Using indole-5-triflate

Another possibility is based on a biomimetic approach, a stereoselective S-endo-epoxide-indole cyclization. Using this methodology, the Kerr group has reported the synthesis of (—) or (+)-balasubramide using ytterbium triflate as the catalyst [15], while the Zhang group used p-toluenesulfonic acid (p-TSA) [16] (Scheme 4.3). 

Copper-catalyzed Direct Phenylation of Indoles. The site-selective direct phenylation of an indole bearing a tetrafluoro-phenyl substituent has been achieved in 64% yield using diphenyUodonium triflate, Cu(OTf)2, and 2,6-di-tert-butylpyridine in dichloromethane (eq 11). This coupUng occurs selectively at the C3 position of the indole ring under copper-catalyzed conditions, with no phenylation occurring at the C2 position of the indole ring or on the tetrafluorophenyl substituent. ... 

The formation of disubstituted alkynes by coupling of terminal alkynes, followed by intramolecular attack of an alcohol or amine, is used for the preparation of benzofurans and indoles. The benzo[il)]furan 356 can be prepared easily by the reaction of o-iodophenol with a terminal alkyne[262]. The 2-substituted indole 358 is prepared by the coupling of 2-ethynylaniline (357) with aryl and alkenyl halides or triflates, followed by Pd(ll)-catalyzed cycliza-tion[263]. 

Lewis acids such as zinc triflate[16] and BF3[17] have been used to effect the reaction of indole with jV-proiected aziridine-2-carboxylate esters. These alkylations by aziridines constitute a potential method for the enantioselective introduction of tryptophan side-chains in a single step. (See Chapter 13 for other methods of synthesis of tryptophans.)... 

Another triflate ester that recently has found growing application in organic synthesis is commercially available trimethylsilylmethyl trifluoromethanesul fonate. This powerful alkylating reagent can be used for the synthesis of various methylides by an alkylation-desilylation sequence A representative example is the generation and subsequent trapping by 1,3-dipolar cycloaddition of indolium methanides from the corresponding indole derivatives and trimethylsilylmethyl trifluoromethanesulfonate [108] (equation 54)... 

Instead of Bronsted acids, lanthanide triflates can be used to catalyze the reaction of indole with benzaldehyde (Eq. 7.7). The use of an ethanol/water system was found to be the best in terms of both yield and product isolation. The use of organic solvent such as chloroform resulted in oxidized byproducts.17... 

In terms of methodologies for the preparation of A-arylindoles 140, Buchwald reported improved conditions for the palladium-catalyzed coupling of aryl chlorides, bromides, iodides and triflates 138 with a variety of 2-, 7- and polysubstituted indoles 139 utilizing novel electron-rich biaryl(dialkyl)phosphine ligands in combination with Pd2(dba)3 <00OL1403>. Alternatively, Watanabe reports similar A-arylations of pyrrole, indole and carbazoles with aryl bromides and chlorides using Pd(OAc)2/P(f-Bu)3 in xylene at 120°C <00TL481>. 

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]. 

Doi and Mori made excellent use of dihydroindole triflate 189 in Pd-catalyzed cross-coupling reactions. This compound was discussed earlier in the Suzuki section, and it also undergoes Stille couplings as illustrated below [140]. A final dehydrogenation completes the sequence to indoles. 

The research group of Cacchi made extensive use of these tandem cyclization-Heck reactions to prepare a wide variety of indoles [311-314], For example, vinyl triflates react with o-aminophenylacetylene to afford an array of 2-substituted indoles in excellent yield, e.g., 356 to 357 [312], and a similar reaction of 358 with aryl iodides leads to an excellent synthesis of 3-arylindoles 359 [313],... 

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. 

Heterocyclic amines have also been used in conjuction with copper catalysis, as shown by the copper triflate-catalyzed reaction of indole 140 with 5-bromopyrimidine 130, which gave the product 141 in quantitative yield... 

While lanthanide triflates have been demonstrated to promote the reaction of indoles with imines <99SL498>, Johannsen has developed a new synthesis of optically active p-indolyl N-tosyl a-amino acids 110 via the enantioselective addition of A-tosylimnio esters of ethyl glyoxylate 109 to indoles 108 bearing both electron-donor and electron-acceptor substituents at C-5 using 1-5 mol% of a chiral copper(I)-Tol-BINAP catalyst <99CC2233>. 

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