Solvent-Controlled, Atom-Economic, and Highly Regio- and Stereoselective Halo-Chalcogenations of Ynamides: Green Synthesis of Stereodefined Tetrasubstituted Alkenes Bearing Four Different Functional Groups.

Abstract

The synthesis of stereodefined tetrasubstituted alkenes bearing four different functional groups is challenging. Herein, we disclose a 100% atom-economic and highly regio- and stereoselective halo-chalcogenations, in particular, chlorosulfenylation, bromosulfenylation, chloroselenation, and bromoselenation, of ynamides in toluene at room temperature under an aerobic atmosphere for the synthesis of a wide variety of stereodefined tetrasubstituted alkenes bearing four different functional groups in excellent yields. Notably, all the reactions are highly efficient and furnished the desired products in excellent yield (average yield >96%) and stereoselectivity (Z/E = 90:10 to >99:1) within a short time (15-30 min). Interestingly, the high (Z)-stereoselectivity (syn-addition) is controlled by the solvent. The transformation does not require any catalyst, oxidizing or reducing reagent, or external energy. The products were obtained pure by evaporating the solvent after the reaction and washing the crude product with either pentane or ethanol (column-chromatography-free protocol). Moreover, the solvent toluene was recovered and reused in subsequent reactions, which makes the protocol highly sustainable. The protocol is efficiently scalable (96% yield) on a gram scale. Notably, the products were synthetically diversified to other new classes of stereodefined tetrasubstituted alkenes. Significantly, the green chemistry metrics of the protocol are found to be excellent.