Arylboronic acid couplings

The pme enantiomers can then be used in the construction of a final chiral liquid crystal or dopant. The chiral acid 141b can simply be esterified (Scheme 35) onto a simple mesogenic-like core (146) to provide a final chiral material (147). The ethyl ester can be reduced to the alcohol (145a) which can then either be esterified onto a carboxylic acid mesogenic core or, as shown in Scheme 36, be employed in a Mitsunobu etherification (DEAD reaction) to give aryl bromide 148, which is then involved in a conventional arylboronic acid coupling reaction to provide a final chiral liquid crystal (150) which has a particularly wide S range. 

Poor yields are obtained in the coupling of rirt/iri-substituted arylboronic acids[506). Ba(OH) as a base gives good results for the coupling of these sterically hindered compounds[5l3], but unsatisfactory results are observed... 

The Suzuki coupling of arylboronic acids and aryl halides has proven to be a useful method for preparing C-aryl indoles. The indole can be used either as the halide component or as the boronic acid. 6-Bromo and 7-bromoindolc were coupled with arylboronic acids using Pd(PPh3)4[5]. No protection of the indole NH was necessary. 4-Thallated indoles couple with aryl and vinyl boronic acides in the presence of Pd(OAc)j[6]. Stille coupling between an aryl stannane and a haloindole is another option (Entry 5, Table 14.3). 

The more utilitarian means for installing an aryl substituent in position 4 onto the 2(5//)-furanone ring, the Suzuki-type cross-coupling of arylboronic acid with... 

Microwave and fluorous technologies have been combined in the solution phase parallel synthesis of 3-aminoimidazo[l,2-a]pyridines and -pyrazines [63]. The three-component condensation of a perfluorooctane-sulfonyl (Rfs = CgFiy) substituted benzaldehyde by microwave irradiation in a single-mode instrument at 150 °C for 10 min in CH2CI2 - MeOH in the presence of Sc(OTf)3 gave the imidazo-annulated heterocycles that could be purified by fluorous solid phase extraction (Scheme 9). Subsequent Pd-catalyzed cross-coupling reactions of the fluorous sulfonates with arylboronic acids or thiols gave biaryls or aryl sulfides, respectively, albeit it in relatively low yields. 

Soluble polymers have also been used as support. These exploit the combined advantage of homogeneous with those of soHd-phase chemistry [36]. PEG linked 5-bromothiophene-2-carboxyUc acid was cross-coupled with several arylboronic acids under microwave irradiation (constant power of 75 W) using water as the solvent (Scheme 17). Interestingly, microwave irradiation gave less ester cleavage than classical heating (70 °C). The polymeric support remained stable under both conditions. 

Remarkably, one year later Leadbeater described that biaryls can be synthesized via a Suzuki-type coupling under transition-metal free conditions [51, 52]. The reaction conditions were almost identical to those reported for the ligand-free process, with the difference being that a larger amoimt of Na2C03 and arylboronic acid were used. Only one successful example of a heteroaryl haUde substrate is shown namely, the coupling of 2-bromopyridine with phenylboronic acid (Scheme 32). 3-Bromothiophene did not couple under the same reaction conditions. Unfortimately, attempts to use heteroarylboronic acids such as 3-pyridinylboronic acid, 3-thienylboronic acid, and lH-indol-5-ylboronic acid on 4-bromoacetophenone completely failed. 

SUZUKI CROSS-COUPLING OF ARYLCHLORIDES WITH ARYLBORONIC ACIDS... 

A closely related reaction that is currently receiving much attention is the palladium-catalysed Suzuki coupling of arylboronic acids with aryl halides (Fu and Littke, 1998). For example, this technology has recently been applied by Clariant workers for the production of o-tolyl-benzonitrile (Eqn. (13)), an intermediate to a series of so-called angiotensin-II antagonists, a new class of antihypertensive drugs (Bernhagen, 1998). 

One catalyst that has been found amenable to alkyl systems is CH3P(r-Bu)2 or the corresponding phosphonium salt.228 A range of substituted alkyl bromides were coupled with arylboronic acids. 

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