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Asymmetric Diels–Alder Cycloaddition of 1‐Aminocyclohexadiene to Chiral Acrylate: Synthesis of Enantiopure Bridgehead‐Aminobicyclo[2.2.2]octane‐2‐carboxylic Acid Derivatives
Author(s) -
Songis Olivier,
Didierjean Claude,
Laurent Camille,
Martinez Jean,
Calmès Monique
Publication year - 2007
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.200700236
Subject(s) - enantiopure drug , bicyclic molecule , chemistry , octane , selectivity , carboxylic acid , stereochemistry , acrylate , cycloaddition , ene reaction , yield (engineering) , organic chemistry , enantioselective synthesis , catalysis , polymer , monomer , materials science , metallurgy
The acrylate derivative of the ( R )‐4‐(3‐hydroxy‐4,4‐dimethyl‐2‐oxopyrrolidin‐1‐yl)benzoic acid benzyl ester ( R ) ‐2 reacted with 1‐(benzyloxycarbonylamino)cyclohexadiene 3 under microwave irradation in solvent‐free conditions to yield [4+2] cycloadducts in good yields (91 %). The reaction proceeded with moderate endo selectivity (67 %) and good facial selectivity (90 %). The major cycloadducts were isolated and transformed to afford three enantiopure bicyclic β‐amino acids: (1 S ,2 R ,4 R )‐1‐(benzyloxycarbonylamino)bicyclo[2.2.2]oct‐5‐ene‐2‐carboxylic acid [(1 S ,2 R ,4 R )‐ 4 ], (1 R ,2 R ,4 S )‐1‐(benzyloxycarbonylamino)bicyclo[2.2.2]oct‐5‐ene‐2‐carboxylic acid [(1 R ,2 R ,4 S )‐ 5 ] and ( R )‐1‐aminobicyclo[2.2.2]octane‐2‐carboxylic acid [( R )‐ 6 ]. This work has led to the preparation of these enantiopure bicyclic β‐amino acids and provides a rare example of an asymmetric Diels–Alder reaction by microwave activation. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)