Synthesis 2016; 48(22): 3821-3862
DOI: 10.1055/s-0036-1588303
review
© Georg Thieme Verlag Stuttgart · New York

Direct (Hetero)arylation Reactions of (Hetero)arenes as Tools for the Step- and Atom-Economical Synthesis of Biologically Active Unnatural Compounds Including Pharmaceutical Targets

Renzo Rossi*
a   Dipartimento di Chimica e Chimica Industriale, University of Pisa, via G. Moruzzi 13, 56124 Pisa, Italy   Email: renzo371@alice.it   Email: fabio.bellina@dcci.unipi.it
,
Marco Lessi
a   Dipartimento di Chimica e Chimica Industriale, University of Pisa, via G. Moruzzi 13, 56124 Pisa, Italy   Email: renzo371@alice.it   Email: fabio.bellina@dcci.unipi.it
b   Consorzio Interuniversitario Reattività Chimica e Catalisi (CIRCC), Via Celso Ulpiani 27, 70126, Bari, Italy
,
Chiara Manzini
a   Dipartimento di Chimica e Chimica Industriale, University of Pisa, via G. Moruzzi 13, 56124 Pisa, Italy   Email: renzo371@alice.it   Email: fabio.bellina@dcci.unipi.it
,
Giulia Marianetti
c   Scuola Normale Superiore, Piazza dei Cavalieri 7, 56126 Pisa, Italy
,
Fabio Bellina*
a   Dipartimento di Chimica e Chimica Industriale, University of Pisa, via G. Moruzzi 13, 56124 Pisa, Italy   Email: renzo371@alice.it   Email: fabio.bellina@dcci.unipi.it
b   Consorzio Interuniversitario Reattività Chimica e Catalisi (CIRCC), Via Celso Ulpiani 27, 70126, Bari, Italy
› Author Affiliations
Further Information

Publication History

Received: 18 May 2016

Accepted after revision: 16 June 2016

Publication Date:
11 October 2016 (online)


Abstract

The significant number of papers and reviews published in this last decade testifies to the utility of the transition-metal-catalyzed direct C–H (hetero)arylation reactions of (hetero)arenes as efficient and powerful tools for the step- and atom-economical, regio- and chemoselective synthesis of natural and unnatural compounds. However, no review has so far been devoted to summarizing the application of these reactions in the synthesis of biologically active compounds. This review with 341 references aims to fill this gap, providing a comprehensive picture of the transition-metal-catalyzed intra- and intermolecular direct C–H (hetero)arylation reactions of (hetero)arenes with (hetero)aryl halides or pseudohalides that have been used as key steps of syntheses of unnatural biologically relevant compounds including pharmaceutical targets, up to the end of September 2015. Attention has also been directed to provide a brief description of the biological properties of the synthesized compounds.

1 Introduction

2 Syntheses via Intramolecular Direct (Hetero)arylation of (Hetero)arene Derivatives

3 Syntheses via Intermolecular Direct (Hetero)arylation Reactions

3.1 Of Arenes

3.2 Of Five-Membered Heteroarenes with One Heteroatom

3.3 Of Five-Membered Heteroarenes with Two Heteroatoms

3.4 Of Five-Membered Heteroarenes with Three and Four Heteroatoms

3.5 Of Five-Membered Heteroarenes Fused to a Six-Membered Heteroarene

3.6 Of Five-Membered Heteroarene Moieties of Tricyclic Heteroarenes

3.7 Of Six-Membered Heteroarenes

4 Syntheses of Nitrogen-Containing Polycyclic Heteroarene via One-Pot Palladium-Catalyzed Domino Direct Arylation/N-Arylation Reactions

