Toward an Ideal Synthesis of (Bio)molecules through Direct Arene Assembling Reactions

C–H (hetero)arylation of aromatic compounds using transition-metal catalysts has garnered much attention from the synthetic chemistry community as a next-generation coupling method for constructing (hetero)biaryl motifs. This account describes our recent achievements in transition-metal-catalyzed aromatic C–H arylation and its applications to the synthesis of bioactive molecules.

[1]  Stephan A. Ohnmacht,et al.  Direct arylations of 2H-indazoles on water. , 2010, Organic letters.

[2]  D. Musaev,et al.  Decarbonylative organoboron cross-coupling of esters by nickel catalysis , 2015, Nature Communications.

[3]  jin-quan yu,et al.  Palladium(II)-catalyzed C-H activation/C-C cross-coupling reactions: versatility and practicality. , 2009, Angewandte Chemie.

[4]  F. Glorius,et al.  Pd/C as a catalyst for completely regioselective C-H functionalization of thiophenes under mild conditions. , 2014, Angewandte Chemie.

[5]  K. Itami,et al.  Synthesis of extended π-systems through C-H activation. , 2015, Angewandte Chemie.

[6]  A. Ohta,et al.  Cross-Coupling Reactions of Chloropyrazines with 1-Substituted Indoles , 1989 .

[7]  Junichiro Yamaguchi,et al.  Palladium-Catalyzed Decarbonylative Cross-Coupling of Azinecarboxylates with Arylboronic Acids. , 2016, Organic letters.

[8]  H. Doucet,et al.  Benzenesulfonyl chlorides: new reagents for access to alternative regioisomers in palladium-catalysed direct arylations of thiophenes , 2014 .

[9]  K. Nicolaou,et al.  Total synthesis of thiopeptide antibiotics GE2270A, GE2270T, and GE2270C1. , 2008, Chemistry, an Asian journal.

[10]  Junichiro Yamaguchi,et al.  Synthesis of dragmacidin D via direct C-H couplings. , 2011, Journal of the American Chemical Society.

[11]  M. Gaunt,et al.  Pd-catalyzed C-H bond functionalization on the indole and pyrrole nucleus. , 2010, Topics in current chemistry.

[12]  A. Studer,et al.  Ni-Catalyzed α-arylation of esters and amides with phenol derivatives. , 2015, Chemical communications.

[13]  Junichiro Yamaguchi,et al.  C-H alkenylation of azoles with enols and esters by nickel catalysis. , 2013, Angewandte Chemie.

[14]  David R. Stuart,et al.  The Catalytic Cross-Coupling of Unactivated Arenes , 2007, Science.

[15]  Junichiro Yamaguchi,et al.  Oxidative C-H/C-H coupling of azine and indole/pyrrole nuclei: Palladium catalysis and synthesis of eudistomin U , 2011 .

[16]  M. Lemaire,et al.  Extension of the Heck reaction to the arylation of activated thiophenes , 1998 .

[17]  Junichiro Yamaguchi,et al.  Palladium-catalyzed Decarbonylative Alkynylation of Aromatic Esters , 2017 .

[18]  R. Rossi,et al.  Recent advances in the synthesis of (hetero)aryl-substituted heteroarenes via transition metal-catalysed direct (hetero)arylation of heteroarene C–H bonds with aryl halides or pseudohalides, diaryliodonium salts, and potassium aryltrifluoroborates , 2009 .

[19]  E. Laurini,et al.  Pd-catalyzed direct C-H bond functionalization of spirocyclic σ1 ligands: generation of a pharmacophore model and analysis of the reverse binding mode by docking into a 3D homology model of the σ1 receptor. , 2012, Journal of medicinal chemistry.

[20]  O. Daugulis,et al.  Palladium- and copper-catalyzed arylation of carbon-hydrogen bonds. , 2009, Accounts of chemical research.

[21]  T. Satoh,et al.  Palladium-catalyzed multiple arylation of thiophenes. , 2002, Journal of the American Chemical Society.

