Arylboronates

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). 

Arylboron compounds as acid catalysts in transformations of heterocycles 99EJ0527. 

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... 

Aryl-5-oxo-1,2,3,5-tetrahydropyrido[ 1,2,3-i/e]quinoxaline-6-carboxy-mides were prepared from 7-chloro derivatives and arylboronic acids in the presence of Na2C03, diphenylphosphinated divinylbenzene-crosslinked polystyrene and Pd(PPh3)4 catalyst. 7-Chloro derivatives were obtained from 7-hydroxy derivatives by heating in POCI3 at 50°C for 3 h (01MIP12). 

Chiral boron(III) Lewis acid catalysts have also been used for enantioselective cycloaddition reactions of carbonyl compounds [17]. The chiral acyloxylborane catalysts 9a-9d, which are also efficient catalysts for asymmetric Diels-Alder reactions [17, 18], can also catalyze highly enantioselective cycloaddition reactions of aldehydes with activated dienes. The arylboron catalysts 9b-9c which are air- and moisture-stable have been shown by Yamamoto et al. to induce excellent chiral induction in the cycloaddition reaction between, e.g., benzaldehyde and Danishefsky s dienes such as 2b with up to 95% yield and 97% ee of the cycloaddition product CIS-3b (Scheme 4.9) [17]. 

For the synthesis of a suitable arylboron compound, usually an aryl halide is converted to an aryllithium or aryl Grignard derivative, and then reacted with a trialkoxyborane to yield an arylboronic ester, e.g. the phenylboronic acid diisopropyl ester 13 from bromobenzene 11 ... 

This method has been applied to a large-scale preparation of 6-bromoindole, which reacts with various arylboronic acids via the Suzuki reaction to afford 6-aryhndoles fEq. 10.50. 6-Bromo-5-methoxyindole for use in the synthesis of marine bromoindole " and 5-amino-7-ethoxycarbonyhndole for use in synthesis of l//-pyrrolo[3,2-g quina2ohne ring system fEq. 10.51 " have been prepared from the appropriate o-nitrotoluene. 

SOLVENT ISOTOPE EFFECTS FOR REACTION OF ARYLBORONIC ACIDS WITH ACID IN... 

The Suzuki reaction97 allows tire coupling of two aromatic rings by reaction of an arylboronic compound with a iodo or bromo aryl derivative. The tetrakis (U iphenylphosphine) Pd is the catalyst working in the basic medium. This reaction was recently used98 in aqueous media for the preparation of different isomers of diphenyldicarboxylic acids (Fig. 5.21) but also for the synthesis of soluble rodlike polyimides99 by coupling the 3,6-diphenyl- V, V,-bis(4-bromo-... 

SYNTHESIS OF ORTHO SUBSTITUTED ARYLBORONIC ESTERS BY IN SITU TRAPPING OF UNSTABLE LITHIO INTERMEDIATES 2-(5,5-DIMETHYL-l,3,2-DIOXABORINAN-2-YL)BENZOIC ACID ETHYL ESTER... 

Arylboronic acids have traditionally been prepared via the addition of an organomagnesium or organolithium intermediate to a trialkyl borate. Subsequent acidic hydrolysis produces the free arylboronic acid. This limits the type of arylboronic acids one can access via this method, as many functional groups are not compatible with the conditions necessary to generate the required organometallic species, or these species may not be stable intermediates. 

Complete characterization of arylboronic acids is often difficult because they are readily transformed into stable cyclic anhydrides called boroxines5 and other polymeric species. Arylboronic acids are also known to be hygroscopic. Thus, arylboronic acids are often prepared and used directly as a mixture of different entities. Commercial arylboronic acids will very often contain varying amount of anhydrides. 

The direct isolation of the well defined and stable neopentyl glycol arylboronic esters, without the need for an intermediate aqueous work-up. 

As first described by Krizan and Martin,6 the in situ trapping protocol, i.e., having the base and electrophile present in solution simultaneously, makes it possible to lithiate substrates that are not applicable in classical ortho-lithiation reactions.7 Later, Caron and Hawkins utilized the compatibility of lithium diisopropylamide and triisopropyl borate to synthesize arylboronic acid derivatives of bulky, electron deficient neopentyl benzoic acid esters.8 As this preparation illustrates, the use of lithium tetramethylpiperidide instead of lithium diisopropylamide broadens the scope of the reaction, and makes it possible to functionalize a simple alkyl benzoate.2... 

The conversion of arylboronic acids to the corresponding neopentyl glycol arylboronic esters has several advantages The esters are readily soluble in organic solvents, shelf stable, non-hygroscopic and easily characterized as a single entity.9 Furthermore, boronic esters can be utilized in many of the transformations where arylboronic acids usually are employed, making them an attractive alternative from a practical point of view. 

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. 

Oxidative Heck arylation of enamides with arylboronic acids, using oxygen gas as a reoxidant for Pd(0) and 2,9-dimethyl-1,10-phenanthroline as a chelating regiocontrolling ligand, yielded a (= internally) arylated reaction product as the major compound with a very good a//3 selectivity [92]. Microwave irradiation with prepressurized sealed vials proved useful in reducing the reaction time (Scheme 82). 

Salicylideneamino alcohols are easily prepared ligands that react readily with arylboronic acids to form the corresponding esters, which may be monomeric 45-49 or dimeric 50-59 (Fig. 16) [87-94]. 

Fig. 16. Salicylideneamino alcohols react with arylboronic acids to form monomeric (45-49) or dimeric complexes (50-59)...

If 2,6-pyridinedimethanol is condensed with arylboronic acids in non-polar solvents, the tetrameric boron complexes 74 and 75 are formed rapidly (within 15-30 min) in yields of 80 and 93% (Fig. 20). In both cases only the RSRSI SRSR enantiomeric pair with approximate S4-symmetry is obtained, so that the reaction is diastereoselective. 

Fig. 20. Reaction of 2,6-pyridinedimethanol with arylboronic acids gives the tetrameric macrocycles 74 and 75. Dimeric compounds are known with silicon 76 and 77 and sulfur 78...

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

The Suzuki reaction has proved extremely versatile and has found extensive use in natural product. synthesis. " Arylboronic acids [ArB(OH)2 are the usual substrates in this reaction together with arylhalides or triflates (Ar X, X = halogen... 

---