5 Conclusions

 
  • References

  • 1 Suzuki A. Angew. Chem. Int. Ed. 2011; 50: 6722
  • 2 Kallman NJ, Liu C, Yates MH, Linder RJ, Ruble JC, Kogut EF, Patterson LE, Laird DL. T, Hansen MM. Org. Process Res. Dev. 2014; 18: 501
  • 3 Hong JB, Davidson JP, Jin Q, Lee GR, Matchett M, O’Brien E, Welch M, Bingenheimer B, Sarma K. Org. Process Res. Dev. 2014; 18: 228
  • 4 Dugar S, Hollinger FP, Kuila B, Arora R, Sen S, Mahajan D. Bioorg. Med. Chem. Lett. 2015; 25: 3142
  • 5 Wang M, Tzintzun R, Gao M, Xu Z, Zheng Q.-H. Bioorg. Med. Chem. Lett. 2015; 25: 3831
  • 6 Theodoulou NH, Bamborough P, Bannister AJ, Becher I, Bit RA, Che VH, Chung C.-w, Dittmann A, Drewes G, Dewry DH, Gordon L, Grandi P, Leveridge M, Lindon M, Michon A.-M, Molnar J, Robson SC, Tomkinson NC. O, Kouzarides T, Prinjha RK, Humphreys PG. J. Med. Chem. 2015; 58: 5649
  • 7 Press NJ, Taylor RJ, Fullerton JD, Tranter P, McCarthy C, Keller TH, Arnold N, Beer D, Brown L, Cheung R, Christie J, Denholm A, Haberthuer S, Hatto JD. I, Keenan M, Mercer MK, Oakman H, Sahri H, Tuffnell AR, Tweed M, Trifilieff A. J. Med. Chem. 2015; 58: 6747
  • 8 Nagathan S, Andersen DL, Andersen NG, Lau S, Lohse A, Sørensen MD. Org. Process Res. Dev. 2015; 19: 721
  • 9 Xie Y, Chi H.-W, Guan A.-Y, Liu C.-L, Ma H.-J, Cui D.-L. J. Agric. Food Chem. 2014; 62: 12491
  • 10 Tian Q, Cheng Z, Yajima HM, Savage SJ, Green KL, Humphries T, Reynolds ME, Babu S, Gosselin F, Askin D. Org. Process Res. Dev. 2013; 17: 97
  • 11 Geuns-Meyer S, Cee VJ, Deak HL, Du B, Hodous BL, Nguyen HN, Olivieri PR, Schenkel LB, Vaida KR, Andrews P, Bak A, Be X, Beltran PJ, Bush TL, Chaves MK, Chung G, Dai Y, Eden P, Hanestad K, Huang L, Lin M.-HJ, Tang J, Ziegler B, Radinsky R, Kendall R, Patel VF, Payton M. J. Med. Chem. 2015; 58: 5189
  • 12 Chao J, Enyedy I, Van Vloten K, Marcotte D, Guertin K, Hutchings R, Powell N, Jones H, Bohnert T, Peng C.-C, Silvian L, Hong VS, Little K, Banerjee D, Peng L, Taveras A, Viney JL, Fontenot J. Bioorg. Med. Chem. Lett. 2015; 25: 2991
  • 13 Velter AI, Bischoff FP, Berthelot D, De Cleyn M, Oehlrich D, Jaroskova L, Macdonald G, Minne G, Pieters S, Rombouts F, Van Brandt S, Van Roosbroeck Y, Surkyn M, Trabanco AA, Tresadern G, Wu T, Borghys H, Mercken M, Masungi C, Gijsen H. Bioorg. Med. Chem. Lett. 2014; 24: 5805
  • 14 Zimmermann K, Sang X, Mastalerz HA, Johnson WL, Zhang G, Liu Q, Batt D, Lombardo LJ, Vyas D, Trainor GL, Tokarski JS, Lorenzi MV, You D, Gottardis MM, Lippy J, Khan J, Saek JS, Purandare AV. Bioorg. Med. Chem. Lett. 2015; 25: 2809
  • 15 O’Donovan MR, Mee CD, Fenner S, Teasdale A, Phillips DH. Mut. Res. Genet. Toxicol. Environ. Mutagen. 2011; 724: 1
  • 16 Hansen MM, Jolly RA, Linder RJ. Org. Process Res. Dev. 2015; 19: 1507
  • 17 ICH M7, Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk; Step 4 version, June 23, 2014.
    • 18a El Kazzouli S, Koubachi J, El Brahmi N, Guillaumet G. RSC Adv. 2015; 5: 15292
    • 18b Rossi R, Bellina F, Lessi M, Manzini C. Adv. Synth. Catal. 2014; 356: 17
    • 18c Rossi R, Bellina F, Lessi M, Manzini C, Perego LA. Synthesis 2014; 46: 2833
    • 18d Bonin H, Sauthier M, Felpin F.-X. Adv. Synth. Catal. 2014; 356: 645
    • 18e Yamaguchi J, Itami K. Biaryl Synthesis through Metal-Catalyzed C–H Arylation . In Metal-Catalyzed Cross-Coupling Reactions and More . Vol. 3. de Meijere A, Bräse S, Oestreich M. Chapt. 17 Wiley-VCH; Weinheim: 2014: 1315
    • 18f Shibahara F, Murai T. Asian J. Org. Chem. 2013; 2: 624
    • 18g Daugulis O. Chem. Heterocycl. Compd. 2012; 48: 21
    • 18h Lei A, Zhang H. RSC Catalysis Series 2013; 11: 310
    • 18i Sharma A, Vacchani D, Van der Eycken E. Chem. Eur. J. 2013; 19: 1158
    • 18j Su Y.-X, Sun L.-P. Mini-Rev. Org. Chem. 2012; 9: 87
    • 18k Yamaguchi J, Yamaguchi AD, Itami K. Angew. Chem. Int. Ed. 2012; 51: 8960
    • 18l Bellina F, Rossi R. Adv. Synth. Catal. 2010; 352: 1223
    • 18m Livendáhl M, Echavarren AM. Isr. J. Chem. 2010; 50: 630
    • 18n Roger J, Gottumukkala AL, Doucet H. ChemCatChem 2010; 2: 20
    • 18o Daugulis O. Top. Curr. Chem. 2010; 292: 57
    • 18p McGlacken GP, Bateman LM. Chem. Soc. Rev. 2009; 38: 2447
    • 18q Bellina F, Rossi R. Tetrahedron 2009; 65: 10269
    • 18r Ackermann L, Vicente R, Kapdi AR. Angew. Chem. Int. Ed. 2009; 48: 9792
    • 18s Fairlamb IJ. S. Chem. Soc. Rev. 2007; 36: 1036
    • 18t Seregin I.-V, Gevordyan V. Chem. Soc. Rev. 2007; 36: 1173
    • 18u Satoh T, Miura M. Chem. Lett. 2007; 36: 200
    • 18v Campeau L.-C, Stuart R, Fagnou K. Aldrichimica Acta 2007; 40: 35
    • 18w Alberico D, Scott ME, Lautens M. Chem. Rev. 2007; 107: 174
  • 19 Kimishima A, Umihara H, Mizoguchi A, Yokoshima S, Fukuyama T. Org. Lett. 2014; 16: 6244
  • 20 Freund M, Speyer E. J. Prakt. Chem. 1916; 94: 135
  • 21 Riley J, Eisenberg E, Müller-Schwefe G, Drewes AM, Arendt-Nielsen L. Curr. Med. Res. Opin. 2008; 24: 175
  • 22 Marek GJ, Carpenter LL, McDougle CJ, Price LH. Curr. Opin. Investig. Drugs 2002; 3: 106
  • 23 Ponnala S, Gonzales J, Kapadia N, Navarro HA, Harding WW. Bioorg. Med. Chem. Lett. 2014; 24: 1664
  • 24 Merchant JR, Desai K. Indian J. Chem. 1973; 11: 342
  • 25 Chaudhary S, Pecic S, LeGendre O, Navarro HA, Harding WW. Bioorg. Med. Chem. Lett. 2009; 19: 2530
  • 26 Cappoen D, Jacobs J, Van TN, Claessens S, Diels G, Anthonissen R, Einarsdottir T, Fauville M, Verschaeve L, Huygen K, De Kimpe N. Eur. J. Med. Chem. 2012; 48: 57
  • 27 Van TN, Kesteleyn B, De Kimpe N. Tetrahedron 2002; 58: 121
  • 28 Yadav AK, Verbeeck S, Hostyn S, Franck P, Sergeyev S, Maes BU. W. Org. Lett. 2013; 15: 1060
  • 29 Hostyn S, Van Baelen G, Lemière GL. F, Maes BU. W. Adv. Synth. Catal. 2008; 350: 2653
  • 30 Van Baelen G, Hostyn S, Dhooghe L, Tapolesesányi P, Mátyus P, Lemiére G, Dommisse R, Kaiser M, Brun R, Cos P, Maes L, Hajós G, Riedl Z, Nagy I, Maes BU. W, Pieters L. Bioorg. Med. Chem. 2009; 17: 7209
    • 31a Cimanga K, De Bruyne T, Pieters L, Claeys M, Vlietink A. Tetrahedron Lett. 1996; 37: 1703
    • 31b Bracca AB. J, Heredia DA, Larghi EL, Kaufman TS. Eur. J. Org. Chem. 2014; 7979
  • 32 Hostyn S, Maes BU. W, Pieters L, Lemière GL. F, Mátyus P, Hajos G, Dommisse RA. Tetrahedron 2005; 61: 1571
  • 33 Van Miert S, Hostyn S, Maes BU. W, Cimanga K, Brun R, Kaiser M, Mátyus P, Dommisse R, Lemière G, Vlietinck A, Pieters L. J. Nat. Prod. 2005; 68: 674
  • 34 Van Baelen G, Meyers C, Lemière GL. F, Hostyn S, Dommisse R, Maes L, Augustyns K, Haemers A, Pieters L, Maes BU. W. Tetrahedron 2008; 64: 11802
  • 35 Sitnikov NS, Kokisheva AS, Fukin GK, Neudörfl J.-M, Sutorius H, Prokop A, Fokin VV, Schmalz H.-G, Fedorov AYu. Eur. J. Org. Chem. 2014; 6481
  • 36 Boyé O, Brossi A In The Alkaloids: Chemistry and Pharmacology . Vol. 41. Brossi A, Cordell GA. Academic Press; San Diego: 1992: 125
  • 37 Kashyap M, Das D, Preet R, Mohapatra P, Satapathy SR, Siddharth S, Kundu CN, Guchhait SK. Bioorg. Med. Chem. Lett. 2012; 22: 2474
  • 38 Guchhait SK, Kashyap M. Synthesis 2012; 44: 619
  • 39 Beresneva T, Mishnev A, Jaschenko E, Shestakova I, Gulbe A, Abele E. ARKIVOC 2012; (ix): 185
  • 40 Beresneva T, Abele E. Heterocycl. Lett. 2011; 1: 73
  • 41 Mineno M, Sera M, Ueda T, Mizufune H, Zanka A, O’Bryan C, Brown J, Scorah N. J. Org. Chem. 2015; 80: 1564
  • 42 Carmena M, Ruchaud S, Earnshaw WC. Curr. Opin. Cell Biol. 2009; 21: 796
  • 43 Farrell P, Shi I, Matuszkiewicz J, Balakrishna D, Hoshino T, Zhang L, Elliott S, Fabrey R, Lee B, Halkowycz P, Sang B, Ishino S, Nomura T, Teratani M, Ohta Y, Grimshaw C, Paraselli B, Satou T, de Jong R. Mol. Cancer Ther. 2013; 12: 460
    • 44a Seki M, Nagahama M. J. Org. Chem. 2011; 76: 10198

