5-indolylboronic acid

Another selective approach to 2-trifluoromethyIindole is copper-mediated oxidative cross-coupling of 2-indolylboronic acid with TMSCF3. Reaction proceeds in mild conditions to give A-Boc-2-trifluoromethylindole 6 d in 61 % yield [29],... 

Indoles with carbocyclic halogen or triflate substituents are potential starting materials for vinylation, arylation and acylation via palladium-catalysed pro-cesses[l]. Indolylstannanes. indolylzinc halides and indolylboronic acids are also potential reactants. The principal type of substitution which is excluded from such coupling reactions is alkylation, since saturated alkyl groups tend to give elimination products in Pd-catalysed processes. 

Recognizing the distinct difference in reactivity for each site of N-protected 2,4,5-triiodoimidazole 23, Ohta s group successfully arylated 23 regioselectively [32, 33], In the total synthesis of nortopsentin C, they coupled 23 with one equivalent of 3-indolylboronic acid 24 to elaborate imidazolylindole 25. The Suzuki reaction occurred regioselectively at C(2) of the imidazole ring. 

Like simple aryl halides, furyl halides take part in Suzuki couplings as electrophiles [41, 42]. Young and Martin coupled 2-bromofuran with 5-indolylboronic acid to prepare 5-substituted indole 37 [43]. Terashima s group cross-coupled 3-bromofuran with diethyl-(4-isoquinolyl)borane 38 to make 4-substituted isoquinoline 39 [44]. Similarly, 2- and 3-substituted isoquinolines were also synthesized in the same fashion [45]. 

Indolylboronic acid (21), easily obtained from commercially available 5-bromoindole, was coupled with 2-chloropyrazine (13) to efficiently furnish 5-(2-pyrazinyl)indole (22) [18]. 

The coupling of 2- and 5-pyrimidinylbromides with 5-indolylboronic acid afforded 5-pyrimidinylindoles [25]. 5-Indolylboronic acid was readily prepared from commercially available 5-bromoindole by a one-pot process involving treating 5-lithio-l-potassioindole with tributylborate followed by acidic hydrolysis. Meanwhile, it was also discovered that... 

Several other groups have reported the synthesis and Suzuki reactions of an N-methylindolyl-3-carboxamido-2-boronic acid for the synthesis of benzo[a]carbazoles [128], an iV-Boc-5-sulfonamidoindolyl-2-boronic acid for the synthesis of novel KDR kinase inhibitors [129], indolyl-4-boronic acid in a new synthesis of lysergic acid [130], and 5-, 6-, and 7-indolylboronic acids for the synthesis of aryl-substituted indoles [131]. Carbazole-2,7-bis (boronates) have been employed to construct diindolocaibazoles [132]. 

The coupling of 2- and 5-pyrimidinylbromides with 5-indolylboronic acid afforded... 

An interesting example of the Petasis reaction was employed as a highly stereoselective synthesis of indolyl jV-substituted glycines by the reaction of indolyl-3-boronic acids <01TL2545>. Thus, reaction of 7V-tosyl-3-indolylboronic acids 176 with (R)-a-methyl-benzylamine (177) and glyoxylic acid (178) provides the indolyl iV-substituted glycines 179 in optically pure form. 

Heterocyclic aromatic boronic acids, in particular pyridinyl, pyrrolyl, indolyl, thienyl, and furyl derivatives, are popular cross-coupling intermediates in natural product synthesis and medicinal chemistry. The synthesis of heterocyclic boronic acids has been reviewed recently [222], and will not be discussed in detail here. In general, these compounds can be synthesized using methods similar to those described in the above section for arylboronic acids. Of particular note, all three isomers of pyridineboronic acid have been described, including the pinacol ester of the unstable and hitherto elusive 2-substituted isomer, which is notorious for its tendency to pro-todeboronate [223]. Improvements and variants of the established methods for synthesizing heterocyclic boronic acids have been constantly reported [13, 182]. For example, a Hg-to-B transmetallation procedure was recently employed to synthesize a highly functionalized indolylboronic acid (entry 19, Table 1.3) [187]. 

Bis(indolyl)-4-trifluoromethylpyridine has been synthesized using Suzuki coupling between 2,6-dichloro-4-trifluoromethylpyridine and N-tosyl-3-indolylboronic acid. This compound was evaluated for cytotoxic activity against P388 (Equation 43) [52]. 

Aoyama has also shown that 5-indolylboronic acid (3) imdergoes fluorescence quenching upon complexation with oligosaccharides [38]. The stability constants of monosaccharides followed the trend observed by Lorand and Edwards [12] however, higher oligomers of saccharides enjoyed increased stabilization relative to lower oligomers due to a secondary interaction with the indole N-H. The observed stability constants (fC pp) for 3 were D-fructose 630 M", D-glucose 7.1 M" and D-melibiose 58 in water at pH 9. 

Nagai, Y., Kobayashi, K., Toi, H., and Aoyama, Y. (1993) Stabilization of sugar-boronic esters of indolylboronic acid in water via sugar-indol interaction A notable selectivity in oligasaccharides. Bull. Chem. Soc., Jpn., 66, 2965-2971. 

The influence of pyranose to furanose interconversion on the observed stability constants (iifobs) of boronic acid complexes can be effectively demonstrated in the fluorescence response of boronic acid appended sensors with disaccharides. In examining the stabilities of disaccharides with the 5-indolylboronic acid 38, Aoyama and co-workers noted that for non-reducing sugars the observed stability constants (Aiobs) were significantly reduced or zero. This phenomenon was ascribed to the lack of an anomeric hydroxyl, which inhibited the... 

Jiang, B. and Yang, C. (2000) Synthesis of indolylpyrimidines via crosscoupling of indolylboronic acid with chloropyrimidines facile synthesis of meridianin D. Heterocycles, 53,1489-1498. 

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