Ligand-Controlled Regiodivergent Pathways of Rhodium(III)-Catalyzed Dihydroisoquinolone Synthesis: Experimental and Computational Studies of Different Cyclopentadienyl Ligands

• Published in: Chemistry : a European journal 2014-11, Vol.20 (47), p.15409-15418
• Main Authors: Wodrich, Matthew D., Ye, Baihua, Gonthier, Jérôme F., Corminboeuf, Clémence, Cramer, Nicolai
• Format: Article
• Language: English
• Subjects: Activation; Adducts; Catalysis; Catalysts; Chemistry; density functional calculations; Formations; homogeneous catalysis; Insertion; ligand control; Pathways; Rhodium; transition state theory
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201404515

RhIII‐catalyzed directed CH functionalizations of arylhydroxamates have become a valuable synthetic tool. To date, the regioselectivity of the insertion of the unsaturated acceptor into the common cyclometalated intermediate was dependent solely on intrinsic substrate control. Herein, we report two different catalytic systems that allow the selective formation of regioisomeric 3‐aryl dihydroisoquinolones and previously inaccessible 4‐aryl dihydroisoquinolones under full catalyst control. The differences in the catalysts are computationally examined using density functional theory and transition state theory of different possible pathways to elucidate key contributing factors leading to the regioisomeric products. The stabilities of the initially formed rhodium complex styrene adducts, as well as activation barrier differences for the migratory insertion, were identified as key contributing factors for the regiodivergent pathways. RhIII‐catalyzed directed CH functionalization of aryl hydroxamates enables the selective formation of regioisomeric 3‐aryl or 4‐aryl dihydroisoquinolones with two different catalytic systems. The different selectivities are examined using DFT and transition state theory. The stabilities of the rhodium complex adducts and migratory‐insertion activation barriers are key factors for the regiodivergent pathways (see scheme; rs=regioselectivity).