    • For additional papers on nitrogen-directed ortho-arylation reactions catalyzed by ruthenium derivatives, see:
    • 44b Ackermann L, Vicente R, Althammer A. Org. Lett. 2008; 10: 2299
    • 44c Oi S, Funayama R, Hattori T, Inoue Y. Tetrahedron 2008; 64: 6051
    • 44d Oi S, Sasamoto H, Funayama R, Inoue Y. Chem. Lett. 2008; 37: 994
    • 44e Ackermann L, Born R, Viucente R. ChemSusChem 2009; 2: 546
    • 44f Arockiam PB, Fischmeister C, Bruneau C, Dixneuf PH. Angew. Chem. Int. Ed. 2010; 49: 6629
  • 45 Nishimura T, Hashimoto J, Ohkubo I, Kikuya M, Metoki N, Asayama K, Totsune K, Imai Y. Clin. Exp. Hypertens. 2005; 27: 477
    • 46a Wexler RR, Greenlee WJ, Irvin JD, Goldberg MR, Prendergast K, Smith RD, Timmermans PB. W. M. J. Med. Chem. 1996; 39: 625
    • 46b Bernhart CA, Perreaut PM, Ferrari BP, Muneaux YA, Assens J.-L, Clément J, Haudricourt F, Muneaux CF, Taillades JC, Vignal M.-A, Gougat J, Guiradou PR, Lacour CA, Roccon A, Cazaubon CF, Brlière J.-C, Lew Fur G, Nisato D. J. Med. Chem. 1993; 36: 3371
  • 47 Diers E, Kumar NY. P, Mejuch T, Marek I, Ackermann L. Tetrahedron 2013; 69: 4445
  • 48 For the introduction of 2,4,6-trimethylbenzoic acid (MesCOOH) as a cocatalytic additive for reliable Ru(II)-catalyzed direct C–H arylation reactions in apolar solvents, see ref. 44b.
  • 49 Ding Y.-J, Li Y, Dai S.-Y, Lan Q, Wang X.-S. Org. Biomol. Chem. 2015; 13: 3198
    • 50a Li J, Ackermann L. Chem. Eur. J. 2015; 21: 5718

    • For additional papers on Co-catalyzed direct arylation reactions, see:
    • 50b Liu W, Cao H, Xin J, Jin L, Lei A. Chem. Eur. J. 2011; 17: 3588
    • 50c Chan TL, To CT, Liao B.-S, Liu S.-T, Chan KS. Eur. J. Inorg. Chem. 2012; 485
    • 50d Qian YY, Wong KL, Zhang MW, Kwok TY, To CT, Chan KS. Tetrahedron Lett. 2012; 53: 1571
    • 50e Song W, Ackermann L. Angew. Chem. Int. Ed. 2012; 51: 8251
  • 51 Goossen LJ, Melzer B. J. Org. Chem. 2007; 72: 7473

    • For leading references on the synthesis of biaryls via palladium-catalyzed decarboxylative coupling reactions, see:
    • 52a Forgione P, Brochu M.-C, St-Onge M, Thesen KH, Bailey MD, Bilodeau F. J. Am. Chem. Soc. 2006; 128: 11350
    • 52b Goossen LJ, Deng G, Levy LM. Science 2006; 313: 662
    • 52c Becht J.-M, Catala C, Le Drian C, Wagner A. Org. Lett. 2007; 9: 1781
    • 52d Goossen LJ, Rodriguez N, Melzer B, Linder C, Deng G, Levy LM. J. Am. Chem. Soc. 2007; 129: 4824
    • 52e Zhao H, Wei Y, Xu J, Kan J, Su W, Hong M. J. Org. Chem. 2011; 76: 882
    • 52f Hu P, Shang Y, Su W. Angew. Chem. Int. Ed. 2012; 51: 5945
    • 52g Rameau N, Cadot S, Paquet A, Pinel C, Djakovitch L. Top. Catal. 2014; 57: 1430
    • 52h Suresh R, Muthusubramanian S, Kumaran RS, Manickam G. Asian J. Org. Chem. 2014; 3: 604
    • 52i Chennamaneni LR, William AD, Johannes CW. Tetrahedron Lett. 2015; 56: 1293
    • 52j Tang J, Biafora A, Goossen LJ. Angew. Chem. Int. Ed. 2015; 54: 13130
  • 53 Fenton C, Scott LJ. Drugs 2005; 65: 537
  • 54 Seki M. ACS Catal. 2014; 4: 4047
  • 55 For a previous synthesis of Candesartan Cilexetil involving a Ru-catalyzed C–H arylation of 1-benzyl-5-phenyl-1H-tetrazole (81) with 4-bromobenzyl acetate, see: Seki M. Synthesis 2012; 44: 3231
  • 56 Mao Y, Xiong R, Liu Z, Li H, Shen J, Shen J. Heterocycles 2010; 81: 1503
  • 57 Wang P, Zheng G.-j, Wang Y.-p, Wang X.-j, Li Y, Xiang W.-S. Tetrahedron 2010; 66: 5402
  • 58 Caron L, Campeau L.-C, Fagnou K. Org. Lett. 2008; 10: 4533
    • 59a Ehrenfreund J, Lamberth C, Tobler H, Walter H. PCT Int. Appl WO 2004/058723, 2004
    • 59b Kuck K.-H, Gisi U In Modern Crop Protection Compounds . Vol. 2. Krämer W, Schrimer U. Wiley-VCH; Weinheim: 2007: 415

      For additional references on the direct regioselective arylation of nitro(hetero)arene derivatives, see:
    • 60a Iaroshenko VO, Gevorgyan A, Mkrtchyan S, Grigoryan T, Movsisyan E, Villinger A, Langer P. ChemCatChem 2015; 7: 316
    • 60b Wang C, Yu Y.-B, Fan S, Zhang X. Org. Lett. 2013; 15: 5004
    • 60c Yan T, Zhao L, He M, Soulé J.-F, Bruneau C, Doucet H. Adv. Synth. Catal. 2014; 356: 1586
    • 60d He M, Soulé J.-F, Doucet H. ChemCatChem 2015; 7: 2130
    • 60e Ivanov A, Iaroshenko VO, Villinger A, Langer P. Synlett 2015; 26: 2285
    • 61a Engel S, Oberding T. PCT Int. Appl WO 2006/092429, 2006
    • 61b Eicken K, Rack M, Wetterich F, Ammermann E, Lorenz G, Strathmann S. German Patent DE 19735224, 1999 ; Chem. Abstr. 1999, 130, 182464

      For additional syntheses of Boscalid®, see:
    • 62a Glasnov TN, Kappe CO. Adv. Synth. Catal. 2010; 352: 3089
    • 62b Dunst C, Knochel P. Synlett 2011; 2064
    • 62c Pratsch G, Wallaschkowski T, Heinrich MR. Chem. Eur. J. 2012; 18: 11555
  • 63 Erickson G, Guo J, McClure M, Mitchell M, Salaun M.-C, Whitehead A. Tetrahedron Lett. 2014; 55: 6007
  • 64 Sardesai SD, Storniolo AM. Women’s Health 2015; 11: 281

