Asymmetric Imine Hydroboration Catalyzed by Chiral Diazaphospholenes

Abstract

The first use of diazaphospholenes as chiral catalysts has been demonstrated with enantioselective imine hydroboration. Ac hiral diazaphospholene prepared in as imple three-step synthesis from commercial materials has been shown to achieve the highest enantioselectivity for the hydroboration of alkyli mines with pinacolborane reported to date. Enantiomer ratios of up to 88:12 were obtained with low (2 mol %) catalyst loadings.T wenty examples of asymmetric reduction employing this main-group catalysis protocol, including the synthesis of the pharmaceuticals ent-rasagiline and fendiline,a re shown. Scheme 1. Systems for the metal-free synthesis of secondary amines.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Stay positive: catalysis with 1,3,2-diazaphospholenes

“…First generation chiral scaffolds have been based around commercially-available chiral amines, giving quick and efficient access to the targeted DAPs 13-18. 22,23 Subsequent chiral DAPs have employed annulated chiral manifolds to give more rigid DAP structures with conformationally locked stereochemical environments (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). 20,24 The methodologies (both racemic and enantioselective) in which these catalysts and precatalysts have been utilized will now be systematically discussed.…”

Chiral 1,3,2‐Diazaphospholenes as Catalytic Molecular Hydrides for Enantioselective Conjugate Reductions

“…was reported. [17] Theconjugate reduction of acyl pyrrole 1awas selected as the initial benchmark transformation (Table 1). Ac ombination of achiral catalyst P1 and pinBH as the terminal reductant provided product 2a in 88 %yield at room temperature in acetonitrile (entry 1).…”

“…(entry 13). However,catalysts with bulkier 3,5-diethyl-or 3,5-di-tert-butylphenyl groups or para-substituted aryl groups were inferior in terms of reactivity and selectivity (entries [14][15][16][17]. Compound P17 with 3,5-xylyl substituents and amethoxy group in the backbone was retained as the best performing and most easily purified catalyst (entry 18).…”

Chiral 1,3,2‐Diazaphospholenes as Catalytic Molecular Hydrides for Enantioselective Conjugate Reductions

“…[16] During the preparation of our manuscript, ac hiral-DAP-catalyzed asymmetric reduction of imines with enantiomeric ratios from 55:45 to 88:12 e.r. [17] Theconjugate reduction of acyl pyrrole 1awas selected as the initial benchmark transformation (Table 1). [17] Theconjugate reduction of acyl pyrrole 1awas selected as the initial benchmark transformation (Table 1).…”

“…However,catalysts with bulkier 3,5-diethyl-or 3,5-di-tert-butylphenyl groups or para-substituted aryl groups were inferior in terms of reactivity and selectivity (entries [14][15][16][17]. Thea ddition of substituents in the meta position was beneficial in the case of the 3,5-xylyl group,resulting in the formation of 2a with 88.5:11.5 e.r.…”