Tandem cyclisation of vinyl radicals: a sustainable approach to indolines utilizing visible-light photoredox catalysis

A tin-free method for the synthesis of substituted indolines has been developed generating vinyl radicals by visible-light-promoted photocatalysis in a reductive quenching cycle. This strategy offers a mild, robust, and high yielding pathway to a wide range of indolines containing diverse electronic substituents. The so obtained 2,3-disubstituted indolines serve as valuable precursors for the synthesis of biologically active molecules, which is demonstrated with the formal synthesis of tryptamines and furoindolines.

[1]  George G. Malliaras,et al.  Single-Layer Electroluminescent Devices and Photoinduced Hydrogen Production from an Ionic Iridium(III) Complex , 2005 .

[2]  D. MacMillan,et al.  Photoredox Catalysis in Organic Chemistry , 2016, The Journal of organic chemistry.

[3]  E. Barreiro,et al.  From nature to drug discovery: the indole scaffold as a 'privileged structure'. , 2009, Mini reviews in medicinal chemistry.

[4]  E. Fischer,et al.  Ueber die Hydrazine der Brenztraubensäure , 1883 .

[5]  B. König,et al.  Chromoselective Photocatalysis: Controlled Bond Activation through Light-Color Regulation of Redox Potentials. , 2016, Angewandte Chemie.

[6]  B. Costall,et al.  The effect of GR38032F, novel 5‐HT3‐receptor antagonist on gastric emptying in the guinea‐pig , 1987, British journal of pharmacology.

[7]  J. G. Neduvelil,et al.  2-Aryl tryptamines: selective high-affinity antagonists for the h5-HT2A receptor. , 2000, Bioorganic & medicinal chemistry letters.

[8]  L. Meijer,et al.  Paullones, a series of cyclin-dependent kinase inhibitors: synthesis, evaluation of CDK1/cyclin B inhibition, and in vitro antitumor activity. , 1999, Journal of medicinal chemistry.

[9]  D. Taber,et al.  Indole synthesis: a review and proposed classification. , 2011, Tetrahedron.

[10]  C. Cheon,et al.  Synthesis of 2‐Aryl‐Substituted Indole‐3‐acetic Acid Derivatives via Intramolecular Imino‐Stetter Reaction of Aldimines with Cyanide , 2016 .

[11]  G. Fabrizi,et al.  Preparation of Indoles from o-Alkynyltrifluoroacetanilides Through the Aminopalladation­-Reductive Elimination Process , 2004 .

[12]  O. Reiser,et al.  Visible Light‐Mediated Coupling of α‐Bromochalcones with Alkenes , 2014 .

[13]  A. Guidotti,et al.  Participation of mitochondrial diazepam binding inhibitor receptors in the anticonflict, antineophobic and anticonvulsant action of 2-aryl-3-indoleacetamide and imidazopyridine derivatives. , 1993, The Journal of pharmacology and experimental therapeutics.

[14]  A. Guidotti,et al.  Chemistry, binding affinities, and behavioral properties of a new class of "antineophobic" mitochondrial DBI receptor complex (mDRC) ligands. , 1993, Journal of medicinal chemistry.

[15]  M. A. Ischay,et al.  Visible light photocatalysis as a greener approach to photochemical synthesis. , 2010, Nature chemistry.

[16]  N. Kohl,et al.  2-Arylindole-3-acetamides: FPP-competitive inhibitors of farnesyl protein transferase. , 2001, Bioorganic & medicinal chemistry letters.

[17]  K. Skubi,et al.  Dual Catalysis Strategies in Photochemical Synthesis , 2016, Chemical reviews.

[18]  Chung Hyeok Kim,et al.  Biomedical Importance of Indoles , 2013, Molecules.

[19]  R. Vicente Recent advances in indole syntheses: new routes for a classic target. , 2011, Organic & biomolecular chemistry.

[20]  O. Reiser,et al.  Visible Light Photoredox Catalyzed Cascade Cyclizations of α‐Bromochalcones or α‐Bromocinnamates with Heteroarenes , 2014 .

[21]  Jon I Day,et al.  Advances in Photocatalysis: A Microreview of Visible Light Mediated Ruthenium and Iridium Catalyzed Organic Transformations. , 2016, Organic process research & development.

