Synthesis and Reactions of Iodo Lactams

Spencer Knapp, Anthony T. Levorse

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

The synthesis of a series of iodo lactams has been achieved by a new cyclization method that depends on generating N,O-bis(trimethylsilyl)imidate derivatives as intermediates. Treatment of an unsaturated amide with trimethylsilyl triflate in pentane and then iodine in tetrahydrofuran gives the iodo lactam. Some reactions of this new difunctional group with bases, nucleophiles, and Michael acceptors leading to functionalized or elaborated lactams are presented. In general, iodo lactams undergo direct SN2 reactions with reactive (but weakly basic) nucleophiles like azide and triphenylphosphine and elimination or decomposition in the presence of bases or basic nucleophiles. Sodium hydride may be used to generate an N-acylaziridine intermediate, which can be opened with azide to deliver an azido lactam with overall retention of stereochemistry. Silver-assisted solvolysis of iodo lactams gives the hydroxy lactams with retention of configuration, probably also because of participation by the lactam nitrogen. The sodium salt of 5-(iodomethyl)-2-pyrrolidinone (3), generated at -20 °C, undergoes an annulation reaction with unsaturated esters (but not sulfones), leading to pyrrolizidine derivatives.

Original languageEnglish (US)
Pages (from-to)4006-4014
Number of pages9
JournalJournal of Organic Chemistry
Volume53
Issue number17
DOIs
StatePublished - Jan 1 1988

Fingerprint

Lactams
Nucleophiles
Azides
Imidoesters
Derivatives
Sulfones
Stereochemistry
Cyclization
Silver
Amides
Iodine
Esters
Nitrogen
Salts
Sodium
Decomposition

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

Knapp, Spencer ; Levorse, Anthony T. / Synthesis and Reactions of Iodo Lactams. In: Journal of Organic Chemistry. 1988 ; Vol. 53, No. 17. pp. 4006-4014.
@article{0198912f257c4c5bbe5a3570055a570b,
title = "Synthesis and Reactions of Iodo Lactams",
abstract = "The synthesis of a series of iodo lactams has been achieved by a new cyclization method that depends on generating N,O-bis(trimethylsilyl)imidate derivatives as intermediates. Treatment of an unsaturated amide with trimethylsilyl triflate in pentane and then iodine in tetrahydrofuran gives the iodo lactam. Some reactions of this new difunctional group with bases, nucleophiles, and Michael acceptors leading to functionalized or elaborated lactams are presented. In general, iodo lactams undergo direct SN2 reactions with reactive (but weakly basic) nucleophiles like azide and triphenylphosphine and elimination or decomposition in the presence of bases or basic nucleophiles. Sodium hydride may be used to generate an N-acylaziridine intermediate, which can be opened with azide to deliver an azido lactam with overall retention of stereochemistry. Silver-assisted solvolysis of iodo lactams gives the hydroxy lactams with retention of configuration, probably also because of participation by the lactam nitrogen. The sodium salt of 5-(iodomethyl)-2-pyrrolidinone (3), generated at -20 °C, undergoes an annulation reaction with unsaturated esters (but not sulfones), leading to pyrrolizidine derivatives.",
author = "Spencer Knapp and Levorse, {Anthony T.}",
year = "1988",
month = "1",
day = "1",
doi = "10.1021/jo00252a024",
language = "English (US)",
volume = "53",
pages = "4006--4014",
journal = "Journal of Organic Chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
number = "17",

}

Synthesis and Reactions of Iodo Lactams. / Knapp, Spencer; Levorse, Anthony T.

In: Journal of Organic Chemistry, Vol. 53, No. 17, 01.01.1988, p. 4006-4014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synthesis and Reactions of Iodo Lactams

AU - Knapp, Spencer

AU - Levorse, Anthony T.

PY - 1988/1/1

Y1 - 1988/1/1

N2 - The synthesis of a series of iodo lactams has been achieved by a new cyclization method that depends on generating N,O-bis(trimethylsilyl)imidate derivatives as intermediates. Treatment of an unsaturated amide with trimethylsilyl triflate in pentane and then iodine in tetrahydrofuran gives the iodo lactam. Some reactions of this new difunctional group with bases, nucleophiles, and Michael acceptors leading to functionalized or elaborated lactams are presented. In general, iodo lactams undergo direct SN2 reactions with reactive (but weakly basic) nucleophiles like azide and triphenylphosphine and elimination or decomposition in the presence of bases or basic nucleophiles. Sodium hydride may be used to generate an N-acylaziridine intermediate, which can be opened with azide to deliver an azido lactam with overall retention of stereochemistry. Silver-assisted solvolysis of iodo lactams gives the hydroxy lactams with retention of configuration, probably also because of participation by the lactam nitrogen. The sodium salt of 5-(iodomethyl)-2-pyrrolidinone (3), generated at -20 °C, undergoes an annulation reaction with unsaturated esters (but not sulfones), leading to pyrrolizidine derivatives.

AB - The synthesis of a series of iodo lactams has been achieved by a new cyclization method that depends on generating N,O-bis(trimethylsilyl)imidate derivatives as intermediates. Treatment of an unsaturated amide with trimethylsilyl triflate in pentane and then iodine in tetrahydrofuran gives the iodo lactam. Some reactions of this new difunctional group with bases, nucleophiles, and Michael acceptors leading to functionalized or elaborated lactams are presented. In general, iodo lactams undergo direct SN2 reactions with reactive (but weakly basic) nucleophiles like azide and triphenylphosphine and elimination or decomposition in the presence of bases or basic nucleophiles. Sodium hydride may be used to generate an N-acylaziridine intermediate, which can be opened with azide to deliver an azido lactam with overall retention of stereochemistry. Silver-assisted solvolysis of iodo lactams gives the hydroxy lactams with retention of configuration, probably also because of participation by the lactam nitrogen. The sodium salt of 5-(iodomethyl)-2-pyrrolidinone (3), generated at -20 °C, undergoes an annulation reaction with unsaturated esters (but not sulfones), leading to pyrrolizidine derivatives.

UR - http://www.scopus.com/inward/record.url?scp=0000193117&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0000193117&partnerID=8YFLogxK

U2 - 10.1021/jo00252a024

DO - 10.1021/jo00252a024

M3 - Article

AN - SCOPUS:0000193117

VL - 53

SP - 4006

EP - 4014

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 17

ER -