Aryl halides coupling reaction with alkenes

Palladium-catalyzed coupling reactions of alkenyl/aryl halides or triflates with alkenes, alkynes, or organometaUic reagents are readily used during the synthesis of pharmaceuticals because of the high yield and great selectivity that can be achieved under mild reaction conditions in these processes [108]. At the same time, there are only a few examples for the same reaction carried out in carbon monoxide atmosphere. 

Transition metal-catalyzed transformations are of major importance in synthetic organic chemistry [1], This reflects also the increasing number of domino processes starting with such a reaction. In particular, Pd-catalyzed domino transformations have seen an astounding development over the past years with the Heck reaction [2] - the Pd-catalyzed transformation of aryl halides or triflates as well as of alkenyl halides or triflates with alkenes or alkynes - being used most often. This has been combined with another Heck reaction or a cross-coupling reaction [3] such as Suzuki, Stille, and Sonogashira reactions. Moreover, several examples have been published with a Tsuji-Trost reaction [lb, 4], a carbonylation, a pericyclic or an aldol reaction as the second step. 

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... 

Similar cross-coupling procedures have been used to prepare styrenes by the reaction of metalated aromatics with vinyl halides/triflates or, conversely, metalated alkenes with aromatic halides/triflates in the presence ofPd(Ph3P)4 (eq 6). Typically, ArCl are poor substrates in Pd(PPh3)4-catalyzed coupling reactions. However, by forming the chromium tricarbonyl complex of the aryl chloride, a facile coupling reaction with vinyl-stannanes can be achieved (eq 7). ... 

Fig, 8 Synthesis of alkenes through coupling of heterocyclic tosylhydrazones with aryl halides, (a) reaction from hydrazone (b) reaction from ketone... 

In particular, sulfonylhydrazones are valuable coupling partners in Pd-catalyzed cross-coupling reactions with aryl halides and pseudohalides giving rise to alkenes. As an example, the reaction of a chloroarene with the tosylhydrazone derived from 4-tert-butylcyclohexanone leads to an aryl substituted cyclohexenone (Experimental Procedure below). " " Moreover, the reaction can be conducted directly from the carbonyl... 

A co-solvent that is poorly miscible with ionic liquids but highly miscible with the products can be added in the separation step (after the reaction) to facilitate the product separation. The Pd-mediated FFeck coupling of aryl halides or benzoic anhydride with alkenes, for example, can be performed in [BMIM][PFg], the products being extracted with cyclohexane. In this case, water can also be used as an extraction solvent, to remove the salt by-products formed in the reaction [18]. From a practical point of view, the addition of a co-solvent can result in cross-contamination, and it has to be separated from the products in a supplementary step (distillation). More interestingly, unreacted organic reactants themselves (if they have nonpolar character) can be recycled to the separation step and can be used as the extractant co-solvent. 

The coupling reaction of aryl-alkenyl halides with alkenes in the presence of a palladium catalyst and a base is known as the Heck coupling (Scheme 9.4).6 Since the early 1980s, this type of coupling reaction has been used for die syndiesis of poly(arylenevinylene) and related polymers by polymerization of AB- or AA/BB-type of monomers (Scheme 9.5).7... 

---