamic and kinetic studies of H and N binding to bimetallic nickel-group 13 complexes and neutron structure of a Ni(η-H) adduct.

Understanding H binding and activation is important in the context of designing transition metal catalysts for many processes, including hydrogenation and the interconversion of H with protons and electrons. This work reports the first thermodynamic and kinetic H binding studies for an isostructural series of first-row metal complexes: NiML, where M = Al (), Ga (), and In (), and L = [N(-(NCHPPr)CH)]. Thermodynamic free energies (Δ°) and free energies of activation (Δ ) for binding equilibria were obtained variable-temperature P NMR studies and lineshape analysis.

Changing the Mechanism for CO Hydrogenation Using Solvent-Dependent Thermodynamics.

A critical scientific challenge for utilization of CO is the development of catalyst systems that function in water and use inexpensive and environmentally friendly reagents. We have used thermodynamic insights to predict and demonstrate that the HCo (dmpe) catalyst system, previously described for use in organic solvents, can hydrogenate CO to formate in water with bicarbonate as the only added reagent. Replacing tetrahydrofuran as the solvent with water changes the mechanism for catalysis by altering the thermodynamics for hydride transfer to CO from a key dihydride intermediate.

A Bimetallic Nickel-Gallium Complex Catalyzes CO Hydrogenation via the Intermediacy of an Anionic d Nickel Hydride.

Large-scale CO hydrogenation could offer a renewable stream of industrially important C chemicals while reducing CO emissions. Critical to this opportunity is the requirement for inexpensive catalysts based on earth-abundant metals instead of precious metals. We report a nickel-gallium complex featuring a Ni(0)→Ga(III) bond that shows remarkable catalytic activity for hydrogenating CO to formate at ambient temperature (3150 turnovers, turnover frequency = 9700 h), compared with prior homogeneous Ni-centered catalysts.

Detection of an Iridium-Dihydrogen Complex: A Proposed Intermediate in Ionic Hydrogenation.

Addition of high pressures of H to five-coordinate [(POCOP)Ir(CO)(H)]OTf [(POCOP) = κ-CH-2,6-(OP(Bu))] complexes results in observation of two new iridium-dihydrogen complexes. If the aryl moiety of the POCOP ligand is substituted with an electron withdrawing protonated dimethylamino group at the para position, hydrogen coordination is enhanced. Five-coordinate Ir-H complexes generated by addition of triflic acid to (POCOP)Ir(CO) species show an Ir-H H NMR chemical shift dependence on the number of equivalents of acid present.

Hydrogenation of CO at Room Temperature and Low Pressure with a Cobalt Tetraphosphine Catalyst.

Large-scale implementation of carbon neutral energy sources such as solar and wind will require the development of energy storage mechanisms. The hydrogenation of CO into formic acid or methanol could function as a means to store energy in a chemical bond. The catalyst reported here operates under low pressure, at room temperature, and in the presence of a base much milder (7 pK units lower) than the previously reported CO hydrogenation catalyst, Co(dmpe)H.

Improved Catalytic Activity and Stability of a Palladium Pincer Complex by Incorporation into a Metal-Organic Framework.

A porous metal-organic framework Zr6O4(OH)4(L-PdX)3 (1-X) has been constructed from Pd diphosphinite pincer complexes ([L-PdX](4-) = [(2,6-(OPAr2)2C6H3)PdX](4-), Ar = p-C6H4CO2(-), X = Cl, I). Reaction of 1-X with PhI(O2CCF3)2 facilitates I(-)/CF3CO2(-) ligand exchange to generate 1-TFA and I2 as a soluble byproduct. 1-TFA is an active and recyclable catalyst for transfer hydrogenation of benzaldehydes using formic acid as a hydrogen source.

1,2-Addition of dihydrogen across rhodium(III)-OMe bonds.

The Rh(III) complexes [((t)bpy)2Rh(OMe)(L)][X]n ((t)bpy = 4,4'-di-tert-butyl-2,2'-bipyridyl; L = MeOH, n = 2, X = OTf (OTf = trifluoromethanesulfonate), TFA (TFA = trifluoroacetate); L = TFA, n = 1, X = OTf) have been shown to activate dihydrogen via net 1,2-addition of the H-H bond across the Rh(III)-OMe bond. The bis(methoxide) complex [((t)bpy)2Rh(OMe)2][OTf] was synthesized by addition of CsOH·H2O in methanol to [((t)bpy)2Rh(OTf)2][OTf] in CH3CN. The addition of HTFA to [((t)bpy)2Rh(OMe)2][OTf] leads to the formation of [((t)bpy)2Rh(OMe)(MeOH)][OTf][TFA], which exists in equilibrium with [((t)bpy)2Rh(OMe)(TFA)][OTf].

Activation of carbon-hydrogen bonds and dihydrogen by 1,2-CH-addition across metal-heteroatom bonds.

The controlled conversion of hydrocarbons to functionalized products requires selective C-H bond cleavage. This perspective provides an overview of 1,2-CH-addition of hydrocarbons across d(0) transition metal imido complexes and compares and contrasts these to examples of analogous reactions that involve later transition metal amide, hydroxide and alkoxide complexes with d(6) and d(8) metals.