Studies On The Cul-Catalyzed Intramolecular Vinylation Of Aryl Ketones And PPh₃-catalyzed Intramolecular Cyclization Of Propiolic Amides And Synthesis Of Pentazocine

Four-membered ring compounds are very important building blocks in organic synthesis. Our attention was focused on the synthesis of cyclobutenones via copper-catalyzed intramolecular cyclization of aryl ketones as the strategy. We also developed a methodology for the synthesis of α-methylene-β-lactams through phosphine-catalyzed intramolecular cyclization of propiolic amides. Additionally, we also made some efforts on synthesis of pentazocine. The dissertation could be described as the following three parts:1. The feasibility of the intramolecular C-vinylation of aryl ketones in a4-exo mode under typical Ullmann reaction conditions was explored. Employing Cul (20mol%),3,4,7,8-tetramethyl-1,10-phenanthroline (40mol%) and Cs2CO3(2equiv.) in refluxing THF as the optimized reaction conditions, the four-membered cyclobutenones could be efficiently synthesized. The competition experiments revealed that the4-exo ring closure is fundamentally preferred over5-exo cyclization. With improved temperature, the cyclization of alkyl ketone proceeded smoothly. By using the sterically hindered substrate, we can get4-exo O-cyclization product instead of C-cyclization product.2. With PPh3(10mol%) as the catalyst, EtOH as the solvent, the intramolecular cyclization of proliolic amides proceeded smoothly. Through this procedure, we could synthesis α-methylene-β-lactams in a very effective and short way comparing to proceeding methods. Through inspection of the efficacy of substrates with different structures, we found three factors having important influence on our cyclization reactions:conformation of amides, steric hindrance and inductive effects. And we found the conformation of amides being the most important factor.3. Synthesis of pentazocine was investigated. Though many reaction conditions being tried, efforts to construct the key8-menbered ring structure through intramolecular Friedel-Craft reaction failed.