Direct Mannich‐Type Reactions Promoted by Frustrated Lewis Acid/Brønsted Base Catalysts

Abstract

Direct Mannich-type reactions that affordb oth aand b-amino esters by the reaction of ab road range of carbonyl compounds and aldimines are disclosed. The transformation is promoted by as terically frustrated Lewis acid/ Brønsted base pair,w hich is proposed to operate cooperatively:Within the catalyst complex, an enolate is generated that then reacts with ah ydrogen-bond-activated imine.N oncovalent interactions between reactants and the catalyst provide selectivity and new opportunities for future catalyst design.Scheme 1. Use of acid/base catalysts to promote direct Mannich-type reactions. EDG = electron-donating group.

Catalysis, FLPs, and Beyond

“…31 For example, a wide variety of p-block FLPs have been exploited for transfer hydrogenations, [32][33][34] hydroborations, [35][36][37][38][39][40][41] C-H borylations, [42][43][44][45][46] hydroarylations, [47][48][49] and aminations, 50 as well as enantioselective a-aminations and Mannich-type reactions. [51][52][53][54] FLPs have also proved effective catalysts for polymerization 55 of a variety of acrylates, lactones, cyanamides, vinyl monomers, conjugated polar alkenes, and acrylamide monomers. P(V) and P(III) Lewis acids effect the hydrosilylation of a variety of substrates, as well as the deoxygenation of ketones and the arylation of benzyl fluorides and alkyl and aryl CF 3 derivatives.…”

Enhancement of Acid‐Catalyzed Esterification by the Addition of Base

“…In such systems, it has been documented that the acidic and basic points should be spatially separated to avoid inactivation of each active site. In the case of frustrated Lewis pair (FLP), a simple mixture of Lewis acid and base acts as the effective cooperative catalyst because salt formation is suppressed by steric hindrance . A salt of certain amine with a strong acid can be a mild and selective acid‐catalyst, where the ammonium salt acts as the acid with the cooperation of the counter anion .…”

“…In the case of frustrated Lewis pair (FLP), a simple mixture of Lewis acid and base acts as the effective cooperative catalyst because salt formation is suppressed by steric hindrance. [21] A salt of certain amine with a strong acid can be a mild and selective acid-catalyst, where the ammonium salt acts as the acid with the cooperation of the counter anion. [22,23] However, the enhancement of acid-catalyzed reaction by the addition of a simple base has not been reported.…”

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

“…[9][10][11][12] Our laboratory has described the development of strongly acidic B(C 6 F 5 ) 3 and chiral diamine catalysts for direct enantioselective CÀNb ond forming reactions between ketones and dialkyl azodicarboxylates. [14] Therefore,w econsidered the development of an FLP catalyst system that promotes asymmetric direct Mannich-type reactions between an assortment of carbonyl pronucleophiles and imines (Scheme 1B). [14] Therefore,w econsidered the development of an FLP catalyst system that promotes asymmetric direct Mannich-type reactions between an assortment of carbonyl pronucleophiles and imines (Scheme 1B).…”

“…[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. [14] Therefore,w econsidered the development of an FLP catalyst system that promotes asymmetric direct Mannich-type reactions between an assortment of carbonyl pronucleophiles and imines (Scheme 1B). Ac ritical advantage of the proposed strategy is that covalent tethering of acidic and basic catalyst components is not necessary,t hus enabling the facile and independent modification of each component for the optimization of reaction efficiency and/or stereoselectivity.…”