Coupling, metal mediated, alkyl

This methodology clearly enriches the tool box of the synthetic organic chemist. Other spin-offs from the studies described above, such as the incorporation of dioxygen as an oxidant and the use of alkyl carbon-het-eroatom coupling as a product release step for other metal-mediated organic transformations, may also emerge over the next several years. 

To expand the diversity of their libraries Brill et al.16 also modified various heterocycles by alkylation, acylation, or metal-mediated coupling reaction prior to resin capture. A remaining chloro substituent was still available for nucleophilic displacement or a palladium-mediated coupling reaction with anilines, phenols, and boronic acids on solid phase [see Fig. 10 for the preparation of purine derivative (62)]. 

The use of hypervalent iodine reagents in carbon-carbon bond forming reactions is summarized with particular emphasis on applications in organic synthesis. The most important recent methods involve the radical decarboxylative alkylation of organic substrates with [bis(acyloxy)iodo]arenes, spirocyclization of para- and ortho-substituted phenols, the intramolecular oxidative coupling of phenol ethers, and the reactions of iodonium salts and ylides. A significant recent research activity is centered in the area of the transition metal-mediated coupling reactions of the alkenyl-, aryl-, and alkynyliodonium salts. 

Almost all alkylations at the carbocyclic rings of quinolines are effected by metal-mediated processes either by quenching of a quinolyl organometallic species with a suitable electrophile or by transition metal-mediated coupling of a haloquinoline or quinolyltriflate with an alkylmetal derivative. 

Complexes of the type [Cp Rh(R)(/4-CH2)]2 have been studied to probe details of the coupling of alkyl and methylene groups that could be relevant to mechanisms for the Fischer-Tropsch process (see Organic Synthesis Using Metal-mediated Coupling Reactions) Reaction... 

Novel C-C coupling reactions are about to enter the scope of metal complex catalysis. Examples are asymmetric aldolizations (Mukaiyama [79]), Diels-Alder reactions [80], and indium- or zinc-mediated alkylations [86]. 

Barbier coupling reaction Metal-mediated addition of alkyl, allyl or benzyl halides to carbonyl compounds. 38... 

As in the case of quinolines, isoquinolines can be prepared by metal-mediated annotation processes. Reaction of t-butylimines of iodo-benzaldehydes with acetylenes in the presence of palladium catalyst affords 3,4-disubstituted isoquinolines. The power of this reaction relies on its ability to introduce different type of substituents on 4-position of the heterocycle by using the formed intermediate palladium complex in the cross-coupling reaction with aryl and alkyl halides or alkenes. This methodology was successfully applied to the total synthesis of decumbenine... 

In this method, Furstner converts N-BOC protected pyrrole to the 2,5-dibromo compound (122) with NBS and this is followed by metalation and carbomethoxylation with t-butyl lithium in THF and subsequent trapping of the metalated species with methyl chloroformate to yield a pyrrole diester (123). Bromination of this diester at positions 3 and 4 with bromine in water followed by Suzuki cross-coupling with 3,4,5-trimethoxyphenyl boronic acid yields the symmetrical tetrasubstituted pyrrole (125). Base-mediated N-alkylation of this pyrrole with 4-methoxyphenethyl bromide produces the key Boger diester (126) and thereby constitutes a relay synthesis of permethyl storniamide A (120). 

Pletcher and associates [155, 159, 160] have studied the electrochemical reduction of alkyl bromides in the presence of a wide variety of macrocyclic Ni(II) complexes. Depending on the substrate, the mediator, and the reaction conditions, mixtures of the dimer and the disproportionation products of the alkyl radical intermediate were formed (cf. Section 18.4.1). The same group [161] reported that traces of metal ions (e.g., Cu2+) in the catholyte improved the current density and selectivity for several cathodic processes, and thus the conversion of trichloroacetic acid to chloroacetic acid. Electrochemical reductive coupling of organic halides was accompanied several times by hydrodehalogena-tion, especially when Ni complexes were used as mediators. In many of the reactions examined, dehalogenation of the substrate predominated over coupling [162-165]. 

The Lee group originated rhodium alkenylidene-mediated catalysis by combining acetylide/alkenylidene interconversion with known metal vinylidene functionalization reactions [31], Thus, the first all-intramolecular three-component coupling between alkyl iodides, alkynes, and olefins was realized (Scheme 9.17). Prior to their work, such tandem reaction sequences required several distinct chemical operations. The optimized reaction conditions are identical to those of their original two-component cycloisomerization of enynes (see Section 9.2.2, Equation 9.1) except for the addition of an external base (Et3N). Various substituted [4.3.0]-bicyclononene derivatives were synthesized under mild conditions. Oxacycles and azacycles were also formed. The use of DMF as a solvent proved essential reactions in THF afforded only enyne cycloisomerization products, leaving the alkyl iodide moiety intact. 

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