Studies On The Rhodium-Catalyzed Cycloisomerization Of N-Tethered 1,6-Enynes

The transition metal-catalyzed carbocyclization of 1,6-enynes is efficient and atom-economic way to construct ring frameworks which widely exist in natural products and biologically active molecules. We have realized a cycloisomerization reaction of N-tethered 1,6-enynes with an intramolecular halogen shift by using a cationic rhodium catalytic system ([Rh(cod)Cl]2/dppb/AgSbF6). Starting from N-(4-chlorobut-2-enyl) amides and amines, we can make stereodefinedγ-butyrolactam and pyrrolidine derivatives with exocyclic vinyl-chloride structure.This kind of reaction has a large scope to the electron-deficient substrates, while the reactivities to the electron-rich substrates are sensitive to the substituents on the nitrogen atom. In the study of the results, we presumed that the nitrogen atom in the subtrate may coordinate with the rhodium species in the catalytic cycle, which may influence the course of the reaction. Particularly for the amine substrates, the coordinating ablity of the nitrogen atom is determined by the electronic feature of the substituents on it. This is the key reason which made different reaction activities between amide and amine substrates. On the other hand, the coordinating ablity of the nitrogen atom made it possible to achieve the cyclization of the E-isomers of N-tethered enynes with high yields, which set off the shortcomings and further broadened the scope of this kind of reaction.In the study of Rh(I)-catalyzed asymmetric cycloisomerization of 1,6-enynes, we found that the counter-ion in the system had a great influence on the enantioselectivities of the reaction. After screening a series of C₂-symmetric atropisomeric diphosphine ligands, we found both steric feature and electronic feature of the phosphine ligand had effect on the enantioselectivities. Since the ee values of the products were also determined by the tethered atoms, E/Z structure and the substituents on the acetylenic terminal of the substrates, we can hardly demonstrate a general rule for choosing ligand for different substrates. The ee values were up to 97.9% under optimized reaction conditions.We found that halogen exchange between allyl and alkyl halides are quite common in the presence of Wilkinson catalyst and proposed a possible mechanism. The possible mechanism of the reaction involves oxidative addition and reductive elimination of the C(sp3)-X bonds, which was rare in organometallic chemistry. The concentration of alkyl halide is one of the decisive factors in controlling the completion of this transformation. The results of some control experiments supported the hypothesis that the oxidative addition step of C(sp3)-X bond involving a radical reaction.