Coupling of activated alkenes

Coupling of Activated Alkenes With Aldehydes and Ketones... 

Carbon-Carbon Bond Formation - A number of anodic and cathodic coupling reactions are known. The Kolbe oxidation of carboxylate salts and pinacol formation from ketone reduction are familiar examples. Somewhat less well known is the reductive coupling of activated alkenes. 

Our research group has examined similar TiC -mediated coupling of activated alkenes with various aldehydes in the presence of various Lewis bases such as amines (DBU, EtsN and Et2NH), " quaternary ammonium salt (TBAB), " chalcogenides (Me2S) " and oxy-compounds (alcohols, ethers, and ketones) to furnish either halo aldols 251 or allylic chlorides 252 as major product under different conditions. Notably, the usual MBH adduct 253... 

Boldrini, G.P., Savoia, D., Tagliavini, E. et al. (1986) Nickel-catalyzed coupling of activated alkenes with organic halides. J. Organomet. Chem., 301, C62-4. 

Electrodimerization of activated alkenes in aprotic solvents occurs by radical-ion, radical-ion coupling. There is ample evidence for steric inhibition to this process. In contrast to the low reactivity of 11,4-methylbenzabnalononitriIe radical-ion dimeiises with a rate constant of 5.8 x 10 M s in dimethylformamide containing tetraalkylammonium ions [48]. Dimethyl maleate radical-anion diraerises faster than dimethylftimarate radical-anion by a factor of lO in dimethylformamide [49]. 

The electro-synthetic reactions of activated alkenes involve carbon-carbon bond formation, which, after much controversy, is now believed generally to involve radical-anion/radical anion coupling rather than the alternative radical-anion/substrate reaction. The history of this mechanistic debate is well documented168. 

Anodic oxidation of Mn(OAc)2 (catalytic amounts) in the presence of nonacti-vated alkenes and ethyl acetoacetate provides a route to dihydrofurans (cf, 6, 356). This electrooxidation of Mn(OAc)2 has been extended to coupling of activated methylene compounds with alkenes and dienes. 

With regard to ruthenium complexes, in 1992 Moore and coworkers reported the ruthenium-catalyzed three-component coupling of pyridine, alkene, and carbon monoxide to produce 2-pyridyl alkyl ketone (Eq. 11.30) [73], This reaction involves ruthenium-catalyzed C-H bond activation followed by the insertion of CO and alkene to give the product. 

Tan KL, Bergman RG, Ellman JA (2002) Intermolecular coupling of isomerizable alkenes to heterocycles via rhodium-catalyzed C-H bond activation. J Am Chem Soc 124 13964-13965... 

The intermolecular coupling of unactivated alkenes to thiazoles using Rh(l) catalyst provides an easy entry into substituted thiazoles <04JOC7329>. The optimized conditions involve HCl PCys (Cy = cyclohexyl) and HCl P-i-BuiEt as additives for this reaction. For example, three 2-substituted 4,5-dimethylthiazoles 111-113 are prepared from 4,5-dimethylthiazole via C-H bond activation. 

As was the case for the intermolecular coupling reactions, activated alkenes and alkynes constitute one important class of acceptors for the ketyl radical anions. Notably, even highly strained four-membered rings can be accessed via a 4-exo cyclization process (Eq. 56) [65]. 

Arylations. NiBr is a useful catalyst for the electrochemical arylation of activated alkenes. Cross coupling of aryl halides with activated alkyl halides (e.g., a-halo ketones) occurs under similar conditions. 

In the reaction of the activated alkene 151 with allyl carbonate, Michael attack of an alkoxide to the alkene occurs at first. Then the generated anion 152 is allylated to afford 153. The THF derivative 155 was obtained in high yield by the coupling of the alkene 151 with monocarbonate of 2-buten-l,4-diol 154 in the absence of a base [54],... 

Currier, McClure and Balzer and Anderson. Since Morita and coworkers first reported the coupling reaction of activated alkenes with aldehydes or fumaric/maleic esters 188 in the presence of tricyclohexylphosphine to provide interesting multifunctional molecules 189 (Scheme 2.92), many kinds of phosphines have been used as catalysts in various reactions involving the coupling of aldehydes and activated alkenes. ... 

The three reactions are likely to have phosphido complexes as intermediates. Pt-, Pd- and Ln-catalysed hydrophosphination of activated alkenes and Pd-catalysed phosphination of aryl halides (a cross-coupling reaction) have been known for some time whereas Pt and Ru-catalysed alkylation of secondary phosphines are more recent. 

Enholm EJ, Kinter KS. Eree-radical cyclization promoted by allylic 0-stannyl ketyls the intramolecular coupling of the P-carbons of activated alkenes. J. Am. Chem. Soc. 1991 113 (20) 7784-7785. 

Interestingly, a related copper catalyst system was recently utilized by Evano and co-workers for the synthesis of N,N-acetals when coupling 1,1-dibromoalkenes with certain amides [107]. Unexpectedly, this particular transformation did not proceed through two consecutive copper-catalyzed C-N bond formations and experiments conducted on ynamides under the same experimental conditions supported the plausible role of the latter species as active intermediates in the amidation process (Scheme 28). The mechanism pathway proposed by the authors consists of a first C-N cross-coupling of the alkene with the amide, followed by dehydrobromination of the coupling product and subsequent hydroamidation of the... 

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