[22]  Jeffrey T. Kuethe,et al.  Practical methodologies for the synthesis of indoles. , 2006, Chemical reviews.

[23]  O. Reiser,et al.  Copper in Photocatalysis , 2014 .

[24]  S. Routier,et al.  Mild and selective deprotection of carbamates with Bu4NF , 2004 .

[25]  J. M. Uribe,et al.  POLYDENTATE SNXM (X = S,O,N) LIGANDS BY SELECTIVE REDUCTION OF ORGANOSULFUR HETEROCYCLES WITH TRIBUTYLTIN HYDRIDE , 1996 .

[26]  Visible-light photoredox catalysis: dehalogenation of vicinal dibromo-, α-halo-, and α,α-dibromocarbonyl compounds. , 2011, The Journal of organic chemistry.

[27]  Maurizio Fagnoni,et al.  Carbon-Carbon Bond Forming Reactions via Photogenerated Intermediates. , 2016, Chemical reviews.

[28]  Liyao Zheng,et al.  Rhodium(III)-catalyzed C-H activation and indole synthesis with hydrazone as an auto-formed and auto-cleavable directing group. , 2014, Chemistry.

[29]  N. Chatani,et al.  Synthesis of 2-boryl- and silylindoles by copper-catalyzed borylative and silylative cyclization of 2-alkenylaryl isocyanides. , 2010, The Journal of organic chemistry.

[30]  Wei Zhang,et al.  Copper(I)-catalyzed cascade dearomatization of 2-substituted tryptophols with iodonium [corrected] salts. , 2012, Organic letters.

[31]  J. Castro,et al.  Solid-phase synthesis of 2,3-disubstituted indoles: discovery of a novel, high-affinity, selective h5-HT2A antagonist. , 2000, Bioorganic & medicinal chemistry letters.

[32]  Duane D. Miller,et al.  Indole molecules as inhibitors of tubulin polymerization: potential new anticancer agents. , 2012, Future medicinal chemistry.

[33]  S. Hashimoto,et al.  Catalytic enantioselective C-H functionalization of indoles with α-diazopropionates using chiral dirhodium(II) carboxylates : asymmetric synthesis of the (+)-α-methyl-3-indolylacetic acid fragment of acremoauxin A , 2011 .

[34]  M. Hamann,et al.  Marine indole alkaloids: potential new drug leads for the control of depression and anxiety. , 2010, Chemical reviews.

[35]  C HISCOCK,et al.  EPIDEMICS OF TYPHOID FEVER. , 1964, Lancet.

[36]  Alon A Gorodetsky,et al.  Efficient yellow electroluminescence from a single layer of a cyclometalated iridium complex. , 2004, Journal of the American Chemical Society.

[37]  C. Moody,et al.  Indole synthesis – something old, something new , 2013 .

[38]  Jianzhang Zhao,et al.  Long-lived room-temperature deep-red-emissive intraligand triplet excited state of naphthalimide in cyclometalated Ir(III) complexes and its application in triplet-triplet annihilation-based upconversion. , 2012, Chemistry.

[39]  Tributyltin hydride: a selective reducing agent for 1,3-dithiolanes , 1980 .

[40]  Derek J. Wilson,et al.  A Single-Stage, Continuous High-Efficiency Extraction Device (HEED) for Flow Synthesis , 2016 .

[41]  D. MacMillan,et al.  Visible light photoredox catalysis with transition metal complexes: applications in organic synthesis. , 2013, Chemical reviews.

[42]  Oliver Reiser,et al.  Shining Light on Copper: Unique Opportunities for Visible-Light-Catalyzed Atom Transfer Radical Addition Reactions and Related Processes. , 2016, Accounts of chemical research.

[43]  T. Opatz,et al.  Preparation of Indoles from α-Aminonitriles: A Short Synthesis of FGIN-1-27 , 2006 .

[44]  John D. Nguyen,et al.  Engaging unactivated alkyl, alkenyl and aryl iodides in visible-light-mediated free radical reactions , 2012, Nature Chemistry.

[45]  M. Fisher,et al.  Heterocyclic derivatives of 2-(3,5-dimethylphenyl)tryptamine as GnRH receptor antagonists. , 2001, Bioorganic & medicinal chemistry letters.