Coupling, organometallic mediated

Aryl bromides and iodides undergo a series of aryl coupling reactions mediated by organometallic derivatives. An example is the Heck reaction in which an organopalladium iodide complex is formed and coupled with an alkene (Scheme 4.12). 

Hillier, A. C., Grasa, G. A., Viciu, M. S., Lee, H. M., Yang, C., Nolan, S. P. Catalytic cross-coupling reactions mediated by palladium/nucleophilic carbene systems. Journal of Organometallic Chemistry 2002, 653, 69-82. 

The following paragraphs on aryl/aryl(het-eroaryl)- and aryl/alkyl-bond formation centre on organometallic mediated C-C coupling reactions. For want of space, certain methods have had to be omitted and only those most commonly used have been included. Indeed, in certain cases combina-... 

In summary, palladium-mediated reactions, especially cross-coupling reactions have found many applications in quinoline synthesis. It is noteworthy that due to the a and S activation for the C(2) and C(4) positions, even 2-chloro- and 4-chloro-quinolines are viable substrates for palladium-catalyzed reactions under standard conditions. With the advent of the palladium chemistry and more commercially available organometallic substrates, more palladium-mediated quinoline syntheses are to be added to the repertoire of quinoline chemistry. 

The Pd-mediated cross-coupling reactions on the pyrazine ring of quinoxaline with organometallic reagents are more cumbersome. In one example, the Stille reaction between 2-chloroquinoxaline 87 and benzylstannane 88, attainable from the SN2 displacement of... 

A molybdenum-mediated oxidative coupling of aniline 1 with cyclohexene 2a provides carbazole 3. Alternatively, the same overall transformation of aniline 1 to carbazole 3 is achieved by iron-mediated oxidative coupling with cyclo-hexa-1,3-diene 2b or by palladium-catalyzed oxidative coupling with arenes 2c. The use of appropriately substituted anilines and unsaturated six-membered hydrocarbons opens up the way to highly convergent organometallic syntheses of carbazole alkaloids. 

Carbon-carbon bond formation between sp -hybridized carbons is not easy even with organometallic reagents. John Vederas of the University of Alberta reports (Organic Lett. 5 2963, 2003) that UV irradiation at low temperature of diacyl peroxides such as 4 gives the coupled product 5. The diacyl peroxides can be prepared by the DCC-mediated condensation of acids with peracids,... 

There are two ways to approach this problem. One way is to activate the target C-H with the organometallic catalyst. This process can be remarkably selective. Yasutaka Ishii of Kansai University, Osaka has reported (J. Org. Chem. 2004,69, 1221) that Pd-mediated oxidation of 1, for instance, proceeds predominantly at the para position, leading, after Heck coupling, to the product 2. 

Scheme 8.13. Possible mechanism of the homocoupling of the organometallic component of Pd-mediated cross-couplings [119,121].

Numerous examples of unwanted or deliberate Pd-mediated homocoupling of organometallic reagents have been reported (Scheme 8.14) [38, 122, 123]. Suitable oxidants include a-halo ketones [116, 124, 125] (which can, therefore, not be used as electrophilic component in cross-coupling reactions), oxygen [120, 124, 126], 1,2-diiodoethene [127], 2,3-dibromopropionic acid esters [119], and CuCl2 [128]. 

Zhang, H.-C. Daves, G. D. Water facilitation of Pd-mediated coupling reactions. Organometallics 1993, 12,1499-1500. 

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. 

Fig. 13 The principle mode of action of trifunctional radiopharmaceuticals (a) cell receptor-specific binding and receptor-mediated endocytosis (b) cleavage of targeting function (e.g., petide) (c) uptake into the nucleus and intercalation into DNA, bringing the radionuclide close to the double strand, (d) Auger or a-emission and (e) double or single strand break leading to cell death. Coupling of the two biological function via the organometallic complex...

Fig. 14 The synthesis of a nuclear targeting complex according to the [2 + 1] principle. The first function for nucleus targeting is acridine orange, the dipicolinic acid may serve for binding the second function. The organometallic complex mediates the coupling of the two biological vectors...

Coupling of the cyclobutadiene complex 88 [48] with the protected acetylene 89 furnished the tetrayne 90, copper-mediated coupling of which, after removal of its acetylenic trime-thylsilyl groups, yielded the organometallic complex 91 [49]. 1H NMR analysis of this... 

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