cis-Selective Hydrogenation of Aryl Germanes: A Direct Approach to Access Saturated Carbo- and Heterocyclic Germanes.

A catalytic approach of synthesizing the cis-selective saturated carbo- and heterocyclic germanium compounds (3D framework) is reported via the hydrogenation of readily accessible aromatic germanes (2D framework). Among the numerous catalysts tested, Nishimura's catalyst (Rh2O3/PtO2·H2O) exhibited the best hydrogenation reactivity with an isolated yield of up to 96%. A broad range of substrates including the synthesis of unprecedented saturated heterocyclic germanes was explored. This selective hydrogenation strategy could tolerate several functional groups such as -CF3, -OR, -F, -Bpin, and -SiR3 groups. The synthesized products demonstrated the applications in coupling reactions including the newly developed strategy of aza-Giese-type addition reaction (C-N bond formation) from the saturated cyclic germane product. These versatile motifs can have a substantial value in organic synthesis and medicinal chemistry as they show orthogonal reactivity in coupling reactions while competing with other coupling partners such as boranes or silanes, acquiring a three-dimensional structure with high stability and robustness.

Access to Unexplored 3D Chemical Space: cis-Selective Arene Hydrogenation for the Synthesis of Saturated Cyclic Boronic Acids.

A new class of saturated boron-incorporated cyclic molecules has been synthesized employing an arene-hydrogenation methodology. cis-Selective hydrogenation of easily accessible, and biologically important molecules comprising benzoxaborole, benzoxaborinin, and benzoxaboripin derivatives is reported. Among the various catalysts tested, rhodium cyclic(alkyl)(amino)carbene [Rh-CAAC] (1) pre-catalyst revealed the best hydrogenation activity confirming turnover number up to 1400 with good to high diastereoselectivity. A broad range of functional groups was tolerated including sensitive substituents such as -F, -CF3 , and -silyl groups. The utility of the synthesized products was demonstrated by the recognition of diols and sugars under physiological conditions. These motifs can have a substantial importance in medicinal chemistry as they possess a three-dimensional structure, are highly stable, soluble in water, form hydrogen bonds, and interact with diols and sugars.

Acceptorless Dehydrogenation of Methanol to Carbon Monoxide and Hydrogen using Molecular Catalysts.

The acceptorless dehydrogenation of methanol to carbon monoxide and hydrogen was investigated using homogeneous molecular complexes. Complexes of ruthenium and manganese comprising the MACHO ligand framework showed promising activities for this reaction. The molecular ruthenium complex [RuH(CO)(BH4 )(HN(C2 H4 PPh2 )2 )] (Ru-MACHO-BH) achieved up to 3150 turnovers for carbon monoxide and 9230 turnovers for hydrogen formation at 150 °C reaching pressures up to 12 bar when the decomposition was carried out in a closed vessel. Control experiments affirmed that the metal complex mediates the initial fast dehydrogenation of methanol to formaldehyde and methyl formate followed by subsequent slow decarbonylation. Depending on the catalyst and reaction conditions, the CO/H2 ratio in the gas mixture thus varies over a broad range from almost pure hydrogen to the stoichiometric limit of 1:2.

Manganese(I)-Catalyzed ß-Methylation of Alcohols Using Methanol as C1 Source.

Highly selective ß-methylation of alcohols was achieved using an earth-abundant first row transition metal in the air stable molecular manganese complex [Mn(CO)2 Br[HN(C2 H4 Pi Pr2 )2 ]] 1 ([HN(C2 H4 Pi Pr2 )2 ]=MACHO-i Pr). The reaction requires only low loadings of 1 (0.5 mol %), methanolate as base and MeOH as methylation reagent as well as solvent. Various alcohols were ß-methylated with very good selectivity (>99 %) and excellent yield (up to 94 %). Biomass derived aliphatic alcohols and diols were also selectively methylated on the ß-position, opening a pathway to "biohybrid" molecules constructed entirely from non-fossil carbon. Mechanistic studies indicate that the reaction proceeds through a borrowing hydrogen pathway involving metal-ligand cooperation at the Mn-pincer complex. This transformation provides a convenient, economical, and environmentally benign pathway for the selective C-C bond formation with potential applications for the preparation of advanced biofuels, fine chemicals, and biologically active molecules.

