Catalytic Asymmetric CN Bond Formation: Phosphine‐Catalyzed Intra‐ and Intermolecular γ‐Addition of Nitrogen Nucleophiles to Allenoates and Alkynoates

Abstract

The first examples are described of catalyzed γ-additions of nitrogen nucleophiles to γ-substituted alkynoates or allenoates that proceed with good efficiency, specifically, intra- and intermolecular processes that employ distinct and useful families of nitrogen nucleophiles (anilines and 2,2,2-trifluoroacetamide), catalyzed by spirophosphine 1. Furthermore, the first demonstrations are reported of asymmetric reactions, affording interesting classes of target molecules such as enantioenriched pyrrolidines, indolines, and γ-amino-α,β-unsaturated carbonyl compounds.

Advances in nucleophilic phosphine catalysis of alkenes, allenes, alkynes, and MBHADs

“…79 Here, they employed the chiral spirophosphepine 127 as the catalyst, forming functionalized γ-amino acrylates (Scheme 87). There are a few interesting features of this study.…”

“…79 Moderate to good yields of pyrrolidines and 2,3-dihydroindoles have been isolated with excellent enantiomeric excesses (Scheme 89). Good yields of pyrrolidines were isolated with excellent enantiocontrol (entries 1 and 2).…”

Catalytic Asymmetric Synthesis of Trifluoromethylated γ‐Amino Acids through the Umpolung Addition of Trifluoromethyl Imines to Carboxylic Acid Derivatives

“…Ye and coworkers [8] reported the use of a cinchona alkaloid-derived chiral nucleophilic catalyst to mediate a highly enantioselective γ-amination of α, β-unsaturated acyl chlorides with azodicarboxylates, after which the products were transformed into enantiomerically enriched γ-substituted γ-amino acids (Scheme 1a). By exploring phosphine nucleophilic catalysis, Fu and coworkers [9] developed a chiral phosphine catalyst to realize an efficient enantioselective γ-amination of allenoates with 2,2,2-trifluoroacetamide to generate optically active α, β-unsaturated γ-amino esters (Scheme 1a). Jacobsen and coworkers [10] designed a chiral phosphinothiourea bifunctional catalyst for the asymmetric γ-amination of allenyl esters with N -methoxy carbamates (Scheme 1a).…”

Stereoselective syntheses of α,β-unsaturated γ-amino esters through phosphine-catalyzed γ-umpolung additions of sulfonamides to γ-substituted allenoates

“…8 Although phosphine-catalyzed γ-additions of amines to allenoates and alkynoates have been reported sporadically, 9 the preparation of α,β-unsaturated γ-amino esters through phosphine-catalyzed γ-additions of sulfonamides to γ-substituted allenoates has not been studied systematically. Herein, we report the results of an investigation into the stereoselective syntheses of α,β-unsaturated γ-amino esters through phosphine-catalyzed γ-umpolung additions of sulfonamides to γ-substituted allenoates under mild conditions.…”