Nickel-Catalyzed Reductive Couplings Of Alkynes Research Articles

Ni-Catalyzed Reductive Coupling of Alkynes and Amides to Access Multi-Functionalized Indoles.

A nickel-catalyzed reductive coupling of alkynes and amides, followed by base-free transmetalation, proceeded selectively in the presence of an uncommon bidentate primary aminophosphine ligand to access highly functionalized indoles comprising biologically important trifluoromethyl groups and challenging electron-rich alkenyl groups at the 2- and 3-positions, respectively. Indole molecules were installed within natural products or drug molecules under mild conditions, and a trifluoromethylated analogue of a drug molecule (pravadoline) was also synthesized.

NHC ligand-enabled Ni-catalyzed reductive coupling of alkynes and imines using isopropanol as a reductant

A nickel-catalyzed reductive coupling of alkynes and imines using readily available isopropanol as the reducing agent was developed.

Enantioselective Nickel-Catalyzed Reductive Coupling of Alkynes and Imines

The nickel-catalyzed reductive coupling of alkynes and imines with Et(2)Zn as a reductant by using electron-rich phosphine ligands has been developed, affording various allylic amines with high yields and excellent chemoselectivities. Chiral induction was also achieved in this reductive coupling reaction when a nickel catalyst containing a chiral spiro phosphine ligand was used.

Origins of regioselectivity and alkene-directing effects in nickel-catalyzed reductive couplings of alkynes and aldehydes.

The origins of reactivity and regioselectivity in nickel-catalyzed reductive coupling reactions of alkynes and aldehydes were investigated with density functional calculations. The regioselectivities of reactions of simple alkynes are controlled by steric effects, while conjugated enynes and diynes are predicted to have increased reactivity and very high regioselectivities, placing alkenyl or alkynyl groups distal to the forming C-C bond. The reactions of enynes and diynes involve 1,4-attack of the Ni-carbonyl complex on the conjugated enyne or diyne. The consequences of these conclusions on reaction design are discussed.

Cobalt‐ and Nickel‐Catalyzed Regio‐ and Stereoselective Reductive Coupling of Alkynes, Allenes, and Alkenes with Alkenes

Transition-metal-catalyzed coupling of two different C-C pi components through a metallacycle intermediate is a highly atom economical method to construct C-C bonds in organic synthesis. The metal-catalyzed coupling of an alkene and alkyne generally gives an Alder-ene or reductive coupling product. In this article, we focus on the cobalt- and nickel-catalyzed reductive coupling of alkynes, allenes, and alkenes with alkenes. These reductive coupling reactions provide convenient methods for the synthesis of various alkenes, dienes, functionalized alkanes, lactones, lactams, and cyclic alcohols in a highly regio- and stereoselective manner. A chemselective formation of metallacyclopentene intermediate from the two different C-C pi components and a low-valence metal species plays a key role for the high regio- and stereoselectivity of the catalytic reaction.

Anti-1,2-Diols via a Ni-Catalyzed Reductive Coupling

anti-1,2-Diols were prepared using a nickel-catalyzed reductive coupling of alkynes to α-oxyaldehydes. Both the MOM- and PMB-protected alcohols gave the anti-1,2-diol products despite the fact that these protecting groups typically display a preference for syn-1,2-diols. The observed sense of induction was explained by the absence of a chelating metal in the reaction allowing a ‘dipolar’ transition state to predominate. Larger substituents on the side of the alkyne where C-C bond formation occurs improves the diastereoselectivity but gives poorer yields. Heteroatom substituents on the alkyne are also tolerated.

Nickel-catalyzed reductive coupling of alkynes and epoxides.

Nickel-catalyzed, intramolecular and intermolecular reductive coupling of alkynes and epoxides affords synthetically useful homoallylic alcohols of defined alkene geometry. Very high regioselectivity is generally observed, and cyclizations proceed with complete selectivity for endo epoxide opening. This catalytic reaction represents the first use of a non-pi-based electrophile in a growing class of nickel-catalyzed, multicomponent coupling reactions, and is the first catalytic method of reductive coupling of alkynes and epoxides that is effective for both intermolecular and intramolecular cases, and mechanistically distinct from these, possibly involving a nickella(II)oxetane.