Cycloaddition 2- azetidinone ring

This procedure illustrates a general method for preparing aliphatic and, in certain cases, aromatic /3-lactarns containing a free NH group and substituted in either the 4 position or in both the-3 and 4 positions of the 2-azetidinone ring. The major byproduct of the cycloaddition step is a /3,7-unsaturated carbox-amide-N-sulfonyl chloride which, in the case of certain aromatic olefins, may predominate. Reactions of both /3-lactam-N-sulfonyl chlorides and the /3,y-unsaturated carboxamide-N-sulfonyl chlorides have been tabulated.3... 

The [2H-2]-cycloaddition of ketenes with imines is an excellent method for the generation of azetidinones, generally providing good yields and allowing a wide latitude in substitution pattern on the product. The major advances in this field during the period covered by this review have been in the synthesis of optically active compounds by asymmetric induction in the cycloaddition step. Chiral auxiliaries have been employed at all four positions of the azetidinone ring. 

The preparation of novel, strained tricyclic (3-lactams (Fig. 22) containing a cyclobutane ring has been developed to be performed by intramolecular [2+2] cycloaddition reactions of 2-azetidinone-tethered enallenols [299],... 

A rather intriguing route that both forms bond b as well as the annulated ring in a single step is outlined in Equation (2) <2005SL2370>. The starting azetidinone 12 is prepared by a ketene-imine cycloaddition. Treatment of 12 with methanolic HCl at reflux provides the aziridino-7-lactone 13 in excellent yield. 

The [2 -I- 2] cycloaddition of ketenes and imines is an important route to the P-lactam ring (azetidinone), which is a crucial structural feature of the penicillin class of antibiotics. A number of theoretical treatments of this reaction indicate that in solution phase this is a two-step reaction, with the second step being rate determining. The stepwise nature of the reaction is accommodated by the relative stability of both charged moieties, an iminium cation and an enolate anion. 

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