[22]  A. Studer,et al.  Hindered biaryls by C–H coupling: bisoxazoline-Pd catalysis leading to enantioselective C–H coupling , 2012 .

[23]  jin-quan yu,et al.  Ligand-Enabled Reactivity and Selectivity in a Synthetically Versatile Aryl C–H Olefination , 2010, Science.

[24]  B. Wünsch,et al.  Late-Stage C–H Bond Arylation of Spirocyclic σ1 Ligands for Analysis of Complementary σ1 Receptor Surface , 2012 .

[25]  R. Noyori,et al.  Direct coupling of arenes and iodoarenes catalyzed by a rhodium complex with a strongly π-accepting phosphite ligand , 2008 .

[26]  Junichiro Yamaguchi,et al.  Pd- and Cu-catalyzed C-H arylation of indazoles , 2012 .

[27]  Junichiro Yamaguchi,et al.  Nickel-catalyzed α-arylation of ketones with phenol derivatives. , 2014, Angewandte Chemie.

[28]  B. Wünsch,et al.  Synthesis of thiophene-based TAK-779 analogues by C-H arylation. , 2013, The Journal of organic chemistry.

[29]  Junichiro Yamaguchi,et al.  Isolation, structure, and reactivity of an arylnickel(II) pivalate complex in catalytic C-H/C-O biaryl coupling. , 2013, Journal of the American Chemical Society.

[30]  T. Jamison,et al.  Recent advances in homogeneous nickel catalysis , 2014, Nature.

[31]  K. Itami,et al.  Iridium catalysis for C-H bond arylation of heteroarenes with iodoarenes. , 2009, Angewandte Chemie.

[32]  Junichiro Yamaguchi,et al.  Biaryl Synthesis through Metal-Catalyzed C-H Arylation , 2013 .

[33]  F. Felpin,et al.  Transition Metal‐Mediated Direct CH Arylation of Heteroarenes Involving Aryl Radicals , 2014 .

[34]  T. Satoh,et al.  Transition-Metal-CatalyzedRegioselective Arylation and Vinylation of CarboxylicAcids , 2010 .

[35]  Zhangjie Shi,et al.  C-O/C-H Coupling of Polyfluoroarenes with Aryl Carbamates by Cooperative Ni/Cu Catalysis. , 2016, Organic letters.

[36]  Junichiro Yamaguchi,et al.  Synthesis and characterization of hexaarylbenzenes with five or six different substituents enabled by programmed synthesis. , 2015, Nature chemistry.

[37]  J. Canivet,et al.  Nickel-catalyzed biaryl coupling of heteroarenes and aryl halides/triflates. , 2009, Organic letters.

[38]  Richard M. Maceiczyk,et al.  β-Selective C-H arylation of pyrroles leading to concise syntheses of lamellarins C and I. , 2014, Journal of the American Chemical Society.

[39]  Junichiro Yamaguchi,et al.  Recent Progress in Nickel‐Catalyzed Biaryl Coupling , 2013 .

[40]  R. Rossi,et al.  Development and Application of Effective Protocols for the Synthesis of Arylheteroarenes and Biheteroaryls, Including Bioactive Derivatives, by Highly Regioselective Transition Metal-Catalyzed Direct Intermolecular Arylation Reactions of Five-Membered Heteroarenes with (Hetero)aryl Halides , 2008 .

[41]  J. Hartwig.  Evolution of C-H Bond Functionalization from Methane to Methodology. , 2016, Journal of the American Chemical Society.

[42]  F. Glorius,et al.  Completely regioselective direct C-H functionalization of benzo[b]thiophenes using a simple heterogeneous catalyst. , 2013, Journal of the American Chemical Society.

[43]  S. Oi,et al.  Pd-catalyzed β-selective direct C-H bond arylation of thiophenes with aryltrimethylsilanes. , 2012, Organic letters.

[44]  H. Kondo,et al.  Aromatic C–H coupling with hindered arylboronic acids by Pd/Fe dual catalysts , 2013 .

[45]  T. Bach,et al.  Modular synthesis of phenanthro[9,10-c]thiophenes by a sequence of C-H activation, suzuki cross-coupling and photocyclization reactions. , 2014, Chemistry.

