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

P J M Taylor, S D Bull

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Abstract

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.
Original languageEnglish
Pages (from-to)1170-1178
Number of pages9
JournalTetrahedron: Asymmetry
Volume17
Issue number8
DOIs
Publication statusPublished - 2006

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Trifluoroacetic acid
Trifluoroacetic Acid
phenylalanine
Ethers
Lithium
Ether
esters
ethers
Esters
Salts
hydrochlorides
synthesis
integrity
bromides
templates
lithium
salts
acids
benzyl bromide
phenylalanine methyl ester

Cite this

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title = "An improved synthesis of deuterated Schollkopf's bis-lactim ether and its use for the asymmetric synthesis of (R)-[alpha-H-2]-phenylalanine methyl esters",
abstract = "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.",
author = "Taylor, {P J M} and Bull, {S D}",
note = "ID number: ISI:000238409500004",
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TY - JOUR

T1 - An improved synthesis of deuterated Schollkopf's bis-lactim ether and its use for the asymmetric synthesis of (R)-[alpha-H-2]-phenylalanine methyl esters

AU - Taylor, P J M

AU - Bull, S D

N1 - ID number: ISI:000238409500004

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

U2 - 10.1016/j.tetasy.2006.04.005

DO - 10.1016/j.tetasy.2006.04.005

M3 - Article

VL - 17

SP - 1170

EP - 1178

JO - Tetrahedron: Asymmetry

JF - Tetrahedron: Asymmetry

SN - 0957-4166

IS - 8

ER -