Pyrimidines, Suzuki-Miyaura coupling

Consecutive 5 substitution of hydrogen and Suzuki-Miyaura coupling of 5-bromopyrimidine allows the formation of pyrimidines carrying pyrrole or indole groups at the 4-position and aryl groups at the 5-position as outlined in Scheme 12. Structures of rr-adduct intermediates, such as (138), have been established by X-ray crystallographic analysis. ... 

Mayer, E., Valis, L., Huber, R., Amann, N. and Wagenknecht, H. A. (2003). Preparation of pyrene-modified purine and pyrimidine nucleosides via Suzuki-Miyaura cross-couplings and characterization of their fluorescent properties. Synthesis 2335-2340. 

The first example of a Suzuki-Miyaura reaction on a pyridopyrimidine skeleton was used for decoration of a 4-diloro[2,3-d]pyrimidin-7(8H)one scaffold. Phe-nylboronic acid was used as a coupling partner with a good isolated yield (Scheme 15.18) [51]. 

Arylation of a wide range of NH/OH/SH substrates by oxidative cross-coupling with boronic acids in the presence of catalytic cupric acetate and either triethyl-amine or pyridine at room temperature in air. The reaction works for amides, amines, anilines, azides, hydantoins, hydrazines, imides, imines, nitroso, pyrazi-nones, pyridones, purines, pyrimidines, sulfonamides, sulfinates, sulfoximines, ureas, alcohols, phenols, and thiols. It is also the mildest method for NIO-vinylation. The boronic acids can be replaced with siloxanes or starmanes. The mild condition of this reaction is an advantage over Buchwald-Hartwig s Pd-catalyzed cross-coupling. The Chan-Lam C-X bond cross-coupling reaction is complementary to Suzuki-Miyaura s C-C bond cross-coupling reaction. 

Utilized Pd(OAc)2 and SPhos 24 as the catalyst system to effectively catalyze Suzuki-Miyaura cross-couplings with only 1.1 equiv. of trifluoroborates [84e]. More recently, Molander and coworkers have developed a general cross-coupling system to many classes of heteroaromatic trifluoroborates employing Pd(OAc)2 and RuPhos 23 [84j]. Furan 135, thiophene 132, pyrrole 126, pyrazole 130, isoxazole 131, pyridine 127, pyrimidine 133, indole 129, benzothiophene 136, benzofuran 135, quinoline 128, and isoquinoUne could all be cross-coupled with only 1.04 equiv. of trifluoroborate salts, affording the corresponding cross-coupled products in good yield (Scheme 2.25). 

The [AE, (addition-elimination)] and [AO, (addition-oxidation)] reactions of 5-bromopyrimidine with pyrroles and indoles for the synthesis of 4-(lR-pyr-rol-2-yl)-and 4-(lR-indol-3-yl)-5-(hetero)aryl-substituted pyrimidines by combination of the Suzuki-Miyaura cross-coupling and nucleophilic aromatic substitution of hydrogen reactions was carried out by Verbitskiy et al. (2012a). 

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