Stereoselective alkylation of glycine units in dipeptide derivatives: "Chirality transfer" via a pivalaldehyde N,N-acetal center

Robin Polt, Dieter Seebach

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Dipeptide esters (of glycylglycine, glycylalanine, alanylglycine) and aldehydes (isobutyraldehyde, pivalaldehyde, benzaldehyde) are condensed to (4-oxoimidazolidin-3-yl)acetates and -propionates (1-3). Lithium enolates of these derivatives are generated (deprotonation of the ring and/or side-chain α-carbonyl positions) with LDA, LDA/LiBr, or LHMDS and alkylated with high diastereoselectivity (products 4, 6, 7). Dipeptides of either R,R or S,S configuration can be prepared from the glycine-containing precursors. Surprising proton-transfer effects (Schemes VI-IX, XII) are interpreted as a consequence of "intimate complexation" among LDA, LiBr, lithium enolates, and diisopropylamine.

Original languageEnglish (US)
Pages (from-to)2622-2632
Number of pages11
JournalJournal of the American Chemical Society
Volume111
Issue number7
StatePublished - 1989
Externally publishedYes

Fingerprint

Acetals
Dipeptides
Chirality
Alkylation
Lithium
Glycine
Amino acids
alanylglycine
Glycylglycine
Derivatives
Deprotonation
Proton transfer
Propionates
Complexation
Aldehydes
Protons
Esters
Acetates
benzaldehyde
diisopropylamine

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

@article{cf68664ee7834720948c7e08e1e9a1ad,
title = "Stereoselective alkylation of glycine units in dipeptide derivatives: {"}Chirality transfer{"} via a pivalaldehyde N,N-acetal center",
abstract = "Dipeptide esters (of glycylglycine, glycylalanine, alanylglycine) and aldehydes (isobutyraldehyde, pivalaldehyde, benzaldehyde) are condensed to (4-oxoimidazolidin-3-yl)acetates and -propionates (1-3). Lithium enolates of these derivatives are generated (deprotonation of the ring and/or side-chain α-carbonyl positions) with LDA, LDA/LiBr, or LHMDS and alkylated with high diastereoselectivity (products 4, 6, 7). Dipeptides of either R,R or S,S configuration can be prepared from the glycine-containing precursors. Surprising proton-transfer effects (Schemes VI-IX, XII) are interpreted as a consequence of {"}intimate complexation{"} among LDA, LiBr, lithium enolates, and diisopropylamine.",
author = "Robin Polt and Dieter Seebach",
year = "1989",
language = "English (US)",
volume = "111",
pages = "2622--2632",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "7",

}

TY - JOUR

T1 - Stereoselective alkylation of glycine units in dipeptide derivatives

T2 - "Chirality transfer" via a pivalaldehyde N,N-acetal center

AU - Polt, Robin

AU - Seebach, Dieter

PY - 1989

Y1 - 1989

N2 - Dipeptide esters (of glycylglycine, glycylalanine, alanylglycine) and aldehydes (isobutyraldehyde, pivalaldehyde, benzaldehyde) are condensed to (4-oxoimidazolidin-3-yl)acetates and -propionates (1-3). Lithium enolates of these derivatives are generated (deprotonation of the ring and/or side-chain α-carbonyl positions) with LDA, LDA/LiBr, or LHMDS and alkylated with high diastereoselectivity (products 4, 6, 7). Dipeptides of either R,R or S,S configuration can be prepared from the glycine-containing precursors. Surprising proton-transfer effects (Schemes VI-IX, XII) are interpreted as a consequence of "intimate complexation" among LDA, LiBr, lithium enolates, and diisopropylamine.

AB - Dipeptide esters (of glycylglycine, glycylalanine, alanylglycine) and aldehydes (isobutyraldehyde, pivalaldehyde, benzaldehyde) are condensed to (4-oxoimidazolidin-3-yl)acetates and -propionates (1-3). Lithium enolates of these derivatives are generated (deprotonation of the ring and/or side-chain α-carbonyl positions) with LDA, LDA/LiBr, or LHMDS and alkylated with high diastereoselectivity (products 4, 6, 7). Dipeptides of either R,R or S,S configuration can be prepared from the glycine-containing precursors. Surprising proton-transfer effects (Schemes VI-IX, XII) are interpreted as a consequence of "intimate complexation" among LDA, LiBr, lithium enolates, and diisopropylamine.

UR - http://www.scopus.com/inward/record.url?scp=0000948155&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0000948155&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:0000948155

VL - 111

SP - 2622

EP - 2632

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 7

ER -