8-thia-2-azabicyclo octanes

Cavalleri et al. (219) studied the cycloaddition of thioisomiinchnones with 5-amino-4-methylene-l,2,3-triazolines. The resulting cycloadducts afford 2-pyridones with Raney Ni or 8-thia-6-azabicyclo[3.2.1]octanes with acid. Kato has continued his extensive exploration of cycloaddition studies of mesoionic heterocycles with atypical dipolarophiles. Thus, whereas thioisomiinchnone (320) gave a complex mixture with 6,6-dimethylfulvene (119), it reacted with 2-tert-butyl-6,6-dimethylfulvene to afford 321 in 17% yield (151,152). The cycloaddition of 320 with benzocyclobutadiene was much cleaner to give 322 in 70% yield (114). 

The cephalosporins, discovered in the 1950s, are produced by various species of the mold Cephalosporium. Cephalosporin C (9.46) is the prototype of these antibiotics, and its structure shows a close similarity to the penam stmcture. The 5-thia-l-azabicyclo[4.2.0] octane ring system is therefore called the cepham ring. The parent compound carries the aminoadipate side chain, which can be cleaved to supply the 7-amino-cephalosporanic acid. This amine can easily be acylated and thus forms the basis of many useful derivatives. The 3-acetoxymethyl substiment is also amenable to modifications. 

Chlorosulfene, generated in situ from chloromethanesulfonyl chloride and triethylamine, reacted with l-methyl-4-(4-morpholinyl)-l,2,5,6-tetrahydropyridine to form 117a and 117b, the two possible stereoisomers of 7-chloro-8,8-dioxo-3-methyl-6-(4-morpholinyl)-8-thia-3-azabicyclo[4.2.0]octane, in a ratio of 56 to 44."5 The reaction of the... 

N-Condensed benzothiazoles. A soln. of N-(o-bromophenyl)-5-/ r/-butylthio-2-pyrrolidone and Bu3SnD in deaerated benzene containing a little azodiisobutyro-nitrile refluxed under N2 until reaction complete (4-18 h) 2,3-benzo-8-oxo-4-thia-l-azabicyclo[3.3.0]octane. Y 89%. F.e. incl. N-condensed 2//-l,3-benzothiazines from N-(o-bromobenzyl)-analogs s. A.L.J. Beckwith, D.R. Boate, J. Org. Chem. 53, 4339-48 (1988). 

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