    • For literature data on the palladium-catalyzed direct C-5 arylation reactions of 2-substituted furans, see:
    • 65a Battace A, Lemhadri M, Zair T, Doucet H, Santelli M. Organometallics 2007; 26: 472
    • 65b Smaliy RV, Beaupérin M, Cattey H, Meunier P, Hierso J.-C, Roger J, Doucet H, Coppel Y. Organometallics 2009; 28: 3152
    • 65c Dong JJ, Roger J, Pozgan F, Doucet H. Green Chem. 2009; 11: 1832
    • 65d Laidaoui N, Miloudi A, El Abed D, Doucet H. Synthesis 2010; 2553
    • 65e Laidaoui N, Roger J, Miloudi A, El Abed D, Doucet H. Eur. J. Org. Chem. 2011; 4373
    • 65f Roger J, Pozgan F, Doucet H. Adv. Synth. Catal. 2010; 352: 696
    • 65g Chen L, Roger J, Bruneau C, Dixneuf PH, Doucet H. Adv. Synth. Catal. 2011; 353: 2749
  • 66 McClure MS, Osterhout MH, Roschangar F, Sacchetti MJ. PCT Int. Appl WO 2002/02552, 2002
  • 67 Ryan Q, Ibrahim A, Cohen MH, Johnson J, Ko CW, Sridhara R, Justice R, Pazdur R. Oncologist 2008; 13: 1114
  • 68 Cobos EJ, Entrena JM, Nieto FR, Cendán CM, Del Pozo E. Curr. Neuropharmacol. 2008; 6: 344
  • 69 Meyer C, Schepmann D, Yanagisawa S, Yamaguchi J, Itami K, Wünsch B. Eur. J. Org. Chem. 2012; 5972

    • For previous examples of palladium-catalyzed highly selective β-arylation reactions of thiophenes with iodoarenes in the presence of P[OCH(CF3)2]3 ligand, see:
    • 70a Ueda K, Yanagisawa S, Yamaguchi J, Itami K. Angew. Chem. Int. Ed. 2010; 49: 8946
    • 70b Yanagisawa S, Ueda K, Sekikawa H, Itami K. J. Am. Chem. Soc. 2009; 131: 14622
  • 71 Fornier dit Chabert J, Marquez B, Neville L, Joucla L, Broussous S, Bourhours P, David E, Pellet-Rostaing S, Marquet B, Moreau N, Lemaire M. Bioorg. Med. Chem. 2007; 15: 4482
  • 72 For a review on recent advances in multi-drug resistance efflux pump inhibitors of Gram-positive bacteria S. aureus, see: Handzlik J, Matys A, Kiec-Kononowicz K. Antibiotics 2013; 2: 28

    • For additional examples of palladium-catalyzed ligand-free direct arylation reactions involving the use of n-Bu4NBr as an additive, see:
    • 73a Lavenot L, Gozzi C, Ily K, Orlova I, Penalva V, Lemaire M. J. Organomet. Chem. 1998; 567: 49
    • 73b Sévignon M, Hassan J, Gozzi C, Schulz E, Lemaire M. C. R. Acad. Sci., Ser. IIc 2000; 3: 569
    • 73c Abdo NI, El-Shehawy AA, El-Barbary AA, Lee J.-S. Eur. J. Org. Chem. 2012; 5540
  • 74 Rodrigues AD, Imberdis T, Perrier V, Robitzer M. Tetrahedron Lett. 2015; 56: 368
  • 75 Robitzer M, Perrier V, Verdier JM. PCT Int. Appl WO 2009/081372 A1, 2009
    • 76a Gorelsky SI, Lapointe D, Fagnou K. J. Am. Chem. Soc. 2008; 130: 10848
    • 76b Lapointe D, Fagnou K. Chem Lett. 2010; 39: 1118
    • 76c Gorelsky SI, Lapointe D, Fagnou K. J. Org. Chem. 2012; 77: 658
    • 76d Gorelsky SI. Coord. Chem. Rev. 2013; 257: 153
  • 77 Gaulier SM, McKay R, Swain NA. Tetrahedron Lett. 2011; 52: 6000
  • 78 Penning TD, Talley JJ, Bertenshaw SR, Carter JS, Collins PW, Docter S, Graneto MJ, Lee LF, Malecha JW, Miyashiro JM, Rogers RS, Rogier DJ, Yu SS, Anderson GD, Burton EG, Cogburn JN, Gregory SA, Koboldt CM, Perkins WE, Seibert K, Veenhuizen AW, Zhang YY, Isakson PC. J. Med. Chem. 1997; 40: 1347
    • 79a Schoenthal AH, Chen TC, Hofman FM, Louie SG, Petasis NA. Expert Opin. Investig. Drugs 2008; 17: 197
    • 79b Battistone MJ, Sawitzke AD. Clin. Med. Insights 2010; 2: 245

      For additional examples of palladium-catalyzed regioselective intermolecular direct C5-arylation reactions of 1-substituted pyrazole derivatives, see:
    • 80a Yagi K, Ogura T, Numata A, Ishii S, Arai K. Heterocycles 1997; 45: 1463
    • 80b René O, Fagnou K. Adv. Synth. Catal. 2010; 352: 2116
    • 80c Mateos C, Mendiola J, Carpintero M, Minguez JM. Org. Lett. 2010; 12: 4924
    • 80d Smari I, Youssef C, Yuan K, Beldhria A, Ben Ammar H, Ben Hassine B, Doucet H. Eur. J. Org. Chem. 2014; 1778
    • 80e Kumpulainen ET. T, Pohjakallio A. Adv. Synth. Catal. 2014; 356: 1555

      For additional syntheses of Celecoxib, see:
    • 81a Ref. 78;
    • 81b Singh SK, Saibaba V, Rao YK. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 2005; 44: 1115
    • 81c Oh LM. Tetrahedron Lett. 2006; 47: 7943
    • 81d Hu J, Chen S, Sun Y, Yang J, Rao Y. Org. Lett. 2012; 14: 5030
    • 81e Dadiboyena S, Hamme II AT. Curr. Org. Chem. 2012; 16: 1390
    • 81f Shang Y, Du J, Cui H. Org. Prep. Proced. Int. 2014; 46: 132
    • 82a Hattori K, Yamaguchi K, Yamaguchi J, Itami K. Tetrahedron 2012; 68: 7605

    • For additional examples of palladium-catalyzed direct C3-arylation of 1H-indazoles, see:
    • 82b Ye M, Edmunds AJ. F, Morris JA, Sale D, Zhang Y, Yu J.-Q. Chem. Sci. 2013; 4: 2374
    • 82c Ben-Yahia A, Naas M, El Kazzouli S, Essassi EM, Guillaumet G. Eur. J. Org. Chem. 2012; 7075
  • 83 Yeo E.-J, Chun Y.-S, Cho YS, Kim J, Lee J.-C, Kim M.-S, Park J.-W. J. Natl. Cancer Inst. 2003; 95: 516
  • 84 Lee F.-Y, Lien J.-C, Huang L.-J, Huang T.-M, Tsai S.-C, Teng C.-M, Wu C.-C, Cheng F.-C, Kuo S.-C. J. Med. Chem. 2001; 44: 3746
  • 85 Wu CC, Huang SW, Hwang TL, Kuo SC, Lee FY, Teng CM. Br. J. Pharmacol. 2000; 130: 1289
  • 86 Slade JD, Pelz FN, Bodnar W, Lampe W, Watson SP. J. Org. Chem. 2009; 74: 6331
  • 87 Ohnmacht SA, Culshaw AJ, Greaney MF. Org. Lett. 2010; 12: 224

