Herein we report at otal synthesis of the indolohydroazocine natural product actinophyllic acid. The target molecule was retrosynthetically deconvoluted to render ag reatly simplified and symmetrical [4.4.1] bicyclic trienone, the desymmetrization of which was carefully examined under av ariety of conditions,i ncluding oxidative,r eductive,a nd transition-metal-catalyzed transformations.U ltimately,t he successful synthetic strategy featured chemoselective catalytic dihydroxylation, desymmetrizing nitrile oxide dipolar cycloaddition, and palladium-catalyzed aminoarylation to sequentially modify the three olefins within the trienone,followed by al ate-stage reductive cascade indolization and alkylation to complete the target molecule.
Enantiocontrolled construction of B-E rings of penitrem E was accomplished from 4-iodoindole in 13 steps with an overall yield of 1.7%. Diastereoselective Tf2NH-catalyzed (2+2)-cycloaddition between silyl enol ether and methyl acrylate furnished a tetracyclic product possessing the characteristic cyclobutane ring bearing a hydroxyl group.
Herein we report at otal synthesis of the indolohydroazocine natural product actinophyllic acid. The target molecule was retrosynthetically deconvoluted to render ag reatly simplified and symmetrical [4.4.1] bicyclic trienone, the desymmetrization of which was carefully examined under av ariety of conditions,i ncluding oxidative,r eductive,a nd transition-metal-catalyzed transformations.U ltimately,t he successful synthetic strategy featured chemoselective catalytic dihydroxylation, desymmetrizing nitrile oxide dipolar cycloaddition, and palladium-catalyzed aminoarylation to sequentially modify the three olefins within the trienone,followed by al ate-stage reductive cascade indolization and alkylation to complete the target molecule. Scheme 1. a) Selected recent examples of desymmetrization in targetoriented synthesis. b) Use of the [4.4.1] bicyclic trienone 2,w ith aplane of symmetry,a saprecursor to actinophyllica cid (1).
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