An improved synthesis of deuterated Schollkopf's bis-lactim ether and its use for the asymmetric synthesis of (R)-[α-2H]-phenylalanine methyl esters

Treatment of (S)-3-isopropyl-2,5-dimethoxy-3,6-dihydropyrazine with trifluoroacetic acid in MeOD results in regioselective deuteration at its C-6-position affording its corresponding (S)-[6-H-2(2)]-isotopomer in excellent yield with no loss of stereochemical integrity at its C-3-stereocentre. The lithium aza-enolate of this deuterated chiral template has been alkylated with a range of substituted benzyl bromides to afford (3S,6R)-[6-H-2]-3-isopropyl-6-benzyl-bis-lactim ethers that were hydrolysed to afford their corresponding (R)-[alpha-H-2]-phenylalanine methyl esters as hydrochloride salts in good yield. (c) 2006 Elsevier Ltd. All rights reserved.