First Highly Diastereoselective Synthesis of syn α-Methyl β-Fluoroalkyl β-Amino Esters

Abstract

A new two-step approach for the diastereoselective synthesis of the syn α-methyl β-fluoroalkyl β-amino esters 4 has been developed. This approach is based on the chemical reduction of the fluorinated β-enamino esters 3, which have been previously obtained from imidoyl chlorides 1 and lithium ester enolates, with ZnI2/NaBH4 as the reducing agent. The process takes place with high syn diastereoselectivity and good to excellent yields. A metal-chelated six-membered model has been suggested to explain the stereochemical outcome of the reduction reaction.

Synthesis of Fluorinated β-Amino Acids

“…When these tautomers were reduced with sodium borohydride and zinc iodide, an excellent syn diastereoselectivity was observed and the resulting product 68 was finally deprotected with cerium(IV) ammonium nitrate to yield racemic b-amino ester 69. 37…”

Nitrogen-Containing Organofluorine Derivatives: An Overview

“…38 The chemo-and stereoselective reduction of chiral nonracemic b-enamino ester derivatives constitutes a simple and attractive route to enantiopure b-amino acids. Howev- er, few examples of this strategy for preparing fluorinated b-amino acids had been reported before 1999, 39 when our group described an efficient, two-step procedure for the diastereoselective synthesis of racemic 40 and chiral nonracemic syn-a-alkyl-b-fluoroalkyl-b-amino acid derivatives. 41 Using our method, fluorinated derivatives 8 were converted into the corresponding racemic syn-b-amino ester derivatives through chemical reduction of the imino/ enamino moiety.…”

Efficient Syntheses of ω-Trifluoromethyl Substituted ω-Amino Acids

“…21,22 (5) Chemo-and stereoselective reduction of b-fluoroalkyl-b-enamino esters. 23,24 (6) Stereoselective biomimetic transamination of bfluoroalkyl-b-keto esters. 25 Recently we reported a synthesis of b,b-bis(trifluoromethyl) b-amino acids based on the Morita-Baylis-Hillman reaction.…”