Suzuki-coupling synthesis

As for the biaryl ether containing macrocycles, an array of bioactive macrocycles with an endo aryl-aryl bond exist in nature. A new palladium catalyzed reaction has been recently developed in which bis(pinacolato)diborane(4) mediated the process to reach such a structural motif. The reaction consists of a domino process involving a Miyaura s arylboronic ester synthesis and an intramolecular Suzuki-coupling. Synthesis of a bicyclic A-B-O-C ring system of RP-66453 273, a neurotensine receptor antagonist, with an endo aryl-aryl and an endo aryl-aryl ether bond was described (Scheme 53).141... 

Suzuki coupling. Synthesis of temperature in the presence of the W reusable polymer-supported (Ph,P Rd c arylboronic acids with poly(ethylcnc j... 

Sasaki, M., Ishikawa, M., Fuwa, H., and Tachibana, K. (2002) A general strategy for the convergent synthesis of fused polycyclic ethers via B-alkyl Suzuki coupling synthesis of the ABCD ring fragment of ciguatoxins. Tetrahedron, 58,1889-1911. 

Of particular synthetic importance is the coupling of aryl- and hetarylboronic acids to aryl- and hetaryl halides (or triflates), allowing for a convenient synthesis of biphenyls, even sterically demanding derivatives such as 14, hetaryl phenyls and Zj/ -hetaryls. With appropriately disubstituted aromatic substrates, the Suzuki coupling reaction can be applied in the synthesis of polyphenylene materials. 

Palladium-mediated catalysis has only been exploited relatively recently in the synthesis of substituted PPV derivatives. The use of aryl dibromides as monomers is particularly useful as it allows the synthesis of PPVs substituted with alkyl rather than alkoxy sidechains. The Suzuki [53, 54], Heck [55], and Stille [56] reactions have been used in the synthesis of new PPV derivatives, but attaining high molecular weight PPV derivatives by these methodologies has proved problematic. A phenyl-subslilutcd PPV material PPPV 31 was synthesized by a Suzuki coupling (Scheme 1-10) of dibromoethene and fo/.v-boronic acid 30. Its absorption (2ni ix=385 nm) and emission (2max=475 nm) maxima were strongly... 

Scheme 1-10. Synthesis of PPV 25 by Suzuki coupling a) Pd(PPh3)4. Na2C03, toluene, 60 C.

The utility of the Suzuki reaction in the challenging arena of natural product total synthesis has been explored. The constitution of bombykol (106) (see Scheme 26), a well-known pheromone, lends itself to a Suzuki coupling. Indeed, in a short stereospecific synthesis of 106, Suginome et al. demonstrated that ( )-vinylboronic acid ( )-104 can be smoothly cross-coupled with (Z)-l-pentenyl bromide [(Z)-105] 44 the configurations of both coupling partners are preserved in the C-C bond forming process. 

A stereospecific Suzuki coupling is also the key step in the synthesis of trisporol B benzyl ether (111) by Suzuki et al. (see... 

Using Kishi s modification of the Suzuki coupling procedure,45 Nicolaou et al. accomplished the convergent union of compounds 112 and 113 (see Scheme 28).38b 46 This coupling is the key step in a synthesis of (55,6/ )-dihydroxyeicosatetraenoic acid [(55,6/ )-diHETE] methyl ester (115). Importantly, the configurations of the two coupling partners are reflected in the Suzuki coupling product 114. 

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... 

SYNTHESIS OF 3-PYRIDYLBORONIC ACID AND ITS PINACOL ESTER. APPLICATION OF 3-PYRIDYLBORONIC ACID IN SUZUKI COUPLING TO PREPARE 3-PYRIDIN-3-YLQUINOLINE... 

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... 

The Suzuki-Miyaura synthesis is one of the most commonly used methods for the formation of carbon-to-carbon bonds [7]. As a palladium catalyst typically tetrakis(triphenylphosphine)palladium(0) has been used, giving yields of44—78%. Recently, Suzuki coupling between aryl halides and phenylboronic acid with efficient catalysis by palladacycles was reported to give yields of 83%. 

Another example of a one-pot indole synthesis, which proceeds through a Heck carbonylation and a Suzuki coupling, is shown below. The reaction conditions are similar to the previous example however microwave heating is employed [174] (Scheme 6.54). 

Miao, W. Chan, T.H. (2003) Exploration of Ionic Liquids as Soluble Supports for Organic Synthesis. Demonstration with a Suzuki Coupling Reaction. Organic Letters, 5, 5003-5005. 

Suzuki couplings have been used in the synthesis of complex molecules. For example, coupling of two large fragments of the epothilone A structure was accomplished in this way.229... 

The biaiyl phenol (X) was the penultimate intermediate in the synthesis of this final drag substance. Thus after the Suzuki coupling reaction is performed to give the phenol, the levels of Pd have to be lowered to < 10 ppm. In the pharma industry this can be a significant problem. Additionally there is always batch to batch variability observed when catalysts like Pd2(dba)3 have been used in Suzuki couphng reactions. 

Recently, synthesis of the 4-arylindole portion of the antitumor agent diazonamide has been achieved starling from 3-bromo-2-methylnitrobenzene via Suzuki coupling and the Batcho reaction.67b... 

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