Activated alkenes, coupling

Rhodium-catalyzed Heck-type coupling of boronic acids with activated alkenes was carried out in an aqueous emulsion.82 The couplings between arylboronic acids and activated alkenes catalyzed by a water-soluble tm-butyl amphosrhodium complex were found to progress at room temperature to generate Heck-type products with high yields and excellent selectivity. It was necessary to add two equivalents of the... 

In terms of scope, activated alkenes beyond vinyl arenes, such as nor-bornene, couple effectively to aromatic and ,( >-unsaturated anhydrides, in-... 

Nickel-bpy and nickel-pyridine catalytic systems have been applied to numerous electroreductive reactions,202 such as synthesis of ketones by heterocoupling of acyl and benzyl halides,210,213 addition of aryl bromides to activated alkenes,212,214 synthesis of conjugated dienes, unsaturated esters, ketones, and nitriles by homo- and cross-coupling involving alkenyl halides,215 reductive polymerization of aromatic and heteroaromatic dibromides,216-221 or cleavage of the C-0 bond in allyl ethers.222... 

The electrochemistry of cobalt-salen complexes in the presence of alkyl halides has been studied thoroughly.252,263-266 The reaction mechanism is similar to that for the nickel complexes, with the intermediate formation of an alkylcobalt(III) complex. Co -salen reacts with 1,8-diiodo-octane to afford an alkyl-bridged bis[Co" (salen)] complex.267 Electrosynthetic applications of the cobalt-salen catalyst are homo- and heterocoupling reactions with mixtures of alkylchlorides and bromides,268 conversion of benzal chloride to stilbene with the intermediate formation of l,2-dichloro-l,2-diphenylethane,269 reductive coupling of bromoalkanes with an activated alkenes,270 or carboxylation of benzylic and allylic chlorides by C02.271,272 Efficient electroreduc-tive dimerization of benzyl bromide to bibenzyl is catalyzed by the dicobalt complex (15).273 The proposed mechanism involves an intermediate bis[alkylcobalt(III)] complex. 

Dialkyl(trimethylsilyl)phosphines undergo 1,4-addition to a,/3-unsaturated ketones and esters to give phosphine-substituted silyl enol ethers and silyl ketene acetals, respectively. A three-component coupling reaction of a silylphosphine, activated alkenes, and aldehydes in the presence of a catalytic amount of GsF affords an aldol product (Scheme 76).290 291... 

Iridium-phosphine complexes were found to be efficient carbonylative alkyne-alkene coupling catalysts [62]. Although frequently applied in other transformations, the dimeric complex [ Ir( x-Cl)(cod) 2] appeared to be a very active catalyst in the coupling of silylated diynes with CO [63], giving bicyclic products with a carbonyl moiety (Scheme 14.12). 

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]. 

Allylic alcohols 18 (Y = OH) are uniquely active in this coupling process [99]. Even non-terminal alkenes such as 21 are activated towards coupling by the adjacent hydroxyl function, llie allyl alcohol centre also plays an important role in... 

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. 

The same transition metal systems which activate alkenes, alkadienes and alkynes to undergo nucleophilic attack by heteroatom nucleophiles also promote the reaction of carbon nucleophiles with these unsaturated compounds, and most of the chemistry in Scheme 1 in Section 3.1.2 of this volume is also applicable in these systems. However two additional problems which seriously limit the synthetic utility of these reactions are encountered with carbon nucleophiles. Most carbanions arc strong reducing agents, while many electrophilic metals such as palladium(II) are readily reduced. Thus, oxidative coupling of the carbanion, with concomitant reduction of the metal, is often encountered when carbon nucleophiles arc studied. In addition, catalytic cycles invariably require reoxidation of the metal used to activate the alkene [usually palladium(II)]. Since carbanions are more readily oxidized than are the metals used, catalysis of alkene, diene and alkyne alkylation has rarely been achieved. Thus, virtually all of the reactions discussed below require stoichiometric quantities of the transition metal, and are practical only when the ease of the transformation or the value of the product overcomes the inherent cost of using large amounts of often expensive transition metals. 

Using enantiopure 4-oxoazetidine-2-carbaldehydes, the same authors have also reported the coupling reaction with various activated alkenes, in the presence of a Lewis acid, leading to homoallyl (3-lactams (III, Fig. 14), [276]. 

This coupling of an activated alkene derivative with an aldehyde is catalyzed by a tertiary amine (for example DABCO = 1,4-Diazabicyclo[2.2.2]octane). Phosphines can also be used in this reaction, and enantioselective reactions may be carried out if the amine or phosphine catalyst is asymmetric. 

The palladium-catalyzed C-C coupling between aryl halides or vinyl halides and activated alkenes in the presence of a base is referred as the Heck Reaction . Recent developments in the catalysts and reaction conditions have resulted in a much broader range of donors and acceptors being amenable to the Heck Reaction. 

