Nickel thioesters

In the synthesis of a-amino acids [290] through addition of the carbanion of MMTS to nitriles the overall process involves three other steps frequently encountered in sulfur-mediated chemistry a Pummerer-type rearrangement, with a less common migration of a methylthio group, and a Raney nickel desulfurization following transesterification of the thioester function. 

Despite the toxicity of volatile metal carbonyls, particularly Ni(CO)4, several useful transformations have been developed employing these reagents. Monocarbonylation of gem-dibromocyclopropanes may be accomplished with Ni(CO)4 in the presence of alcohols, amines or (less successfully) thiols, to afford cyclopropane carboxylic esters, amides or thioesters, respectively (equation 202)400. Silylamine or silylsulfide reagents may take the place of amines or thiols401. The intermediacy of a nickel enolate in the carbonylations is... 

Well-defined nickel-sulfur complexes that enable a stepwise combination of CO, alkyl, and thiol groups to give thioesters can be anticipated to yield deeper insight into the molecular mechanism of the acetyl-CoA synthesis (142, 149). The complex [Ni(C3Me2—S4)] afforded an example for such a thioester synthesis. In principle, it is even catalytic and Scheme 36 summarizes the individual steps (10). 

A comparison of Eq. 54 and Scheme 36 reveals that the nickel center performs two functions. First, the nickel center acts as mediator of the two electron-transfer reactions during which S—C bonds are cleaved and formed (36 —> 37 and 39 —> 40). Second, it facilitates the formation of an acyl group from an alkyl group and CO (38 —> 39). This reaction is expected to be favored when the nickel center has a coordination number lower than 5. A low coordination number of nickel also facilitates the final release of the thioester in the consecutive reaction of 39 with excess CO, because intermediates such as complex 42 can readily form. 

In conclusion, the [NiS] mediated formation of thioesters from alkyl, CO, and thiol groups lends support to an acetyl-CoA formation pathway that comprises CO insertion into a Ni Me and an intramolecular S -C bond formation between nickel-bound acyl groups and thiolate ligands. These reactions are favored at square-planar nickel complexes that enable two-electron redox reactions and readily add fifth ligands. 

Unlike two previous theories of life origin, only a few pieces of experimental evidence exist at present to prove the theoretical speculations. However, we have to notice the verification of the basic mechanism of molecular hydrogen generation as a reducing power, furthermore, the amide bond synthesis has been also demonstrated, both at temperatures within the range of hydrothermal vents (100 °C). In addition, the evidence for at least sulfide-based amino acid synthesis and polymerization from simple precursors has been shown. The formation of acetic acid and an activated thioester from carbon monoxide, methanethiol and various combinations of ferrous and nickel sulfides has been experimentally proved as well. However, further verification is necessary for the modes and rates of organic synthesis. 

The highest yields of the decanoate product were observed with nickel and cobalt sulfides, but significant activity was also observed with pyrite. In addition, the formation of methyl nonyl sulfide was observed with the methyl group originating from the reduction of CO. In this case, copper and iron sulfides were the most effective catalysts. It should be noted, however, that many important bio-molecules, such as thioesters and nucleic acids, are unstable in hot water, making some aspects of the evolution of life as we know it highly unlikely at high temperatures. 

In addition, reductive elimination of palladium and nickel complexes to form esters (Equations 8.67 and 8.68), amides, and tiiioesters has been reported. -" The reductive eliminations of esters and amides were observed during mechanistic studies on the palladium-catalyzed formation of esters and amides from aryl halides, carbon monoxide, and alcohols or amines. This catalytic process is presented in Qiapter 17 (carbonylation processes). The reductive elimination of thioesters from nickel complexes were studied, in part, to understand the C-S bond-forming process of acetyl coenzyme A synthase. Prior to this work, an iron-mediated synthesis of p-lactams had been reported that appears to occur by reductive elimination to form the amide C-N bond of the lactam. ... 

Metal complexes are known to insert CO into carbon-sulfur bonds [118], even catalytically [119], Stoichiometric precedents exist for the formation offhioesters from nickel-alkyls, CO, and thiols [120], For example, NiMe2(bipy) reacts with thiols to afford mefhylnickel(ll) fhiolates, which carbonylate to afford acetyl-nickel(ll) fhiolates. These acetylnickel(II) thiolates reductively eliminate fhioester in the presence of CO [121], More biologically relevant is the reactivity of nickel acyls toward fhiolates, which gives fhe thioester concomitant with reduction to Ni(0) (Eq. 12.10) [122]. Thiolates are known to reduce Ni(II) to Ni(0) under an atmosphere of CO [123]. 

Thioesters of malonic acids [R R C(COSEt)2] are reduced to the alcohols, R R CHCH20H, in 70—80% yield on treatment with W-2 Raney Nickel. ° N-Nitroso-a-amino-acids undergo smooth thermal decarboxylation to give... 

Bis-thioesters undergo smooth Dieckmann cyclizations [NaH EtSH(cat.), (MeOCH2)2, 2—6 h, 20 °C] to give cyclic j8-keto-thioesters. As with the oxygen analogues, only five- or six-membered rings can be efficiently prepared in this way. Decarboxylation occurs on desulphurization with W2 Raney nickel (EtOH, 20 °C). j8-Keto-thioesters are also available by treatment of ketone enolates with excess S,5 -dimethyl dithiocarbonate " they can also be alkylated in much the same way as jS-keto-esters. ... 

R.H. Holm et al. - Reaction Sequence Related to that of Carbon Monoxide Dehydrogenase (Acetyl Coenzyme A Synthase) Thioester Eormation Mediated at Structurally Defined Nickel Centers, J. Am. Chem. Soc. 112, 5385, 1990. 

Aliphatic nitriles react slowly with phenols and phenyl ethers in the presence of trifluoromethanesulphonic acid to give ketones after hydrolysis, in a variation of the Houben-Hoesch reaction. The crystalline complex of copper(i) triflate and benzene induces the acylation of aromatic substrates with selenol esters, affording a transition-metal mediated version of the Friedel-Crafts reaction. Aromatic carboxylic acids can be converted into symmetrical diaryl ketones in good yield by treatment of their 5-(2-pyridyl)thioesters with bis-(l,5-cyclo-octadiene)nickel [equation (15)]. In contrast to other methods for preparing symmetrical aromatic ketones, this method allows their preparation from a single starting material. 

Analogous decarbonylation reactions were observed with acyl halides [18], esters [19], acyl cyanides [20], thioesters [21], selenoesters [21b], acylphospho-nates [22], and even ketones (preceding chapters). Acid anhydrides underwent a fragmentation reaction upon treatment with a nickel catalyst to afford alkenes,... 

Most conventional antioxidants either trap the oxy radicals or decompose the hydroperoxides (COOH). Radical traps forperoxy and alkoxy radicals are the familiar amines and phenols. Examples of peroxide decomposing antioxidants are phosphate stabilizers such as tris(nonylphenyl) phosphite (Naugard P), thioester stabilizers such as dilauryl thiodiproprionate (DLTDT), and dithiocarbamate stabilizers such as nickel di-n-butyldithiocarbamate (Naugard NBC). 

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