Study on the synthesis of the cyclopenta[f]indole core of raputindole A

Abstract

SummaryThe raputindoles from the rutaceous tree Raputia simulans share a cyclopenta[f]indole partial structure the synthesis of which is subject of this investigation. An efficient route to a series of 1,5-di(indol-6-yl)pentenones was developed via Mo/Au-catalyzed Meyer–Schuster rearrangement of tertiary propargylic alcohol precursors. However, none of the enones underwent the desired Nazarov cyclization to a cyclopenta[f]indole. More suitable were 6-hydroxyallylated indolines which gave good yields of cyclopenta[f]indolines after treatment with SnCl4, as soon as sterically demanding β-cyclocitral adducts were reacted. Most successful were Pt(II) and Au(I)-catalyzed cyclizations of N-TIPS-protected indolin-6-yl-substituted propargylacetates which provided the hydrogenated tricyclic cyclopenta[f]indole core system in high yield.

Recent Developments in the Meyer‐Schuster Rearrangement

“…The MSR is also found in a study toward the preparation of the cyclopenta[f]indole core of another alkaloid, raputindole A (Scheme 61). [117] Reaction of the Grignard reagents 246 with the ketone 247 gave in fair to good yields the propargylic alcohols 248 . Acid‐mediated MSR was avoided due to the presence of the acid sensitive N ‐Boc group.…”

“…The MSR is also found in a study toward the preparation of the cyclopenta[f]indole core of another alkaloid, raputindole A (Scheme 61). [117] Reaction of the Grignard reagents 246 with the products, they could prepare a fully decorated tetracyclic core structure but unfortunately it proved to be impossible to graft the appropriate propargylic alcohol required for the crucial MSaza Michael step.…”

Diastereoselective Total Synthesis of (+)-Raputindole A: An Iridium- Catalyzed Cyclization Approach

“…In an attempt to improve the ratio of the trans isomer, the installation of the southern indole moiety previous to the reaction with methallyltrimethylsilane was examined. Although the Heck reaction of 6 with tosylindole 9, prepared according to literature procedure 24 , provided bisindole 17 in 48% yield, its subsequent reaction with methallyltrimethylsilane promoted by bismuth tribromide provided a complex mixture of products. Despite the poor stereoselectivity observed in the installation of the isobutenyl side chain, we moved forward with the 2:1 mixture of cis and trans-13a:13b and proceeded to the isomerization of the double bond to convert the exo double bond to the required isobutenyl side chain.…”

Total Synthesis of (+)-Raputindole A: An Iridium-Catalyzed Cyclization Approach

“…In an attempt to improve the ratio in favor of the required (5 R ,7 S )- 14a , a second approach was also investigated where the order of the two key steps was reversed. A Heck reaction of (5 R ,7 R )- 6 with N -tosyl 6-iodoindole ( 17 ), prepared according to the literature procedure, 24 provided bisindole (5 R ,7 R )- 15 in 48% yield. Unfortunately, attempts to perform the bismuth-tribromide-mediated methallylation were unsuccessful, providing only a complex mixture containing the desired product 16 ( Scheme 4 ).…”