These vinyl sulfoximines undergo nickel-catalyzed cross-coupling reactions with organometallic reagents to give optically active alkenes (see Section V.D for details). 

Scheme 3-37 Inter-intramolecular alkenyl-alkene coupling cascades involving C H activation on an alkene and arene, respectively [188d,e]. A = Pd(OAc), K2CO3, Bu NBr, DMF, 80 °C.

Ally lie alcohols are especially active in this coupling process [50]. Even nonterminal alkenes such as IX are activated toward coupling by the adjacent hydroxyl function. A chiral allylalcohol center will also play an important role in promoting coupling with a... 

This section concerns the classical hydrodimerization of alkenes activated by electron-withdrawing substituents, as in Eq. (1). The literature in this area is extensive and this chapter cannot be exhaustive. The focus will be on typical reactions and general conclusions, which may serve as guidelines for further work. Special emphasis will be put on the effect of reaction conditions on the mechanisms, product selectivity, and stereochemistry. Section II.A deals with the monoactivated alkenes, that is, structures of the type 1 where R and R" are H, alkyl, or aryl Sec. II.B deals with intramolecular coupling reactions where two identically activated alkenes are linked together within the same molecule. The reactions of alkenes activated by two electron-withdrawing groups either in a, a- or in a,yS-positions, are treated in Sec. II.C. 

Enones may react either as ketones (cf. Chapter 10) or as activated alkenes thus giving pinacols, y6,y6 -coupling, or mixed coupling products. Another feature of enone reduction is that the radical anions, A, in the presence of proton donors are protonated at oxygen in a fast process, and the resulting enol radical, B , is more difficult to reduce than the neutral substrate (Sec. II.A. 1). Radical anions derived from other activated double bonds tend to protonate at carbon in the presence of proton donors, and the resulting radical is more easily reduced than the neutral substrate (Schemes 1 and 3). 

When two identical activated alkene functions are included in the same molecule, inter-molecular coupling has to compete with intramolecular hydrocyclization. In most cases the intramolecular reaction, which corresponds to an overall two-electron process, takes precedence. Few mechanistic studies of intramolecular couplings have been reported. The main question is whether the coupling takes place at the mono-radical anion stage in an RS-type reaction (one unit reduced, the other not reduced), or at the bis(radical anion) stage in an RR-type reaction (both units reduced). The last case implies weak electronic interaction between the electrophores. 

Coelectrolysis of different activated alkenes may lead to cross-coupling and fonnation of the mixed hydrocoupling product (MHC) [Eq. (14)]. Only cross-couplings where a simple activated alkene (acrylonitrile, 7, or, e.g., 13a) is one of the substrates have been studied systematically [4,29,104,149,150]. 

These findings, together with those of more general mechanistic work on homocoupling of acativated alkenes, indicate that the most likely pathway for MHC formation is coupling between the two different radical anions. The beneficial effect of a small difference in reduction potentials is consistent with electron transfer to the less activated alkene either directly at the cathode or by electron transfer in solution from the other radical anion. Similarly, formation of an adequate concentration of the radical anion of the less activated alkene is favored by the use of this alkene in excess. 

Reduction of 7 takes place at approximately —1.9 V. Thus, 7 is normally the component that is most difficult to reduce and used in excess or even as solvent (Table 14). In a few cases, mixed coupling of 7 with less-activated alkenes (hydrocarbons) has been attempted (Table 14). In most cases, hydrogenation (2 F) of one or both of the alkenes takes place in addition to coupling, analogous to results from attempted homocoupling of poorly activated alkenes. 

Bis(activated alkenes) such as 42a have been reduced in the presence of CO2, and the extend to which intramolecular coupling takes place was shown to depend on the length of the link and on the medium [165] (Table 15). In this case, electron transfer from the radical anion of the substrate to CO2 is also possible. 

V-Haloamides such as 76 are reductively cleaved (2 F) to give an anion by loss of a halide ion coupling takes place when an excess of an activated alkene is added, as in Eq. (31) [189]. 

Based on these results and results for reduction of other combinations of allyl halides and activated alkenes, it has been suggested that when the allyl halide is more easily reduced than the alkene, the allylic anion (2-F reduction) adds to the activated double bond of the alkene, giving predominantly the terminal alkene [Eq. (32)]. In contrast, initial formation of the radical anion of the (di)activated alkene may lead to an S>j2 reaction between the radical anion and the allyl halide followed by further reduction of the intermediate radical and final protonation [Eq. (33)] [190,191]. However, electron transfer between the alkene radical anion and especially allyl iodide followed by coupling of the allyl radical and a radical anion cannot be ruled out. 

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