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Useful Dual Diels–Alder Behavior of 2‐Azetidinone‐Tethered Aryl Imines as Azadienophiles or Azadienes: A β ‐Lactam‐Based Stereocontrolled Access to Optically Pure Highly Functionalized Indolizidine Systems
Author(s) -
Alcaide Benito,
Almendros Pedro,
Alonso Jose M.,
Aly Moustafa F.
Publication year - 2003
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.200304712
Subject(s) - chemistry , imine , aryl , cycloaddition , medicinal chemistry , lactam , diels–alder reaction , combinatorial chemistry , catalysis , stereochemistry , organic chemistry , alkyl
Imines derived from 4‐oxoazetidine‐2‐carbaldehydes have been found to be versatile Diels–Alder reagents in that they exhibit two reactivity patterns. 2‐Azetidinone‐tethered imines undergo diastereoselective reaction with Danishefsky's diene in the presence of different Lewis acids. The effect of the amount of catalyst on the conversion rate as well as on the product ratio has been studied. Under standard reaction conditions, indium( III ) chloride and zinc( II ) iodide provided the best yields, and indium( III ) triflate the highest diastereoselectivity in the Lewis acid promoted aza‐Diels–Alder cycloaddition. Treatment of the aforementioned imines with cyclopentadiene, 2,3‐dimethyl‐1,3‐butadiene or 3,4‐dihydro‐2 H ‐pyran led to cycloadducts arising from inverse electron‐demand condensation involving the β ‐lactam‐tethered aryl imine as the heterodiene component. In addition, the first methodology for preparing indolizidines from β ‐lactams has been developed. This process involves amide bond cleavage of the β ‐lactam ring in the aza‐Diels–Alder cycloadducts with concomitant cyclization. Full chirality transfer occurs when the reaction is performed with an enantiomerically pure substrate.