    • For additional examples of transition-metal-catalyzed direct (hetero)arylation reactions in which water was used as solvent, see:
    • 88a Turner GL, Morris JA, Greaney MF. Angew. Chem. Int. Ed. 2007; 46: 7996
    • 88b Ohnmacht SA, Mamone P, Culshaw AJ, Greaney MF. Chem. Commun. 2008; 1241
    • 88c Joucla L, Batail N, Djakovitch L. Adv. Synth. Catal. 2010; 352: 2929
    • 88d Su Y.-X, Deng Y.-H, Ma T.-T, Li Y.-Y, Sun L.-P. Green Chem. 2012; 14: 1979
    • 88e Gerelle M, Dalencon AJ, Willis MC. Tetrahedron Lett. 2012; 53: 1954
    • 88f Chen F, Min Q.-Q, Zhang X. J. Org. Chem. 2012; 77: 2992
    • 88g Ackermann L, Pospech J, Potukuchi HK. Org. Lett. 2012; 14: 2146
    • 88h Carrër A, Brion J.-D, Alami M, Messaoudi S. Adv. Synth. Catal. 2014; 356: 3821
    • 88i Cho BS, Bae HJ, Chung YK. J. Org. Chem. 2015; 80: 5302
  • 89 Steffan RJ, Matelan EM, Bowen SM, Ullrich JW, Wrobel JE, Zamaratski E, Kruger L, Olsen Hedemyr AL, Cheng A, Hansson T, Unwalle RJ, Miller CP, Rhomnstad PP. US Pat. Appl US 2006/030612 A1, 2006 ; Chem. Abstr. 2006, 144, 212770
  • 90 Goetz MP, Toft DO, Ames MM, Erlichman C. Ann. Oncol. 2003; 14: 1196
  • 91 Ohnmacht SA, Micco M, Petrucci V, Todd AK, Reszka AP, Gunaratnam M, Carvalho MA, Zloh M, Neidle S. Bioorg. Med. Chem. Lett. 2012; 22: 5930
    • 92a van Leusen AM, Hoogenboom BE, Siderius H. Tetrahedron Lett. 1972; 13: 2369
    • 92b Strotman NA, Chobanian HR, Guo Y, He J, Wilson JE. Org. Lett. 2010; 12: 3578
  • 93 Ohnmacht SA, Ciancimino C, Vignaroli G, Gunaratnam M, Neidle S. Bioorg. Med. Chem. Lett. 2013; 23: 5351
  • 94 Yamamoto T, Muto K, Komiyama M, Canivet J, Yamaguchi J, Itami K. Chem. Eur. J. 2011; 17: 10113
    • 95a Nencetti S, Rossello A, Orlandini E. ChemMedChem 2013; 8: 1617
    • 95b Scott LJ. Drugs 2014; 74: 1371
    • 95c Bulawa CE, Connelly S, DeVit M, Wang L, Weigel C, Fleming JA, Packman J, Powersa ET, Wiseman RL, Foss TR, Wilson IA, Kelly JW, Labaudinière R. Proc. Natl. Acad. Sci., U.S.A. 2012; 109: 9629
  • 96 For a previous synthesis of Tafamidis, an evaluation of the activity and mechanism of action of this compound and other benzoxazoles, see: Razair H, Palaninathan SK, Powers ET, Wiseman RL, Purkey HE, Mohamedhaideen NN, Deechongkit S, Chiang KP, Dendle MT. A, Sacchettini JC, Kelly JW. Angew. Chem. Int. Ed. 2003; 42: 2758
  • 97 Cho SY, Lee BH, Jung H, Yun CS, Ha JD, Kim HR, Chae CH, Lee JH, Seo HW, Oh K.-S. Bioorg. Med. Chem. Lett. 2013; 23: 6711
  • 98 Lee J, Han S.-Y, Jung H, Yang J, Choi J.-W, Chae CH, Park CH, Choi SU, Lee K, Ha JD, Lee CO, Ryu JW, Kim HR, Koh JS, Cho SY. Bioorg. Med. Chem. Lett. 2012; 22: 4044
  • 99 Liu X, Newton RC, Scherle PA. Expert Opin. Investig. Drugs 2011; 20: 1225
  • 100 Okamoto K, Eger BT, Nishino T, Kondo S, Pai EF, Nishino T. J. Biol. Chem. 2003; 278: 1848
  • 101 Becker MA, Schumaker HR. Jr, Wortmann RL, MacDonald PA, Eustace D, Palo WA, Streit J, Joseph-Ridge N. New Engl. J. Med. 2005; 353: 2450
  • 102 Cohen A, Verhaeghe P, Crozet MD, Hutter S, Rathelot P, Vanelle P, Azas N. Eur. J. Med. Chem. 2012; 55: 315

    • For selected reviews on chloroquine, see:
    • 103a Slater AF. G. Pharm. Therap. 1993; 57: 203
    • 103b Solomon VR, Lee H. Eur. J. Pharmacol. 2009; 625: 220
    • 103c Misbahi H. J. Pharm. Clin. 2013; 32: 143
    • 103d Thomé R, Lopes SC. P, Coata FT. M, Verinaud L. Immunol. Lett. 2013; 153: 50
    • 104a Briolant S, Fusai T, Rogier C, Pradines B. The Open Tropical Medicine Journal 2008; 1: 31
    • 104b Tan KR, Magill AJ, Parise ME, Arguin PM. Am. J. Trop. Hyg. 2011; 84: 517
  • 105 Thompson R, Eastman A. Br. J. Clin. Pharmacol. 2013; 76: 358
  • 106 Dudkin VY, Wang C, Arrington KL, Fraley ME, Hartman GD, Stirdivant SM, Drakas RA, Riekert K, Walsh ES, Hamilton K, Buser CA, Hardwick J, Tao W, Beck SC, Mao X, Lobell RB, Sepp-Lorenzino L. Bioorg. Med. Chem. Lett. 2012; 22: 2613
  • 107 Arrington KL, Dudkin VY, Fraley ME, Wang C, Hoffman JM, Kreatsoulas C. PCT Int. Appl WO 2006/135604 A2, 2006
    • 108a Thomas M, Owen C. Curr. Opin. Pharmacol. 2008; 8: 267
    • 108b Wu P, Liu T, Hu Y. Curr. Med. Chem. 2009; 16: 916
    • 108c Zhang N, Ayral-Kaloustian S, Anderson JT, Yu K, Hollander I, Mallon R. Bioorg. Med. Chem. Lett. 2010; 20: 3526
    • 108d Lee J.-H, Lee H, Yun S.-M, Jung KH, Jeong Y, Yan HH, Hong S, Hong S.-S. Cancer Lett. 2013; 329: 99
  • 109 Furet P, Guagnano V, Fairhurst RA, Imbach-Weese P, Bruce I, Knapp M, Fritsch C, Blasco F, Blanz J, Aichholz R, Hamon J, Fabbro D, Caravatti G. Bioorg. Med. Chem. Lett. 2013; 23: 3741
  • 110 Yokooji A, Okazawa T, Satoh T, Miura M, Nomura M. Tetrahedron 2003; 59: 5685
  • 111 Fritsch C, Huang A, Chatenay-Rivauday C, Schnell C, Reddu A, Liu M, Kauffmann A, Guthy D, Erdmann D, De Pover A, Furet P, Gao H, Ferretti S, Wang Y, Trappe J, Brachmann SM, Maira S.-M, Wilson C, Boehm M, Garcia-Echeverria C, Chene P, Wiesmann M, Cozens P, Lehar J, Schlegel R, Caravatti G, Hofmann F, Sellers WR. Mol. Cancer Ther. 2014; 13: 1117
  • 112 Swahn B.-M, Wensbo D, Sandell J, Sohn D, Slivo C, Pyring D, Malström J, Arzel E, Vallin M, Bergh M, Jeppsson F, Johnson AE, Juréus A, Neelissen J, Svensson S. Bioorg. Med. Chem. Lett. 2010; 20: 1976
    • 113a Mathis CA, Wang Y, Holt DP, Huang G.-F, Debnath ML, Klunk WE. J. Med. Chem. 2003; 46: 2740
    • 113b Klunk WE, Engler H, Norberg A, Wang Y, Blomqvist G, Holt DP, Bergström M, Savitcheva I, Huang G.-F, Estrada S, Ausen B, Debnath ML, Barletta J, Price JC, Sandell J, Lopresti BJ, Wall A, Koivisto P, Antoni G, Mathis CA, Långström B. Ann. Neurol. 2004; 55: 306
  • 114 Swahn B.-M, Sandell J, Pyring D, Bergh M, Jeppsson F, Juéus A, Neelissen J, Johnström P, Schou M, Svensson S. Bioorg. Med. Chem. Lett. 2012; 22: 4332
  • 115 Schnürch M, Waldner B, Hilber K, Mihovilovic MD. Bioorg. Med. Chem. Lett. 2011; 21: 2149

