3 Amino 4 alkyl 2 azetidinones

Scheme 46 Synthesis of 3-amino-4-alkyl-2-azetidinones by [2+2] cycloaddion of aliphatic hydra-zones to N-benzyl-A-(benzyloxycarbonyl)aminoketene...

In 2001, 3-unsubstituted 4-alkyl-4-carboxy-2-azetidinones have been reported to be prepared by base-assisted intramolecular alkylation of /V-benzvI -/V-chloroacetyl amino acid derivatives [180]. /V-benzyl or /V--methoxvbenzvI) amino acid derivatives in THF, treated with propylene oxide and chloroacetyl chloride afforded the /V-chloroacetyl amino acid derivatives. The treatment of the latter in CH3CN with CS2CO3 (or NaH) produced the intramolecular cyclization of 4,4-disubstituted (3-lactams, (Scheme 81). 

A general approach towards the asymmetric synthesis of amino acid derived 4-alkyl-4-carboxy-2-azetidinones has been described [192], The (+)- or (-)-lO-(N, Af-dicyclohexylsulfamoyl)isobomeol was used as chiral auxiliary in the intramolecular cyclization of /V-(/>methoxybenzyI)-/V-chloroacetyl Phe and Ala derivatives for the stereocontrolled base-catalyzed construction of the (1-lactam ring (Scheme 85). 

The photochemical behavior of aminocyclohexenones depends on the substituents on nitrogen. Cyclization of iV-arylketoenamines to 2-carbazolones is achieved photochemic-ally332 (equation 251). However JV-benzyl-jV-tosyl-a-ketoenamines yield stereospecific-ally on irradiation a-keto azetidinones. Branched N-alkyl substituents suffer desulphona-tion and intramolecular aryl migration to give 2-amino-3-aryl-2-cyclohexenones333 (equation 252). 

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. 

The chemistry of substituted cyclopropanones is even more engagingly complicated. For example, 2,2-dimethylcyclopropanone acetals were shown to react with alkyl azides in the presence of BFs-OEta to afford a-amino-of-diazomethylketones like 12 along with a small amount of 3-azetidinones 13 (Scheme 7.10). Interestingly, aryl-substituted... 

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