Indol-2-yl triflate

Indolyltriflates have been used in Suzuki couplings by Mdrour [138, 139]. Thus, the readily available l-(phenylsulfonyl)indol-2-yl triflate (131) smoothly couples with arylboronic acids in 65-91% yield. Similarly, Pd-catalyzed cross-coupling of phenylboronic acid with l-benzyl-2-carbomethoxyindol-3-yl triflate affords the 3-phenyl derivative (62% yield) [139]. 

Adapting Gribble s method for synthesizing indol-3-yl triflate [37], Mdrour et al converted 2-formyl- l-(phenylsulfonyl)- l//-indole (31) to indol-2-yl triflate 32 in two steps. 32 was subsequently coupled with benzofuryl-2-boronic acid to furnish 2-benzofurylindole 33 [38, 39]. In another case, 2-bromoacetaniline was coupled with 2-formyl-3-furylboronic acid 35 [40]. The resulting Suzuki coupling adduct underwent a spontaneous cyclization, forming tricyclic furo[2,3-c]quinoline 36. 

The vinyl triflate of Komfeld s ketone has been subjected to Heck reactions with methyl acrylate, methyl methacrylate, and methyl 3-(Af-rerf-butoxycarbonyl-lV-methyl)amino-2-methylenepropionate leading to a formal synthesis of lysergic acid [259]. A similar Heck reaction between l-(phenylsulfonyl)indol-5-yl triflate and dehydroalanine methyl ester was described by this research group [260]. Chloropyrazines undergo Heck couplings with both indole and 1-tosylindole, and these reactions are discussed in the pyrazine Chapter [261], Rajeswaran and Srinivasan described an interesting arylation of bromomethyl indole 229 with arenes [262]. Subsequent desulfurization and hydrolysis furnishes 2-arylmethylindoles 230. Bis-indole 231 was also prepared in this study. 

Both vinyl- and aryl triflates have been cross-coupled with 2-furylzinc chloride [26-28]. Since vinyl triflates are easily obtained from the corresponding ketones, they are useful substrates in Pd-catalyzed reactions. In the following example, a Negishi coupling of 2-furylzinc chloride and indol-5-yl triflate (22) provided an expeditious entry to 2-(5 -indolyl)furan (23). Protection of the NH in the indole ring was not required. A similar reaction was successful with pyridyl- and quinolinyl triflates. 

The aza-Diels-Alder reaction of substituted lf/-indole-2-carbaldehydes 1323 with Danishevsky s diene 1324 proceeds with a high degree of diastereoselectivity providing highly functionalized l-R -2-(Tmethyl-lf/-indol-2-yl)-2,3-dihydro-4(l//)-pyridinones 1325 which were further elaborated into novel polycyclic heterocycles (Equation 289) <2002TL29>. Attempts to form the imine of 12/-indole-2-carbaldehyde 1326 in situ in the presence of diene 1324 and zinc chloride or zinc triflate at 0 °C or at room temperature did not afford the expected cycloadduct 1327. Instead, 2-(177-indol-2-yl)-2,3-dihydro-477-pyran-4-one 1328 and the 5-hydroxy-l-methoxy-5-(l/7-indol-2-yl)-Tpenten-3-one 1329 were isolated in 45% and 25% yields, respectively (Equation 290). 

Beccalli et al. reported a new synthesis of staurosporinone (293) from 3-cyano-3-(lH-indol-3-yl)-2-oxo propionic acid ethyl ester (1464) (790). The reaction of 1464 with ethyl chlorocarbonate and triethylamine afforded the compound 1465, which, on treatment with dimethylamine, led to the corresponding hydroxy derivative 1466. The triflate 1467 was prepared from 1466 by reaction with trifluoromethanesulfonic anhydride (Tf20) in the presence of ethyldiisopropylamine. The palladium(O)-catalyzed cross-coupling of the triflate 1467 with the 3-(tributylstannyl)indole 1468 afforded the vinylindole 1469 in 89% yield. Deprotection of both nitrogen atoms with sodium ethoxide in ethanol to 1470, followed by photocyclization in the presence of iodine as the oxidizing agent provided the indolocarbazole 1471. Finally, reductive cyclization of 1471 with sodium borohydride-cobaltous chloride led to staurosporinone (293) in 40% yield (790) (Scheme 5.248). 

Methyl trifluoropyruvate alkylates a series of substituted indoles catalysed by the chiral non-racemic 2,2/-bipyridylcopper(II) triflate complex (32) to form methyl 3,3,3- trifluoro-2-hydroxy-2-indole-3-yl propanoates [e.g. (33)] in high enantiomeric excess and good yield.37... 

Ytterbium triflate-catalyzed Michael addition of iV-methylindole to mesityl oxide 452 was carried out using a modification of the Kerr procedure (4% of Yb(OTf>3, 4equiv of compound 452) <1996SL1047, 1998CJC1256> to give the desired 4-(indol-3-yl)-4-methyl-2-pentanone 453 in 81% yield (Scheme 96) <2001TL6835>. Product 453 was converted into the a-diazo- )-keto ester 454 having an iV-methylindole unit. 

Procedures for Pd-catalyzed coupling with carbonylation to give 2-acyl indoles were also reported. Triethyl(l-methylindol-2-yl)borate, which can be prepared from 1-methylindole by lithiation followed by addition to triethylborane, was coupled with aryl iodides and vinyl triflates to give 2-acyl indoles in 20-80% yield. <94J0C2634> The reactions were run with PdClj(PPh3)2 as catalyst under 15 atm of CO at 90 . 

To a dried 2-dram vial in a drybox was added an appropriate amount scandium(III) triflate, 4 A MS (15 mg/0.13 mmol of substrate), and 1.2 equiv (5)-Indapybox ligand. The vial was capped with a septum and purged with 1 mL dichloromethane. The catalyst was allowed to age for 2 h at rt. The dichloromethane was removed by a steady stream of N2 to afford catalyst complex 196. To 2 mol % (0.0021 mmol) 196 was added 1 mL of acetonitrile. The reaction was cooled to -40 °C for 15 min before 30 mg (0.103 mmol, 1 equiv) ( )-6-(l//-indol-3-yl)-l-(l-methyl-17/-imidazol-2-yl)hex-2-en-l-one 206 was added to the vial. After 18 h of moderate stirring at -40 °C, the title compound was purified by flash silica chromatography (Rf = 0.31, 50% EtOAc/hexanes) to afford 30 mg (99% yield, 97% ee) 207. 

The title reagent can be employed in a multicatalytic tandem reaction with Ag(OTf) to synthesize l-(indol-3-yl)-2-aminoisoquinolinium triflates, providing access to a range of substituted indoles (eq 2). ... 

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