Magnesium lactam enolates

This method has been used to prepare the antibiotic thienamycin. The magnesium enolate of the /3-lactam was prepared from the 6-iodo derivative in THF (equation 9/ . 

Aldol reactions of simple amide enolates give poor stereoselection. Stimulated by the interest in /3-lactams, the stereochemistry of aldol reactions of chiral magnesium enolates of /3-lactams has been studied . The best results have been obtained with 6,6-dibromopenams 85 (equation 108). After bromine-magnesium exchange with MeMgBr,... 

Chlorophenyl)glutarate monoethyl ester 87 was reduced to hydroxy acid and subsequently cyclized to afford lactone 88. This was further submitted to reduction with diisobutylaluminium hydride to provide lactol followed by Homer-Emmons reaction, which resulted in the formation of hydroxy ester product 89 in good yield. The alcohol was protected as silyl ether and the double bond in 89 was reduced with magnesium powder in methanol to provide methyl ester 90. The hydrolysis to the acid and condensation of the acid chloride with Evans s chiral auxiliary provided product 91, which was further converted to titanium enolate on reaction with TiCI. This was submitted to enolate-imine condensation in the presence of amine to afford 92. The silylation of the 92 with N, O-bis(trimethylsilyl) acetamide followed by treatment with tetrabutylammonium fluoride resulted in cyclization to form the azetidin-2-one ring and subsequently hydrolysis provided 93. This product was converted to bromide analog, which on treatment with LDA underwent intramolecular cyclization to afford the cholesterol absorption inhibitor spiro-(3-lactam (+)-SCH 54016 94. 

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