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
收藏
页码：1222 / 1229
页数：8
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