Diastereoselective Syntheses of (3R,4R)- and (3R,4S)-4-Aryl-3-methyl-4-piperidinemethanol and Fluoro Analogues

被引：3

作者：

Schmitt, Sebastien ^{[1
,2
,3
]}

Brown, Richard C. D. ^{[4
]}

Perrio, Cecile ^{[1
,2
,3
]}

机构：

[1] CNRS, LDM TEP, UMR ISTCT 6301, GIP Cyceron, F-14074 Caen, France

[2] Univ Caen Basse Normandie, LDM TEP, UMR ISTCT 6301, GIP Cyceron, F-14074 Caen, France

[3] CEA, DSV I2BM, UMR ISTCT 6301, LDM TEP,GIP Cyceron, F-14074 Caen, France

[4] Univ Southampton, Sch Chem, Southampton SO17 1BJ, Hants, England

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2013年 / 78卷 / 03期

关键词：

DIRECT ALPHA-ARYLATION; NUCLEOPHILIC-SUBSTITUTION; OPIOID ANTAGONISTS; ARYL HALIDES; NITRILES; POTENT; DISCOVERY; IDENTIFICATION; MILD;

D O I：

10.1021/jo302303h

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Two concise and high-yielding diastereoselective syntheses of 4-aryl-3-methyl-4-piperidinemethanols were realized from 1,3-dimethyl-4-piperidinone. The key reactions to control the C3-C4 relative stereochemistry were the alkoxymethylation of a metalloenamine generated from 4-aryl-3-methyl-1,2,3,6-tetrahydropyridine that afforded the (3R*,4S*)-form and the nucleophilic substitution of a fluoroarene with deprotonated 3-methyl-4-piperidinenitrile giving the (3R*,4R*)-isomer. The corresponding fluoromethyl analogues were subsequently obtained through the fluorination of the piperidinemethanols using DAST.

引用

页码：1222 / 1229

页数：8

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Diastereoselective Syntheses of (3R*,4R*)- and (3R*,4S*)-4-Aryl-3-methyl-4-piperidinemethanol and Fluoro Analogues

Diastereoselective Syntheses of (3R,4R)- and (3R,4S)-4-Aryl-3-methyl-4-piperidinemethanol and Fluoro Analogues