Palladium-Catalyzed Enantioselective Decarboxylative Allylic Alkylation of Acyclic α-N-Pyrrolyl/Indolyl Ketones.

The synthesis of fully substituted α-N-pyrrolyl and indolyl ketones via enantioselective palladium-catalyzed allylic alkylation is described. The acyclic ketones are alkylated in high yields with high enantioselectivities through the use of an electron-deficient phosphinooxazoline ligand, furnishing a highly congested and synthetically challenging stereocenter. The obtained alkylation products contain multiple reactive sites poised for additional functionalizations and diversification.

[1]  B. Stoltz,et al.  Palladium-Catalyzed Enantioselective Decarboxylative Allylic Alkylation of Protected Benzoin-Derived Enol Carbonates. , 2019, Advanced synthesis & catalysis.

[2]  G. C. Fu,et al.  Enantioconvergent Alkylations of Amines by Alkyl Electrophiles: Copper-Catalyzed Nucleophilic Substitutions of Racemic α-Halolactams by Indoles. , 2019, Journal of the American Chemical Society.

[3]  B. Stoltz,et al.  Palladium-catalyzed α,β-dehydrogenation of acyclic ester equivalents promoted by a novel electron deficient phosphinooxazoline ligand. , 2019, Tetrahedron.

[4]  R. Singh,et al.  Medicinal chemistry of indole derivatives: Current to future therapeutic prospectives. , 2019, Bioorganic chemistry.

[5]  A. Bahamonde,et al.  Enantioselective N-Alkylation of Indoles via an Intermolecular Aza-Wacker-Type Reaction. , 2019, Journal of the American Chemical Society.

[6]  M. Iqbal,et al.  Pyrrole: An insight into recent pharmacological advances with structure activity relationship. , 2018, European journal of medicinal chemistry.

[7]  B. Stoltz,et al.  Catalytic Enantioselective Synthesis of Acyclic Quaternary Centers: Palladium-Catalyzed Decarboxylative Allylic Alkylation of Fully Substituted Acyclic Enol Carbonates. , 2018, Journal of the American Chemical Society.

[8]  D. Moon,et al.  Palladium-Catalyzed Asymmetric Nitrogen-Selective Addition Reaction of Indoles to Alkoxyallenes. , 2018, Organic letters.

[9]  F. Gosselin,et al.  Lithium Hexamethyldisilazide-Mediated Enolization of Highly Substituted Aryl Ketones: Structural and Mechanistic Basis of the E/Z Selectivities. , 2017, Journal of the American Chemical Society.

[10]  B. Trost,et al.  Controlling Regioselectivity in the Enantioselective N-Alkylation of Indole Analogues Catalyzed by Dinuclear Zinc-ProPhenol. , 2017, Angewandte Chemie.

[11]  F. Gosselin,et al.  Highly Stereoselective Synthesis of Tetrasubstituted Acyclic All-Carbon Olefins via Enol Tosylation and Suzuki-Miyaura Coupling. , 2017, Journal of the American Chemical Society.

[12]  B. Stoltz,et al.  Enantioselective Construction of Acyclic Quaternary Carbon Stereocenters: Palladium-Catalyzed Decarboxylative Allylic Alkylation of Fully Substituted Amide Enolates. , 2017, Journal of the American Chemical Society.

[13]  O. Silakari,et al.  Indoles as therapeutics of interest in medicinal chemistry: Bird's eye view. , 2017, European journal of medicinal chemistry.

[14]  Jianwei Sun,et al.  Catalytic Asymmetric N-Alkylation of Indoles and Carbazoles through 1,6-Conjugate Addition of Aza-para-quinone Methides. , 2017, Angewandte Chemie.

[15]  J. Lisnock,et al.  Discovery of novel non-steroidal reverse indole mineralocorticoid receptor antagonists. , 2016, Bioorganic & medicinal chemistry letters.

[16]  S. Gholap,et al.  Pyrrole: An emerging scaffold for construction of valuable therapeutic agents. , 2016, European journal of medicinal chemistry.

[17]  G. C. Fu,et al.  Asymmetric copper-catalyzed C-N cross-couplings induced by visible light , 2016, Science.

[18]  Alexander H Sandtorv.  Transition Metal-Catalyzed CH Activation of Indoles , 2015 .

[19]  J. T. Njardarson,et al.  Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA approved pharmaceuticals. , 2014, Journal of medicinal chemistry.

[20]  W. Xiao,et al.  Highly enantioselective Friedel-Crafts alkylation/N-hemiacetalization cascade reaction with indoles. , 2013, Angewandte Chemie.

[21]  Hanmin Huang,et al.  Enantioselective N-H functionalization of indoles with α,β-unsaturated γ-lactams catalyzed by chiral Brønsted acids. , 2011, Angewandte Chemie.

[22]  S. You,et al.  Enantioselective intramolecular aza-Michael additions of indoles catalyzed by chiral phosphoric acids. , 2010, Angewandte Chemie.

[23]  Lei Wang,et al.  Asymmetric organocatalytic N-alkylation of indole-2-carbaldehydes with alpha,beta-unsaturated aldehydes: one-pot synthesis of chiral pyrrolo[1,2-a]indole-2-carbaldehydes. , 2010, Chemistry.

[24]  M. Bandini,et al.  Catalytic functionalization of indoles in a new dimension. , 2009, Angewandte Chemie.

[25]  J. Hartwig,et al.  Iridium-catalyzed regio- and enantioselective N-allylation of indoles. , 2009, Angewandte Chemie.

[26]  R. Cheng,et al.  HCV NS5B polymerase inhibitors 2: Synthesis and in vitro activity of (1,1-dioxo-2H-[1,2,4]benzothiadiazin-3-yl) azolo[1,5-a]pyridine and azolo[1,5-a]pyrimidine derivatives. , 2009, Bioorganic & medicinal chemistry letters.

[27]  K. Jiang,et al.  Chemoselective asymmetric N-allylic alkylation of indoles with Morita-Baylis-Hillman carbonates. , 2009, Angewandte Chemie.

[28]  A. Carroll,et al.  Flinderoles A-C: antimalarial bis-indole alkaloids from Flindersia species. , 2009, Organic letters.

[29]  M. Bandini,et al.  Enantioselective phase-transfer-catalyzed intramolecular aza-Michael reaction: effective route to pyrazino-indole compounds. , 2008, Angewandte Chemie.

[30]  B. Trost,et al.  Chemo-, regio-, and enantioselective Pd-catalyzed allylic alkylation of indolocarbazole pro-aglycons. , 2002, Organic letters.