Suzuki coupling/reaction

3 Suzuki Coupling Reaction Suzuki reaction is palladium-catalyzed cross-couphng between organoboronic acid and halides. Recently, newly developed catalysts and methods have broadened possible applications enormously, so that the scope of the reaction partners is not restricted to aryls but includes alkyls, alkenyls, and alkynyls. Potassium trifluoroborates and organoboranes or boronate esters may be used instead of boronic acids. Some pseudohaUdes (e.g., triflates) may also be used as coupling partners. 

SCHEME 7.19 Synthesis of Aristolactam BII (cepharanone B), Aristolactam BIB, Aristolactam FI (piperolactam A), A-methyl piperolactam A and Sauristolactam. Sonagashira coupling reaction. 

The Sonagashira coupling reaction has become one of the most general, rehable and effective methods for the synthesis of substituted alkynes [40]. This reaction of terminal alkynes with aryl or vinyl halides is performed by using a palladium catalyst, a copper(I) cocatalyst, and an amine base. 

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To date a number of reactions have been carried out in ionic liquids [for examples, see Dell Anna et al. J Chem Soc, Chem Commun 434 2002 Nara, Harjani and Salunkhe Tetrahedron Lett 43 1127 2002 Semeril et al. J Chem Soc Chem Commun 146 2002 Buijsman, van Vuuren and Sterrenburg Org Lett 3 3785 2007]. These include Diels-Alder reactions, transition-metal mediated catalysis, e.g. Heck and Suzuki coupling reactions, and olefin metathesis reactions. An example of ionic liquid acceleration of reactions carried out on solid phase is given by Revell and Ganesan [Org Lett 4 3071 2002]. 

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. 

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. 

Under all the conditions studied, addition of bare Si02-SH to Heck or Suzuki coupling reactions using a variety of bases, aryl halides and solvents resulted in complete cessation of the catalytic activity (35). These results suggest that catalysis with this precatalyst is also associated with labile palladium species that... 

Suzuki coupling reactions with aryl halides. Two as-prepared BaCei cPd c03. ( materials (x = 0.05 and 0.10) were successfully utihzed in several Suzuki coupling reactions. Both aryl iodides and aryl bromides react smoothly with 4-phenylboronic acid, eq 1, to yield the corresponding biatyls in high yields (> 95%). For both 4-bromoanisole and 4-iodoanisole, the biatyl yields reached nearly 100% in 3 min with BaCeo 95Pdoo503 5 as the catalyst, corresponding to an effective TON of ca. 2,000 and an effective TOF of nearly 50,000 h. Resnlts are smmnarized in Table 27.1. 

General procedure for Suzuki coupling reaction. A 100 mL of round-... 

We have broadened the scope of this reverse addition protocol to prepare a variety of boronic acids bearing different functional groups for use in Suzuki coupling reactions. The yield and quality of the boronic acid prepared by this reverse addition protocol is usually better than the sequential approach. The boronic acids can be used without further purification (formation of pinacols) in Suzuki coupling reactions. 

Suzuki Coupling Reaction (IV). The coupling of boronic acid (II) with iodooxazole (III) was the first Suzuki reaction done on-scale at Bristol Myers Squibb. Our hope from the beginning was to isolate isopropyl ester of the coupled biaryl, so that issues related to removal of Pd can be separated from other quality issues of the coupling reaction as outlined in Scheme 3. 

In connection with another project being developed we needed large quantities of a biaryl phenol or biaryl aryl methyl ether which was being prepared by a Suzuki coupling reaction (Scheme 6). 

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. 

A parallel synthesis of a library of 2-aryl-6-chlorobenzothiazoles 112 involves a regioselective palladium-catalyzed Suzuki coupling reaction of 2,6-dichlorobenzothiazole 111 with arylboronic acids (1.1 equiv) under microwave irradiation <06TL3091>. When excess phenylboronic acid is used, Pd(PPh3)4 still provides 2-phenyl-6-chlorobenzothiazole exclusively, while 2-dicyclohexylphosphinobiphenyl 113 generates 2,6-diphenylbenzothiazole as the major product. 

Polymer 163 (and similar alternating copolymers of 9,9-dioctylfluorene and oxadiazole <2002MM3474>) with blue-light-emitting activity were synthesized by the Suzuki coupling reaction and studied by GPC, MALDI-TOF MS, LJV spectroscopy, and several other techniques <2002ANC6252>. 

Stewart and Whiting have reported a useful application of sequential Heck and Suzuki coupling reactions of a vinylborane pinacol ester with palladium catalysis to generate a tetraene (equation 147)260. 

A divergent protocol for a solid-phase synthesis of 3-substituted 2,5-biarylfurans was reported. Thus, reaction of furan zincate A with polymer bound aryl bromide or iodide provides resin intermediates 61. Subsequent bromination-Suzuki coupling reaction followed by further transformations gives rise to structurally diverse 2,3,5-trisubstituted furans 68 in good overall yields and chemical purities <00TL5447>. 

Another Suzuki coupling reaction was described by Zhang et al., to produce arylindoles 116a and b, using solid-phase synthesis [76]. The synthesis was achieved by palladium-mediated coupling/intramolecular indole cycli-zation of resin-bound 2-trimethylsilylindole 117, Scheme 29. 

Baxendale IR, Griffiths-Jones CM, Ley SV, Tranmer GK (2006b) Microwave-assisted Suzuki coupling reactions with an encapsulated palladium catalyst for batch and continuous-flow transformations. Chem Eur J 12 4407-4416 Baxendale IR, Deeley J, Griffiths-Jones CM, Ley SV, Saaby S, Tranmer GK (2006c) A flow process for the multi-step synthesis of the alkaloid natural product oxomaritidine a new paradigm for molecular assembly. J Chem Soc Chem Commun 2566-2568... 

As we have seen in Chapter 1, the Suzuki coupling reaction is a powerful method for preparing biaryls and several applications in pyrrole chemistry have been described. Schliiter reported the first pyrrole boronic acid 57, but, surprisingly, the related pyrrole borate 58 could not be hydrolyzed [15]. 

Ketcha has prepared l-(phenylsulfonyl)pyrrole-2-boronic acid (65) in low yield and effected Suzuki coupling reactions to afford the corresponding 2-aryl derivatives 66 [58]. 

SCHEME 2.25 Synthesis of PF via Suzuki-coupling reaction. (From Ranger, M. and Leclerc, M., Chem. Commun., 1597, 1997.)... 

S. Guillerez and G. Bidan, New convenient synthesis of highly regioregular poly(3-octylthiophene) based on the Suzuki coupling reaction, Synth. Met., 93 123-126, 1998. 

Kim, S.W. et al., Fabrication of hollow palladium spheres and their successful application to the recyclable heterogeneous catalyst for Suzuki coupling reactions, J. Am. Chem. Soc., 124, 7642, 2002. 

Some of the reactions (e.g., that of dimethylaluminum chloride in Table 2) involve redistribution of alkyl and halide groups between the metals. The boronic acids, ArB(OH>2, prepared by Sn/B transmetallation, have been used in Suzuki coupling reactions. It is remarkable that the bistributyltin derivative of 1,1 -binaphthyl undergoes... 

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