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Synthesis and Structural Elucidation of 1,2‐Disubstituted 3‐Fluoropiperidines
Author(s) -
Fischer Pauline,
Morris Morgan,
MüllerBunz Helge,
Evans Paul
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202000026
Subject(s) - chemistry , sulfonyl , sulfonamide , adduct , stereochemistry , selectfluor , nuclear magnetic resonance spectroscopy , amination , medicinal chemistry , organic chemistry , catalysis , alkyl
The work described details the reaction between Selectfluor® and a series of 1‐carbonyloxy and 1‐sulfonyl 2‐piperidines in order to generate 3‐fluoro‐2‐methoxypiperidines 3a – f . Their subsequent reaction with allyltrimethylsilane, in the presence of BF 3 and TiCl 4 , is then reported. Studies involving a combination of single‐crystal X‐ray crystallography and NMR spectroscopy indicate that the allylation process is cis ‐selective for both carbamate and sulfonamide variants and that optimal levels of diastereoselectivity are obtained using the N ‐2‐nitrobenzene sulfonyl (2‐Ns) group. In this manner, the synthesis of a series of 2‐allyl 3‐fluoro‐substituted piperidines ( 5a , c – f ) was achieved. The conversion of both the cis and trans‐N ‐tosyl adducts ( 5d ) into 3‐fluorinated analogues of the natural products pelletierine ( 10 ) and coniine ( 11 ) is subsequently detailed.