Alkyl isocyanates 2-azetidinones from

The first synthesis 104, 105) of racemic thienamycin by the Merck group made use of the azetidinone (113) derived from acetoxybutadiene and chlorosulphonyl isocyanate (CSI). Reduction, hydrolysis and condensation with acetone gave the 1,3-tetrahydrooxazine (114). Introduction of the hydroxyethyl side chain by way of an aldol condensation produced predominantly the thermodynamically more stable tra s-P-lactam (115) as a mixture of R)- and (5)-isomers in the side chain. On removal of the acetone residue a proportion of the unwanted (5)-isomer crystallised from the mixture. The synthesis was continued with the mixture by way of the aldehyde (116) and the thio-acetal (117). Bromination, elimination and introduction of the iV(l) malonate residue gave (119) ready for an intramolecular alkylation reaction. 

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