Coupling with carbon nucleophiles

Lastly, Roth has described the reaction of cobalt-complexed propargyl cations with enamines leading to intermediate iminium ion salts which were treated in situ with carbon nucleophiles decomplexation gives precursors for the synthesis of five- and six-membered nitrogen heterocycles [204], 

5 Tandem Nucleophilic Coupling/Pauson-Khand Reaction 

The formation of 1,5-diyne complexes as side-products in some reactions of cations 92 with metal alkyls [41] and the facile, regioselective reduction of a propargylic chloride complex by Zn/HOAc, used in the synthesis of the insect pheromone 5-(Z)-tetradecenyl acetate [221], provided early evidence for the intermediacy of (propargyl)Co2(CO)5 mdicals. In a similar vein, the binuclear molybdenum-complexed propargyl cations react with Na/Hg to produce 

5- diyne derivatives [32, 33]. More recent studies by Melikyan and Nicholas have focused on the intentional generation and chemistry of these novel organometallic radicals. Thus, reaction of primary and secondary Co2-cation complexes with Zn regioselectively produces 

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Alkylpalladium complexes generated by oxidative addition of Pd(0) to alkyl halides with a /3 hydrogen can undergo /3-elimination to yield an alkene and a Pd-hydrido complex (as in the Heck reaction Scheme8.7). Nevertheless, this process is relatively slow compared with transmetalations and reductive eliminations, and simple alkyl halides or tosylates with /3 hydrogen can be cross-coupled with carbon nucleophiles under optimized conditions if the nucleophile is sufficiently reactive [9, 73-75] (Scheme8.6). 

Two systems have been developed to the level of useful organic synthesis methodology spontaneous coordination of the alkene to Pd and the preparation of discrete Cp(CO)2Fe-alkene cationic complexes. With the Pd system, efficient catalytic processes have been developed for the addition of heteroatom nucleophiles, while the coupling with carbon nucleophiles is mainly relegated to stoichiometric reactions these two topics will be presented separately. In the iron series, the reactions involve stable intermediates and are invariably not amenable to catalysis. 

Alkenes in (alkene)dicarbonyl(T -cyclopentadienyl)iron(l+) cations react with carbon nucleophiles to form new C —C bonds (M. Rosenblum, 1974 A.J. Pearson, 1987). Tricarbon-yi(ri -cycIohexadienyI)iron(l-h) cations, prepared from the T] -l,3-cyclohexadiene complexes by hydride abstraction with tritylium cations, react similarly to give 5-substituted 1,3-cyclo-hexadienes, and neutral tricarbonyl(n -l,3-cyciohexadiene)iron complexes can be coupled with olefins by hydrogen transfer at > 140°C. These reactions proceed regio- and stereospecifically in the successive cyanide addition and spirocyclization at an optically pure N-allyl-N-phenyl-1,3-cyclohexadiene-l-carboxamide iron complex (A.J. Pearson, 1989). 

Direct coupling of carbon nucleophiles with 1,3-dinitrobenzene is promoted by ultraviolet irradiation in the presence of quaternary ammonium fluorides, which can act not only as the base to generate the carbon nucleophile, but also as a proton transfer agent in the rearomatization step [83], The dinitrobenzene acts as the electron acceptor in the photochemical step. No reaction occurs in the absence of the fluoride and, surprisingly, although simple ketones, nitriles, esters and fl-kcto esters react, pentan-2,4-dione does not. 

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. 

Mechanistically, alcohol carbonylation reactions catalyzed by the HCo(CO)4/ Co(CO)4 system appear to be governed by several features which are unique to this system. In particular, the high inherent acidity of the HCo(CO)4 species (45), coupled with the nucleophilicity of the conjugate base (55), is responsible for the activation of the substrate and formation of the alkyl-cobalt bond. In addition, the facility of homolytic cleavage of cobalt-carbon bonds (46, 47) may be responsible for the complications in selectivity not normally observed with other systems. 

Many organometallic zinc species are too unreactive to undergo cross-coupling reactions with carbon nucleophiles. This general statement cannot be applied to allylic organometallic species which smoothly react with several electrophiles, such as carbonyl compounds [35,36], nitriles [37,38], or triple bonds [39] (Scheme 9-10). 

Diazopyrazol-3-one salts have been prepared in situ and kept for a short period at low temperature by either diazotization of 4-aminopyrazol-3-ones or by diazo group transfer onto 4-unsubstituted 2,4-dihydropyrazol-3-ones from 4-toluenesulfo-nylazide or aziridinium salts. Coupling these diazonium salts with carbon nucleophiles is the most common reaction (04AHC(87)141). 

The described procedures are easy to carry out even at multi-gram scale and do not require complicated handling. The scope of the reactions are also quite broad since a wide range of aryl halides with different functional groups can be efficiently coupled. Furthermore, the Heck arylation conditions are mild, using only a weak base (potassium carbonate) and moderate reaction temperatures. Alternative methods for the preparation of triarylated ketones and diarylated aldehydes,[8] are mainly those which relies on direct palladium-catalysed coupling of carbon nucleophiles (enolates) with aryl halides in the presence of a strong base.[9-12]... 

Synthesis via coupling aromatic diazonium salts with carbon nucleophilic 4 atom fragments... 

There has been a review of palladium-catalysed carbonylative coupling reactions of aryl halides with carbon nucleophiles in the presence of carbon monoxide. It has been shown that rhodium is an efficient catalyst for the homocoupling reaction of arylzinc compounds in the presence of 1 atm of carbon monoxide to give diaryl ketones. Under similar conditions, palladium and nickel catalysts yield biaryls. The beneficial catalysis by rhodium is likely to derive from the ease of migration of the aryl ligand to carbon monoxide in the rhodium(III) intermediate. A rhodium catalyst has also been used in the formation of indole-3-carboxylates by reaction of indoles with alcohols in the presence of carbon monoxide. The catalytic cycle. Scheme 5, is likely to involve metallation of the indole at the 3-position, followed... 

B.vi.b. Coupling of Building Block to Solid Support Via jr-Allylpalladium Complexes. The reactions of immobilized nucleophiles with 7r-allylpalladium precursors have been described for various combinations.f A double allylation reaction has been shown using an immobilized nitrogen nucleophile with 2-hydroxymethylallyl methyl carbonate. After the first allylic substitution, acylation and a subsequent coupling with various nucleophiles provided access to substituted glycine derivatives (Scheme 22). ... 

Scheme 11 Cross-coupling reaction of aryl cyanides with carbon nucleophiles catalyzed by...

TT-Allyl palladium species normally only couple with soft nucleophiles (e.g. malonate enolates) it is thus of interest to note that, in the presence of EtaN-HMPA, the relatively hard enolate of methyl cyclohexanecarboxylate reacts with a rr-allyl palladium complex derived from allyl chloride to give the a-cyclopropyl ester (128) in 70% yield. Initial attack by the enolate appears to occur at the central carbon of the complex. The reaction may prove to be limited to enolates of esters with a-branching. The application of high pressures... 

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