Review

Applications of Acceptorless Dehydrogenation and Related Transformations in Chemical Synthesis

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Science  19 Jul 2013:
Vol. 341, Issue 6143, 1229712
DOI: 10.1126/science.1229712

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Structured Abstract

Background

Acceptorless dehydrogenation (AD) reactions can result not only in simple removal of hydrogen gas from various substrates but also, importantly, in surprisingly efficient and environmentally benign (“green”) synthetic methodologies when intermediates resulting from the initial dehydrogenation process undergo further reactions.

Advances

Traditionally, dehydrogenation/oxidation reactions of organic compounds have been performed using stoichiometric amounts of inorganic oxidants, in addition to employing various additives, cocatalysts, and catalytic systems that result in generation of copious stoichiometric, often toxic, waste. Catalytic transfer hydrogenation methods, in which stoichiometric amounts of sacrificial organic acceptor compounds are used, also generate stoichiometric amounts of organic waste. Recent developments in catalysis by metal complexes have resulted in acceptorless dehydrogenation reactions that release hydrogen gas and in related reactions in which dehydrogenation is followed by in situ consumption of the generated hydrogen equivalents and no net hydrogen gas is liberated. These reactions circumvent the need for conventional oxidants or sacrificial acceptors and provide an assortment of applications in organic synthesis, including several methods based on further reactivity of the dehydrogenated intermediate compounds. Moreover, the evolved hydrogen gas is valuable in itself.

Outlook

Further development of new ADs for green, efficient chemical synthesis is expected to be greatly influenced by fundamental organometallic chemistry as a basis for catalyst design. Such processes are highly desirable and are expected to gradually displace elaborate conventional laboratory and industrial synthetic methods. They may also provide opportunities for hydrogen storage cycles, because the dehydrogenation reactions can be reversed under hydrogen pressure using the same catalyst. In general, AD and related dehydrogenative coupling reactions have the potential for redirecting synthetic strategies to the use of sustainable resources, devoid of toxic reagents and deleterious side reactions, with no waste generation.

Embedded Image

Dehydrogenation strategies in organic synthesis. (A) Successive AD with release of hydrogen gas. The catalyst liberates H2 from both starting compound and intermediate, exemplified by dehydrogenative coupling of primary alcohols with amines to form amides. (B) AD with H2 and water release. A dehydrogenated intermediate couples with nucleophiles, exemplified by dehydrogenative coupling of alcohols with amines (liberating water) to form imines that can be isolated or carried on to products such as pyrazines. (C) Borrowing hydrogen. The catalyst dehydrogenates the substrate and formally transfers the H atoms to an unsaturated intermediate, exemplified by coupling of ammonia or amines with alcohols to form new amines, liberating water, but not H2. (D) Coupling of redox pairs. Dehydrogenation generates an electrophile and a nucleophile that react to form C−C bonds. Neither H2 nor water is evolved.

Setting Hydrogen Free

Oxidation of organic compounds has traditionally been considered to involve the transfer of hydrogen atoms in the molecular framework to an oxidant such as O2, peroxide, or a metal oxide complex. Gunanathan and Milstein (p. 1229712) review the ongoing development of an alternative process, in which a catalyst coaxes the H atoms to depart on their own in the form of H2. These acceptorless dehydrogenations are appealing because they generate so little waste. In one class of reactions, the liberated H2 gas is actively expelled from the reaction mixture and collected for potential use elsewhere. In another class, the H atoms return to the source molecule after it has undergone an intermediate transformation in their absence.

Abstract

Conventional oxidations of organic compounds formally transfer hydrogen atoms from the substrate to an acceptor molecule such as oxygen, a metal oxide, or a sacrificial olefin. In acceptorless dehydrogenation (AD) reactions, catalytic scission of C−H, N−H, and/or O−H bonds liberates hydrogen gas with no need for a stoichiometric oxidant, thereby providing efficient, nonpolluting activation of substrates. In addition, the hydrogen gas is valuable in itself as a high-energy, clean fuel. Here, we review AD reactions selectively catalyzed by transition metal complexes, as well as related transformations that rely on intermediates derived from reversible dehydrogenation. We delineate the methodologies evolving from this recent concept and highlight the effect of these reactions on chemical synthesis.

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