[46]  I. Larrosa,et al.  Room-Temperature Direct β-Arylation of Thiophenes and Benzo[b]thiophenes and Kinetic Evidence for a Heck-type Pathway , 2016, Journal of the American Chemical Society.

[47]  K. Itami,et al.  Palladium/2,2′-bipyridyl/Ag2CO3 catalyst for C–H bond arylation of heteroarenes with haloarenes , 2011 .

[48]  R. Rossi,et al.  Transition Metal-Free Direct CH (Hetero)arylation of Heteroarenes: A Sustainable Methodology to Access (Hetero)aryl-Substituted Heteroarenes , 2015 .

[49]  Ziwei Gu,et al.  A small molecule that blocks fat synthesis by inhibiting the activation of SREBP. , 2009, Chemistry & biology.

[50]  R. Noyori,et al.  Direct C-H arylation of (hetero)arenes with aryl iodides via rhodium catalysis. , 2006, Journal of the American Chemical Society.

[51]  H. Kondo,et al.  Branch-selective allylic C-H carboxylation of terminal alkenes by Pd/sox catalyst. , 2014, Organic letters.

[52]  H. Shinokubo,et al.  Functionalization of a simple dithienylethene via palladium-catalyzed regioselective direct arylation. , 2011, Organic letters.

[53]  K. Ueda,et al.  Programmed synthesis of tetraarylthiophenes through sequential C-H arylation. , 2009, Journal of the American Chemical Society.

[54]  Yue Zhao,et al.  Nickel-Catalyzed Decarbonylative Borylation and Silylation of Esters , 2016 .

[55]  Junichiro Yamaguchi,et al.  Nickel-catalyzed direct coupling of heteroarenes , 2013 .

[56]  D. Morton,et al.  Recent Advances in C-H Functionalization. , 2016, The Journal of organic chemistry.

[57]  Elisia Villemure,et al.  Elements of regiocontrol in palladium-catalyzed oxidative arene cross-coupling. , 2007, Journal of the American Chemical Society.

[58]  M. Lautens,et al.  Synthesis of annulated 2H-indazoles and 1,2,3- and 1,2,4-triazoles via a one-pot palladium-catalyzed alkylation/direct arylation reaction. , 2008, The Journal of organic chemistry.

[59]  A. Edmunds,et al.  A Robust Protocol for Pd(II)-catalyzed C-3 Arylation of (1H) Indazoles and Pyrazoles: Total Synthesis of Nigellidine Hydrobromide. , 2013, Chemical science.

[60]  Phil S. Baran,et al.  C-H functionalization logic in total synthesis. , 2011, Chemical Society reviews.

[61]  Frank Glorius,et al.  C-H bond activation enables the rapid construction and late-stage diversification of functional molecules. , 2013, Nature chemistry.

[62]  H. Humpf,et al.  2,4‐ and 2,5‐Disubstituted Arylthiazoles: Rapid Synthesis by C–H Coupling and Biological Evaluation , 2014 .

[63]  Peter S. Thuy-Boun,et al.  Ligand-accelerated cross-coupling of C(sp2)-H bonds with arylboron reagents. , 2011, Journal of the American Chemical Society.

[64]  V. Gevorgyan,et al.  Direct transition metal-catalyzed functionalization of heteroaromatic compounds. , 2007, Chemical Society reviews.

[65]  B. Wünsch,et al.  Improvement of σ1 receptor affinity by late-stage C-H-bond arylation of spirocyclic lactones. , 2013, Bioorganic & medicinal chemistry.

[66]  A. Kapdi,et al.  Transition-metal-catalyzed direct arylation of (hetero)arenes by C-H bond cleavage. , 2009, Angewandte Chemie.

[67]  J. Love,et al.  Nickel‐Catalyzed Decarbonylative Cou­pling of Aryl Esters and Arylboronic Acids , 2015 .

[68]  Junichiro Yamaguchi,et al.  Concise syntheses of dictyodendrins A and F by a sequential C-H functionalization strategy. , 2015, Journal of the American Chemical Society.

