Indole 5-ethoxycarbonyl-2-methyl-, ring

Extension of the aminopalladation-reductive elimination domino methodology to the conunercially available ethyl iodoacetate provides a new approach to the construction of indole rings containing the 3-(ethoxycarbonyl)methyl group. Employment of the same conditions reported for the preparation of 2,3-disubstituted indolesf and 2-unsubstituted 3-arylindoles fail to give the desired indole derivatives, at least with the model system, the Af-alkyl derivative being the main or sole reaction product (Scheme 22). 

Ethyl 3-azido-l-methyl-177-indole-2-carboxylate 361 is prepared in 70% yield by diazotization of amine 360 followed by substitution of the created diazonium group with sodium azide. In cycloadditions with nitrile anions, azide 361 forms triazole intermediates 362. However, under the reaction conditions, cyclocondensation of the amino and ethoxycarbonyl groups in 362 results in formation of an additional ring. This domino process provides efficiently 4/7-indolo[2,3-i ]l,2,3-triazolo[l,5- ]pyrimidines 363 in 70-80% yield (Scheme 57) <2006TL2187>. 

In the course of studies aimed at the development of a method for introducing substituents into the indole ring, Yokoyama et d. 61,62,65) succeeded in a simple synthesis of 4-bromodehydrotryptophan 131 by the vinylation of N-tosyl 4-bromoindole (124) in the presence of a stoichiometric amount of palladium salt Vinylation of fV-acetyldehydroalanine methyl ester 127 and N-(ethoxycarbonyl)dehydroalanine methyl ester 222 with 124 occurred in the presence of a stoichiometric amount of PdClj to give the corresponding 4-bromodehydrotryptophan 223 and 224, respectively. This result opened the route for a simple synthesis of tryptophan derivatives. Actual preparation of the 4-bromotryptophan 133 was achiev by the vinylation of 4-bromoindole 124 with the V-Boc-dehydroalanine methyl ester 130 in die presence of a stoichiometric amount of Pd(OAc)2. The literature conditions [1.0 equiv. of... 

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