Stereoselective Cascade Cyclizations with Samarium Diiodide to Tetracyclic Indolines: Precursors of Fluorostrychnines and Brucine

Abstract

As eries of g-indolylketones with fluorine, cyano or alkoxy substituents at the benzene moiety was prepared and subjected to samarium diiodide-promoted cyclization reactions. The desired dearomatizing ketyl cascade reaction formingt wo new rings proceeded in all cases with high diastereoselectivity,b ut with differing product distribution. In most cases, the desired annulated tetracyclic compounds were obtained in moderate to good yields, but as second product tetracyclic spirolactones were isolated in up to 29 % yield. The reaction rate was influencedb yt he substituents at the benzenem oiety of the substrate as expected, with electron-accepting groups acceleratingand electron-donating groups deceleratingt he cyclizationp rocess. In case of a difluoro-substituted g-indolylketone ap artial defluorination was observed.T he intermediate samarium enolateo ft he tetracyclic products could be trappedb ya dding reactive alkylating agents as electrophiles delivering products with quarternaryc arbons. In the case of ad imethoxy-substituted tetracyclic cyclization product as ubsequentr eductivea minations tereoselectively provided ap entacyclic compound that was subsequently N-protected and subjected to aregioselectivee limination.T he obtained functionalized pentacyclic product should be convertible into the alkaloid brucine by four well-established steps. Overall,t he presented report showst hat functionalized tetracyclic compounds with different substituents are rapidly availablew ith the samarium diiodidec ascade cyclization as crucial step. Hence, analogueso ft he landmarka lkaloid strychnine, fore xample, with specific fluorine substitutions, should be easily accessible.Scheme1.Samarium diiodide-promoted cyclizationso fN -acylatedindole derivatives A stereoselectively leadingt ot ricyclic compounds B and proposed transitions tate TS1.Supporting information and the ORCID identification number(s) for the author(s) of this articlecan be found under: https://doi. Scheme5.Cascadec yclizations of fluoro-substituted indole derivatives SM3-SM7 leading to tetracyclic compounds TC3-TC7 and spirolactones SL3-SL7 and cyclizations of cyano-and alkoxy-substitutedi ndolederivatives SM8-SM12 to TC8-TC12 and SL8-SL12.

Chemoselective Reduction of Barbiturates by Photochemically Excited Flavin Catalysts

“…However, SmI 2 favored the reduction of the side-chain ketone. 30 31 This change of reactivity likely originates from the favored formation of the ketone-derived ketyl radical samarium(III) complex. 32…”