Halides boronic acids

Aryl Halide Boronic Acid Product Conditions Yield (%)... 

PCy3, jp-substituted phenyl(PR2) ligands (R = Cy or /-Bu), sulfonated fluorenyl dialkylphosphines, and diaryl- or dialkylphosphine oxides have also shown good reactivity in Suzuki reactions of heteroaryl halides/boronic acids. 

Vinylation can also be done by Pd-catalysed cross-coupling in which one component is used as a halide or triflate and the other as a stannane (Stille reaction) or boronic acid (Suzuki reaction). Entry 9, Table 11.3, is an example of the use of a vinylstannane with a haloindole. lndole-3-boronic acids, which can be prepared by mcrcuration/boration, undergo coupling with vinyl triflates (Entry 10). 

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). 

Dimethylsulfoxide Acyl and aryl halides, boron compounds, bromomethane, nitrogen dioxide, magnesium perchlorate, periodic acid, silver difluoride, sodium hydride, sulfur trioxide... 

Palladium-catalyzed carbon-carbon bond forming reactions like the Suzuki reac-tion as well as the Heck reaction and the Stille reaction, have in recent years gained increased importance in synthetic organic chemistry. In case of the Suzuki reaction, an organoboron compound—usually a boronic acid—is reacted with an aryl (or alkenyl, or alkynyl) halide in the presence of a palladium catalyst. 

The boronic acid 2 is first converted to an activated species 8 containing a tetravalent boron center by reaction with a base. Halides or triflates (OTf = trilluoromethanesulfonate) are used as coupling partners R-X for the boronic acids. In many cases the rate-limiting step is the oxidative addition. With respect to the leaving group X, the rate decreases in the order ... 

At about die same time, die application of the Suzuki coupling, the crosscoupling of boronic acids widi aryl-alkenyl halides in die presence of a base and a catalytic amount of palladium catalyst (Scheme 9.12),16 for step-growth polymerization also appeared. Schliiter et al. reported die synthesis of soluble poly(para-phenylene)s by using the Suzuki coupling condition in 1989 (Scheme 9.13).17 Because aryl-alkenyl boronic acids are readily available and moisture stable, the Suzuki coupling became one of die most commonly used mediods for die synthesis of a variety of polymers.18... 

D. O., Micro-reactor synthesis synthesis of cyanobiphenyls using a modified Suzuki coupling of an aryl halide and aryl boronic acid, in Ehefeld, W. (Ed.), Microreaction Technology 3rd International Conference on Microreaction Technology, Proc. of... 

Transmetallation of aiyl halide (VIII) with n-butyl lithium and treating it with readily available and inexpensive 3-ethoxycyclohexen-l-one followed by acid work-up would provide enone (XI) (Scheme 8). Enone (XI) can be then aromatized to phenol (X) or any other biaryl alkyl ether. By using this protocol, 3-ethoxycyclohexen-l-one is a synthon for 3-hydroxyphenyl boronic acid. The bulk price of 3-ethoxycyclohexen-l-one is 85/kg compared to 3500 for the boronic acid, thereby significantly reducing the cost to prepare biaryl (X). 

Ternary Pd-catalyzed coupling reactions of bicyclic olefins (most often norbor-nadiene is used) with aryl and vinyl halides and various nucleophiles have been investigated intensively over the past few years [44]. A new approach in this field is to combine Heck and Suzuki reactions using a mixture of phenyliodide, phenyl-boronic acid and the norbornadiene dicarboxylate. Optimizing the conditions led to 84% of the desired biphenylnorbornene dicarboxylate [45]. Substituted phenyl-iodides and phenylboronic acids can also be used, though the variation at the norbornadiene moiety is highly limited. 

The Suzuki reaction (the palladium-catalyzed cross-coupling of aryl halides with boronic acids) is arguably one of the most versatile and at the same time also one of the most often used cross-coupling reactions in modern organic synthesis [32], Carrying out high-speed Suzuki reactions under controlled microwave conditions can today be considered almost a routine synthetic procedure, given the enormous literature precedent for this transformation [7]. 

Several microwave-assisted protocols for soluble polymer-supported syntheses have been described. Among the first examples of so-called liquid-phase synthesis were aqueous Suzuki couplings. Schotten and coworkers presented the use of polyethylene glycol (PEG)-bound aryl halides and sulfonates in these palladium-catalyzed cross-couplings [70]. The authors demonstrated that no additional phase-transfer catalyst (PTC) is needed when the PEG-bound electrophiles are coupled with appropriate aryl boronic acids. The polymer-bound substrates were coupled with 1.2 equivalents of the boronic acids in water under short-term microwave irradiation in sealed vessels in a domestic microwave oven (Scheme 7.62). Work-up involved precipitation of the polymer-bound biaryl from a suitable organic solvent with diethyl ether. Water and insoluble impurities need to be removed prior to precipitation in order to achieve high recoveries of the products. 

Entry Boronic Acid Halide Yield% (Purity%)... 

Table 1. Sequential processing of multiple substrates in flow [1 equiv. halide, 1 equiv. boronic acid, 2 equiv. BrqNOAc in EtOH. Flow rate 0.1 mL/min, 50 W with external cooling]...

The pyrrole component can also be employed as the aryl halide in Suzuki coupling with aryl boronic acids. Thus, Chang has effected several such reactions using phenylboronic acid and halopyrroles such as 70 and 71 [60]. 

In addition, arylthiophene 70 was obtained by a one-pot Suzuki coupling of p-methoxyiodobenzene and 3-bromothiophene via an in situ boronate formation using one equivalent of the thermally stable diborane 69 [55], This method avoids the isolation of boronic acids and is advantageous when base-sensitive groups such as aldehyde, nitriles and esters are present. However, the cross-coupling yields are low when both aryl halides are electron-poor because of competitive homocoupling during the reaction. 

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