Direct Synthesis of Cycloalkanes from Diols and Secondary Alcohols or Ketones Using a Homogeneous Manganese Catalyst.

A method for the synthesis of substituted cycloalkanes was developed using diols and secondary alcohols or ketones via a cascade hydrogen borrowing sequence. A non-noble and air-stable manganese catalyst (2 mol %) was used to perform this transformation. Various substituted 1,5-pentanediols (3-4 equiv) and substituted secondary alcohols (1 equiv) were investigated to prepare a collection of substituted cyclohexanes in a diastereoselective fashion. Similarly, cyclopentane, cyclohexane, and cycloheptane rings were constructed from substituted 1,4-butanediol, 1,5-pentanediol, and 1,6-hexanediol, and sterically hindered ketones following a (4 + 1), (5 + 1), and (6 + 1) strategy, respectively. This reaction provides an atom economic methodology to construct two C-C bonds at a single carbon center generating high-value cycloalkanes from readily available alcohols as feedstock using an earth-abundant metal catalyst.

Catalytic Hydrogenation of Cyclic Carbonates using Manganese Complexes.

Catalytic hydrogenation of cyclic carbonates to diols and methanol was achieved using a molecular catalyst based on earth-abundant manganese. The complex [Mn(CO)2 (Br)[HN(C2 H4 Pi Pr2 )2 ] 1 comprising commercially available MACHO ligand is an effective pre-catalyst operating under relatively mild conditions (T=120 °C, p(H2 )=30-60 bar). Upon activation with NaOt Bu, the formation of coordinatively unsaturated complex [Mn(CO)2 [N(C2 H4 Pi Pr2 )2 )] 5 was spectroscopically verified, which confirmed a kinetically competent intermediate. With the pre-activated complex, turnover numbers up to 620 and 400 were achieved for the formation of the diol and methanol, respectively. Stoichiometric reactions under catalytically relevant conditions provide insight into the stepwise reduction form the CO2 level in carbonates to methanol as final product.

Ruthenium-Catalyzed Selective Hydroboration of Nitriles and Imines.

Ruthenium-catalyzed hydroboration of nitriles and imines is attained using pinacolborane with unprecedented catalytic efficiency. Chemoselective hydroboration of nitriles over esters is also demonstrated. A simple [Ru(p-cymene)Cl2]2 complex (1) is used as a catalyst precursor, which upon reaction with pinacolborane in situ generates the monohydrido-bridged complex [{(η6-p-cymene)RuCl}2(µ-H-µ-Cl)] 2. Further oxidative addition of pinacolborane to intermediate 2 leading to the formation of mononuclear ruthenium hydride species is suggested. Mass spectral analysis of the reaction mixture and independent experiments with phosphine-ligated ruthenium complexes indicated the involvement of mononuclear ruthenium intermediates in the catalytic cycle. Consecutive intramolecular 1,3-hydride transfers from the ruthenium center to coordinated nitrile and boronate imine ligands, leading to the reduction and resulting in the formation of diboronate amines, are proposed as a plausible reaction mechanism.

Alcohol-Assisted Hydrogenation of Carbon Monoxide to Methanol Using Molecular Manganese Catalysts.

