Shortcut Approach to Cyclopenta[b]indoles by [3+2] Cyclodimerization of Indole-Derived Cyclopropanes

Abstract

A new straightforward approach to 3-indolyl-derived cyclopenta [b]indoles by a Lewis acid triggered [3+2] cyclodimerization of 2-(3-indolyl)cyclopropane-1,1-dicarboxylic acid diesters was developed. This reaction exhibits exceptional chemo-, regio-, and diastereoselectivities, leading to the formation of an individual diastereomer with a relative configuration that corresponds to that of naturally occurring indole terpenoids.

Dimethyl 2-{[2-(2-Methoxy-1-methoxycarbonyl-2-oxoethyl)-4,5,7-trimethoxy-3-(2,4,5-trimethoxyphenyl)-2,3-dihydro-1H-inden-1-yl]methyl}malonate

“…The second ester group is usually arranged so that the carbonyl oxygen atom has an exo-location relative to the three-membered ring and the methoxy group is endo-located, the torsion angle between two ester groups being dependent on the nature of the cis-aromatic substituent. In line with our ongoing research related to D-A cyclopropane dimerizations [7,8,[11][12][13][14]20], herein, we report the synthesis of polyoxygenated indane 1, which is a structural analog of diazarone, via a B(C 6 F 5 ) 3 -induced (3 + 2)-cyclodimerization of 2-(2,4,5-trimethoxyphenyl)cyclopropane-1,1-diester 2 in one step in highly chemo-, regio-and stereoselective manner.…”

“…For major isomer the trans,trans-arrangement of substituents in five-membered ring was established. The minor isomer of 1 was determined to be the C-1 epimer, and its spectral parameters completely correspond to the literature data for the related dimers [12,13].…”

“…Among the disclosed dimerization processes, one should note the cyclopropane-to-indane transformation as an analogue of styrene-and stilbene-based biosynthesis of indane structures, such as diisoeugenol, pallidol, griffipavixanthone, laetevirenol A, quadrangularin A, parthenocissin A, parvifolol ( Figure 1) exhibiting cytotoxic [21,22], antioxidant [21,[23][24][25][26], and other [25][26][27] activities. In line with our ongoing research related to D-A cyclopropane dimerizations [7,8,[11][12][13][14]20], herein, we report the synthesis of polyoxygenated indane 1, which is a structural analog of diazarone, via a B(C6F5)3-induced (3 + 2)-cyclodimerization of 2-(2,4,5-trimethoxyphenyl)cyclopropane-1,1diester 2 in one step in highly chemo-, regio-and stereoselective manner.…”

“…Starting cyclopropane 2 was synthesized from commercial 2,4,5-trimethoxybenzaldehyde 3 via a two-step synthetic sequence which involves the Knövenagel condensation with dimethyl malonate to afford arylidenemalonate 4 followed by the Corey-Chaykovsky reaction (Scheme 1) [28]. In line with our ongoing research related to D-A cyclopropane dimerizations [7,8,[11][12][13][14]20], herein, we report the synthesis of polyoxygenated indane 1, which is a structural analog of diazarone, via a B(C6F5)3-induced (3 + 2)-cyclodimerization of 2-(2,4,5-trimethoxyphenyl)cyclopropane-1,1diester 2 in one step in highly chemo-, regio-and stereoselective manner.…”

“…Various cyclodimerizations, reported to date, can be divided into three main groups: (1) (3 + 3)-cyclodimerizations affording cyclohexane, 1,2,3,4-tetrahydronaphthalene or 9,10-dihydroanthracene derivatives and their heterocyclic analogues [7][8][9][10]; (2) (3 + 2)-cyclodimerization leading to arylindanes, diarylcyclopentanes, etc. [9][10][11][12][13][14]; (3) other types of cyclodimerizations [10,[15][16][17][18][19][20]. The chemoselectivity of the cyclodimerizations is guided by both the nature of the substituents in the starting D-A cyclopropane and the choice of a suitable Lewis acid.…”