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Diastereodivergent Pictet–Spengler Cyclization of Bicyclic N ‐Acyliminium Ions: Controlling a Quaternary Stereocenter
Author(s) -
de CarnéCarnavalet Benoît,
Krieger JeanPhilippe,
Folléas Benoît,
Brayer JeanLouis,
Demoute JeanPierre,
Meyer Christophe,
Cossy Janine
Publication year - 2015
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.201403469
Subject(s) - stereocenter , chemistry , bicyclic molecule , pictet–spengler reaction , moiety , protonation , nucleophile , stereochemistry , ring (chemistry) , ion , medicinal chemistry , enantioselective synthesis , organic chemistry , catalysis
The diastereoselectivity of the Pictet–Spengler cyclization of bicyclic N ‐acyliminium ions that contain a 3‐azabicyclo[ n .3.0]alkane core and an electron‐rich π‐nucleophilic moiety, such as an indol‐2‐yl, indol‐3‐yl, 1‐methylpyrrol‐2‐yl, or 3,5‐dimethoxyphenyl group, was examined. The N ‐acyliminium ions were generated by protonation of the corresponding enamides or hemiaminals, which were derived from imides. Control of the quaternary stereocenter created at the newly formed ring junction was achieved in a diastereodivergent manner by fine‐tuning the reaction conditions, which determined whether the reaction proceeded under kinetic or thermodynamic control. Mechanistic studies indicated that a retro‐Pictet–Spengler reaction pathway is involved in the equilibration process.