Azetidinones azides

Treatment of N-benzoyl-L-alanine with oxalyl chloride, followed by methanolic triethylamine, yields methyl 4-methyl-2-phenyloxazole-5-carboxylate 32 <95CC2335>. a-Keto imidoyl chlorides, obtained from acyl chlorides and ethyl isocyanoacetate, cyclise to 5-ethoxyoxazoles by the action of triethylamine (e.g.. Scheme 8) <96SC1149>. The azetidinone 33 is converted into the oxazole 34 when heated with sodium azide and titanium chloride in acetonitrile <95JHC1409>. Another unusual reaction is the cyclisation of compound 35 to the oxazole 36 on sequential treatment with trifluoroacetic anhydride and methanol <95JFC(75)221>. 

Various nucleophilic attacks at C(3) and C(4) of -lactams have been employed to introduce desired functionalities. Nucleophilic displacement of a halogen at C(3) by nucleophiles, for example, potassium phthalimide, has been performed (93JCS(Pl)2357). The a-azidation of l-hydroxy-2-azetidi-nones, for example (37), with arenesulfonyl azides in the presence of triethylamine affords 3-azido-2-azetidinones (38) via Otosylation and SN2 -type of displacement of the tosyloxy group (92JA2741, 93JA548, 93BMC2429). 

The p-amino-a-hydroxy esters have been converted to diamino acids [88, 89] and related compounds like the nitrogen-substituted azetidinone shown in Scheme 13, a key structure in the synthesis of the commercially available antibiotic loracarbef [90] by substitution of the alcohol moiety with an azide. Several approaches have been used to achieve this transformation. Mesylation of the alcohol followed by substitution with sodium or trimethylsilyl azide provided cis-diamino acids [88,89]. trans-Diamino acids were obtained by ring opening of the aziridine [88] or by inversion of the alcohol bearing carbon followed by substitution under Mitsunobo conditions [90]. 

Dehydration. This reagent is useful for synthesis of acyl azides from carboxylic acids, NaCN, and pyridine, with tetrabutylammomum bromide as catalyst (75-95% yield). In combination with pyridine, it effects dehydration of oximes to nitriles in 80-90% yield, P-Lactams can be prepared directly in 40-75 )t yield from carboxylic acids and imines with the reagent (1 equiv,) and triethylamine (excess). In general, a mixture of cis- and rra/j5-azetidinones is formed. 

Aza-Claisen rearrangements, 469-470 3-Azalactams, 472 Azetidines, 503 Azetidinones, 490-491 Azides, 394... 

The most versatile method of preparing a-azidocarboximides2 and protected a-amino acids is based on early investigations3. In this study the lithium enolate 2 of the azetidinone 1 [prepared with lithium diisopropylamide (LDA)] is treated with tosyl azide to afford an adduct 3, isolated and characterized by IR spectroscopy as the lithium salt of an acyclic triazene3. 

Aryl diazonium tetrafluoroborates, 298 Aryllithiums, 76 Aryl methyl ethers, 50 1-Axylnaphthalide ligans, 49-50 N-Arylsulfonyl-2-phenylaziridines, 169 1-Aryltetralones, 370 Arylthallium ditrifluoroacetates, 300 Avenaciolide, 305, 306 Azacyclanones, 398 Azetidines, 169 Azetidinone, 192 Azides, 48... 

Nitrogen is introduced into the 3-position of the azetidinone ring as an azido group by reaction of TBS-protected 43 with 2,4,6-triisopropylbenzenesulfonyl azide. The reaction is stereospecific, yielding the desired trans 3S,4R relationship. 

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