Transition-Metal-Catalyzed Novel Carbon-Carbon Bond-Forming Reaction

Carbon-carbon bond formation is the most basic way of constructing organic molecules. Studies focusing on carbon-carbon bond formation have been throughout the history of organic chemistry. Classic carbon-carbon bond-forming reactions such as Grignard, Wittig, and Diels-Alder reactions have played significantly important roles in organic synthesis since their discoveries. During the past four decades, transition-metal-catalyzed carbon-carbon bond-forming reactions have experienced a boost, and have become one of the most important tools in modern organic synthesis. Cyclization and coupling reactions are two prominently attractive and popular areas within the field of transition-metal-catalyzed reactions. In recent years, these two types of transformations have been utilized extensively to produce organic molecules, which are closely related to human life, such as pharmaceuticals, agrichemicals, dyes and materials. Transition-metal-catalyzed reductive cyclization and oxidative coupling are novel directions derived from cyclization and coupling separately. This paper briefly reviewed these novel transformations, and compared them with conventional metal-catalyzed cyclizaition and coupling reactions. Based on the strategies of reductive cyclization and oxidative coupling, this paper studied novel methods of constructing carbon-carbon bond. It mainly consists of the following three parts:1. The nickel-catalyzed reductive cyclization of unactivated 1,6-enynes has been developed. In this transformation, low-cost and air-stable Ni(acac)2 was used as the pre-catalyst, dialkylzinc reagent was employed as a reductant. As carbon-carbon bonds have been successfully constructed, as well as substrates have been reduced, various pyrrolidine and tetrahydrofuran derivatives have been afforded in a generally highly setereoselective manner from the corresponding nitrogen- or oxygen-tethered 1, 6-enynes. Proposed mechanism was confirmed through the deuterium-experiment.2. The palladium-catalyzed oxidative cross-coupling between terminal alkynes and alkylzinc reagents has been developed using air as an oxidant and carbon monoxide as a ligand. A broad scope of substrates could be employed in this carbon-carbon bond-forming reation. Confirmed by ligand experiments, carbon monoxide, which acted as aπ-acidic ligand, played a critical role during this transformation. Monitored with in situ FTIR, the production and consumption of alkynylzinc reagents was discovered under catalytic conditions. It uncovered that the essence of this transformation was the coupling between different zinc nucleophiles. At the same time, based on the results of kinetic experiments, we proposed the cause for the excellent selectivity of this oxidative cross-coupling. It could be rationalized in terms of two reasons:(1) under our catalytic conditions, the rate of carbon-carbon bond formation is Csp-Csp3>Csp-Csp>Csp3-Csp3 and (2) the strategy of generating alkynylzinc reagents in situ could suppress side-reactions of alkynes effectively.3. The palladium-catalyzed aerobic oxidative cross coupling between arylboronic acids and allylic alcohols has been accomplished in the presence of catalytic amount of copper salts. With this general carbon-carbon bond forming protocol, variousβ-aryl ketones and aldehydes could be prepared via a highly selectiveβ-H elimination pathway with no need of any ligands, bases or additives. When substrates containing highly active arylbromide and aryliodide, which are unable to be tolerated in traditional metal-catalyzed coupling, were subjected to this reaction, corresponding target molecules could be produced in high yields. Investigations including blank experiments, experiments with different copper salts and extra additives etc. have revealed the dual role of copper salts. One is functioning as the electron-transfer-mediators to promote the oxygenation of the palladium while the other is acting as Lewis acids to enhance the regioselectivity ofβ-H elimination. Meanwhile, the palladium catalyzed cascade oxidation/1,4-addition pathway was unambiguously excluded based on the results of individual experiments. Moreover, when the reaction monitored by in situ FTIR was performed under stoichiometric conditions, an intermediate supposed to be the enolate species was discovered by serendipity.