Alcohol-assisted hydrogenation of carbon monoxide (CO) to methanol was achieved using homogeneous molecular complexes. The molecular manganese complex [Mn(CO)2Br[HN(C2H4P i Pr2)2]] ([HN(C2H4P i Pr2)2] = MACHO- i Pr) revealed the best performance, reaching up to turnover number = 4023 and turnover frequency 857 h-1 in EtOH/toluene as solvent under optimized conditions (T = 150 °C, p(CO/H2) = 5/50 bar, t = 8-12 h). Control experiments affirmed that the reaction proceeds via formate ester as the intermediate, whereby a catalytic amount of base was found to be sufficient to mediate its formation from CO and the alcohol in situ. Selectivity for methanol formation reached >99% with no accumulation of the formate ester. The reaction was demonstrated to work with methanol as the alcohol component, resulting in a reactive system that allows catalytic "breeding" of methanol without any coreagents.

Carbon monoxide and hydrogen (syngas) as a C1-building block for selective catalytic methylation.

A catalytic reaction using syngas (CO/H2) as feedstock for the selective ß-methylation of alcohols was developed whereby carbon monoxide acts as a C1 source and hydrogen gas as a reducing agent. The overall transformation occurs through an intricate network of metal-catalyzed and base-mediated reactions. The molecular complex [Mn(CO)2Br[HN(C2H4P i Pr2)2]] 1 comprising earth-abundant manganese acts as the metal component in the catalytic system enabling the generation of formaldehyde from syngas in a synthetically useful reaction. This new syngas conversion opens pathways to install methyl branches at sp3 carbon centers utilizing renewable feedstocks and energy for the synthesis of biologically active compounds, fine chemicals, and advanced biofuels.

Manganese-catalyzed hydroboration of carbon dioxide and other challenging carbonyl groups.

Reductive functionalization of the C=O unit in carboxylic acids, carbonic acid derivatives, and ultimately in carbon dioxide itself is a challenging task of key importance for the synthesis of value-added chemicals. In particular, it can open novel pathways for the valorization of non-fossil feedstocks. Catalysts based on earth-abundant, cheap, and benign metals would greatly contribute to the development of sustainable synthetic processes derived from this concept. Herein, a manganese pincer complex [Mn(Ph2PCH2SiMe2)2NH(CO)2Br] (1) is reported to enable the reduction of a broad range of carboxylic acids, carbonates, and even CO2 using pinacolborane as reducing agent. The complex is shown to operate under mild reaction conditions (80-120 °C), low catalyst loadings (0.1-0.2 mol%) and runs under solvent-less conditions. Mechanistic studies including crystallographic characterisation of a borane adduct of the pincer complex (1) imply that metal-ligand cooperation facilitates substrate activation.

Ruthenium-Catalyzed Regioselective 1,4-Hydroboration of Pyridines.

Simple ruthenium precursor [Ru(p-cymene)Cl2]2 1 catalyzed regioselective 1,4-dearomatization of pyridine derivatives using pinacolborane is reported. Two catalytic intermediates, [Ru(p-cymene)Cl2Py] 2 and [Ru(p-cymene)Cl2(P(Cy)3)] 3, involved in this process are identified, independently synthesized, characterized, and further used directly as effective catalysts; two more catalytic intermediates [Ru(p-cymene)Cl2(Py)(P(Cy)3)] 4 and [Ru(p-cymene)(H)Cl(Py)(P(Cy)3)] 5 are identified in solution. Complex 5 is the active catalytic intermediate. An intramolecular selective 1,5-hydride transfer in 5 leading to the regioselective 1,4-hydroboration of pyridine compounds is proposed.

Ruthenium Catalyzed Selective Hydroboration of Carbonyl Compounds.

Using the [Ru(p-cymene)Cl2]2 (1) complex, catalytic hydroboration of aldehydes and ketones with pinacolborane under neat and mild conditions is reported. At rt, chemoselective hydroboration of aldehydes over the ketones is also attained. Mechanistic studies confirmed the immediate formation of monohydride bridged dinuclear complex [{(η(6)-p-cymene)RuCl}2(µ-H-µ-Cl)] (1b) from the reaction of 1 with pinacolborane, which catalyzed the highly efficient hydroboration reactions. The catalytic cycle containing mononuclear Ru-H species and intramolecular 1,3-hydride transfer is postulated.