Nickel distal

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. 

Indeed, both kinds of cycloaddition products (Type A and Type B) can be obtained in the presence of Ni(0) catalysts while Pd(0) catalysts exclusively lead to Type A codimers. The real course of these reactions however is somewhat more complicated. While distal ring-opening via Route a really leads to cycloaddition products of Type A, proximal ring-opening via Route b results only in an isomerization of methylenecyclopropane. Cycloaddition products of Type B are obtained indirectly via oxidative coupling of two alkene units with low-valent nickel followed by a cyclo-propylmethyl/3-butenyl rearrangement22,148b). Reductive elimination terminates the catalytic cycle (Eq. 78). 

Interestingly, bicyclopropylidene (7) also reacts with selected electron-deficient open-chain al-kenes, e.g. diethyl fumarate. When tris(2-phenylphenyl) phosphite is employed to modify the nickel catalyst, the yield of the [2 + 2] cycloadduct 10 amounts to 34% and the [3 + 2] cycloadduct 11 is formed as a minor product. Additionally, two diastereomers of the double [3 + 2] cyclo-adduct 12, formally arising from 7 by proximal cleavage of one cyclopropane ring and distal cleavage of the other, are formed in 15.6% yield. ... 

Interestingly, when substituted norbornenes, such as dimethyl bicyclo[2.2.1]hept-2-ene-2,3-dicarboxylate (23), are employed in a nickel-catalyzed reaction, the only reaction product is dimethyl cxn-4-methylenetricyclo[5.2.1.0 ]decane-2,6-dicarboxylate (24), arising from an unusually selective, formal distal ring cleavage of the MCP. ... 

Whereas palladium(0)-catalyzed reactions of dialkyl fumarate and dialkyl maleate yield reaction products identical to those obtained from the phosphane-modified nickel-catalyzed reactions (vide supra), analogous palladium(0)-catalyzed reactions with ( )-but-2-enoic or (E)-cinnamic acid derivatives lead to different products to the nickel-catalyzed reactions, i.e. in the palladium-catalyzed reactions formal distal cleavage of but-2-enoic MCP occurs to provide methyl tra i-2-methyl-4-methylenecyclopentanecarboxylate (12, R = Me) and methyl trans-4-methylene-2-phenylcyclopentanecarboxylate (12, R = Ph), respectively." Yields and stereoselectivities are slightly higher with palladium(O) catalysts. When R = Me, 7.4% of the C-C double bond isomerization product, methyl traM -2,4-dimethylcyclopent-3-enecarboxylate (13, R = Me), is additionally obtained, raising the combined yield of cyclocodimers to 49.9%. With methyl (jE )-cinnamate, analogous isomerization only occurs upon workup, i.e. distillation of the crude product. 

Analogous face-directing effects are also observed with 5-alkoxyfuran-2(5//)-ones. Even with phosphanes of increased steric demand and reduced donor capability, such as tris(2-phenyl-phenyl) phosphite, to modify the nickel catalyst, only low yields and product selectivities are obtained. Whereas complete face selectivity is observed in the reaction of MCP with 5-methoxy-furan-2(5//)-one, a mixture of products arising from proximal 25 and distal 26 ring cleavage of the MCP is formed. 

With both nickel(O) and palladium(O) catalysts distal ring cleavage occurs. Only when nickel is used does efficient rearrangement of the primary intermediates take place. From the pal-ladium(0)-catalyzed reaction of (Z)-5, one diastereomer 7C is obtained selectively in high yield. As an explanation, minimal steric hindrance in the transition state can be assumed, as the C —O bond of the dioxolane is eclipsed only by the C —H bond but not the C —C bond of the cyclopentane moiety. 

A special case of a transannular cycloisomerization occurs with the ethyl acrylate derivative 22. lO a.b Nickel(O), as well as palladium(O), catalysts effect this reaction in generally high yields, leading to the formation of the [3.3.3]propellane derivative 23. Even in the nickel(0)-catalyzed reaction, no isomeric compound arising from proximal cleavage of the methylenecyelopropane is formed, presumably due to activation of the distal bond arising from the tetrasubstitution of the methylene group. 

The reaction of triester 28 provides an example where nickel(O) and palladium(O) catalysts effect different types of reactions, i.e. proximal vs. distal ring cleavage of the methylenecyclo-propane. 

Disubstituted methylenecyclopropanes react successfully with modified or unmodified nickel catalysts via distal ring cleavage to form type A products in which the two substituents are found largely at the double bond. This procedure is equally successful with nonactivated olefins e.g., norbornene51. 

X-ray crystal structures of CODH/ACS proteins show that they are large (300 kDa) homodimeric proteins with the two CODH domains j3 subunits) at the core, and the two ACS domains (a subunits) tethered to the side of each of these (3 subunits. The (3 subunits each contain one Ni and 10 Fe ions that are arranged into three FeS clusters (the so-called B-, C-, and D-clusters), whereas the a subunits each contains the active site A-cluster, a [Fe4S4] " cubane that is bridged by the sulfur of a cysteinyl residue to the proximal metal (Mp) of a binuclear center. This binuclear center contains a square planar nickel ion, referred to as the distal Ni (Ni(j), which is coordinated by the two thiolates and two backbone amides of a Cys-Gly-Cys motif There has been some debate as to the identity of Mp, as Ni, Cu, and Zn ions have been shown to occupy this site however, it is now generally accepted that the A-cluster is a binuclear Ni—Ni center bridged by a cysteine thiol to a [4Fe— 4S] cluster. " ... 

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