Expanding the Scope of Metal‐Free Catalytic Hydrogenation through Frustrated Lewis Pair Design

Abstract

The further development of the field of catalysis is based on the discovery, understanding, and implementation of novel activation modes that allow unprecedented transformations and open new perspectives in synthetic chemistry. In this context, the recently introduced concept of frustrated Lewis pair (FLP) from the Stephan research group represents a fundamental and novel strategy to develop catalysts based on main-group elements for small-molecule activation.[1] These sterically encumbered Lewis acid-base systems are not able to form a stable donor-acceptor adduct, nevertheless, an intermolecular association of the Lewis acidic (LA) and basic (LB) components to a unique "frustrated complex" was proposed. [2,3] Our research group has also shown that this encounter pair cleaves hydrogen in a cooperative manner and the steric congestion implies a strain, which can be directly utilized for bond activation. [2] Using steric hindrance as a critical design element, several combinations of bulky Lewis acid-base pairs were effectively probed for heterolytic cleavage of hydrogen. [4][5][6] Moreover, this remarkable capacity of FLPs was exploited in metal-free hydrogenation procedures.[7] Additionally, the bifunctional and unquenched nature of the FLPs makes them capable of reacting with alkenes, [8] dienes, [9] acetylenes, [10] and THF.[5f]Although this type of reactivity represents a breakthrough in main-group chemistry, its enhanced and non-orthogonal nature obviously limits the synthetic applicability of FLPs. Herein we report an attempt to develop frustrated Lewis pairs with orthogonal reactivity and improved functional-group tolerance for catalytic metal-free hydrogenation. The previously reported FLP-based hydrogen activation relied mostly on tris(pentafluorophenyl)borane [11] (1) as the LA component.[12] Because of the hard-type Lewis acidity of boron in 1 and its inactivation by common oxygen-and/or nitrogen-containing molecules, careful substrate design was needed for successful catalytic hydrogenation reactions. This synthetic limitation triggered us to develop FLP catalysts that have a broader range of applications and possible selectivity in reduction processes.Our design concept for increased functional-group tolerance is based on the simple hypothesis that steric hindrance in FLPs is a relative phenomenon (Figure 1): further increase of congestion around the boron center in FLP I and its parallel decrease around the LB could lead to a Lewis pair (FLP II) that may have a markedly higher tolerance for the functionalities of common organic molecules. Thus, the steric demands imposed on the boron center by additional orthoaryl substituents are such that they can prevent or markedly decrease the complexation ability with normal Lewis bases but still allow the cleavage of the small hydrogen molecule. Additionally, we assumed that the increased shielding around boron in FLP II could preclude its addition to olefins, therefore creating a unique opportunity to investigate the chemoselectivity of FLP-catalyzed hydroge...

Frustrated Lewis Pairs

“…In addition, they reported one example of an reduction of an enone to the corresponding ketone. [39][40][41][42] It was Repo et al 43 that further broadened the substrate scope for FLP reductions to include non-functionalized internal alkynes (Table 1). Using the intramolecular FLP o-C 6 H 4 (NMe 2 )(B(C 6 F 5 ) 2 ), the corresponding cis-alkenes were obtained.…”

Catalysis of Oxygen Reduction by Metal-Free Porphyrins in One- and Two-Phase Liquid Systems

“…Active centers were identified for frustrated Lewis pairs (FLP) examined. 94 The interaction energies of the most stable forms of the H 2 complexes with FLP were obtained. Combined DFT calculations and deuterium labeling studies were applied to elucidate the mechanism of the metal-free double-hydrogenation process using FLP.…”

“…94 The stabilization energies were calculated at the M05-2X/6-311++G** level for the M05-2X/6-31G* optimized geometries of weakly bound complexes of several Lewis pairs with H 2 . Active centers were identified for frustrated Lewis pairs (FLP) examined.…”

Title Pages

“…Metal-free alternatives to traditional catalytic procedures are an obvious bonus economically. Here, the concept of hydrogenation with 'frustrated' Lewis pairs (72, 24; 75, 31) has developed into a highly selective hydrogenation of azomethines with the combination of bis(pentafluorophenyl)mesitylborane and an inexpensive bicyclic tertiary amine 41 . The quantitative reduction of enamines with methanol under microwave irradiation 42 seems almost 'too good to be true', as does a simple, eco-friendly isomerization of allyl acetates with silica gel 43 .…”