We introduce iridium-based conditions for the conversion of primary alcohols to potassium carboxylates (or carboxylic acids) in the presence of potassium hydroxide and either [Ir(2-PyCH2(C4H5N2))(COD)]OTf (1) or [Ir(2-PyCH2PBu2t)(COD)]OTf (2). The method provides both aliphatic and benzylic carboxylates in high yield and with outstanding functional group tolerance. We illustrate the application of this method to a diverse variety of primary alcohols, including those involving heterocycles and even free amines. Complex 2 reacts with alcohols to form crystallographically-characterized catalytic intermediates [IrH(η1,η3-C8H12)(2-PyCH2PtBu2)] (2a) and [Ir2H3(CO)(2-PyCH2PtBu2){μ-(C5H3N)CH2PtBu2}] (2c). The unexpected similarities in reactivities of 1 and 2 in this reaction, along with synthetic studies on several of our iridium intermediates, enable us to form a general proposal of the mechanisms of catalyst activation that govern the disparate reactivities of 1 and 2, respectively in glycerol and formic acid dehydrogenation. Moreover, careful analysis of the organic intermediates in the oxidation sequence enable new insights into the role of Tishchenko and Cannizzaro reactions in the overall oxidation.

Selective hydrogen transfer remains a central research focus in catalysis: hydrogenation and dehydrogenation have central roles, both historical and contemporary, in all aspects of fuel, agricultural, pharmaceutical, and fine chemical synthesis. Our lab has been involved in this area by designing homogeneous catalysts for dehydrogenation and hydrogen transfer that fill needs ranging from on-demand hydrogen storage to fine chemical synthesis. A keen eye toward mechanism has enabled us to develop systems with excellent selectivity and longevity and demonstrate these in a diversity of high-value applications. Here we describe recent work from our lab in these areas that are linked by a central mechanistic trichotomy of catalyst initiation pathways that lead highly analogous precursors to a diversity of useful applications.

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We describe the mechanism, scope, and catalyst evolution for our ruthenium-based coupling of amines and alcohols, which proceeds from a [(η6-cymene)­RuCl­(PyCH2P t Bu2)]­OTf (1) precatalyst. The method selectively produces secondary amines through a hydrogen borrowing mechanism and is successfully applied to several heterocyclic carbinol substrates. Under the reaction conditions, precatalyst 1 evolves through a series of catalytic intermediates: [(η6-cymene)­RuH­(PyCH2P t Bu2)]­OTf (3), [Ru3H2Cl2(CO)­(PyCH2P t Bu2)2{μ-(C5H3N)­CH2P t Bu2}]­OTf (4), and a diastereomeric pair of [Ru2HCl­(CO)2(PyCH2P t Bu2)2(μ-O2C n Pr)]­X (trans-5, X = Cl; cis-6, X = OTf). The structures of 4 and 6 were established by single-crystal X-ray diffraction. A study of catalytic activity shows that 4 is a dormant (but alive) form of the catalyst, whereas 5 and 6 are the ultimate dead forms. Electrochemical studies show that 4 is redox active and undergoes electrochemically reversible one-electron oxidation at E 1/2 = 0.442 V (vs Fc+/Fc) in CH2Cl2 solution. We discuss the factors that govern the formation of 3–6 and the role of selective ruthenium carbonylation, which is essential for enabling generation of the active catalyst. We also connect these discoveries to the identification of conditions for amination of aliphatic alcohols, which eluded us until we understood the catalyst’s complex speciation behavior.

We report a pyridyl-phosphine ruthenium­(II) catalyzed tandem alcohol amination/Pictet–Spengler reaction sequence to synthesize tetrahydro-β-carbolines from an alcohol and tryptamine. Our conditions use a Lewis acid cocatalyst, In­(OTf)3, that is compatible with typically base catalyzed amination and an acid catalyzed Pictet–Spengler cyclization. This method proceeds well with benzylic alcohols, heterocyclic carbinols, and aliphatic alcohols. We also show how combining this reaction with a subsequent cycloamination enables a direct synthesis of tetracyclic alkaloids like harmicine.