Metal-catalysed coupling

CM products from vinylhalides are highly desirable especially because of the possible use in metal catalysed coupling reactions. Johnson and co-workers, performed detailed studies of the possible deactivation pathways [161]. The Fischer-carbene complexes of the vinyl halides have an increased stabihty compared to their alkylidene counterparts and the Fischer carbenes may be deactivated either by migration of the phosphine or by elimination of HX leading to a carbide. 

The chemistry of diazines remains an area of intense interest, both academic and industrial, with applications in many areas, from biomedical to materials science and electronics. They are versatile, having very varied reactivity, giving many opportunities for manipulation of substituents. Nucleophilic substitutions, electrophilic substitution in oxy and amino derivatives, organometallic and transition metal-catalysed coupling reactions are all subjects of substantial research effort. There are obvious similarities in reactivity of the three diazine systems but also many interesting and practically important, often subtle, differences. 

Organozinc reagents, including the Reformatsky reagents, are extensively used in transition metal catalysed coupling reactions with aryl halides or triflates, vinyl halides, and allylic halides or acetates, as reviewed by Erdik156. Nickel and palladium complexes are... 

Dithioacetals (see also dithianes and dithiolanes) alkylation of 98 as acyl anion equivalents 75 carbanions of 87,97-102 cleavage of 14-18,98,102 desulfurization of 78 metal-catalysed coupling 127 reaction with Grignard reagents 127 reductive lithiation of 89 synthesis of 12-19,97-102 Dithioacids synthesis of 40... 

This chapter concentrates on selected recent findings in the field of microwave-assisted metal-catalysed coupling reactions. (Two thorough reviews of this field have recently been published1,2.)... 

Many aromatic and heteroaromatic acyl silanes have been prepared by transition metal catalysed coupling (e.g. Scheme 10)23,81. This is a very successful approach for most aromatic substrates, including furyl, thienyl, pyrryl and electron-deficient aryl acyl silanes, which can otherwise be difficult to prepare. 

IV. METAL-CATALYSED COUPLING REACTIONS A. The Stille Coupling Reaction... 

The transition metal-catalysed coupling of aryl halides with alkenes (alkenyla-tion of aromatic halides) is referred to as the Heck reaction [66-75]. Heitz et al. [76-82] were the first to utilise the Heck reaction to synthesise high molecular weight poly(arylene vinylene)s by the self-coupling of bromostyrene [scheme (2)] or the cross-coupling of dibromoarene with ethylene [scheme (4)] or divi-nylarene [scheme (5)]. 

The transition metal-catalysed coupling reaction of aryl halides with alkynes (alkynylation of aryl halides) is frequently also considered as a Heck reaction [68, 108-111], Polymers containing arylacetylene and diarylacetylene units in the backbone have been obtained by the self-coupling of ethynylaryl halides [scheme (3)] and the cross-coupling of aromatic dihalides with acetylene [scheme (6)] or diethynylbenzenes [scheme (7)] [112-121]. The majority of... 

As in previous years, the applications of Grignard reagents in organic synthesis have been a major area of research in 2008. Recent reports can be divided broadly into fundamental mechanistic studies,26,27 metal-catalysed coupling, addition and substitution reactions,28 33 the exploration of novel types of reactions involving Grignards34 40 and the development of new... 

Aliphatic iodides, and especially secondary and tertiary representatives, are subject to hydride ehmination and are not generally useful substrates in transition metal catalysed coupling reactions. The last reaction in Scheme 14 [31], for instance, cannot be executed using current transition metal-based technology. In contrast, vinyl and aryl iodides, which are superb partners in many classical metal-induced couphng reactions, are very poor substrates in the present radical process because of the high energy of vinyl and aryl radicals. The two methods thus nicely complement each other. 

A copper-catalysed amination - the Ullmann reaction - was the forerunner (1904) of all transition-metal-catalysed couplings, bnt the vigorous conditions that are required limited its use. In recent years there has been a resnrgence in copper catalysis, dne in part to the development of better ligands and understanding... 

Both benzofuran-2-one, known trivially in the older literature as coumaranone, and best viewed as a lactone, and the isomeric benzofuran-3-one, form ambident anions by deprotonation at a methylene gronp, the former requiring a stronger base than the latter. " Triflates suitable for metal-catalysed coupling processes are easily obtained from benzofuran-3-ones. ... 

Transition metal catalysed coupling with tevt-prenol. Recently, several Pd- and Ru-catalysed 3-ferf-prenylations of indole have been published, all of which start... 

Organometallic chemistry has been a popular subject for the Nobel prize committee. In 1912 Grignard (Mg) won the award, in 1973 Wilkinson and Fischer for sandwich compounds (such as ferrocene), in 2005 Chauvin, Grubbs, and Schrock for alkene metathesis, and in 2010 Fleck, Negishi, and Suzuki (Stille had died in 1989) for transition-metal catalysed couplings. 

Other metal-catalysed couplings were studied by Gilheany and co-work-ers to prepare P-stereogemc MOPs. Their results are summarised in Scheme 2.59. 

L.N. Pridgen, Synthesis, 1984, 1047. Transition metal catalysed coupling of RMgX with 2-MeS-oxazoles. 

This cycloaddition is thermally forbidden under the Woodward-Hoffmann rules, but can be achieved by the transition metal catalysed coupling of two dienes (Scheme 11.55). The transformation of butadiene into a variety of products, including cyclooctadiene 11.163, has been known for many years. The [4 + 4] cycloaddition reaction has been applied in an intramolecular fashion to form eight-membered rings (Scheme 11.56). In the presence of a source of nickel(O) and phosphine ligands, tetraene 11.164 cyclizes to the bicyclic product 11.165, mainly as the cu-isomer. The ratio of isomers is dependent on the phosphine. A stereogenic centre present in the tether between the two dienes can result in useful diastereoseleetivity, once again dependent on the phosphines. This chemistry has been used to synthesize asteriscanolide 11.166, which contains a substituted cyclooctane, by intramolecular cycloaddition of tetraene 11.168 to... 

The recent developments on the metallation chemistry of oxazoles and benzoxazoles, isoxazoles and benzisoxazoles, pyrazoles and indazoles, thiazoles and benzo-thiazoles, and isothiazoles, benzo[c]isothiazoles, and benzoMisothiazoles have been reviewed. The two-decade history of catalytic carbon-carbon bond formation via direct borylation of alkane C-H bonds catalysed by transition metal complexes has been reported. The alkane functionalization via electrophilic activation has been underlined. " Recent advances of transition-metal-catalysed addition reactions of C-H bonds to polar C-X (X=N, O) multiple bonds have been highlighted and their mechanisms have been discussed. The development and applications of the transition metal-catalysed coupling reactions have been also reviewed. - ... 

On a more practical level, the utility of transition-metal-catalysed coupling reactions has been further demonstrated by the coupling of an aromatic nucleus to the methyl of a dimethylamino function. Scheme 61 shows the proposed... 

Frederick E. Nytko III is a post-doctoral research fellow in the Chemistry and Pharmaceutical Sciences Department at Howard University. Dr Nytko received his PhD from the University of Maryland, College Park in 2014, with a specialization in synthetic organic chemistry and transition metal-catalysed coupling reactions. He currently works on both improving the syntheses of commercially available HIV/AIDS and tuberculosis active pharmaceutical ingredients (APIs), and also researching market trends for the international sale of APIs, in order to ensure that equitably priced treatments are available to at-risk individuals in the developing world. 

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