Transition metal-catalyzed C-C bond formation and reduction using carbene precursors

Abstract

1. Rhodium-Catalyzed C-8 Alkylation and Alkynylation of Quinoline N-Oxides via C-H Bond Activation Quinolines and their derivatives are an important class of N-heterocyclic compounds widely utilized in medicinal and materials chemistry. As a result, the derivatization of quinolines has received considerable attention in synthetic chemistry. We report herein a direct introduction of alkyl and alkynyl groups at the C-8 position of quinoline N-oxide, in which the N-oxide is an effective directing group. Under the optimized rhodium-catalyzed conditions, C-8 alkylation products are obtained using highly stabilized diazo compounds and C-8 alkynylation is achieved with the alkynylated hypervalent iodine reagent. The reaction is generally conducted at room temperature and proceeds efficiently with excellent regioselectivity. In addition, zinc-mediated deoxygenation of the N-oxide products takes place leading to the corresponding quinoline derivatives under mild conditions. 2. Catalytic Deoxygenation of N-Oxides via Oxygen Atom Transfer from N-Oxides to Copper-Carbenoids A new catalytic procedure of deoxygenation of various types of N-oxides including both heterocyclic and amine derivatives has been developed. With use of diazo compounds as the oxygen acceptor, the reaction proceeds by the catalytic oxygen atom transfer from N-oxides to in situ generated copper-carbenoids. Deoxygenation occurs smoothly over a broad range of substrates with excellent functional group tolerance under mild conditions. In addition, the current method successfully applied to the one-pot synthesis of 8-functionalized quinoline by directly using quinoline. Therefore, this new procedure can be highly useful especially when it is combined with the direct C-H bond activation strategy for the derivatization of heterocyclic compounds using N-oxide as a directing group. 3. Rhodium-Catalyzed C-H Functionalization of Benzamides with Conjugated Ene-Yne-Ketones for the Synthesis of Heterocyclic Compounds We have developed a novel rhodium-catalyzed C-H functionalization of benzamides employing conjugated ene-yne-ketones as the coupling partner. The dual reactivity of conjugated ene-yne-ketones allowed the formation of both furyl-substituted isoindolinones through rhodium-carbene migratory insertion followed by C-N bond formation and tricyclic isoquinolinones through alkyne insertion followed by intramolecular cyclization. This is the first example of incorporating conjugated ene-yne-ketones into the C-H bond activation, and provides new synthetic methods for heterocyclic compounds. Further studies will focus on controlling the dual reactivity of conjugated ene-yne-ketones and demonstrating the synthetic utility of this methodology.