N-Hydroxy-2-azetidinones

Reduction of hydroxamic acids. Buffered TiC lj can reduce simple hydroxamic acids (equation I). Yields are high when R1 is an alkyl group when it is hydrogen, aldehydes are obtained as by-products. The reagent also reduces substituted N-hydroxy-2-azetidinones to /Mactams (equation 11). 

Hydroxyacenaphthene, 438 a-Hydroxy aldehydes, 19-20, 419 9a-Hydroxy-4-androstene-3,17-dione, 36 N-Hydroxy-2-azetidinones, 504... 

P-Lactams.1 A biomimetic synthesis of /3-lactams from chiral amino acids such as L-serine has been developed by Mattingly and co-workers. The protected amino acid (1) is first converted into the O-alkyl or O-acyl hydroxamate (2), which undergoes cyclization to derivatives of l-hydroxy-2-azetidinones on treatment with triphenylphosphine-carbon tetrachloride. This cyclization is also possible with triphenylphosphine-diethyl azodicarboxylate.2 The final step involves reduction of the N—OH group with TiClj.3 The advantage of this method over that of Wasserman (9,428), which involves cyclization of /3-haloamides, is that a strong base such as NaH is not required. 

S-Hydroxy-l-azetidinones. A biomimetic synthesis of the y3-lactam 4 from BOC-L-serine (1) has been reported. The protected serine derivative is converted into the hydroxamic acid 2 by condensation with O-benzylhydroxylamine mediated by the water-soluble l-ethyl-3(3 -dimethylaminopropyl)carbodiimide (1, 371). The product is cyclized directly in high yield to the / -lactam 3 by treatment with diethyl azodicarboxylate and triphenylphosphine. No racemization is observed. Deprotection by catalytic hydrogenation gives the N-hydroxy-jS-lactam 4. Previous biomimetic syntheses of 2-azetidinones have involved cyclization ot /3-cMoroamides with sodium hydride (e.g., 7, 335). 

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