Studies On The Transition Metal-Catalyzed Aromatic C-H Functionalization

Heterocyclic compounds in medicine, pesticides, dyes, polymers, especially in the life sciences have very important applications. The synthesis of heterocyclic compounds has become a hot topic area in organic synthesis. On the other hand, great efforts have already been made on the transition metal-catalyzed cyclization of functionalized allene in our group. Based on these observations, the main theme of my dissertation is focus on gold and platinum-catalyzed aromatic C-H bond functionalization to construct indole, carbazoles and naphthalene compounds. This dissertation includes five chapters:1. An activated zinc or indium-mediated Barbier-type addition reaction of 2,3-allenals with allyl bromide was developed to provide an efficient route to 1,5,6-alkatrien-4-ols, which is synthetically very useful. No 1,4-addition reaction was observed.2. Transition metal-catalyzed cyclization of allenols can generate the vinyl metal intermediate. In the attempt of the electron-rich aromatic C-H bond functionalization with this intermediate, we developed a highly regioselective PtCl4-catalyzed reaction of indoles withα-,β-orγ-allenols affording indole derivatives containing a five-, six-or seven-member ether ring at the 3-position. Based on a D-labeling experiment, a mechanistic rationale was proposed.3. Based on the intermolecular C-H functionazation reaction of allenols in the presence of indoles, we developed a new modular synthesis of differently substituted carbazoles via the PtCl2-catalyzed cyclization of 1-(indol-2-yl)-2,3-allenols, which involves 1,2-H, alkyl, or aryl migration of metal carbene intermediates. The migratory tendency of 1,2-migration of the metal carbene have been observed:(1) Compare hydrogen with alkyl and aryl group,1,2-hydrogen migration is exclusive; (2) Compare the 1,2-alkyl with 1,2-aryl migration, aryl served as the 1,2-migration group exclusively. Furthermore, this method has also been applied in the synthesis of some natural products with biological activity, especially carbazoles alkaloid such as clauszoline-K, clauszoline-L,3-formyl-7-hydroxycarbazole, clausine M, clausine N and siamenol.4. We further extended the reaction to electron-rich benzene rings, by developing a highly efficient method for synthesis of naphthalene compounds. Iodination of the gold species afforded iodonaphthalenes, which are useful building blocks to introduce molecular complexity and diversity. A possible mechanism of the reaction involving the formation of naphthyl Au specie instead of metal carbene was proposed based on the mechanistic study.5. We also expand the reaction scope to indole-substituted propargyl alcohol to construct carbazoles.