Methyl l-methoxyindole-3-carboxylate

In fact, iodination of methyl l-methoxyindole-3-carboxylate (109), a wasabi phytoalexin (98P1959), with KI and NaI04 (60LA84, 911OC5903) in TFA-HjO provides methyl 5-iodo-l-methoxyindole-3-carboxylate (110,72%) predominantly... 

Pedras and co-workers (98P1959) isolated a phytoalexin from Wasabi (Wasabia japonica, syn. Eutrema wasabi) and determined its structure to be methyl l-methoxyindole-3-carboxylate (109) (Scheme 38). Compound 109 had already been synthesized by Acheson and co-workers [78JCS(P1)1117] in ten steps from o-nitroaniline. Pedras and co-workers (98P1959) combined our tungstate method and Acheson s work, and synthesized 109 in 9% overall yield but in an impure state. 

Hydrolysis of 1-acetoxy- or l-hydroxy-3-cyanoindole (115) by hydrogen peroxide or 1 M sodium hydroxide gave the corresponding amide, while QM sodium hydroxide gave the 3-carboxylic acid which decomposed rapidly at room temperature with diazomethane, the last compound gave the stable methyl l-methoxyindole-3-carboxylate [78JCS(P1)1117]. 1-... 

Nevertheless, there are several other oxidation (dehydrogenation) routes to indoles from indolines. In a series of papers, Somei and colleagues used sodium tungstate to synthesize A-hydroxyindole derivatives from the corresponding indolines (Scheme 11, equations 1 and 2) [64, 103-107]. The simple l-hydroxy-6-nitroindole [106] and 4-, 6-, and 7-ethoxy-l-methoxyindoles were synthesized in similar fashion [107]. Pedras and coworkers employed the Somei method to prepare the natural phytoalexin methyl l-methoxyindole-3-carboxylate [108], and McNab and... 

Additional halogenation of 78 and 81 exhibits interesting results [28]. Bromination (1.3-mol eq.) of the former in AcOH provides methyl 6-bromo-5-iodoindole-3-carboxylate (82, 56%) and the corresponding carboxylic add (83, 18%). On the other hand, bromination of the latter gives complex mixtures of products under various reaction conditions. Relatively clean reaction takes place with Br2 (1.3-mol eq.) in AcOH at 100 °C providing methyl 6-bromo- (84, 17%), methyl 2-bromo-5-iodo-l-methoxyindole-3-carboxylates (85, 33%), 5-iodo-l-methoxyindole-3-carboxylic acid (86, 7%),... 

Friedel-Crafts acylation of 77b with chloroacetyl chloride and AICI3 in nitrobenzene provides cleanly methyl 5-chloroacetyl- (90a, 52%) and 6-chloroacetyl-l-methoxyindole-3-carboxylates (91a, 20%) with the ratio of 2.5 1 (Scheme 11) [28]. Under similar reaction conditions, Nakatsuka and co-workers reported the chloroacetylation of methyl l-methylindole-3-carboxylate (89) to give 90b and 91b in the ratio of 3 1 [29]. Comparing these results with ours, it would be safe to conclude that the introduction of a methoxy group onto the N(l) prefers the 6- to 5-substitution in Friedel-Crafts acylation. 

Dehydrogenation of indoUnes using DDQ has been used to prepare 6-nitroindole (benzene, reflux, 86%) [32], 7-bromo-5-nitroindole (98%) [33], 6-azido-4,5,7-trif-luoroindole (benzene, 88%) [34], 4,5,6,7-tetrahydroindole (benzene, reflux, 68%) [35], methyl l-acetyl-2-cyclopro-pyl-5-methoxyindole-3-carboxylate (toluene, reflux, 87%) [36], 5,6-dicyano-l-methylindole (benzene, reflux, 97%)... 

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