3- Acetoxy-3//-indole

Oxidants and electrophilic reagents attack pyrroles and furans at positions 2 and 5 in the case of indoles the common point of attack is position 3. Thus, autoxidation of indoles (e.g. 130) gives 3-hydroperoxy-3//-indoles (e.g. 131). Lead tetraacetate similarly reacts at the 3-position to give a 3-acetoxy-3//-indole. Ozone and other oxidants have been used to cleave the 2,3-bond in indoles (132 —> 133) (81BCJ2369). 

A mixture of 9.5 g pyrrolyl-2-aldehyde, 29.2 g dimethyl-succinate and NaH (9.6 g of 50% suspension in oil) in 100 ml benzene is stirred at room temperature 6 hours, cooled and carefully acidified with glacial acetic acid. Add water and ether and dry, evaporate in vacuum or work up (JACS 72,501 (1950), JCS 1025(1959)) to get ca. 17 g (80%) 3-methoxycarbonyl-4-(2 -pyrrolyl)-3-butenoic acid (I) (recrystallize-acetone-benzene). A mixture of 12 g (I), 7 g sodium acetate and 70 ml acetic anhydride is left overnight at room temperature with occasional shaking. Then gradually raise the temperature to 70-75° over 2 hours, maintain for 4 hours and work up (see JCS 1714(1955), 986( 1958)) to get ca. 8 g (60%) methyl-4-acetoxy-indole-6-carboxylate (II) (recrystallize-petroleum ether). If desired, this can be converted to 4-OH-indole-6-COOH and 4-methoxyindole-COOH as described in the ref. or decarboxylated as described elsewhere here. If the 1-methyl cpd. is used, 1-Me-indole results. 

Acetoxy-indole 1141 [Pg.1068]

C2iHi8N2O, 2-Phenyl-3-(N-p-methoxyphenyl)amine-indole, 46B, 262 C21H2iNOs, Ethyl 1-(p-methoxyphenyl)-2-methyl-4-hydroxy-5-acetoxy-indole-3-carboxylate, 40B, 258... 

A two-step synthesis of indoles from o-nitrobenzaldehydes proceeds by condensation with nitromcthanc followed by reductive cyclization. Like the Leim-gruber Batcho method, the principal application of the reaction is to indoles with only carbocyclic substituents. The forniation of the o,p-dinitrostyrenes is usually done under classical Henry condensation conditions but KF/18-crown-6 in propanol was found to be an advantageous reaction medium for acetoxy-substituted compounds[1]. The o,p-dinitrostyrenes can also be obtained by nitration of p-nitrostyrenes[2]. 

Meerwein reactions can conveniently be used for syntheses of intermediates which can be cyclized to heterocyclic compounds, if an appropriate heteroatom substituent is present in the 2-position of the aniline derivative used for diazotization. For instance, Raucher and Koolpe (1983) described an elegant method for the synthesis of a variety of substituted indoles via the Meerwein arylation of vinyl acetate, vinyl bromide, or 2-acetoxy-l-alkenes with arenediazonium salts derived from 2-nitroani-line (Scheme 10-46). In the Meerwein reaction one obtains a mixture of the usual arylation/HCl-addition product (10.9) and the carbonyl compound 10.10, i. e., the product of hydrolysis of 10.9. For the subsequent reductive cyclization to the indole (10.11) the mixture of 10.9 and 10.10 can be treated with any of a variety of reducing agents, preferably Fe/HOAc. 

The l3C-NMR spectra for several indoles and 1-hydroxy-, 1-acetoxy-, and 1-methoxyindoles have been very carefully measured, and selected data is presented in Table V. In the oxygenated compounds, which have quite similar spectra, the 3-carbon atom moves significantly upheld, as does the 7-carbon atom, but to a smaller extent. Detailed correlations between the various substituents and the chemical shifts and coupling... 

The C-9-substituted 8-oxopyrrolo[l,2-a]indole systems 80a-c were prepared using methodology developed previously in our route to pyr-rolo[3,2-c]pyridin-4-ones and indolequinones.8c,f Thus, treatment of C-9 acetoxy compound 80a with MeLi (2.0 equiv) at -78 °C followed by ZV-phenyltriflimide afforded the triflate 80b in high yield. Exposure of 80b to modified74 palladium-catalyzed methoxy-carbonylation conditions provided ester 80c in 82% yield (Eq. 13). Exposure of this com-... 

The aromatic phenol was varied to explore the scope of the O-to-C conversion with mannosyl phosphates. Using phosphate 9, the a-C-mannosides of 2-naphthol and 3-benzyloxy phenol (23 and 25, Table 1) were synthesized in excellent yield. O-Mannosides were obtained exclusively with less nucleophilic aromatic systems, such as 3-acetoxy phenol. Several non-phenolic aromatic systems were unsuccessful in the formation of C-aryl or O-aryl glycosides. Reaction of 9 with furan, thiophene, trimethoxybenzene, and indole in the presence of TMSOTf did not result in any product formation. Interestingly, activation of 9 in the absence of any aromatic nucleophiles gave 26 as the major product via an intramolecular C-glycosylation (Figure 1) (79). 

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