PREPARATION AND 1,3-DIPOLAR CYCLOADDITION REACTIONS OF BETA-CARBOLINE AZOMETHINE YLIDES - A DIRECT ENTRY INTO C-1- AND/OR C-2-FUNCTIONALIZED INDOLIZINO[8,7-B] INDOLE DERIVATIVES

摘要

Treatment of norharman with (trimethylsilyl)methyl triflate in dichloromethane gave 2-N-[(trimethylsilyl)methyl]-beta-carboline triflate (10). The latter reacted with diethyl acetylenedicarboxylate (11a) or ethyl propiolate (11b) in the presence of cesium fluoride to afford, via 1,3-dipolar cycloaddition, the indolizino[8,7-b]indole derivatives 13a or 13b, respectively. In a similar manner, the (trimethylsilyl)methyl triflate salt of ethyl 9-N-(p-toluenesulfonyl)-beta-carboline-3-carboxylate (16) reacted with 11a to give the cycloaddition product 17. The (trimethylsilyl)methyl triflates of 3,4-dihydro-beta-carbolines were also prepared (20a-c) and shown to be more reactive than their fully aromatic counterparts 10 and 16 in cycloaddition reactions. Thus, the 9-N-benzyl derivative 20b reacted with 11a in the presence of cesium fluoride to give the cycloaddition products 21 and 22 as well as the novel azepine derivative 23. Moreover, unlike 10 and 16, the azomethine ylides generated from 20a-c reacted with electron-deficient olefins, producing 1,2,3,5,6,11b-hexahydroindolizino[8,7-b]indole derivatives. In the case of symmetrically substituted olefins (dimethyl maleate, dimethyl fumarate, fumaronitrile), the cycloaddition reactions were completely stereospecific. However, with unsymmetrically substituted olefins (methyl acrylate, acrylonitrile), cycloaddition reactions were generally neither regio- nor diastereoselective. In the case of 20b, both the regio- and the diastereoselectivities of the cycloaddition reactions were greatly improved compared to 20a and 20c, suggesting that these two stereochemical factors can be controlled by manipulation of the protecting group at the 9-N position of the 3,4-dihydro-beta-carbolines. The hexahydroindolizino[8,7-b]indoles 33 and 37 could be selectively dehydrogenated at the 11b, 1 positions using potassium permanganate in THF to afford the tetrahydro derivatives 58 and 59, respectively. Treatment of 58 with 1 equiv of DDQ led to further selective dehydrogenation at the 2,3 positions, producing the 5,6-dihydro compound 60. Alternatively, 33 and 37 could be completely dehydrogenated using 3 equiv of DDQ to give the fully aromatic indolizino[8,7-b]indole-1,2-dicarboxylates 56 and 57, respectively. [References: 57]