Synthesis of (-)-(S, S)-clemastine by invertive N → C aryl migration in a lithiated carbamate

Anne M. Fournier; Robert A. Brown; William Farnaby; Hideki Miyatake-Ondozabal; Jonathan Clayden

doi:10.1021/ol100627c

Synthesis of (-)-(S, S)-clemastine by invertive N → C aryl migration in a lithiated carbamate

Anne M. Fournier, Robert A. Brown, William Farnaby, Hideki Miyatake-Ondozabal, Jonathan Clayden^*

^*Corresponding author for this work

School of Chemistry

Research output: Contribution to journal › Article (Academic Journal) › peer-review

56 Citations (Scopus)

Abstract

The first enantioselective synthesis of the antihistamine agent clemastine, as its (S,S)-stereoisomer, has been achieved by ether formation between a proline-derived chloroethylpyrrolidine and an enantiomerically enriched tertiary alcohol. The tertiary alcohol was formed from the carbamate derivative of α-methyl-p-chlorobenzyl alcohol by invertive aryl migration on lithiation. The (S,S)-stereochemistry of the product confirms the invertive nature of the rearrangement.

Original language	English
Pages (from-to)	2222-2225
Number of pages	4
Journal	Organic Letters
Volume	12
Issue number	10
Early online date	20 Apr 2010
DOIs	https://doi.org/10.1021/ol100627c
Publication status	Published - 21 May 2010

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title = "Synthesis of (-)-(S, S)-clemastine by invertive N → C aryl migration in a lithiated carbamate",

abstract = "The first enantioselective synthesis of the antihistamine agent clemastine, as its (S,S)-stereoisomer, has been achieved by ether formation between a proline-derived chloroethylpyrrolidine and an enantiomerically enriched tertiary alcohol. The tertiary alcohol was formed from the carbamate derivative of α-methyl-p-chlorobenzyl alcohol by invertive aryl migration on lithiation. The (S,S)-stereochemistry of the product confirms the invertive nature of the rearrangement.",

author = "Fournier, {Anne M.} and Brown, {Robert A.} and William Farnaby and Hideki Miyatake-Ondozabal and Jonathan Clayden",

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T1 - Synthesis of (-)-(S, S)-clemastine by invertive N → C aryl migration in a lithiated carbamate

AU - Fournier, Anne M.

AU - Brown, Robert A.

AU - Farnaby, William

AU - Miyatake-Ondozabal, Hideki

AU - Clayden, Jonathan

PY - 2010/5/21

Y1 - 2010/5/21

N2 - The first enantioselective synthesis of the antihistamine agent clemastine, as its (S,S)-stereoisomer, has been achieved by ether formation between a proline-derived chloroethylpyrrolidine and an enantiomerically enriched tertiary alcohol. The tertiary alcohol was formed from the carbamate derivative of α-methyl-p-chlorobenzyl alcohol by invertive aryl migration on lithiation. The (S,S)-stereochemistry of the product confirms the invertive nature of the rearrangement.

AB - The first enantioselective synthesis of the antihistamine agent clemastine, as its (S,S)-stereoisomer, has been achieved by ether formation between a proline-derived chloroethylpyrrolidine and an enantiomerically enriched tertiary alcohol. The tertiary alcohol was formed from the carbamate derivative of α-methyl-p-chlorobenzyl alcohol by invertive aryl migration on lithiation. The (S,S)-stereochemistry of the product confirms the invertive nature of the rearrangement.

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U2 - 10.1021/ol100627c

DO - 10.1021/ol100627c

M3 - Article (Academic Journal)

C2 - 20405879

AN - SCOPUS:77952410561

SN - 1523-7060

VL - 12

SP - 2222

EP - 2225

JO - Organic Letters

JF - Organic Letters

IS - 10

ER -

Synthesis of (-)-(S, S)-clemastine by invertive N → C aryl migration in a lithiated carbamate

Abstract

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