Broadening the synthetic organic applications of Frustrated Lewis Pairs

Abstract

Interactions between hindered Lewis acids and Lewis bases result in well-known frustrated Lewis pair behavior. Recent research has tended to concentrate on very hindered systems, resulting in high levels of activation, but not necessarily reactivity. In this article, we review the state-of-the-art and try to identify how FLP chemistry may develop further to give a wider range of applicable catalytic reactions, i.e. through softening both Lewis acid and base strengths, reducing hindrance and by controlling associative processes through tether length and dynamic effects.

A Bifunctional B,N‐Based Asymmetric Catalytic Nitrostyrene‐Michael Addition Acting through a 10‐Membered Ring Cyclic Transition State

“…The application of catalysts involving B,N‐bifunctional catalysts in asymmetric synthesis is still in its infancy, perhaps due to the challenges of accessing suitable catalysts that allow both the Lewis ‐acidic and Lewis ‐basic functions to behave cooperatively without either self‐interaction causing deactivation, or without creating catalysts which are difficult to prepare and use [12] . Homoboroproline‐based B,N‐bifunctional catalysts based around 1 do show early utility in both aldol reactions, [9–11] and reported herein, nitro‐ Michael asymmetric additions involving an enolate equivalent (enamine) nucleophile.…”

“…The application of catalysts involving B,N-bifunctional catalysts in asymmetric synthesis is still in its infancy, perhaps due to the challenges of accessing suitable catalysts that allow both the Lewis-acidic and Lewisbasic functions to behave cooperatively without either self-interaction causing deactivation, or without creating catalysts which are difficult to prepare and use. [12] Homoboroproline-based B,N-bifunctional catalysts based around 1 do show early utility in both aldol reactions, [9 -11] and reported herein, nitro-Michael asymmetric additions involving an enolate equivalent (enamine) nucleophile. Although asymmetric induction is moderate to good, our initial envisaged asymmetric nucleophilic addition mode seems to borne out in practice, and in fact, through Lewis-acidity tuning of the boronate function, one can generate in situ (through diol esterification of the boronic acid moiety) a highly efficient enamine-generating catalyst.…”

“…Hence, the design of the catalyst, including the relative Lewis acidity and basicity of the boronate amino functions respectively, and their relative arrangements are crucial to efficient catalytic processes. [9][10][11] Hence, by avoiding the extreme levels of activation represented by frustrated Lewis pair systems, [12] less reactive aminoboronate-derived bifunctional catalysts provide the potential for more subtle and tuneable catalysts to be designed, which in turn, may be applicable to different reactions. [7] Exemplifying this idea in previous work (Scheme 1), we reported the proline-related boronate ester 1 as a proof-of-concept that a B,N-bifunctional asymmetric catalyst system could be developed that employed an enamine-mediated asymmetric aldol reactions, together boronate-mediated Lewis acid activation of a substrate aldehyde.…”

Diverse Uses of the Reaction of Frustrated Lewis Pair (FLP) with Hydrogen

“…At the same time, it is important to note the FLP chemistry has and continues to expand well beyond reactions involving H 2 . Applications in organic synthesis, polymer chemistry and polymerization catalysis , are among the areas garnering attention. Nonetheless, the original finding of metal-free activation of H 2 has and continues to spawn a great deal of useful and interesting science with a range that is well beyond that envisioned 15 years ago.…”

Activation of Small Molecules and Hydrogenation of CO2 Catalyzed by Frustrated Lewis Pairs

“…This ratio can be used as a guiding parameter in designing of FLPs in the future. In recent years, FLPs are being increasingly used in polymerization catalysis [107][108][109], polymer chemistry [110,111], and organic synthesis [112,113] as well.…”