US EPA

7546996 

Journal Article 

Stereoselective synthesis of 3-hydroxy-2,6-dialkylpiperidines 

Harding, KE; Jones, MW 

1989 

Yes 

Heterocycles
ISSN: 0385-5414 

PERGAMON-ELSEVIER SCIENCE LTD 

OXFORD 

28 

2 

663-668 

English 

10.3987/com-88-s109 

WOS:A1989U446100021 

A new method for stereoselective synthesis of 3-hydroxy-2,6-dialkylpiperidine alkaloids is reported. The key trans-oxazolidine intermediate 8 was generated by mercuric ion-initiated cyclofunctionalization of an N-acylaminomethyl ether derivative of allylic alcohol 5 (6 → 7). Racemic deoxocassine (3) was synthesized by addition of a C11 chain (8 → 9), cleavage of the oxazolidine ring under basic conditions (9 → 17), and reductive amination to generate the piperidine ring (17 → 3). It was found that attempts to cleave the cyclohexyl carbamate group of oxazolidine 9 under acidic conditions resulted in rapid rearrangement to oxazolidinone 10 with inversion of stereochemistry at the O-substituted carbon. This oxazolidinone was converted to racemic isodeoxycassine (4) by ring cleavage (10 → 14) and reductive amination. Treatment of oxazolidine 9 under strongly acidic conditions led to isolation of the 3-acetoxy-2,5-dialkylpiperidine 11, the product of an intramolecular Mannich reaction. © 1989.