[69]  T. Hirota,et al.  C-H activation generates period-shortening molecules that target cryptochrome in the mammalian circadian clock. , 2015, Angewandte Chemie.

[70]  jin-quan yu,et al.  Ligand-accelerated C-H activation reactions: evidence for a switch of mechanism. , 2010, Journal of the American Chemical Society.

[71]  Junichiro Yamaguchi,et al.  Synthesis of Triarylpyridines in Thiopeptide Antibiotics by Using a C-H Arylation/Ring-Transformation Strategy. , 2016, Chemistry.

[72]  A. Mori,et al.  Palladium-catalyzed coupling reactions of bromothiophenes at the C-H bond adjacent to the sulfur atom with a new activator system, AgNO3/KF. , 2005, Organic letters.

[73]  Junichiro Yamaguchi,et al.  Palladium-Catalyzed C-H and C-N Arylation of Aminothiazoles with Arylboronic Acids , 2013 .

[74]  Junichiro Yamaguchi,et al.  Nickel-catalyzed C-H/C-O coupling of azoles with phenol derivatives. , 2012, Journal of the American Chemical Society.

[75]  H. Doucet,et al.  Access to Alternative Regioisomers for Palladium‐Catalysed Direct Arylations of (Benzo)thiophenes , 2013 .

[76]  D. Musaev,et al.  Key mechanistic features of Ni-catalyzed C-H/C-O biaryl coupling of azoles and naphthalen-2-yl pivalates. , 2014, Journal of the American Chemical Society.

[77]  K. Hirano,et al.  Recent Advances in Copper-mediated Direct Biaryl Coupling , 2015 .

[78]  S. W. Youn,et al.  Activation : A Complementary Tool in the Total Synthesis of Complex Natural Products , 2012 .

[79]  M. White,et al.  Enantioselective Allylic C-H Oxidation of Terminal Olefins to Isochromans by Palladium(II)/Chiral Sulfoxide Catalysis. , 2016, Angewandte Chemie.

[80]  J. Canivet,et al.  Nickel-catalyzed C-H arylation of azoles with haloarenes: scope, mechanism, and applications to the synthesis of bioactive molecules. , 2011, Chemistry.

[81]  T. Satoh,et al.  Catalytic Direct Arylation of Heteroaromatic Compounds , 2007 .

[82]  Y. Nakao.  Hydroarylation of alkynes catalyzed by nickel. , 2011, Chemical record.

[83]  Junichiro Yamaguchi,et al.  Decarbonylative C-H coupling of azoles and aryl esters: unprecedented nickel catalysis and application to the synthesis of muscoride A. , 2012, Journal of the American Chemical Society.

[84]  F. Kakiuchi,et al.  Transition-Metal-CatalyzedCarbon-Carbon Bond Formation via Carbon-HydrogenBond Cleavage , 2008 .

[85]  B. Wünsch,et al.  Exploitation of an additional hydrophobic pocket of σ1 receptors: late-stage diverse modifications of spirocyclic thiophenes by C-H bond functionalization. , 2011, Organic & biomolecular chemistry.

[86]  K. Houk,et al.  Mechanisms and origins of switchable chemoselectivity of Ni-catalyzed C(aryl)-O and C(acyl)-O activation of aryl esters with phosphine ligands. , 2014, Journal of the American Chemical Society.

[87]  Xingwei Li,et al.  Palladium-catalyzed oxidative cross-coupling between pyridine N-oxides and indoles. , 2011, Organic letters.

[88]  Sukbok Chang,et al.  Palladium-catalyzed C-H functionalization of pyridine N-oxides: highly selective alkenylation and direct arylation with unactivated arenes. , 2008, Journal of the American Chemical Society.

[89]  A. J. Blake,et al.  Total synthesis of siphonazole and its O-methyl derivative, structurally unusual bis-oxazole natural products. , 2008, Organic & biomolecular chemistry.

