Nickel-Catalyzed Reductive Couplings and Cyclizations

Hasnain A. Malik, Ryan D. Baxter, and John Montgomery 

Catalysis Without Precious Metals. Edited by R. Morris Bullock 2010 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 978-3-527-32354-8 

Three-Component Couplings via Alkyl Croup Transfer-Methods Development 

Reductive Couplings via Hydrogen Atom Transfer-Methods Development 

The ability to promote reductive coupling provides a powerful complement to the alkylative coupling methodology discussed previously (Section 8.2.1), as either E- or Z-isomers of the exocyclic olefin 1 can be stereoselectively produced in an 

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MCRs Involving Ni-NHC Catalysts Nickel-catalyzed reductive couplings and cyclizations allow access to important organic stractures through MCRs that involve two or more r-components, like alkenes and carbonyl groups [83], In this section, these types of catalytic processes based on Ni-NHC are discussed. 

The core skeleton of geissoschizine, an important biosynthetic precursor to numerous polycyclic indole scaffolds, was the target of a nickel-catalyzed alkylative coupling strategy. Cyclization precursor 13 was prepared by ozonolysis and double reductive amination of cyclopentene 12 (Scheme 8.13) [35]. Nickeldeprotection/oxidation sequence followed, and chromatography led to complete inversion of the C3 stereocenter. A Fisher indole synthesis followed to afford ( )-deformyl-isogeissoschizine, the core skeleton of geissoschizine. 

Although the titanium-based methods are typically stoichiometric, catalytic turnover was achieved in one isolated example with trialkoxysilane reducing agents with titanocene catalysts (Scheme 28) [74], This example (as part of a broader study of enal cyclizations [74,75]) was indeed the first process to demonstrate catalysis in a silane-based aldehyde/alkyne reductive coupling and provided important guidance in the development of the nickel-catalyzed processes that are generally more tolerant of functionality and broader in scope. 

C-C bond formation mediated by silane.6,6a 6f With respect to the development of intramolecular variants, these seminal studies lay fallow until 1990, at which point the palladium- and nickel-catalyzed reductive cyclization of tethered 1,3-dienes mediated by silane was disclosed. As demonstrated by the hydrosilylation-cyclization of 1,3,8,10-tetraene 21a, the /rarcr-divinylcyclopentanes 21b and 21c are produced in excellent yield, but with modest stereoselectivity.46 Bu3SnH was shown to participate in an analogous cyclization.46 Isotopic labeling and crossover experiments provide evidence against a mechanism involving initial diene hydrosilylation. Rather, the collective data corroborate a mechanism involving oxidative coupling of the diene followed by silane activation (Scheme 15). 

Montgomery J. Nickel-catalyzed reductive cyclizations and couplings. Angew. Chem. Int. Ed. 2004 43 3890-3908. 

Nickel-catalyzed reductive cyclizations and couplings in the syntheses of heterocycles including coupling of alkynes with epoxides and syntheses of indole and indolizidine alkaloids 04AG(E)3890. 

Reaction conditions amenable to nickel-catalyzed reductive cyclization of alkynyl enones were ineffective in the intermolecular variant In the course of developing catalytic [3 -l- 2] cycloadditions of alkynes and enals [24], it was discovered that by simply using an enone instead of an enal electrophile, catalytic intermolecular reductive coupling could be achieved in a Ni(COD)2/Bu3P catalyst system using EtsB as a reducing agent in a MeOH/THF (8 1) solvent system (Scheme 8.5) [25). 

The nickel catalyzed cyclization of 7-oxabenzonorbomadiene and methyl butyn-2-oate in the presence of a stoichiometric amount of zinc led to the formation of 4-methyl-benzocoumarin in good yield (4.43.), In the proposed mechanism of the process the reductive coupling of the starting materials gives a naphthylacrylic acid derivative, which under the applied conditions undergoes spontaneous Z-E isomerisation and ring closure to furnish the tricyclic product.57... 

Heinicke and co-workers [41, 42] developed a two-step synthesis of 1/7-1,3-benzazaphospholes (33) involving nickel-catalyzed coupling of 2-bromo- or 2-chloroanilides with triethylphosphite followed by reductive cyclization with excess LiAlH4 (Scheme 10). 

Similar to the results discussed for the silylcarbocyclizations of carbon-carbon multiple bonds, reductive cyclizations in the presence of carbonyl compounds are readily achieved. Crowe has developed a titanium-catalyzed procedure for the intramolecular reductive coupling of i5, -unsaturated carbonyl compounds in the presence of triethoxysilane (eq 18).The electronic advantage of triethoxysilane is demonstrated by the lack of reductive coupling in the presence of less reactive silanes, such as triethylsilane and diphenylsilane. With this method, Mori has utilized nickel(O) catalysts to generate five- and six-membered carbocycles and pyrrolidine derivatives. Furthermore, coordination of a chiral phosphine ligand to the nickel catalyst renders the reaction moderately enantioselective. ... 

The first example reported in the literature is the cyclization of dihydrobilin to octadehydrocorrin [51-54]. The reaction is catalyzed by the presence of nickel or cobalt salts. As in the case of corrole and its metal complexes such ring closure reaction has been carried out in alcoholic solution, it is oxidative and base catalyzed. It has been demonstrated that the formation of the corrin ring is part of an equilibrium where the oxidative ring closure is coupled with a reductive ring opening reaction [55]. 

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