1,3-dipolar cycloaddition chemistry for the preparation of novel indolizinone-based compounds.
[Chemical reaction: See text] Starting from methyl 5-oxo-6-trifluoromethanesulfonyloxy-1,2,3,5-tetrahydroindolizine-8-carboxylate, obtained by a Rh(II)-catalyzed 1,3-dipolar cycloaddition reaction of 1-(2-benzenesulfonyl-2-diazoacetyl)pyrrolidin-2-one and methyl acrylate, several indolo- and furano-fused indolizinones were efficiently prepared. In the first case, a palladium-mediated C-N coupling of the triflate with a variety of substituted anilines provided the desired methyl 5-oxo-6-(arylamino)-1,2,3,5-tetrahydroindolizine-8-carboxylates in high yield. Methyl 6-(2-bromophenylamino)-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylate as well as its decarboxylated analogue, 6-(2-bromophenylamino)-2,3-dihydro-1H-indolizin-5-one, were synthesized in excellent yield and were found to undergo an intramolecular Heck cyclization to give 1,2,3,6-tetrahydroindolizino[6,7-b]indol-5-ones. To prepare furano-fused indolizinones, methyl 6-hydroxy-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylate was etherified with different allyl halides, and the resultant allyl ethers were subjected to a thermal Claisen rearrangement to give the corresponding methyl 7-allyl-6-hydroxy-5-oxo-1,2,3,4-tetrahydroindolizine-8-carboxylates. Cyclization under Wacker oxidation conditions afforded methyl 2-methyl-8-oxo-5,6,7,8-tetrahydro-1-oxa-7a-aza-s-indacene-4-carboxylates in near-quantitative yield.
Mmutlane
Edwin M
EM
Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA.
Harris
Joel M
JM
Padwa
Albert
A
D002166:Camptothecin / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D006844:Hydrocarbons, Cyclic / Q000138:chemical synthesis; D007202:Indicators and Reagents; D007212:Indolizines / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010165:Palladium
D006844:Hydrocarbons, Cyclic; D007202:Indicators and Reagents; D007212:Indolizines; D010165:Palladium; D002166:Camptothecin