Penem 2-hydroxy

Cyclizations with nitrogen nucleophiles involving alkynes and allenes have received little attention until recently. The cyclizations of several a-aminoallenes to 3-pyrrolines with silver tetrafluoroborate was reported by Claesson and coworkers (equation 133).264 A similar cyclization to form A -carba-penems has been reported (equation 134).265 Diastereomeric allenes (R1 R2) were shown to cyclize with complete stereocontrol. Cyclization with palladium chloride in the presence of allyl bromide or electrophilic alkenes allowed for the intermediate vinylpalladium species to be trapped by the electrophile.2651 A related product was obtained by cyclization of an alkynic substrate (equation 13S).265 Other examples of 5-endo cyclization of p-aminoalkynes50 include the formation of indoles by cyclization of 2-alkynylanilines with mercury salts200 or palladium chloride,266a,266b,266c formation of 1-pyrrolines with catalytic palladium chloride (equation 136)198 and formation of pyrroles by cyclization of hydroxy-substituted p-aminoalkynes.198,2666... 

The azetidinone ring is cleaved in penem (62) to give thiazole (63) and 3-hydroxy-butyric acid in methanolic solution in the crystals, intramolecular hydrogen abstraction occurs and the biradical is trapped by oxygen to yield hydroperoxide (64) (see... 

The synthesis of penems has been the object of intensive research in the last decade. Stereoselective synthesis of azetidinones, chemoselective cleavage of the thiazolidine ring of penicillins, hydroxy-ethylation at the lactam a carbon, and penem annulation reactions are the important issues addressed in this work. By confronting possibilities with achievements, a comprehensive but readable survey of this chapter of antibiotic chemistry is attempted. 

Mention has already been made of attempts to obtain 2-hydroxy- and 3-hydroxypenams (compounds 301 and 303), from which penems might have been generated by loss of the elements of water. The reductive elimination performed on the 2,3-diphenylthiopenam 316 by Kametani [182], and the oxidative elimination accomplished by Hanessian on the 2-methylthio compound 298 [29], are successful examples of penem synthesis achieved from isolated penam intermediates. Other examples of this strategy involve Pummerer-type rearrangements. The preparation of penem 306 by treatment of penam sulfoxide... 

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