4 Alkyl 4 carboxy 2 azetidinones

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 asymmetric synthesis of 4-alkyl-4-carboxy-2-azetidinones 18 has been achieved through base-mediated intramolecular cyclization of the corresponding Af-a-chloroacetyl derivatives bearing (+)- or (-)-10-(W,A,-dicyclohexylsulfamoyl)isobomeol as chiral auxiliary (ee up to 82%) <02JOC3953> <02H501>. 

---