Frustrated Lewis Acid/Brønsted Base Catalysts for Direct Enantioselective α-Amination of Carbonyl Compounds

Abstract

A method for enantioselective direct α-amination reaction catalyzed by a sterically "frustrated" Lewis acid/Brønsted base complex is disclosed. Cooperative functioning of the Lewis acid and Brønsted base components gives rise to in situ enolate generation from monocarbonyl compounds. Subsequent reaction with hydrogen-bond activated dialkyl azodicarboxylates delivers α-aminocarbonyl compounds in high enantiomeric purity.

B(C6F5)3‐Catalyzed α‐Deuteration of Bioactive Carbonyl Compounds with D2O

“…[6a] Still, devel-opment of a catalyst system for α-deuteration of carbonyl-based drugs that cannot be readily deprotonated by Lewis base catalysts and/or those containing base-sensitive functional groups stands as a significant challenge. [9][10] A potential complication of this approach is that the Lewis acid may form stable acid-base adducts with D 2 O as well as Lewis basic functional groups that may be contained in 1. [9][10] A potential complication of this approach is that the Lewis acid may form stable acid-base adducts with D 2 O as well as Lewis basic functional groups that may be contained in 1.…”

“…[9][10] A potential complication of this approach is that the Lewis acid may form stable acid-base adducts with D 2 O as well as Lewis basic functional groups that may be contained in 1. [9,[12][13][14] We envisioned that B(C 6 F 5 ) 3 could activate 1, [9] thereby facilitating deprotonation by D 2 O to generate a boronenolate and D 2 O + À H (I to II). [9,[12][13][14] We envisioned that B(C 6 F 5 ) 3 could activate 1, [9] thereby facilitating deprotonation by D 2 O to generate a boronenolate and D 2 O + À H (I to II).…”

“…[6][7][8] We began by contemplating a method for αdeuteration of bioactive carbonyl compounds (1) by utilizing a Lewis acidic organoborane that can activate 1 towards deprotonation by D 2 O (Scheme 1C; I to II). [9][10] A potential complication of this approach is that the Lewis acid may form stable acid-base adducts with D 2 O as well as Lewis basic functional groups that may be contained in 1. [11][12][13][14] The application of frustrated Lewis pairs (FLPs), consisting of strongly Lewis acidic and hindered B(C 6 F 5 ) 3 and various Lewis bases, has emerged as an attractive strategy for overcoming undesired acid-base complexation.…”

“…[11][12][13][14] The application of frustrated Lewis pairs (FLPs), consisting of strongly Lewis acidic and hindered B(C 6 F 5 ) 3 and various Lewis bases, has emerged as an attractive strategy for overcoming undesired acid-base complexation. [9,[12][13][14] We envisioned that B(C 6 F 5 ) 3 could activate 1, [9] thereby facilitating deprotonation by D 2 O to generate a boronenolate and D 2 O + À H (I to II). [11][12] Ensuing deuteration of the enolate by D 2 O + À H would afford desired product 2.…”

Enantioselective Direct Mannich‐Type Reactions Catalyzed by Frustrated Lewis Acid/Brønsted Base Complexes

“…[9] Although an assortment of enantioenriched FLPs have been prepared, enantioselective FLP-catalyzed transformations have been confined to hydro-genation and hydrosilylation processes until recently. [13] However, there is no precedent for diastereo-and enantioselective C À Cb ond forming reactions catalyzed by an unquenched pair of chiral organoborane and achiral amine catalysts. [13] However, there is no precedent for diastereo-and enantioselective C À Cb ond forming reactions catalyzed by an unquenched pair of chiral organoborane and achiral amine catalysts.…”