[90]  Junichiro Yamaguchi,et al.  C–H arylation and alkenylation of imidazoles by nickel catalysis: solvent-accelerated imidazole C–H activation† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c5sc02942b , 2015, Chemical science.

[91]  M. Lautens,et al.  Construction of nitrogen-containing heterocycles by C-H bond functionalization. , 2009, Chemistry.

[92]  D. Kalyani,et al.  Nickel-catalyzed intramolecular C–H arylation using aryl pivalates as electrophiles , 2013 .

[93]  A. Studer,et al.  Oxidative biaryl coupling of thiophenes and thiazoles with arylboronic acids through palladium catalysis: otherwise difficult C4-selective C-H arylation enabled by boronic acids. , 2011, Angewandte Chemie.

[94]  C. Moody,et al.  The total synthesis of siphonazole, a structurally unusual bis-oxazole natural product. , 2007, Chemical communications.

[95]  S. Grimme,et al.  Mechanistic studies on the Pd-catalyzed direct C-H arylation of 2-substituted thiophene derivatives with arylpalladium bipyridyl complexes. , 2012, Chemistry, an Asian journal.

[96]  M. Ciufolini,et al.  Total synthesis of siphonazoles by the use of a conjunctive oxazole building block. , 2009, Organic letters.

[97]  K. Kopka,et al.  Diverse modifications of the 4-methylphenyl moiety of TAK-779 by late-stage Suzuki-Miyaura cross-coupling. , 2014, Organic & biomolecular chemistry.

[98]  Mark E. Scott,et al.  Aryl-aryl bond formation by transition-metal-catalyzed direct arylation. , 2007, Chemical reviews.

[99]  Junichiro Yamaguchi,et al.  C-H bond functionalization: emerging synthetic tools for natural products and pharmaceuticals. , 2012, Angewandte Chemie.

[100]  M. Gaunt,et al.  Recent developments in natural product synthesis using metal-catalysed C-H bond functionalisation. , 2011, Chemical Society reviews.

[101]  Yukihiro Itoh,et al.  Late-Stage C-H Coupling Enables Rapid Identification of HDAC Inhibitors: Synthesis and Evaluation of NCH-31 Analogues. , 2014, ACS medicinal chemistry letters.

[102]  K. Ueda,et al.  A general catalyst for the β-selective C-H bond arylation of thiophenes with iodoarenes. , 2010, Angewandte Chemie.

[103]  E. Essassi,et al.  Direct C‐3‐Arylations of 1H‐Indazoles , 2012 .

[104]  Shota Tanaka,et al.  Palladium-catalyzed C-H functionalization of heteroarenes with aryl bromides and chlorides. , 2010, The Journal of organic chemistry.

[105]  Junichiro Yamaguchi,et al.  Cyanation of Phenol Derivatives with Aminoacetonitriles by Nickel Catalysis. , 2016, Organic letters.

[106]  Junichiro Yamaguchi,et al.  Programmed synthesis of arylthiazoles through sequential C–H couplings , 2014 .

[107]  Junichiro Yamaguchi,et al.  Nickel-Catalyzed Aromatic C–H Functionalization , 2016, Topics in Current Chemistry.

[108]  R. Sarpong,et al.  The first total synthesis of dragmacidin d. , 2002, Journal of the American Chemical Society.

[109]  R. Rossi,et al.  Palladium‐ and Copper‐Mediated Direct C‐2 Arylation of Azoles — Including Free (NH)‐Imidazole, ‐Benzimidazole and ‐Indole — Under Base‐Free and Ligandless Conditions , 2006 .

[110]  H. Doucet,et al.  Palladium‐Catalyzed C3 or C4 Direct Arylation of Heteroaromatic Compounds with Aryl Halides by CH Bond Activation , 2010 .

[111]  Tieqiao Chen,et al.  Nickel-catalyzed direct C-H/C-O cross couplings generating fluorobenzenes and heteroarenes. , 2015, Organic letters.

[112]  Haizhu Yu,et al.  Mechanistic study of chemoselectivity in Ni-catalyzed coupling reactions between azoles and aryl carboxylates. , 2014, Journal of the American Chemical Society.