    • For additional examples of ligand-free palladium-catalyzed direct C5-arylation reactions of thiazole derivatives, see:
    • 116a Parisien M, Valette D, Fagnou K. J. Org. Chem. 2005; 70: 7578
    • 116b Roger J, Pozgan F, Doucert H. J. Org. Chem. 2009; 74: 1179
    • 116c Primas N, Bouillon A, Lancelot J.-C, El-Kashef H, Rault S. Tetrahedron 2009; 65: 5739
    • 116d Liu X.-W, Shi J.-L, Yan J.-X, Wei J.-B, Peng K, Dai L, Li C.-G, Wang B.-Q, Shi Z.-J. Org. Lett. 2013; 15: 5774
    • 117a Hansen JM, Klass M, Harris C, Csete M. Cell Biol. Int. 2007; 31: 546
    • 117b Chen SE, Jin B, Li YP. Am. J. Physiol. Cell Physiol. 2007; 292: C1660
  • 118 Dao-Huy T, Waldner BJ, Wimmer L, Schnürch M, Mihovilovic MD. Eur. J. Org. Chem. 2015; 4765
    • 119a Pettit GR, Singh SB, Hamel E, Lin CM, Alberts DS, Garcia-Kendall D. Experentia 1989; 45: 209
    • 119b Sackett DL. Pharmacol. Ther. 1993; 59: 163
  • 120 Bellina F, Cauteruccio S, Mannina L, Rossi R, Viel S. J. Org. Chem. 2005; 70: 3997

    • For protocols on the palladium-catalyzed direct C5-arylation of imidazole derivatives that have been developed by research groups other than ours, see:
    • 121a Kondo Y, Komino T, Sakamoto T. Org. Lett. 2000; 2: 3111
    • 121b Liégault B, Lapointe D, Caron L, Vlassova A, Fagnou K. J. Org. Chem. 2009; 74: 1826
    • 121c Joo JM, Touré BB, Sames D. J. Org. Chem. 2010; 75: 4911
    • 121d Kumar PV, Lin W.-S, Shen J.-S, Nandi D, Lee HM. Organometallics 2011; 30: 5160
    • 121e Guo S, Huynh HV. Organometallics 2014; 33: 2004
  • 122 Bellina F, Cauteruccio S, Monti S, Rossi R. Bioorg. Med. Chem. Lett. 2006; 16: 5757
  • 123 Bellina F, Cauteruccio S, Borsotti P, Taraboletti G, Monti S, Giavazzi R, Rossi R. Targeted Oncology 2007; 2 (Suppl. 01) : S22
  • 124 Bonezzi K, Taraboletti G, Borsotti P, Bellina F, Rossi R, Giavazzi R. J. Med. Chem. 2009; 52: 7906
  • 125 Bellina F, Cauteruccio S, Mannina L, Rossi R, Viel S. Eur. J. Org. Chem. 2006; 693

    • For palladium-catalyzed direct C2-arylation reactions of 1-substituted imidazoles that have been reported by research groups other than ours, see:
    • 126a Shibahara F, Yamaguchi E, Murai T. J. Org. Chem. 2011; 76: 2680
    • 126b Shibahara F, Yamaguchi T, Yamagichi E, Murai T. J. Org. Chem. 2012; 77: 8815
    • 126c Gu Z.-S, Chen W.-X, Shao L.-X. J. Org. Chem. 2014; 79: 5806
  • 127 Khanna IK, Weier RM, Yu Y, Xu XD, Koszyk FJ, Collins PW, Kobolds CM, Veenhuizen AM, Perkins WE, Casler JJ, Masferrer JL, Zhang YY, Gregory SA, Seibert K, Isakson PC. J. Med. Chem. 1997; 40: 1634
  • 128 Bellina F, Cauteruccio S, Di Fiore A, Rossi R. Eur. J. Org. Chem. 2008; 5436
  • 129 Campeau L.-C, Stuart DR, Leclerc J.-P, Bertand-Laperle M, Villemure E, Sun H.-Y, Lasserre S, Guimond N, Lecavallier M, Fagnou K. J. Am. Chem. Soc. 2009; 131: 3291
  • 130 Semones M, Feng Y, Johnson N, Adams JL, Winkler J, Hansbury M. Bioorg. Med. Chem. Lett. 2007; 17: 4756
  • 131 Izumi Y, Satoh Y, Kondoh H, Urabe K. J. Mol. Catal. 1992; 72: 37
  • 132 Seerden J.-PG, Leusink-Ionescu G, Leguijt R, Saccavini C, Gelens E, Dros B, Wondenberg-Vrenken T, Molema G, Kamps JA. A. M, Kellogg RM. Bioorg. Med. Chem. Lett. 2014; 24: 1352

