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An Efficient Synthesis of Highly Functionalised 4‐Substituted 2‐Azetidinones by a Stereoselective Intermolecular Diels−Alder Reaction of Different Types of 2‐Azetidinone‐Tethered Dienes
Author(s) -
Alcaide Benito,
Almendros Pedro,
Salgado Nati R.,
MartínezAlcázar Mari Paz,
HernándezCano Félix
Publication year - 2001
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 - 10.1002/1099-0690(200105)2001:10<2001::aid-ejoc2001>3.0.co;2-m
Subject(s) - chemistry , dimethyl acetylenedicarboxylate , cycloaddition , moiety , diels–alder reaction , diene , stereoselectivity , adduct , acetylenedicarboxylate , stereochemistry , medicinal chemistry , organic chemistry , catalysis , natural rubber
The diastereoselectivity of the intermolecular Diels−Alder reaction of 2‐azetidinone‐tethered dienes was investigated. Diene precursors were prepared from 4‐azetidinone‐2‐carbaldehydes through an allylation−dehydration process or by the sequence Wittig reaction/enolate trapping. Dienes with a β‐lactam ring at the allyl carbon of the diene moiety reacted with some acyclic symmetric dienophiles, such as dimethyl acetylenedicarboxylate and dimethyl fumarate, to yield Diels−Alder adducts efficiently in a highly diastereoselective manner. In addition, reaction with an unsymmetrical monoactivated dienophile, methyl propiolate, produced a single regioisomer. Intermolecular Diels−Alder reaction of 2‐azetidinone‐tethered dienes with cyclic dienophiles such as N ‐methyl and N ‐phenylmaleimide proceeded with modest endo/exo diastereoselectivity. Reaction of 2‐azetidinone‐tethered furans with dimethyl acetylenedicarboxylate gave 7‐oxabicyclo[2.2.1]heptanes with modest diastereoselectivity. Retro‐Diels−Alder reaction of these adducts, with cleavage of bonds other than those formed in the initial Diels−Alder cycloaddition, gave 4‐ethynyl‐β‐lactams.