Sequential One-Pot Reactions of Thioformamides with Organolithium and Zinc Reagents

Abstract

Sequential one-pot reactions of thioformamides with organolithium and zinc reagents were carried out. As thioformamides, N,N-dimethylthioformamide and N-ethoxycarbonyl N′-thioformyl piperazine were used. A variety of organolithium reagents such as alkyl, aryl, and heteroaryllithiums were used to give the corresponding amines in moderate to high yields. The efficiency of the reaction was influenced by the substituents on the aromatic rings. Thienyllithium gave the product in good yield, whereas the reaction of furyllithium was less efficient. A similar reaction with lithium acetylides was not successful. As an alternative method, methyl iodide was added to the reaction mixture of thioformamides and lithium silylacetylide to form S,N-acetals as intermediates, and to this were added organozinc reagents to lead to propargylamines. For organozinc reagents, dialkyl zincs and 3-ethoxycarbonylpropylzinc bromide were used. The former reagents showed high efficiency when combined with several organolithium reagents, but the latter gave the corresponding product only when lithium silylacetylide was used as an initial reagent.

Keywords:

• Amines
• organolithium reagents
• organozinc reagents
• piperazines
• sequential reaction

Acknowledgments

This work was supported in part by Grant-in-Aid for Scientific Research on Innovative Areas (Integrated Organic Syntheses) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.