Nickel mediation

The 11-membered ring of humulene, a major impediment to synthesis, was constructed by a novel nickel-mediated cyclization. 

The Gassman indole synthesis involves an one-pot process in which hypohalite, a P-carbonyl sulfide derivative 2, and a base are added sequentially to an aniline or a substituted aniline 1 to provide 3-thioalkoxyindoles 3. Raney nickel-mediated desulfurization of 3 then produces the parent indole... 

In 1974, Gassman et al. reported a general method for the synthesis of indoles. For example, aniline 5 was reacted sequentially with r-BuOCl, methylthio-2-propanone 6 and triethylamine to yield methylthioindole 7 in 69% yield. The Raney-nickel mediated desulfurization of 7 then provided 2-methylindole 8 in 79% yield. The scope and mechanism of the process were discussed in the same report by Gassman and coworkers as well. 

Abstract A literature overview, up to the end of 2004, of the most important microwave-assisted transition-metal-mediated processes used for the decoration and construction of heterocycles is presented. The emphasis of the chapter lies in the use of palladium-assisted reactions but examples of copper- and nickel-mediated processes are also incorporated. 

Deming TJ (1998) Amino acid derived nickelacycles intermediates in nickel-mediated polypeptide synthesis. J Am Chem Soc 120 4240-4241... 

Witte P, Menzel H (2004) Nickel-mediated surface grafting from polymerization of alpha-amino acid-N-carhoxyanhydrides. Macromol Chem Phys 205 1735-1743... 

Scheme 6/4.15. Nickel-mediated formation of the triquinane skeletons.

Scheme 4.21 Efforts toward D-ring formation via nickel-mediated reductive cyclization and Sakurai allenylation...

Both iron- and nickel-mediated cyclooligomerization processes have been used in direct routes to pyrrole derivatives. Preformed ferracyclopentadiene complexes can be converted in moderate yields into 2,3,4,5-tetraphenyl-... 

Scheme 6.79 Hydrosilylation of ketones [164], Dotz benzannulation chemistry [165], cobalt-mediated synthesis of angular [4]phenylenes [166], and nickel-mediated coupling polymerizations [167],...

Barluenga and co-workers reported a novel [2 + 2 + 2 + 1 (-reaction based on the use of two metals, the nickel-mediated [2 + 2 + 2 + l]-reaction of Fischer carbenes with alkynes (Scheme 73).142 While, at present, this process requires the stoichiometric use of both metals, it is highly regioselective, affords good yields, and is a novel route to seven-membered rings. 

Beyond the numerous applications of palladium in transition metal-catalyzed domino reactions there are a lot of other metals inducing domino processes. Ihara et al. found a strategy for the enan-tioselective synthesis of (+)-equilenin catalyzed by mangan and palladium complexes,1841 Whitby et al.1851 initiated domino cyclizations on a zirconocene template and furthermore Scherf et al. generated phenantrones by a nickel-mediated one-pot domino reaction.1861... 

Moreover, the involvement of hydroxyl radicals in the nickel mediated enhancement of lipid peroxidation has been suggested [348], which may have implications in the carcinogenicity of nickel compounds. The enhancement of lipid peroxidation might be the result of depletion in the level of hepatic glutathione peroxidase. 

The regiochemistry of nickel mediated cycloadditions of substituted norbomadienes has been investigated in detail. The regioselectivity, exo/endo selectivity and site selectivity seem to depend strongly on the substituents on both diene and dienophile. Tetracya-noethene, for example, reacted with 2-acetyloxymethyl substituted norbomadiene on the distal side331. 

Adducts were obtained as exclusive adducts or as by-products in the nickel mediated reactions of some substituted norbomadienes with various dienophiles. The formation of these products was considered to result from an intermediate metallocy-clopentane species built up of the metal center, the dienophilic double bond and one of the double bonds of the norbomadiene moiety. 

Prenylaniline (945) required for the synthesis of (+ )-carquinostatin A [( )-278] (see retrosynthesis in Scheme 5.126) was obtained by a nickel-mediated cross-coupling reaction of the N-protected 4-bromoaniline 952 with bis[n-bromo(r -prenyl)nickel] (825) (646) (Scheme 5.128). 

Regioselective electrophilic bromination of the carbazole 1025 afforded the 6-bromocarbazole 1026. Cleavage of the methyl ether to 1027 and subsequent nickel-mediated coupling using a dimeric 7i-prenylnickel bromide complex prepared in situ from prenyl bromide 925 and bis(l,5-cyclooctadiene)nickel(0) led directly to siamenol (89) (546) (Scheme 5.151). 

Oxidation of 3-formyl-6-methoxycarbazole (97) with manganese dioxide and potassium cyanide in methanol afforded methyl 6-methoxycarbazole-3-carboxylate (104). Regioselective bromination of 97 afforded the 5-bromocarbazole 1031. Cleavage of the methyl ether to 1032, followed by nickel-mediated prenylation, provided micromeline (100) (547) (Scheme 5.154). 

Recently, palladium-catalyzed carbonylation of chloropyrimido[4,5-d]pyrimidines has been reported (Equation 51) <2006W0065703>. Raney nickel-mediated desulfurization of alkylthiopyrimido[4,5-, pyrimidines was described in GHEC(1984), and has been applied recently both in the desulfurization of reduced species (Equation 52) <2001WO64679> and for cleavage of sulfur linkages in traceless solid-phase synthesis <1999BMCL965,... 

The Ni(III) oxidation state is biologically significant (101,102). Moreover, high-valent nickel species may be intermediates in some catalytic oxidations (97) and in the nickel-mediated sequence-specific oxidative cleavage of DNA by designed metalloproteins (103) as discussed in Section I,G. The chemistry of Ni(III) macrocyclic complexes has been... 

Figure 8-7. A nickel-mediated pbosphanation of a bromoarene. The precise mechanistic details of this reaction are not known.

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