ABSTRACT:We report the synthesis and reactivity of a chiral aminoborane displaying both rapid and reversible hydrogen activation. The catalyst shows exceptional reactivity in asymmetric hydrogenation of enamines and unhindered imines with stereoselectivity up to 99% ee. The reaction mechanism is analyzed via DFT calculations, which point to the importance of both repulsive steric and stabilizing intermolecular noncovalent forces in the stereodetermining hydride transfer step of the catalytic cycle.One of the most efficient and atom-economic ways of preparing chiral amines is through transition metal catalyzed asymmetric hydrogenation of prochiral imines and enamines. 1 The products, having chiral α-carbons, are important in synthetic chemistry due to their application as ligands, resolving agents, chiral auxiliaries and building blocks. Additionally, the chiral information and tendency to form hydrogen bonds, are essential features in molecular recognition, thus making them potential pharmaceuticals. 2 Drug substance preparation through transition metal catalysis requires tedious product purification due to strict demands on heavy metal residuals in the products. 3 Recently, main-group systems combining sterically hindered Lewis acids and bases have been reported to cleave molecular hydrogen heterolytically under mild reaction conditions. 4 The field commonly referred to as the chemistry of "Frustrated Lewis pairs" (FLP) has attracted an increased scientific and practical interest, mainly owing to their applicability as catalysts in homogeneous metal-free hydrogenations of imines, enamines, 5 N-heterocycles, 6 and first results have been disclosed for the hydrogenation of carbonyl compounds 7 as well. In this regard it is surprising that reports of the corresponding asymmetric reactions are still few. Intermolecular FLP systems involving chiral boranes have been successfully utilized for enantioselective imine hydrogenation. Use of inherently chiral terpene groups (like α-pinene and camphor) on boron has proven to be effective for hydrogenation of acetophenone N-arylimines and ee's up to 83% were reported (Figure 1, 1). 8 A recent development was achieved by introducing chirality through a binaphthyl backbone (2), enabling hydrogenation at room temperature and consequently increasing asymmetric induction. 9 In intramolecular FLP systems appropriate linking of the Lewis acid and base has proven to be crucial for dihydrogen activation as well as for the hydrogen transfer process. 10 In ansa-aminoboranes, the Lewis acid and base are in close vicinity, but bulky substituents hinder dative bond formation. Such structures generate high FLP reactivity and the substrate scope could be expanded to enamines, N-alkyl and alkyl imines. 5d,11 However, previous attempts to incorporate high reactivity of ansa-aminoboranes and asymmetric hydrogenation, namely the introduction of chiral amines via straightforward synthetic approaches into linked systems (Figure 1, 3), have resulted in only moderate enantioselectivities. 11...

Chiral Molecular Tweezers: Synthesis and Reactivity in Asymmetric Hydrogenation. -A new 1,1'-binaphthyl aminoborane is synthesized and shows exceptional catalytical activity in asymmetric hydrogenation of unhindered imines and enamines with up to 99% ee. -(LINDQVIST, M.; BORRE, K.; AXENOV, K.; KOTAI, B.; NIEGER, M.; LESKELAE, M.; PAPAI, I.; REPO*, T.; J. Am. Chem. Soc. 137 (2015) 12, 4038-4041, http://dx.doi.org/10.1021/ja512658m ; Dep. Chem., Univ. Helsinki, SF-00014 Helsinki, Finland; Eng.) -L. Grundl 35-038