Premium
Synthesis of 3‐Fluoropyrrolidines and 4‐Fluoropyrrolidin‐2‐ones from Allylic Fluorides
Author(s) -
Combettes Lorraine E.,
Schuler Marie,
Patel Rakesh,
Bonillo Baltasar,
Odell Barbara,
Thompson Amber L.,
Claridge Tim D. W.,
Gouverneur Véronique
Publication year - 2012
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201201576
Subject(s) - allylic rearrangement , nucleophile , fluorine , chemistry , substituent , diastereomer , electrophile , selectivity , medicinal chemistry , ring (chemistry) , amide , stereochemistry , organic chemistry , catalysis
Various 3‐fluoropyrrolidines and 4‐fluoropyrrolidin‐2‐ones were prepared by 5‐ exo‐trig iodocyclisation from allylic fluorides bearing a pending nitrogen nucleophile. These bench‐stable precursors were made accessible upon electrophilic fluorination of the corresponding allylsilanes. The presence of the allylic fluorine substituent induces syn ‐stereocontrol upon iodocyclisation with diastereomeric ratios ranging from 10:1 to > 20:1 for all N ‐tosyl‐3‐fluoropent‐4‐en‐1‐amines and amides. The sense and level of stereocontrol is strikingly similar to the corresponding iodocyclisation of structurally related allylic fluorides bearing pending oxygen nucleophiles. These results suggest that the syn selectivity observed upon ring closure involves I 2 –π complexes with the fluorine positioned inside .