Review

The broadening reach of frustrated Lewis pair chemistry

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Science  09 Dec 2016:
Vol. 354, Issue 6317, aaf7229
DOI: 10.1126/science.aaf7229

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Cooperation between frustrated partners

What might you do with a hat that had so many decorations dangling from the brim that you couldn't put it on? Lewis acids and bases are the molecular versions of hats and heads. Stephan reviews the surprising chemistry of so-called frustrated Lewis pairs (FLPs), which cannot form their natural complex together. Over the past decade, such systems (most often comprising a borane with a nitrogen or phosphorus partner) have been used to catalyze hydrogenation reactions, activate a number of other small molecules, and generally promote a wide range of cooperative chemical reactivity.

Science, this issue p. 10.1126/science.aaf7229

Structured Abstract

BACKGROUND

Since the work of Sabatier 100 year ago, chemists have turned almost exclusively to metals to activate H2 by weakening or cleaving its central bond. This paradigm changed with a 2006 report of a metal-free molecule that reversibly activated H2 across sterically encumbered Lewis acidic boron and Lewis basic phosphorus sites. Shortly thereafter, similar reactions were mediated by systems described as “frustrated Lewis pairs” (FLPs) that were derived from simple combinations of electron donors and acceptors in which steric demands precluded dative bond formation. The variety of such systems has since been expanded to include a wide range of donors and acceptors. Moreover, FLP reactivity has been shown to result when equilibria governing the formation of Lewis acid-base adducts provides access to free acid and base. Mechanistic studies have demonstrated that the FLP activation of H2 proceeds via a mechanism directly analogous to the Piers mechanism for borane-mediated hydrosilylation of ketones, first described in 1996. Nonetheless, the discovery of these metal-free reactions of H2 has prompted considerable interest in this concept and its application to various chemical systems.

ADVANCES

The application of FLP reactivity with H2 to metal-free hydrogenation catalysis rapidly led to reductions of polar substrates. Over the past decade, the range of reducible substrates has been expanded to a variety of unsaturated compounds, including imines, enamines, olefins, polyaromatics, alkynes, ketones, and aldehydes. Efforts have also extended this technology to asymmetric hydrogenations, with a number of recent systems achieving high selectivity.

Early on, it was recognized that the reactivity of FLPs was not limited to H2. FLPs have shown the capacity to capture and react with a variety of small molecules, including olefins, alkynes, CO2, SO2, NO, CO, N2O, and N-sulfinyltolyllamines (p-tol)NSO (p-tol, para-tolyl). This has led to metal-free strategies for CO and CO2 reduction and SO generation and new avenues to transient, persistent, or stable radicals. FLP chemistry has been further extended to new strategies in synthetic organic chemistry, including FLP-mediated approaches to hydroamination, hydroboration, cyclization, and boration reactions.

Because transition metals may also be acidic or basic, the reactivity of FLP systems in which one or both of the constituents are metal centers has been reported. Further, metal components can also be ancillary fragments for ligand-based FLP chemistry, or they can act as a scaffold, allowing the cooperative action of an FLP and a metal center on a substrate. In related developments, the notion of FLPs has been applied to the design of model systems for the active sites of the [Ni-Fe], [Fe-Fe], or [Fe] hydrogenase enzymes.

Reaching beyond main-group and organic chemistry into polymers and materials chemistry, FLP catalysts have been used to prepare lactone-derived polymers, cyanamide oligomers, and Te-containing heterocycles for applications in photoactive materials. In addition, heterogeneous FLP hydrogenation catalysts have emerged, and the concept also provides a new mechanistic perspective on CO2 reduction on the surface of indium oxide nanocrystals.

OUTLOOK

Applications of FLP chemistry to metal-free reductions, asymmetric hydrogenations, C–C bond formation, and C–H bond functionalization are continuing to evolve. Such advances offer strategies for reduced costs and the elimination of toxic contaminants that will undoubtedly garner interest from the synthetic chemistry communities in academia and industry. The expanding range of main-group and transition metal–based FLPs continues to demonstrate the generality of this concept and its broadening utility. However, the innovative synthetic strategies, reactivity, and new perspectives derived from the application of this simple concept to other areas of chemistry are perhaps the most exciting prospect.

A recent paradigm for chemical reactivity, designated “frustrated Lewis pairs,” is based on impeded dative bonding between a Lewis acid and a Lewis base.

For almost 100 years, the combination of electron acceptors (Lewis acids) and electron donors (Lewis bases) has been known to give Lewis acid-base adducts that incorporate donor-acceptor bonds. However, research over the past decade has shown that the introduction of steric demands or a dissociative equilibrium provides access to free donors and acceptors, allowing them to interact with a third molecule and leading to distinct reactivity. This concept has been applied to a broadening range of chemical problems.

Abstract

The revelation that combinations of Lewis acids and bases for which dative bonding is impeded can activate dihydrogen led to the concept of “frustrated Lewis pairs” (FLPs). Over the past decade, a range of FLP systems and substrate molecules have precipitated a paradigm change in main-group chemistry and metal-free catalysis. The FLP motif has also found application in a growing body of chemical problems in organic synthesis, transition metal and free radical chemistry, materials, enzymatic models, and surface chemistry. The current state of FLP chemistry is assessed herein, and the outlook for the future considered.

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