    • For additional examples of syntheses of 1,2,3-triazole derivatives via CuSO4/sodium ascorbate catalyzed click reactions, see:
    • 133a Glaser M, Arstad E. Bioconjugate Chem. 2007; 18: 989
    • 133b Halila S, Manguian M, Fort S, Cottaz S, Hamaide T, Fleury E, Driguez H. Macromol. Chem. Phys. 2008; 209: 1282
    • 133c Szánti-Pintér E, Balogh J, Csók Z, Kollár L, Gömory A, Skoda-Földes R. Steroids 2011; 76: 1377
    • 133d Kuboyama T, Nakahara M, Yoshino M, Cui Y, Sako T, Wada Y, Imanishi T, Obika S, Watanabe Y, Suzuki M, Doi H. Bioorg. Med. Chem. 2011; 19: 249
    • 133e Dangroo NA, Dar AA, Dar BA. Tetrahedron Lett. 2014; 55: 6729
    • 133f Suresh R, Muthusubramanian S, Paul N, Kalidhasan N, Shanmugaiah V. Med. Chem. Res. 2014; 23: 4367
    • 133g Bolje A, Urankar D, Kosmrlj J. Eur. J. Org. Chem. 2014; 8167
  • 134 Li F, Park Y, Hah J.-M, Ryu J.-S. Bioorg. Med. Chem. Lett. 2013; 23: 1083
  • 135 Chuprakov S, Chernyak N, Dudnik AS, Gevorgyan V. Org. Lett. 2007; 9: 2333
  • 136 For a review on the copper-catalyzed azide-alkyne cycloaddition reactions, see: Meldel M, Tonøe CW. Chem. Rev. 2008; 108: 2952
    • 137a Simoni D, Grisolia G, Giannini G, Roberti M, Rondanin R, Piccagli L, Baruchello R, Rossi M, Romagnoli R, Invidiata FP, Grimaudo S, Jung MK, Hamel E, Gebbia N, Crosta L, Abbadessa V, Di Cristina A, Dusonchet L, Meli M, Tolomeo M. J. Med. Chem. 2005; 48: 723
    • 137b Romagnoli R, Baraldi PG, Pavani MG, Tabrizi MA, Preti D, Fruttarolo F, Piccagli L, Jung MK, Hamel E, Borgatti M, Gambari R. J. Med. Chem. 2006; 49: 3906
    • 137c Romagnoli R, Baraldi PG, Remusat V, Carrion MD, Cara CL, Preti D, Fruttarolo F, Pavani MG, Tabrizi MA, Tolomeo M, Grimaudo S, Balzarini J, Jordan MA, Hamel E. J. Med. Chem. 2006; 49: 6425
    • 137d Romagnoli R, Baraldi PG, Carrion MD, Cara CL, Preti D, Fruttarolo F, Pavani MG, Tabrizi MA, Tolomeo M, Grimaudo S, Di Cristina A, Balzarini J, Hadfield JA, Brancale A, Hamel E. J. Med. Chem. 2007; 50: 2773
    • 137e Romagnoli R, Baraldi PG, Carrion MD, Cruz-Lopez O, Cara CL, Tolomeo M, Grimaudo S, Di Cristina A, Pipitone MR, Balzarini J, Kandil S, Brancale A, Sarkar T, Hamel E. Bioorg. Med. Chem. Lett. 2008; 18: 5041
    • 137f Romagnoli R, Baraldi PG, Sarkar T, Carrion MD, Cara CL, Cruz-Lopez O, Preti D, Tabrizi MA, Tolomeo M, Grimaudo S, Di Cristina A, Zonta N, Balzarini J, Brancale A, Hsieh H.-P, Hamel E. J. Med. Chem. 2008; 51: 1464
    • 137g Romagnoli R, Baraldi PG, Sarkar T, Carrion MD, Cruz-Lopez O, Cara CL, Tolomeo M, Grimaudo S, Di Cristina A, Pipitone MR, Balzarini J, Gambari R, Ileria L, Saletti R, Brancale A, Hamel E. Bioorg. Med. Chem. 2008; 16: 8419
    • 137h Romagnoli R, Baraldi PG, Carrion MD, Cara CL, Cruz-Lopez O, Tolomei M, Grimaudo S, Di Cristina A, Pipitone MR, Balzarini J, Zonta N, Brancale A, Hamel E. Bioorg. Med. Chem. 2009; 17: 6862
    • 137i Tomagnoli R, Baraldi PG, Cruz-Lopez O, Cara CL, Carrion MD, Brancale A, Hamel E, Chen L, Bortolozzi R, Basso G, Viola G. J. Med. Chem. 2010; 53: 4248
    • 137j Romagnoli R, Baraldi PG, Carrion MD, Cruz-Lopez O, Tolomeo M, Grimaudo S, Di Cristina A, Pipitone MR, Balzarini J, Brancale A, Hamel E. Bioorg. Med. Chem. 2010; 18: 5114
    • 137k Romagnoli R, Baraldi PG, Cara CL, Hamel E, Basso F, Borctolozzi R, Viola G. Eur. J. Med. Chem. 2010; 45: 5781
    • 137l Romagnoli R, Baraldi PG, Brancale A, Ricci A, Hamel E, Bortolozzi R, Basso G, Viola G. J. Med. Chem. 2011; 54: 5144
    • 137m Romagnoli R, Baraldi PG, Cara CL, Salvador MK, Bortolozzi R, Basso G, Viola G, Balzarini J, Brancale A, Fu X.-H, Zhang S.-Z, Hamel E. Eur. J. Med. Chem. 2011; 46: 6015
    • 137n Romagnoli R, Baraldi PG, Lopez-Cara C, Cruz-Lopez O, Carrion MD, Salvador MK, Bermejo J, Esévez S, Estévez F, Balzarini J, Brancale A, Ricci A, Chen L, Kim JG, Hamel E. ChemMedChem 2011; 6: 1841
    • 137o Romagnoli R, Baraldi PG, Salvador MK, Camacho ME, Preti D, Tabrizi MA, Bassetto M, Brancale A, Hamel E, Bortolozzi R, Basso G, Viola G. Bioorg. Med. Chem. 2012; 20: 7083
    • 137p Romagnoli R, Baraldi PG, Salvador MK, Preti D, Tabrizi MA, Bassetto M, Brancale A, Hamel E, Castagliuolo I, Bortolozzi R, Basso G, Viola G. J. Med. Chem. 2013; 56: 2606
    • 137q Romagnoli R, Baraldi PG, Lopez-Cara C, Preti D, Tabrizi MA, Balzarini J, Bassetto M, Brancale A, Fu X.-H, Gao Y, Li J, Zhang S.-Z, Hamel E, Bortolozzi R, Basso G, Viola G. J. Med. Chem. 2013; 56: 9296
    • 137r Romagnoli R, Baraldi PG, Salvador MK, Prencipe F, Bertolasi V, Cancellieri M, Brancale A, Hamel E, Castagliuolo I, Consolaro F, Porcù E, Basso G, Viola G. J. Med. Chem. 2014; 57: 6795
    • 137s Romagnoli R, Baraldi PG, Salvador MK, Prencipe F, Lopez-Cara C, Ortega SS, Brancale A, Hamel E, Castagliuolo I, Mitola S, Ronca R, Bortolozzi R, Porcù E, Basso G, Viola G. J. Med. Chem. 2015; 58: 3209
  • 138 Romagnoli R, Baraldi PG, Salvador MK, Preti D, Tabrizi MA, Brancale A, Fu X.-H, Li J, Zhang S.-Z, Hamel E, Bortolozzi R, Basso G, Viola G. J. Med. Chem. 2012; 55: 475
  • 139 Spulak M, Lubjacky R, Senel P, Kunes J, Pour M. J. Org. Chem. 2010; 75: 241
