title: Diastereoselective syntheses of (3R*,4R*)- and (3R*,4S*)-4-aryl-3-methyl-4-piperidinemethanol and fluoro analogues.
abstract: 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.
authors.affiliation: CNRS, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, Boulevard Henri Becquerel, BP5229, F-14074 Caen Cedex, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Schmitt
authors.forename: Richard C D
authors.initials: RC
authors.lastname: Brown
authors.forename: Cécile
authors.initials: C
authors.lastname: Perrio
mesh_terms: D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D000432:Methanol / Q000737:chemistry*; D010881:Piperidones / Q000138:chemical synthesis* / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D006845:Hydrocarbons, Fluorinated; D010881:Piperidones; D011725:Pyridines; D000432:Methanol