Efficient synthesis of an α-trifluoromethyl-α-tosyloxymethyl epoxide enabling stepwise double functionalisation to afford CF3-substituted tertiary alcohols

被引：8

作者：

Keeling, Steven P. ^{[1
]}

Campbell, Ian B. ^{[1
]}

Coe, Diane M. ^{[1
]}

Cooper, Tony W. J. ^{[1
]}

Hardy, George W. ^{[1
]}

Jack, Torquil I. ^{[1
]}

Jones, Haydn T. ^{[1
]}

Needham, Deborah ^{[1
]}

Shipley, Tracy J. ^{[1
]}

Skone, Philip A. ^{[1
]}

Sutton, Peter W. ^{[1
]}

Weingarten, Gordon A. ^{[1
]}

Macdonald, Simon J. F. ^{[1
]}

机构：

[1] GlaxoSmithKline Inc, Med Res Ctr, Resp CEDD, Stevenage SG1 2NY, Herts, England

来源：

TETRAHEDRON LETTERS | 2008年 / 49卷 / 34期

关键词：

alpha-trifluoromethyl epoxide; doubly electrophilic; desymmetrisation; glucocorticoid receptor agonists;

D O I：

10.1016/j.tetlet.2008.06.011

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The efficient synthesis of an alpha-trifluoromethyl-alpha-tosyloxymethyl epoxide is reported. This highly versatile building block may be reacted sequentially with two different nucleophiles to furnish alpha-trifluoromethyl tertiary alcohols. Furthermore, the two enantiomers of this key intermediate have been separated using chiral HPLC and the stereochemistry shown to be conserved during subsequent chemical manipulations. Finally, an enzyme-driven desymmetrisation approach has been successfully employed to confer chirality on an intermediate in the sequence. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：5101 / 5104

页数：4

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