On the origins of diastereoselectivity in the alkylation of diketopiperazine enolates

Steven D. Bull; Stephen G. Davies; A. Christopher Garner; Alastair L. Parkes; Paul M. Roberts; Thomas G. R. Sellers; Andrew D. Smith; Juan A. Tamayo; James E. Thomson; Richard J. Vickers

doi:10.1039/b701628j

On the origins of diastereoselectivity in the alkylation of diketopiperazine enolates

Steven D. Bull, Stephen G. Davies, A. Christopher Garner, Alastair L. Parkes, Paul M. Roberts, Thomas G. R. Sellers, Andrew D. Smith, Juan A. Tamayo, James E. Thomson, Richard J. Vickers

Research output: Contribution to journal › Article › peer-review

Abstract

High levels of diastereoselectivity are observed for benzylation of the lithium enolates of (S)- N, N'-bis- para-methoxybenzyl-3-iso-propyl-piperazine- 2,5-dione, ( S)- N( 1)- para-methoxybenzyl-N( 4)methyl- 3-iso-propyl-piperazine-2,5-dione and ( S)- N( 1)- methyl- N( 4)- para-methoxybenzyl-3-isopropylpiperazine- 2,5-dione. These data suggest that the high diastereofacial selectivity observed for alkylation of these diketopiperazine templates is mainly a consequence of the relay of stereochemical information from C( 3) to C( 6) via the influence of 1,2-torsional strain introduced by the N-alkyl substituents, rather than through minimisation of steric interactions alone.

Original language	English
Pages (from-to)	486-495
Number of pages	10
Journal	New Journal of Chemistry
Volume	31
Issue number	4
DOIs	https://doi.org/10.1039/b701628j
Publication status	Published - 2007

Keywords

ALPHA-AMINO-ACIDS
DIELS-ALDER REACTIONS
CHIRAL RELAY
ASYMMETRIC-SYNTHESIS
ENANTIOSELECTIVE SYNTHESIS
STEREOSELECTIVE-SYNTHESIS
CONJUGATE ADDITION
CYCLIC DIPEPTIDES
ASSIGNMENT
AUXILIARY

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@article{58628a4bbcc745078bef2bb7c522c75d,

title = "On the origins of diastereoselectivity in the alkylation of diketopiperazine enolates",

abstract = "High levels of diastereoselectivity are observed for benzylation of the lithium enolates of (S)- N, N'-bis- para-methoxybenzyl-3-iso-propyl-piperazine- 2,5-dione, ( S)- N( 1)- para-methoxybenzyl-N( 4)methyl- 3-iso-propyl-piperazine-2,5-dione and ( S)- N( 1)- methyl- N( 4)- para-methoxybenzyl-3-isopropylpiperazine- 2,5-dione. These data suggest that the high diastereofacial selectivity observed for alkylation of these diketopiperazine templates is mainly a consequence of the relay of stereochemical information from C( 3) to C( 6) via the influence of 1,2-torsional strain introduced by the N-alkyl substituents, rather than through minimisation of steric interactions alone.",

keywords = "ALPHA-AMINO-ACIDS, DIELS-ALDER REACTIONS, CHIRAL RELAY, ASYMMETRIC-SYNTHESIS, ENANTIOSELECTIVE SYNTHESIS, STEREOSELECTIVE-SYNTHESIS, CONJUGATE ADDITION, CYCLIC DIPEPTIDES, ASSIGNMENT, AUXILIARY",

author = "Bull, {Steven D.} and Davies, {Stephen G.} and Garner, {A. Christopher} and Parkes, {Alastair L.} and Roberts, {Paul M.} and Sellers, {Thomas G. R.} and Smith, {Andrew D.} and Tamayo, {Juan A.} and Thomson, {James E.} and Vickers, {Richard J.}",

year = "2007",

doi = "10.1039/b701628j",

language = "English",

volume = "31",

pages = "486--495",

journal = "New Journal of Chemistry",

issn = "1144-0546",

publisher = "ROYAL SOC CHEMISTRY",

number = "4",

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TY - JOUR

T1 - On the origins of diastereoselectivity in the alkylation of diketopiperazine enolates

AU - Bull, Steven D.

AU - Davies, Stephen G.

AU - Garner, A. Christopher

AU - Parkes, Alastair L.

AU - Roberts, Paul M.

AU - Sellers, Thomas G. R.

AU - Smith, Andrew D.

AU - Tamayo, Juan A.

AU - Thomson, James E.

AU - Vickers, Richard J.

PY - 2007

Y1 - 2007

N2 - High levels of diastereoselectivity are observed for benzylation of the lithium enolates of (S)- N, N'-bis- para-methoxybenzyl-3-iso-propyl-piperazine- 2,5-dione, ( S)- N( 1)- para-methoxybenzyl-N( 4)methyl- 3-iso-propyl-piperazine-2,5-dione and ( S)- N( 1)- methyl- N( 4)- para-methoxybenzyl-3-isopropylpiperazine- 2,5-dione. These data suggest that the high diastereofacial selectivity observed for alkylation of these diketopiperazine templates is mainly a consequence of the relay of stereochemical information from C( 3) to C( 6) via the influence of 1,2-torsional strain introduced by the N-alkyl substituents, rather than through minimisation of steric interactions alone.

AB - High levels of diastereoselectivity are observed for benzylation of the lithium enolates of (S)- N, N'-bis- para-methoxybenzyl-3-iso-propyl-piperazine- 2,5-dione, ( S)- N( 1)- para-methoxybenzyl-N( 4)methyl- 3-iso-propyl-piperazine-2,5-dione and ( S)- N( 1)- methyl- N( 4)- para-methoxybenzyl-3-isopropylpiperazine- 2,5-dione. These data suggest that the high diastereofacial selectivity observed for alkylation of these diketopiperazine templates is mainly a consequence of the relay of stereochemical information from C( 3) to C( 6) via the influence of 1,2-torsional strain introduced by the N-alkyl substituents, rather than through minimisation of steric interactions alone.

KW - ALPHA-AMINO-ACIDS

KW - DIELS-ALDER REACTIONS

KW - CHIRAL RELAY

KW - ASYMMETRIC-SYNTHESIS

KW - ENANTIOSELECTIVE SYNTHESIS

KW - STEREOSELECTIVE-SYNTHESIS

KW - CONJUGATE ADDITION

KW - CYCLIC DIPEPTIDES

KW - ASSIGNMENT

KW - AUXILIARY

U2 - 10.1039/b701628j

DO - 10.1039/b701628j

M3 - Article

SN - 1144-0546

VL - 31

SP - 486

EP - 495

JO - New Journal of Chemistry

JF - New Journal of Chemistry

IS - 4

ER -

On the origins of diastereoselectivity in the alkylation of diketopiperazine enolates

Abstract

Keywords

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