1.2.4- Triazines cross-coupling reactions

Raboisson et al. <2002JOC8063> elaborated a new general approach to pyrazolo[l,5- ][l,3,5]triazine-based C-nucleosides 140 by application of palladium-mediated cross-coupling reaction. The reaction of 139 was carried out by using bis(dibenzylideneacetone)Pd(0), triphenylarsine, and triethylamine to give the product 140 in high yield (75%). 

Silyl enol ethers (CHj = CROSiMe3) react with cyanuryl chloride and replace only one chlorine with a carbon substituent (CH2COR R = cyclopropyl, 70 /o, R = Ph, 90 /o). Friedel-Crafts arylation <83KGS1125,92EUP497734>, the Ullmann reaction of 2-iodo-1,3,5-triazine to form 2,2 -bis-1,3,5-triazine <82NKK1425>, and a palladium-catalyzed cross-coupling reaction of 2-substituted 4,6-dichloro-... 

The Susuki cross-coupling reaction has been applied to obtain 3-substituted-l,2,4-triazines 159 by reacting 3-methylthio-... 

Table 15 Cross-coupling reactions of 3-methylthio-1,2,4-triazine with aryl-, hetaryl-, or vinyl-boronio aoids and organostannane oompounds...

Under certain reaction conditions, even activated arylmethylthioethers can be used as electrophiles in the SM reactions. Thus copper(l) 3-methylsalicylate (CuMeSal) does catalyse the cross-coupling reaction of 3-methylthio-l,2,4-triazine (248) with 2-thienyl boronic acid (249) to afford biaryl 250 in 70% yield, respectively [50], Scheme 3. 

Cross-coupling reactions of 1,2,4-triazines are less common due to rather poor availability of suitable substituted 1,2,4-triazine derivatives. Nevertheless, they attract attention from researchers resulting in development of new synthetic methods for 1,2,4-triazine functionalization. Thus, the synthesis of novel substituted 1,2,4-triazines 33 and 34 containing thiophene and furan rings using palladium-catalyzed cross-coupling reactions of 3-alkylsulfanyl- or 5-cyano-l,2,4-triazine 35, 36 was described (14T4697). 

Lee, C. H. Yamamoto, T. Synthesis of liquid-crystalline, highly luminescent ir-conjugated 1,3,5-triazine derivatives hy palladium-catalyzed cross-coupling reaction. Mol. Cryst. Uq. Cryst. 2002, 378, 13-21. 

The chemistry of fluorinated 1,3,5-triazines is not as well studied as the chemistry of their chloro derivatives. In case of fluorotriazines the reactions directed on the ring nitrogen atoms, displacement of fluorine atoms and reactions on carbon atoms on the ring with retention of the fluorine atoms appear to be the most characteristic ones. In this section the N-alkylation and N-acylation reactions, as well as replacement of fluorine atoms by a variety of nucleophiles will be considered. Metallation of fluorotriazines and synthesis on the basis of organometallic compounds, as well as the cross-coupling reactions were described. Also several examples of photochemical reactions and transformations are presented. 

Cyclin-dependent kinases (CDKs) play a key role in regulating cell cycle machinery. This family of kinases requires association with a cyclin regulatory subunit for activity. Different CDK/cyclin pairs are active during each phase of the cell cycle. Negishi cross-coupling reactions were the key steps in the synthesis of [l,3,5]triazine-pyridine biheteroaryls 161 as a novel series of potent cyclin-dependent kinase inhibitors. ... 

Nucleophilic displacement of chlorine, in a stepwise manner, from cyanuric chloride leads to triazines with heteroatom substituents (see Section 6.12.5.2.4) in symmetrical or unsymmetrical substitution patterns. New reactions for introduction of carbon nucleophiles are useful for the preparation of unsymmetrical 2,4,6-trisubstituted 1,3,5-triazines. The reaction of silyl enol ethers with cyanuric chloride replaces only one of the chlorine atoms and the remaining chlorines can be subjected to further nucleophilic substitution, but the ketone produced from the silyl enol ether reaction may need protection or transformation first. Palladium-catalyzed cross-coupling of 2-substituted 4,6-dichloro-l,3,5-triazine with phenylboronic acid gives 2,4-diaryl-6-substituted 1,3,5-triazines <93S33>. Cyanuric fluoride can be used in a similar manner to cyanuric chloride but has the added advantage of the reactions with aromatic amines, which react as carbon nucleophiles. New 2,4,6-trisubstituted 1,3,5-triazines are therefore available with aryl or heteroaryl and fluoro substituents (see Section 6.12.5.2.4). 

Cibacron Blue is a blue, polyaromatic, sulfonated dye (Fig. 6). It can be attached, as an affinity li nd, to solid matrix supjmrts (e.g. dextran, agarose) by the reaction of the triazine ring with free hydroxyl groups of the supports. The conditions of this triazine coupling method have been described by Bohme Such a dye affinity sorbent is also produced commercially, e.g. under trade name Blue Sepharose CL-6B (Cibacron Blue F3G-A covalently bound to the cross-linked agarose gel Sepharose CL-6B ) by Pharmacia, Sweden. 

---