Heteroaryl boronic acids

Using Pd-mediated cross-coupling reactions, such as Suzuki, Heck, and Sonoga-shira- Hagihara reaction, researchers efficiently constructed a library of 151 coumarin derivatives from eight 3-bromocoumarins cross-coupled with ten aryl/heteroaryl boronic acids, ten alkenes, and ten alkynes (Fig. 4). 

The same authors performed a microwave assisted Stille reaction on the Rink amide (RAM) Tentagel polymer-tethered 4-iodobenzoic acid [5 b]. Successful palladium-catalyzed coupling of heteroaryl boronic acid with anchored 4-iodobenzoic acid enabled both >99% conversion of the starting material within 3.8 min (45 W) and a minimal decomposition of the solid support. The coupling reactions were realized in a mixture of polar solvents (H20-EtOH-DME, 2.5 1.5 6). 

In combinatorial chemistry, the reaction times and reaction temperatures required are frequently crucial factors. Microwave irradiation is used to enhance reaction rates [105]. Larhed et al. recently reported that microwave-assisted, palladium-catalyzed coupling of aryl and heteroaryl boronic acids with iodo- and bromo-substituted benzoic acids, anchored to Tenta-Gel S RAM, provides coupling products in excellent yields after a reaction time of just 3.8 minutes (45 W) [106]. The preparative results are summarized in Table 4. 

Alkenyl, aryl, and heteroaryl boronic acids reacted with 1,2-diamines and glyoxylic acid giving directly piperazi-nones (Equation (123)).571 2-Hydroxymorpholines were synthesized from glyoxal, 2-aminoethanols, and aryl- or 1-alkenylboronic acids (Equation (124)).572... 

NMR experiments on the reactions of halophosphates esters with pyridine showed that equilibria involving the formation of pyridinium salts in these reactions are almost entirely shifted to the left for chloro- and bromo-phosphates and to the right for the corresponding iodophosphates. This explains dramatic differences in chemical reactivity between these compounds. Substituted medium-sized and large N-heterocycles (117) have been prepared via an extension of the Suzuki reaction involving the palladium-catalysed coupling of vinyl-phosphates (118) with aryl or heteroaryl boronic acids (Scheme 27). ... 

The PdCl2-EDTA complex is an efficient catalyst for the Suzuki-Miyaura reactions of aryl and heteroarylhalides with aryl-(heteroaryl)boronic acids in water. Aryl iodides and bromides provide coupled products with TON up to 97,000 (Table 14.3) [194]. 

For Suzuki reactions using haloboronic acids and another halide, the obviously best course is to have a more reactive halide in the substrate than in the boronate, so there are quite a few examples of chloro-heteroaryl-boronic acids coupling efficiently with aryl bromides. This difference is clearly shown by the coupling reactions of 2-chloro- and 2-bromopyridine-5-boronic acids with bromo-heterocycles. ... 

Methoxy- and 6-phenylthio-5-bromonicotinates (226) react with a variety of aryl and heteroaryl boronic acids in coupling reactions (227) (Scheme... 

The heteroaryl derivatives of boron, silicon, and tin, which show related patterns of reactivity, have found considerable application in synthesis. Unlike lithium compounds, they are generally fairly stable to air and water but will undergo a range of selective reactions under relatively mild conditions. Heteroaryl boronic acids and stannanes are particularly useful as the organometallic component in palladium-catalysed coupling reactions (section 2.7.2.2) heteroaromatic silanes such as 2-... 

Suzuki methodology, with a 3-halotriazolopyridine and an aryl or heteroaryl boronic acid, sodium carbonate and tetrakistriphenylphosphine as catalyst, the synthesis of 3-aryl derivatives 6b-g, i, j, ha ve been described (Figure 2). In these reactions a secondary compound was also formed, the 33 -bitriazolopyridine 37 (Figure 10), as a consequence of a homocoupling Ullman reaction. From 7-bromo-3-methyl-triazolopyridine, the synthesis of some 7-aryl derivatives 7a-g in very good yields (60-90%) was also reported (Figure 2) (06TL8101). 

Li et al. [8] described the synthesis of sensitive heteroaryl boronic acids by forming the organometaUic species in situ and reacting it immediately with... 

Guram and coworkers at Amgen have developed air-stable palladium-phosphine complexes for the Suzuki coupling of heteroaryl chlorides with a diverse array of aryl and heteroaryl boronic acids (Equation 2.26), with TONs of up to 10000 possible in certain cases [45). 

In another one-pot procedure, a Suzuki coupling and a Wittig olefination were realized back to back. A great variety of aryl- and heteroaryl halogenides and aldehyde-functionalized aryl- and heteroaryl-boronic acids were used along with ethoxycarbonylmethylenephosphorane (Scheme 95/1). In another variation, 2-bro-mothiophene, (4-formylphenyl)boronic acid and three different phosphoranes were used (Scheme The biaryl/biheteroaryl/arylheteroaryl acrylic or other... 

Finn and Petasis have independently shown that salicylaldehyde is a suitable aldehyde for the Petasis borono-Mannich reaction, with alkenyl, aryl and heteroaryl-boronic acids (Equation 6) [30, 31]. The reaction works best for aliphatic secondary amines, as in the formation of 41 primary amines give modest yields of adducts 41. Benzaldehydes lacking ortho hydroxyl functionality do not react, with even ortho methoxy functionality being unsuitable, which is consistent with a tethering mechanism via putative intermediate 9 (Figure 7.3). Petasis and Boral reported that reactions occurred at room temperature over 24-36 h, using EtOH, MeOH or acetonitrile. 

Keywords Aryl/heteroaryl boronic acids, sulfonyl azides, Cu(I)Cl, air, methanol, room temperature, Chan-Lam coupling, N-aryl/heteroaryl sulfonamides... 

More recently, Lee and MacMillan developed the addition of heteroaryl boronic acids to a,p-unsaturated aide-hyde by what was called a Friedel-Crafts-type reaction. Applying this methodology, the straightforward synthesis of frondosin, a potential treatment against inflammatory... 

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