Coupling aryl bromides

Recently, a Pd(0)-Y zeolite system has been reported by Artok and Bulut. In general, aryl bromides coupled with arylboronic acids at room temperature in a DMF/H2O solvent mixture.The catalyst could be recovered by filtration, but in order to obtain high yields of coupling product the temperature had to be raised to 50 °G. Regeneration of the catalyst by consecutive treatments with O2 and H2 was required to obtain high yields after the second use. 

These can be used for the formation of small rings thus Bradley and Durst have used an intramoleculai alkenyltin/aryl bromide coupling to form methylenebcnzocyclobutanones in medium to good yields [43J, and Baldwin and co-workers coupled acid chloride and alkenyltin functionalities to form five- and six-membered a-methylene lactones (Scheme 4-13) [44]. 

An interesting one-pot two-step cyclization was described by Finch et al. [200], who first used PdCl2(PPh3) to cany out the hydrostannation of a triple bond and then by adding Pd(PPh3)4 closed a seven-membered ring via a vinyltin/aryl bromide coupling (Scheme 4-51). 

SCHEME 10 Synthesis of revised aryl bromide coupling partner 28. 

The allylstannane 474 is prepared by the reaction of allylic acetates or phosphates with tributyltin chloride and Sml2[286,308] or electroreduction[309]. Bu-iSnAlEt2 prepared in situ is used for the preparation of the allylstannane 475. These reactions correspond to inversion of an allyl cation to an allyl anion[3l0. 311], The reaction has been applied to the reductive cyclization of the alkenyl bromide in 476 with the allylic acetate to yield 477[312]. Intramolecular coupling of the allylic acetate in 478 with aryl bromide proceeds using BuiSnAlEti (479) by in situ formation of the allylstannane 480 and its reaction with the aryl bromide via transmetallation. (Another mechanistic possibility is the formation of an arylstannane and its coupling with allylic... 

Bromoquinoline (70), behaving similarly to a simple carbocyclic aryl bromide, was coupled with phenylethyne 121 to provide disubstituted ethyne 122 in 50% yield (2001JCS(P1)978). 

The palladium-catalyzed cross-coupling of alkenylsilanols has been extensively studied with respect to the structure of both the silicon component and the acceptor halide. The preferred catalyst for coupling of aryl iodides is Pd(dba)2 and for aryl bromides it is [allylPdCl]2. The most effective promoter is tetrabutylammonium fluoride used as a 1.0M solution in THF. In general the coupling reactions occur under mild conditions (room temperature, in 10 min to 12 hr) and some are even exothermic. 

Pd/P(t-Bu)., in the presence of Cy2NMe, is an unusually mild and versatile catalyst for Heck reactions of aryl chlorides (Tables 1 and 2) (as well as for room-temperature reactions of aryl bromides).21 22 23 Example A, the coupling of chlorobenzene with butyl methacrylate, illustrates the application of this method to the stereoselective synthesis of a trisubstituted olefin a-methylcinnamic acid derivatives are an important family of compounds that possess biological activity (e.g., hypolipidemic24 and antibiotic25) and serve as intermediates in the synthesis of pharmaceuticals (e.g., Sulindac, a non-steroidal anti-inflammatory drug26). Example B, the coupling of 4-chlorobenzonitrile with styrene, demonstrates that Pd/P(t-Bu). can catalyze the Heck reaction of activated aryl chlorides at room temperature. 

AN IMPROVED SYNTHESIS OF BIARYL DERIVATIVES VIA THE PALLADIUM CATALYZED COUPLING OF ARYL BROMIDES... 

We investigated the catalytic performance of the CU2O coated copper nanoparticles for Ullmann coupling reactions. When the coupling reactions using aryl bromides such as 2-... 

The cobalt-catalysed reaction between aryl bromides and Grignard reagents assisted by IMes HCl is also known, however the substrate scope is quit narrow and good yields are only obtained when non-branched long chain alkyl magnesium chlorides are used as coupling reagents [80] (Scheme 6 19)... 

Cobalt-catalysed coupling between aryl bromides and alkyl Grignards... 

Scheme 6.24 Selected pre-catalysts used for the Suzuki coupling between aryl bromides and iodides with boronic acids...

So far only Pd-based systems have been highlighted in this section however, the use of other metals such as Ni has clear economic advantages. In this regard, Chiu and co-workers have used a bis-carbene tetradentate ligand to catalyse the coupling of aryl bromides and chlorides with both electron rich and electron poor aromatic rings however, the reaction with electron poor aryl bromides lead to superior yields (Scheme 6.30) [113]. 

The first example of a NHC-Pd catalysed Stille reaction between aryl bromides and aryl stannanes was reported by Herrmann in 1999 [120]. Summarised in Scheme 6.36 are the best results obtained when the weU-defined pre-catalyst 22 was employed. Unfortunately, the coupling of aryl chlorides was not possible. 

Subsequently, an in situ Pd(OAc)j-imidazolium salt mixture, developed by Nolan and Grasa, has demonstrated its efficiency for the coupling of aryl bromides and even chlorides with aryl and vinylstannanes. This improved reactivity is due to the TBAF additive, whereby F anions coordinate to Sn forming hypervalent fluorostannate anions that are more reactive towards transmetallation to Pd [121] (Scheme 6.37). 

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