Metalation and Alkylation of 3,6-Dihydrothiazine 1-Oxides Prepared via Diels-Alder Cycloadditions of N-Sulfinyl Dienophiles

Scott I. Bell, M. Parvez, Steven M. Weinreb

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The deprotonation of various 3,6-dihydrothiazine 1-oxides using LDA or methyllithium has been investigated. It was found that the stability and chemistry of these lithiated heterocycles are highly dependent upon the nature of the ring nitrogen substituent. Thus, N-alkyldihydrothiazine oxides can be metalated at C-6 to give species postulated as 9, which undergo predominantly anti alkylation with alkyl halides. Alternatively, with MeOD, 9 is deuterated at C-6 primarily in a syn mode. N-Silylated heterocycles ring open rapidly and stereoselectively upon metalation to give dienic sulfinamides like 19, which can be reclosed to the starting dihydrothiazine oxides. N-Phenyl-substituted 3,6-dihydrothiazine 1-oxides upon metalation give mixtures of pyrroles and N-S bond cleavage products. Attempts to generate the dianion from NH dihydrothiazine oxide 17 led only to low yields of C-4 alkylated products with alkyl halides.

Original languageEnglish (US)
Pages (from-to)373-377
Number of pages5
JournalJournal of Organic Chemistry
Volume56
Issue number1
DOIs
StatePublished - Jan 1 1991

Fingerprint

Cycloaddition
Alkylation
Oxides
Deprotonation
Pyrroles
Nitrogen

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

@article{88ac7431103e450dba9056989c4d1a6a,
title = "Metalation and Alkylation of 3,6-Dihydrothiazine 1-Oxides Prepared via Diels-Alder Cycloadditions of N-Sulfinyl Dienophiles",
abstract = "The deprotonation of various 3,6-dihydrothiazine 1-oxides using LDA or methyllithium has been investigated. It was found that the stability and chemistry of these lithiated heterocycles are highly dependent upon the nature of the ring nitrogen substituent. Thus, N-alkyldihydrothiazine oxides can be metalated at C-6 to give species postulated as 9, which undergo predominantly anti alkylation with alkyl halides. Alternatively, with MeOD, 9 is deuterated at C-6 primarily in a syn mode. N-Silylated heterocycles ring open rapidly and stereoselectively upon metalation to give dienic sulfinamides like 19, which can be reclosed to the starting dihydrothiazine oxides. N-Phenyl-substituted 3,6-dihydrothiazine 1-oxides upon metalation give mixtures of pyrroles and N-S bond cleavage products. Attempts to generate the dianion from NH dihydrothiazine oxide 17 led only to low yields of C-4 alkylated products with alkyl halides.",
author = "Bell, {Scott I.} and M. Parvez and Weinreb, {Steven M.}",
year = "1991",
month = "1",
day = "1",
doi = "10.1021/jo00001a068",
language = "English (US)",
volume = "56",
pages = "373--377",
journal = "Journal of Organic Chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
number = "1",

}

Metalation and Alkylation of 3,6-Dihydrothiazine 1-Oxides Prepared via Diels-Alder Cycloadditions of N-Sulfinyl Dienophiles. / Bell, Scott I.; Parvez, M.; Weinreb, Steven M.

In: Journal of Organic Chemistry, Vol. 56, No. 1, 01.01.1991, p. 373-377.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Metalation and Alkylation of 3,6-Dihydrothiazine 1-Oxides Prepared via Diels-Alder Cycloadditions of N-Sulfinyl Dienophiles

AU - Bell, Scott I.

AU - Parvez, M.

AU - Weinreb, Steven M.

PY - 1991/1/1

Y1 - 1991/1/1

N2 - The deprotonation of various 3,6-dihydrothiazine 1-oxides using LDA or methyllithium has been investigated. It was found that the stability and chemistry of these lithiated heterocycles are highly dependent upon the nature of the ring nitrogen substituent. Thus, N-alkyldihydrothiazine oxides can be metalated at C-6 to give species postulated as 9, which undergo predominantly anti alkylation with alkyl halides. Alternatively, with MeOD, 9 is deuterated at C-6 primarily in a syn mode. N-Silylated heterocycles ring open rapidly and stereoselectively upon metalation to give dienic sulfinamides like 19, which can be reclosed to the starting dihydrothiazine oxides. N-Phenyl-substituted 3,6-dihydrothiazine 1-oxides upon metalation give mixtures of pyrroles and N-S bond cleavage products. Attempts to generate the dianion from NH dihydrothiazine oxide 17 led only to low yields of C-4 alkylated products with alkyl halides.

AB - The deprotonation of various 3,6-dihydrothiazine 1-oxides using LDA or methyllithium has been investigated. It was found that the stability and chemistry of these lithiated heterocycles are highly dependent upon the nature of the ring nitrogen substituent. Thus, N-alkyldihydrothiazine oxides can be metalated at C-6 to give species postulated as 9, which undergo predominantly anti alkylation with alkyl halides. Alternatively, with MeOD, 9 is deuterated at C-6 primarily in a syn mode. N-Silylated heterocycles ring open rapidly and stereoselectively upon metalation to give dienic sulfinamides like 19, which can be reclosed to the starting dihydrothiazine oxides. N-Phenyl-substituted 3,6-dihydrothiazine 1-oxides upon metalation give mixtures of pyrroles and N-S bond cleavage products. Attempts to generate the dianion from NH dihydrothiazine oxide 17 led only to low yields of C-4 alkylated products with alkyl halides.

UR - http://www.scopus.com/inward/record.url?scp=0001214179&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0001214179&partnerID=8YFLogxK

U2 - 10.1021/jo00001a068

DO - 10.1021/jo00001a068

M3 - Article

VL - 56

SP - 373

EP - 377

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 1

ER -