Palladium and Nickel Catalyzed Transformations Forming Functionalized Dihydroisoquinolinones, Chromans, Dihydrobenzofurans and Oxindoles

Transition metal catalysis has been at the forefront of synthetic organic chemistry as it represents new and powerful methods to forge carbon–carbon in high atom- and step-economy. The Lautens group has been particularly focused on Pd- and Rh-catalysis in stereo- and regioselectively generating functionalized heterocycles. In chapter 1, a Pd- and Ni-catalyzed cycloisomerization reaction of aryl iodides to alkyl iodides, known as carboiodination, is described. In the Pd-catalyzed variant, a diastereoselective Pd-catalyzed carboiodination reaction of enantioenriched carboxamides generating dihydrosioquinolinones is explored. The transformation was the key step in the formal synthesis of (+)-corynoline. In the Ni-catalyzed variant, 3,3-disubstituted oxindoles are generated in excellent yield and an enantioselective variant employing a dual ligand system is disclosed. In chapter 2, a Pd-catalyzed diastereoselective anion-capture cascade reaction is discussed. Building on the Pd-catalyzed carboiodination reaction en route to (+)-corynoline, a Pd-catalyzed aryl cyanation is discussed. The alkyl nitrile was synthesized in high yield and d.r. The second method generates borylated chromans as a single diastereomer in good yield. The alkyl boronate was further functionalized to showcase its utility. In chapter 3, a Pd-catalyzed domino process harnessing carbopalladation, C–H activation and π-system insertion to generate spirocycles is reported. In the first method, benzynes are inserted to give spirodihydrobenzofurans and spirooxindoles. A significant limitation in the first method pertains to the low regioselectivity observed. To circumvent these problems, in the second method, polarized alkynes are inserted in >20:1 r.r.Ph.D.2020-10-30 00:00:0