Cross Suzuki-Miyaura Coupling

The Suzuki-Miyaura cross-coupling reaction involves the coupling of an aryl-or vinyl-boronic acid with aryl, vinyl or alkyl halides, commonly catalysed by a Pd complex (Equation (9.3)). 

With pincer complexes 50, acceptable conversions were obtained for activated and deactivated aryl bromides with phenylboronic acid in air. Complex 

NHC scaffolds other than imidazole-based were also investigated. Complex 

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Recently, Caddick and Cloke have developed an extension of this procedure that allows the use of alkyl bromides as coupling partners. The basic changes consist of a stoichiometric amount of the bulkier KO Bu instead of KOMe to activate the borane, and the addition of AgOTf to the reaction mixture [119]. These results, although poor in terms of yield, clearly confirm that sp -sp Suzuki-Miyaura cross-couplings are possible and should be further developed (Scheme 6.35). 

The medicinal chemists subsequently discovered an improved route to racemic acid 9 that started with 2-bromo-2-cyclopente-l-one 11 (Scheme 7.2) [5]. Suzuki-Miyaura cross-coupling of 11 with 4-fluorophenyl boronic acid 12 provided 13 in 67% yield. Conjugate addition of cyanide furnished ketone 14 in 71% yield. Reduction of 14 with NaB H4 gave a 2.8 1 mixture of desired 15 and undesired 16 which were separated by silica gel chromatography. The observed diastereoselec-tivity with the cyano group was similar to ester 6. Hydrolysis of 15 with 5 M NaOH in MeOH gave racemic acid 9 in 91% yield, which was resolved as outlined in Scheme 7.1. 

Chamoin S, Houldsworth S, Kruse CG, Bakker WI, Snieckus V. The Suzuki-Miyaura cross coupling reactions on solid support. Link to solution phase directed ortho metalation. The Leznoff acetal linker approach to biaryl and heterobiaryl aldehydes. Tetrahedron Lett 1998 39 4179-4182. 

Using a conventional dorm-room quality microwave oven, we have successfully performed Suzuki-Miyaura cross-coupling reactions catalyzed by Pd/C. Shorter reaction times are obtained (13 min of irradiation) using microwave irradiation compared to conventional methods of heating (> 1 h). Yields with relatively non-volatile aryl bromides range from 65 to 83%. Lower yields (15 - 27%) are obtained with relatively volatile aryl bromides substrates which may be evaporating during the course of the reaction. Ease of reaction set-up, rate enhancement from the microwave irradiation and facile work-up provided by the use of Pd/C makes this a very efficient procedure to mn. 

General microwave assisted Suzuki-Miyaura cross-coupling procedure... 

Organoboron compounds cannot react without proper activation. The use of oxygen bases is inherent in the standard Suzuki-Miyaura cross-coupling method. Fluorides (usually CsF) can be used as alternative activating agents, which is particularly useful in cases when the reagents are incompatible with oxygen bases for the reactions run under anhydrous conditions,24 (66) 241 Fluoride activation can be effective, however, even under aqueous phase-transfer conditions (67) 242... 

The Ir-catalyzed borylation of the indole nucleus is another important development that promises to find widespread use in complex molecule synthesis. Early reports include the functionalization of C(7) and also of C(2), reported by Malezcka and Smith and by Hartwig, respectively [39, 40]. In a report in 2011, Movassaghi, Miller, and coworkers demonstrated the borylation of tryptamine derivative 61 to afford 62 in 70 % yield [41]. This material was subjected to Suzuki-Miyaura cross coupling with 7-bromoindole (63) to set the stage for studying the oxidative rearrangement of 64, which would eventually provide diketopiperazine indole alkaloids such as asperazine (Scheme 11.11). 

Amann, N. and Wagenknecht, H. A. (2002). Preparation of pyrenyl-modified nucleosides via Suzuki-Miyaura cross-coupling reactions. Syn-lett 687-691. 

Kotha S, Lahiri S, Kashinath D (2002) Recent applications of the Suzuki-Miyaura cross-coupling reaction in organic synthesis. Tetrahedron 58 9633-9695... 

No examples of such reactions have been disclosed. Displacement of halogens on the parent heterocycle through metal-catalyzed processes have surprisingly not been reported to our knowledge on the neutral heterocycle. Recently, Suzuki-Miyaura cross-coupling reactions of imidazolium bromide 113 with various boronic acids or esters were reported <2005T6207> to proceed in good yield, without deprotonation at the C-3 position (Scheme 35). 

The 2-formyl-ip-methylcarbapenem 62 has been obtained in five steps from a readily available P-lactam in 23-26% overall yield <98MI1294>. Suzuki-Miyaura cross-coupling of aiylboronic acids and vinyl triflates is a convenient route to 2-aiylcarbapenems on a small scale but may present problems on a large scale. Vinyl phosphates, mesylates or tosylates are convenient alternatives to triflates <9981471>. Radical cyclizations of readily available enyne-2-azetidinones (e.g., 63) with a tin hydride, RjSnH, provides a route to the... 

Chamoin, S. Houldsworth, S. Kruse, C. G. Bakker, W. I. Snieckus, V. The Suzuki-Miyaura Cross Coupling Reactions on Solid Support. Link to Solution Phase Directed ortho Metalation. The Leznoff Acetal Linker Approach to Biaryl and Heterobiaryl Aldehydes, Tetrahedron Lett. 1998, 39, 4179-4182. 

Vinylsilanes react with boron trichloride to give the corresponding borodesilylation products in good yield which, in turn, can be transformed into boronic esters 124 by alcoholysis (equation 102). The initial dichloroorganoborane products can be used directly in the Suzuki-Miyaura cross-coupling reaction192. Replacement of a carbon-silicon bond by a carbon-tin bond in fluorinated alkenes (e.g. 125) can be achieved by the reaction of silanes with Bu3SnCl and KF in DMF under mild conditions (equation 103)193. It is... 

The reaction of interest was first reported by Miyaura and co-workers in 1997 [1]. It was found that the addition of phenylboronic acid, a reagent pioneered for Pd-catalysed Suzuki-Miyaura cross-coupling, to simple a,p -unsaturated ketones was catalysed by Rh(I) complexes. 

Suzuki-Miyaura cross-coupling and alkene ring closing metathesis reactions.37... 

Kotha, S., Mandal, K., Suzuki-Miyaura cross-coupling and ring-closing metathesis A strategic combination for the synthesis of cyclophane derivatives. Eur. J. Org. Chem. 2006, 5387-5393. 

Potuzak, J. S. Tan, D. S. Synthesis of Cl-alkyl and acylglycals from glycals using a B-alkyl Suzuki-Miyaura cross coupling approach. Tetrahedron Lett. 2004, 45, 1797-1801. 

Synthesis and Cytostatic Activity of Substituted 6-Phenylpurine Bases and Nucleosides Application of the Suzuki—Miyaura Cross-Coupling Reactions of 6-Chloropurine Derivatives with Phenylboronic Acids... 

Havelkova, M. Hocek, M. Cesnek, M. Dvorak, D. The Suzuki-Miyaura Cross-Coupling Reactions of 6-Halopurines with Bo-ronic Acids Leading to 6-Aryl- and 6-Alkenylpurines. Synlett 1999, 1145-1147. 

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