The Cul-Catalyzed Intramolecular C-Vinylation Of Activated Methylene Compounds And O-vinylation Of Ketone Enolates

The CuI-Catalyzed Ullmann type C-X (X=N, O, S etc) coupling reactions have been demonstrated to be a useful and efficient method in organic synthesis. In recent years, it has received a great attention because of its mild, eco-friendly, easy operating and economical condtions. In this dissertation, the synthesis of functionalized alkylidenecyclobutanes, y-lactams and highly substituted furans via intramolecular Ullmann type C-vinylation and O-vinylation was reported. It could be described as the following three parts:1 We first explored the feasibility of the 4-exo C-vinylation of activated methylene compounds under Ullmann reaction conditions. Employing 10 mol% CuI,40 mol % L-proline,3 equivalents Cs2CO3 refluxing in different solvents as the optimized reaction condtions, we first reported the 4-exo C-vinylation of activated methylene compounds and efficiently synthesized functionalized alkylidenecyclobutanes. The configuration of the double bond was retained in the products. The 5-exo and 5-endo reactions were also successful. By competition experiments, we found that the 4-exo cyclization was preferred over the 5-exo ring closure. With reoptimized condtions, the cyclization of 2-cyanoactates proceeded smoothly, indicating that different types of activated methylene compounds require different reaction condtions.2 On the basis of the above C-vinylation, we synthesizedγ-lactams via the intramolecular C-vinylation of amides with vinyl halides. With 10 mol% CuI as the catalyst,40 mol% 3,4,7,8-tetramethyl-1,10-phenanthroline as the ligand and 3.0 equivalents of Cs2CO3 as the base, a series of alkylidenelactams were successfully synthesized. A wide variety of functional groups was tolerated under the reaction condition. Moreover, the formation of quaternary carbon atom made the study of enantioselectivity possible. 3 We also carried out the O-vinylation of ketone enolates. With 10 mol% CuI as the catalyst, 20 mol% 3,4,7,8-tetramethyl-1,10-phenanthroline as the ligand and 2.0 equivalents of Cs2CO3 as the base, refluxing in different solvents as the optimized reaction conditions, we could synthesized a series of multi-substituted furans. By competition experiments, we found that the endo-cyclization was preferred over the exo-cyclization. Moreover, the vinyl chloride and the 6-endo substrates could also give excellent results.