Highly functionalized β-enamino esters via C-C coupling reactions of lithium enolates of protected glycine esters and isothiocyanates

Abstract

Lithium enolates of N,N-diprotected glycine esters were reacted with isothiocyanates, affording Et 2O coordinated lithium thiolates R 1N(H)-C(SLi)C(NR 2)-COOEt ( 2a: R 2 = −Si(CH 3) 2-CH 2CH 2-Si(CH 3) 2-; R 1 = Ph; 2b: R 2 = −Si(CH 3) 2-CH 2CH 2-Si(CH 3) 2-; R 1 = −CH 2Ph; 2c: R = Et; R 1 = Ph), in which the carboxyl oxygen atom is coordinated to lithium. Thiolate 2a was shown to be dimeric in the solid state by X-ray crystal structure determination. Hydrolysis of N-protected lithium thiolates 2a and 2b afforded 2-aminothiomalonamic esters 3a and 3b, resulting from C-protonation. N,N-diethyl substituted lithium thiolate 2c afforded mainly [2-(N,N-diethyl)amino-3-mercapto]-β-enamino ester 3c′, the S-protonated product, which is in slow equilibrium with the C-protonated tautomer. Ring closure to 4-thioxo-β-lactams was unsuccessful. Highly functionalized 3-methylthio-β-enamino esters were obtained via S-alkylation of the lithium thiolates 2 with iodomethane.