Indoles with epoxides

Epoxides and aziridines are also capable of electrophilic subsitution of indoles. Indolylmagncsium bromide and cyclohexene oxide react to give 3-(lrans-2-hydroxycyclohexyl)indole[14]. Reaction of indoles with epoxides also occurs in the presence of Lewis acids. For example, indole reacts with methyl 2S,3R-epoxybutanoate at C3 with inversion of configuration[15]. 

The condensation of indoles with epoxides or aziridines can also be conducted on the surface of silica <2005JOC3490>. 

Hoseini-Sarvari M and Parhizgar G. Regioselective Friedel-Crafts alkylation of indoles with epoxides using nano MgO. Green Chem. Lett. Rev. 2012 5(3) 439-449. 

The Pd(0)-catalyzed allylation of 96 with acrolein dimethyl acetal gives exclusively compound 104. The 7j3-allylpalladium cationic complex (4, R = OMe) is attacked only at the center bearing the substituent MeO (80SC147), thus emphasizing the importance not only of steric effects in the electrophile but also of the electronic effects in the Tsuji-Trost reaction (92T1695). Indole 96 has been also allylated with epoxide 105 under Pd(0) catalysis by Trost and Molander (81JA5969). The intermediate cationic complex is attacked at the exocyclic position, 106 being formed, as shown in Scheme 22. 

Nickel-catalyzed reductive cyclizations and couplings in the syntheses of heterocycles including coupling of alkynes with epoxides and syntheses of indole and indolizidine alkaloids 04AG(E)3890. 

Indoles react with epoxides and aziridines in the presence of Lewis acids (see 20.4.1 for reaction of indolyl anions with such reactants) with opening of the three-membered ring and consequent 3-(2-hydroxyethylation) and 3-(2-aminoethylation) of the heterocycle. Both ytterbium triflate and phenylboronic acid are good catalysts for reaction with epoxides under high pressure silica gel is also an effective catalyst, but reactions are slow at normal pressure and temperature. Reaction with aziridines can be catalysed by zinc triflate or boron trifluoride. °... 

Construction of the Dolby model system began with epoxidation of cyclohexene 209 employing mCPBA in chloroform. The epoxide product was then subjected to a base-promoted cyclization via amide deprotonation and oxirane opening to provide benzamide 210 (Scheme 23). Hydroxyl oxidation using the Jones conditions next furnished cyclohexanone 211. A Fischer indole synthesis on this scaffold, followed by amine deprotection using sodium hydroxide, led to the desired l,3-(iminoethano)carbazole 83. While the yield of this route was low, it was the first example of a method to fashion the 2-azabicyclo[3.3.1]nonan-8-one system 211, and importantly demonstrated that indoHzation on such a scaffold was possible. 

The Saegusa indole synthesis involves the strong-base promoted cyclization of ort/ o-tolylisocyanides to indoles (Scheme 1) [1-5], Thus the Saegusa indolization resembles the Madelung indole synthesis. The reaction proceeds by a 5-endo-dig cyclization of 2 to form indole (equation 1). The isocyanide anion 2 was alkylated and subsequently cyclized to form 3-substituted indoles (equation 2). The quenching of 2 with epoxides yielded tryptophols (equation 3 and 4 and 5). Reaction of the ultimately formed N-lithioindole with electrophiles gave Af-substituted indoles (equation 4). 

The epoxide-forming reaction of sulphonium ylides with carbonyl compounds continues to be widely applied in a routine sense at the same time as new and unique applications are studied. Bravo et al. have reported that, whereas indole and dimethylsulphonium-methylide afford iV-methylindole (i.e. protonation of the ylide followed by sulphonium salt alkylation of the indole), the keto-amide (28) gives an epoxide. Similarly, the amide function in (29) did not interfere with epoxide formation. In... 

Alkylation Reactions of Indole Friedel-Crafts alkylation of indoles and pyrroles with epoxides has been efficiently carried out over three-dimensional (3D) mesoporous aluminosilicates catalysts (AlKlT-5) in water at room temperature (Scheme 19) [88]. The autiiors found that mesoporous silica materials containing an interconnected large-pore cage-type mesoporous system with 3D porous networks supposed to be more valuable than porous materials containing a hexagonal pore structure with a one-dimensional array of pores. 

Benzylic C-H bonds undergo oxidative esterification with TBHP in the presence of tetrabutylammonium iodide as catalyst and carboxylic acids in good to excellent yields. A free radical process has been proposed. Asymmetric epoxidation of electron-poor terminal alkenes bearing different carbonyl groups has been achieved with a cinchona thiourea/TBHP system. The corresponding epoxides, containing a quaternary stereocentre, were isolated in yields up to 98% and enantioselectivity up to 99%. A direct oxidative CDC of indole with A-aryltetrahydroisoquinolines in the 0 presence of a gold catalyst and TBHP resulted in the formation of a variety of alkylated heteroarenes (Scheme 24). ... 

The glycal epoxide method turned out to be useful for the construction of complex 2-branched [3-aryl glycosides, which are salient features of the potent antibiotic vancomycin [75a]. Glycal epoxide glycosylation with sodium salts of indoles pro-... 

As we have seen earlier in this chapter, palladium is often employed to effect JV-alkylation of indoles. Trost and Molander found that indole reacts with vinyl epoxide 375 to give indole 376 [468]. The utility of such AZ-alkylations remains to be established. 

Jacobsen et al. [48], in 1997 for the first time demonstrated KR of racemic terminal epoxides with water as nucleophile for the production of optically pure epoxides and corresponding 1,2-diols. Since then, various other nucleophiles viz., carboxylic acids, phenols, thiols, amines, carbamates and indols were used in KR to produce optically pure epoxides with concomitant production of corresponding enantioenriched l,2-bifimctional moieties [49-52]. 

Scheme 22. ARO of enantiomerically pure epoxide with various indoles using catalyst 51.

Oxindole 89 was cleanly demethylated upon treatment with boron tribromide. The resulting oxindole 90 was subjected to the prenylation conditions, and the desired alkylated product 91 was obtained in 52% yield. The epoxidation/Lewis acid-mediated cyclization proved to be successful on this substrate. The epoxide product was directly treated with SnCl4 in THF to provided the desired 92. When oxindole 92 was treated with NaBHt (1.6 equivjand BF3 OEt2 (3.5 equiv) in THF, the desired 93 was obtained. The indole 93 was treated with TBDMSC1 and imidazole in DMF, to provide the required O-silylated indole, which was easily converted to the gramine 94 through the well known Mannich procedure. 

Recently, Indian workers (61) reported that 2-naphthylmethylene triphenylarsorane reacted with substituted benzaldehydes to give the corresponding epoxides exclusively, whereas l-bromo-2-naphthylmethylene triphenylarsorane reacted with substituted benzaldehydes to give only olefins. In no case were both olefin and epoxide isolated and in all cases only fram-epoxides or trans-olefins were detected. It has also been reported that reaction of indole-3-carboxaldehyde with semistabilized ar-sonium ylides followed only the trans -carbonyl olefination (91). 

Scheme 5. Enantioselective kinetic resolution of 1,2-disubsti-tuted epoxides (a) and desymmetrization of meso stilbene-oxide (b) with indoles catalyzed by4b-4c.

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