Organic base-catalyzed stereodivergent synthesis of (R)- and (S)-3-amino-4,4,4-trifluorobutanoic acids

Abstract

Organic base-catalyzed reaction of (S)-N-tert-butanesulfinyl (3,3,3)-trifluoroacetaldimine with dialkyl malonates was found to be effective for synthesis of both (S,S(S)) and (R,S(S)) β-aminomalonates in high yield with good to excellent diastereoselectivity (76-98% de). The products of this Mannich reaction provide direct access to β-trifluoromethyl-β-alanine of either (R) or (S) absolute configuration.

N‐tert‐Butylsulfinyl‐3,3,3‐trifluoroacetaldimine: Versatile Reagent for Asymmetric Synthesis of Trifluoromethyl‐Containing Amines and Amino Acids of Pharmaceutical Importance

“…An interesting example of stereodivergent synthesis of ( R )‐ and ( S )‐3‐amino‐4,4,4‐trifluorobutanoic acids through addition reactions between imine ( S s )‐ 7 and dialkyl malonates 97 is presented in Scheme …”

The Regio-specific solvent controlled asymmetric Strecker reaction of trifluoromethyl α,β-unsaturated N-tert-butanesulfinyl ketimines with trimethylsilyl cyanide

“…We envisaged that enhancing the substrate's structural conjugation might improve the stereoselectivity of the Strecker reaction due to the increasing coplanarity of the molecular structure backbone. On the basis of our previous work [12][13][14][15] and some related novel published literature [16][17][18][19][20][21][22][23][24][25][26], we reported herein the study of the asymmetrical Strecker reaction of trifluoromethyl a,b-unsaturated N-tert-butanesulfinyl ketimines with trimethylsilyl cyanide under different conditions.…”

Development and Evaluation of Different Methods for Preparation of Fluorine‐Containing (R)‐ and (S)‐N‐tert‐Butanesulfinyl–aldimines

“…As demonstrated by numerous research groups, most notably by O′Shea, Qing, Shibata, [44, 45] Roeschenthaler and Han, CF 3 ‐imines 2 easily react with virtually any type of nucleophiles, including Baylis‐Hillman and Friedel‐Crafts reactions, affording the target 2,2,2‐trifluoro‐1‐(amino)ethyl containing compounds with excellent yields and diastereoselectivity. Considering the wealth of literature data one can assert that chemistry of CF 3 ‐imines 2 is a mature field of a proven, exceptionally high synthetic value. Furthermore, preparation [59] of imines 2 and some of their addition reactions were quite successfully performed on about 1 mole scale, underscoring practicality of this approach.…”