Bifunctional Iminophosphorane Superbase Catalysis: Applications in Organic Synthesis

Abstract

This was the first report of a bif unctional iminophosphorane catalyzed 1,4-addition reaction as well as the f irst enantioselective sulfa-Michael addition of alkyl thiols to unactivated α-substituted acrylate esters.

A bifunctional iminophosphorane squaramide catalyzed enantioselective synthesis of hydroquinazolinesviaintramolecular aza-Michael reaction to α,β-unsaturated esters

“…20 However, only N-aryl nucleophiles were compatible and transformation of the guanidine IAMR product to drug molecules bearing urea motifs -such as in DPC 963 (shown in Figure 1) -was not feasible. Against this backdrop, we envisaged that the enhanced Brønsted basicity and broadly tunable structure of the bifunctional iminophosphorane (BIMP) superbase catalyst system developed in our group 21 could provide the solution to the challenging pK a related reactivity and modest stereocontrol in the IAMR, and herein we wish to report our findings.…”

“…1 ) – was not feasible. Against this backdrop, we envisaged that the enhanced Brønsted basicity and broadly tunable structure of the bifunctional iminophosphorane (BIMP) superbase catalyst system developed in our group 21 could provide the solution to the challenging p K a related reactivity and modest stereocontrol in the IAMR, and herein we wish to report our findings.…”

Bifunctional Iminophosphorane Catalyzed Enantioselective Sulfa-Michael Addition to Unactivated α,β-Unsaturated Amides

“…To this end, in 2013 our group disclosed a new class of superbasic catalysts, the bifunctional iminophosphorane (BIMP), which has proven to be exceptionally active in catalyzing challenging enantioselective conjugate additions, for example with α-substituted acrylate esters, 14a crotonate esters, 14b and alkenyl benzimidazoles 14c as electrophiles. [10][11][12][13][14] Recognizing the limitations in state-of-the-art enantioselective conjugate additions to α,β-unsaturated amides and seeking the opportunity to test the capabilities of new BIMP catalyst systems on conjugate acceptors at the bottom end of Mayr's electrophilicity scale (Figure 1), 5c we sought to realize the first non-metal catalyzed enantioselective conjugate addition reaction to α,β-unsaturated amides. We chose to exemplify this with the sulfa-Michael addition (SMA) and our hope was to identify a suitable BIMP superbase catalyst capable of significant non-covalent activation of the electrophile and simultaneous deprotonation of high pKa pronucleophile, and here we wish to report our findings.…”

A Bifunctional Iminophosphorane Squaramide Catalyzed Enantioselective Synthesis of Hydroquinazolines via Intramolecular Aza-Michael Addition to α,β-Unsaturated Esters

“…[20] However, only N-aryl nucleophiles were compatible and transformation of the guanidine IAMA product to drug molecules bearing urea motifssuch as in DPC 963 (shown in Figure 1)was not feasible. Against this backdrop, we envisaged that the enhanced Brønsted basicity and broadly tunable structure of the bifunctional iminophosphorane (BIMP) superbase catalyst system developed in our group [21] could provide the solution to the challenging pKa related reactivity and modest stereocontrol in the IAMA, and herein we wish to report our findings. Urea 1a bearing an α,β-unsaturated tert-butyl ester was chosen as the model substrate for the IAMA reaction.…”