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{2}O coordinated lithium thiolates R}1{N(H)-C(SLi)@?C(NR{2})-COOEt (2a: R{2} = -Si(CH{3}){2}-CH{2}CH{2}-Si(CH{3}){2}-; R}1{ = Ph; 2b: R{2} = -Si(CH{3}){2}-CH{2}CH{2}-Si(CH{3}){2}-; R}1{ = -CH{2}Ph; 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]-@b-enamino ester 3c', the S-protonated product, which is in slow equilibrium with the C-protonated tautomer. Ring closure to 4-thioxo-@b-lactams was unsuccessful. Highly functionalized 3-methylthio-@b-enamino esters were obtained via S-alkylation of the lithium thiolates 2 with iodomethane.