Aryl-vinyl coupling

Aryl-vinyl coupling fi-aryl-fi-amino acids.2 A novel route to P-amino acids is based on the formal conjugate addition of an aryl iodide to an enantiomerically pure dihydropyrimidinone such as 1, prepared by pivaldehyde acetalization of (R)-aspara-gine (c/., 14, 69-70). Thus 4-iodoanisole couples with 1 under Heck conditions, Pd(OAc)2, Ar3P, triethylamine, and DMF to give 2 in 78% yield. Reduction of 2... 

Recently, the catalytic use of Cu(I) salts was applied to the aryl-aryl and aryl-vinyl couplings and to the allylation of furans and thiophenes, even without the benefit of such activation. In parallel with the use of Cu(I) salts, the reactivity of stoichiometric amounts of Cu(II) was estabhshed for the homocoupling of vinyltins" °°. Copper nitrate was found to be particularly efficient, leading to the cyclotrimerization of l-bromo-2-stannylaUcenes . Lately, the use of catalytic amounts of CuCla was shown to be superior to the use of Cu(I) salts for achieving these homocoupling reactions . ... 

While the Wessling-Zimmermann route is a typical method of polymer synthesis, both PPVs and their corresponding oligomers can be synthesized by the extension of methods used for the synthesis of the easiest building block, stilbene 70 (scheme 13). Conceptionally, this is possible by (i) carbon-carbon double bond formation, for whieh synthetic organic chemistry provides a great number of methods [116], and (ii) by aryl-vinyl coupling [117] some examples of both methods are outlined in scheme 13. 

Scheme 6.16 An intramolecular aryl-vinyl coupling employing a polystyrene-supported terminal vinylstannane [57].

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

Alkenylboranes (R2C=CHBZ2 Z — various groups) couple in high yields with vinylic, alkynyl, aryl, benzylic, and allylic halides in the presence of tetra-kis(triphenylphosphine)palladium, Pd(PPh3)4, and a base to give R C CHR. 9-Alkyl-9-BBN compounds (p. 1013) also couple with vinylic and aryl halides " as well as with a-halo ketones, nitriles, and esters.Aryl halides couple with ArB(IR2 ) species with a palladium catalyst. ... 

In a related reaction, aryl halides couple with vinyl tin reagents to form styrene derivatives in the presence of a nickel catalyst, for example, ... 

The first step in the cycle, analogous to the cross-coupling reactions, is the oxidative addition of an aryl (vinyl) halide or sulfonate onto the low oxidation state metal, usually palladium(O). The second step is the coordination of the olefin followed by its insertion into the palladium-carbon bond (carbopalladation). In most cases palladium is preferentially attached to the sterically less hindered end of the carbon-carbon double bond. The product is released from the palladium in a / -hydrogen elimination and the active form of the catalyst is regenerated by the loss of HX in a reductive elimination step. To facilitate the process an equivalent amount of base is usually added to the reaction mixture. 

The transition metal catalyzed carbon-carbon bond formation between organomagnesium reagents and aryl (vinyl) halides has been one of the pioneering entries into cross-coupling chemistry. The reaction has been widely utilized since than in azine chemistry,22 with the limitation that the functional group tolerance of Grignard reagents is only moderate. Here only some of the more recent developments will be mentioned. 

Substitutions by the SRn 1 mechanism (substitution, radical-nucleophilic, unimolecular) are a well-studied group of reactions which involve SET steps and radical anion intermediates (see Scheme 10.4). They have been elucidated for a range of precursors which include aryl, vinyl and bridgehead halides (i.e. halides which cannot undergo SN1 or SN2 mechanisms), and substituted nitro compounds. Studies of aryl halide reactions are discussed in Chapter 2. The methods used to determine the mechanisms of these reactions include inhibition and trapping studies, ESR spectroscopy, variation of the functional group and nucleophile reactivity coupled with product analysis, and the effect of solvent. We exemplify SRN1 mechanistic studies with the reactions of o -substituted nitroalkanes (Scheme 10.29) [23,24]. 

Scheme8.3. Simplified mechanism of Pd-catalyzed cross-coupling reactions. R, R = aryl, vinyl, a I kynyl, allyl, benzyl, alkyl, acyl ...

Rai, R. Aubrecht, K. B. Collum, D. B. Palladium-catalyzed Stille couplings of aryl-, vinyl-, and alkyltrichlorostannanes in aqueous solution. Tetrahedron Lett. 1995, 36, 3111—3114. 

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