Azetidinone oxazoline

The combination of the electrogenerated chloro cation [Cl] with diphenyldise-lenide is a typical example of the functionalization of an olefin. The electrochemical oxyselenation-deselenation of (1) to (2) proceeds in an MeOH-NaCl-(Pt) system (Scheme 1) [32]. The bromide salt-promoted oxyselenation of olefins is discussed in Sect. 15.2.2. Penicillin (3) can be converted into the oxazoline-azetidinone (4) by a chloride salt-promoted paired reaction in an MeOH-t-BuOH(5 l)-MgCl2-(Pt) system at —40°C in 74 93% yield (Scheme 2) [33, 34]. This conversion probably involves an initial attack of an... 

Scheme 2 Conversion of penicillin into a oxazoline-azetidinone.

Good stereoselectivity is observed in the synthesis of 3,4-dihydroisocoumarins from the oxazoline 49 and the protected leucinal 50 (Scheme 29). Further reaction with an azetidinone introduces a dipeptide unit at C-3 <99JCS(P1)1083>. 

Direct Transformation of Penicillins into Oxazoline-Azetidinones. 161... 

Phthalimidopenicillin 21, which is not able to produce the oxazoline system, affords azetidinone 22 upon electrolysis in acidic media, and subsequent treatment of 22 with triethylamine gives the chlorinated azetidinone 23 in 70% overall yield (from 21, Scheme 2-7) 19>. 

The disulfide-enols 345 were converted to oxazoline-azetidinones 346 by intramolecular trapping of the azetinium cation [or of an intermediate 5-epiclavem 196] by the acylamino oxygen atom (various protocols trimethyl phosphite or triphenyl-phosphine treatment preferred). After mesylation, oxaz-oline cleavage with dry HCl afforded chloroazetidinones 347 with neat inversion of configuration, which underwent ring closure (H2S/TEA) to give the prescribed (5 R )-6-acylamino-2-methylpenems. 

Thus, the key intermolecular, stereoselective oxazoline-opening reaction in the Method 3 affording 4i -allyloxyazetidinone (38) was modified to an intramolecular oxazoline opening reaction with a hydroxy group at the terminal position of side chain attached to N-1 of azetidinone. 

A soln. of 2-phenyl-4-methyl-2-oxazolin-5-one and N-benzylidene-n-butylamine in dry benzene refluxed 2 hrs. -> l-n-butyl-3-benzoylamino-3-methyl-4-phenyl-2-azetidinone. Y 50%. F. e. s. K. K. Prasad and T. Petrzilka, Helv. 58, 2504 (1975). 

Oxazoline-azetidinones are also prepared by degradation of penicillinates with mercury(ii) acetate. The mercuric salt (124) is converted into the propenyl azetidinone (126) when it reacts with DMSO, or the ester (127) with... 

The oxazoline ring of (126) is cleaved with thiols and alcohols in the presence of acid catalysts however, ring-opening is non-stereospecific, affording mixtures of cis- and trnwi-azetidinones. Methods for the removal of the propenyl substituent have been developed for the ring-opened compounds [e.g. (126) -> (128) (129)]. ... 

In addition to the S—C-2 bond cleavages described thus far, both S—C-5 and C-3—N bond cleavage have been explored in penicillin degradation. Chlorinolysis of penicillin effects S—C-5 cleavage, affording the 4-chloro-2-azetidinone (105 t,y), from which the cephalosporin disulphide (106 f,z) was prepared (Scheme 4). The structure and stereochemistry of (106) were determined by X-ray techniques. Chlorinolysis of an N-trityl-anhydropeni-cillintoluene-p-sulphonate (107 g) gave, after hydrolysis, a sulphur-free 2-azetidinone (108 z, R = NHi), which cyclized to the oxazoline (109) on reaction with chloroformate esters. Allylic bromination of (108 f, y) afforded a monobromide (110), from which the azacephem (111 f, y) was obtained by... 

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