  • 140 Grandane A, Tanc M, Zalubovskis R, Supuran CT. Bioorg. Med. Chem. 2014; 22: 1522
    • 141a Grandane A, Belyakov S, Trapencieris P, Zalubovskis R. Tetrahedron 2012; 68: 5541
    • 141b Cho YJ, Rho KY, Keum SR, Kim SH, Yoon CM. Synth. Commun. 1999; 29: 2061
    • 142a Chambers MS, Goodacre SC, Hallett DJ, Jennings A, Jones P, Lewis RT, Moore KW, Street LJ, Szekeres HJ. PCT Int. Appl WO 2002/074772 A1, 2002
    • 142b Chambers MS, Goodacre SC, Hallett DJ, Jennings A, Jones P, Lewis RT, Moore KW, Russell MG. N, Street LJ, Szekeres HJ. PCT Int. Appl WO 2002/074773 A1, 2002
  • 143 Jensen MS, Hoerrner RS, Li W, Nelson DP, Javedi GJ, Dormer PG, Cai D, Larsen RD. J. Org. Chem. 2005; 70: 6034
  • 144 Cameron M, Foster BS, Lynnch JE, Shi Y.-J, Dolling U.-H. Org. Process Res. Dev. 2006; 10: 398
  • 145 Goodacre SC, Street LJ, Hallett DJ, Crawforth JM, Kelly S, Owens AP, Blackaby WP, Lewis RT, Stanley J, Smith AJ, Ferris P, Sohal B, Cook SM, Pike A, Brown N, Wafford KA, Marshall G, Castro JL, Atack JR. J. Med. Chem. 2006; 49: 35
  • 146 Humphries AC, Gancia E, Gilligan MT, Goodacre S, Hallett D, Merchant KJ, Thomas SR. Bioorg. Med. Chem. Lett. 2006; 16: 1518
  • 147 Bettati M, Blurton P, Carling WR, Chambers MS, Hallett DJ, Jennings A, Lewis RT, Russell MG. N, Street LJ, Szekeres HJ, Van Niel MB. PCT Int. Appl WO 2002/038568 A1, 2002
  • 148 Atack JR, Hallett DJ, Tye S, Wafford KA, Ryan C, Sanabria-Bohórquez SM, Eng W.-S, Gibson RE, Burns HD, Dawson GR, Carling RW, Street LJ, Pike A, De Lepeleire I, Van Laere K, Bormans G, de Hoon JN, Van Hecken A, McKernan RM, Murphy MG, Hargreaves RJ. J. Psychopharm. 2010; 25: 329
  • 149 Gauthier DR. Jr, Limanto J, Devine PN, Desmond RA, Szumigala RH. Jr, Foster BS, Volante RP. J. Org. Chem. 2005; 70: 5938
  • 150 Park J.-H, El-Gamal MI, Lee YS, Oh C.-H. Eur. J. Med. Chem. 2011; 46: 5769
  • 151 Gadaleta-Caldarola G, Infusino S, Divella R, Ferraro E, Mazzocca A, De Rose F, Filippelli G, Abbate I, Brandi M. Future Oncology 2015; 11: 1863
  • 152 Gigante A, Priego E.-M, Sánchez-Carrasco P, Ruiz-Pérez LM, Vande Voorde J, Camarasa M.-J, Balzarini J, González-Pacanowska D, Pérez-Pérez M.-J. Eur. J. Med. Chem. 2014; 82: 459
    • 153a Madrid DC, Ting L.-M, Waller KL, Schramm VL, Kim K. J. Biol. Chem. 2008; 283: 35899
    • 153b Cassera MB, Hazleton KZ, Merino EF, Obaldia III N, Ho M.-C, Murkin AS, DePinto R, Gutierez JA, Almo SC, Evans GB, Babu YS, Schramm VL. PLoS One 2011; 6: e26916
  • 154 Stec MM, Andrews KL, Bo Y, Caenepeel S, Liao H, McCarter J, Mullady EL, San Miguel T, Subramanian R, Tamayo N, Whittington DA, Wang L, Wu T, Zalameda LP, Zhang N, Hughes PE, Norman MH. Bioorg. Med. Chem. Lett. 2015; 25: 4136
  • 155 Bode C, Boezio A, Cheng AC, Choquette D, Coats JR, Copeland KW, Huang H, La D, Lewis R, Liao H, Potashman M, Stellwagen J, Yi S, Norman M, Stec M, Peterson EA, Graceffa R. PCT Int. Appl WO 2010/132598 A1, 2010
  • 156 Konishi H, Okamoto K, Ohmori Y, Yoshino H, Ohmori H, Ashihara M, Hirata Y, Ohta A, Sakamoto H, Hada N, Katsume A, Kohara M, Morikawa K, Tsukuda T, Shimina N, Foster GR, Alazawi W, Aoki Y, Arisawa M, Sudoh M. Sci. Rep. 2012; 2: 259
  • 157 Huang S, Qing J, Wang S, Wang H, Zhang L, Tang Y. Org. Biomol. Chem. 2014; 12: 2344
  • 158 Ye M, Gao G.-L, Edmunds AJ. F, Worthington PA, Morris JA, Yu J.-Q. J. Am. Chem. Soc. 2011; 133: 19090
  • 159 Bergstrom DA, Carlson JH, Bromsley SD, Jackson DM, Walters JR. Eur. J. Pharmacol. 1986; 124: 75
  • 160 Lahti AC, Weiler MA, Corey PK, Lahti RA, Carlsson A, Tamminga CA. Biol. Psychiatry 1998; 43: 2
  • 161 For a previous synthesis of the racemic form of preclamol, see: Nilsson K, Hallberg A. J. Org. Chem. 1992; 57: 4015
  • 162 Shao B, Victory S, Ilyin VI, Goehring RR, Sun Q, Hogenkamp D, Hodges DD, Islam K, Sha D, Zhang C, Nguyen P, Robledo S, Sakellaropoulos G, Carter RB. J. Med. Chem. 2004; 47: 4277
  • 163 Ma D, Cai Q. Org. Lett. 2003; 5: 3799
  • 164 Wolfe JP, Tomori H, Sadighi JP, Yim J, Buchwald SL. J. Org. Chem. 2000; 65: 1158
  • 165 Katritzky AR, Pilarski B, Urogdi L. Synthesis 1989; 949
  • 166 Schipper DJ, El-Safiti M, Whipp CJ, Fagnou K. Tetrahedron 2009; 65: 4977
    • 167a Martin-Galiano AJ, Gorgojo B, Kunin CM, De la Campa AG. Antimicrob. Agents Chemother. 2002; 46: 1680
    • 167b Kunin CM, Ellis WY. Antimicrob. Agents Chemother. 2000; 44: 848
    • 168a LaMontagne MP, Marcovac A, Blumbergs P. J. Med. Chem. 1974; 17: 519
    • 168b Schmidt LH, Crosby R, Rasco J, Vaughan D. Antimicrob. Agents Chemother. 1978; 14: 420
    • 168c Kim KH, Hansch C, Fukunaga JY, Steller EE, Jow PY. C, Craig PN, Page J. J. Med. Chem. 1979; 22: 366
    • 168d Franke R, Streich W. J. Quant. Struct. Act. Relatsh. 1985; 4: 51
  • 169 Candito DA, Lautens M. Angew. Chem. Int. Ed. 2009; 48: 6713
  • 170 For a one-pot synthesis of N-silylaldimines from the corresponding aldehydes, see: Lou S, Moquist PN, Schaus SE. J. Am. Chem. Soc. 2007; 129: 15398
  • 171 Blanchot M, Candito DA, Larnaud F, Lautens M. Org. Lett. 2011; 13: 1486
  • 172 Fukuda M, Inomata M, Nishio K, Fukuoka K, Kanzawa F, Arioka H, Ishida T, Fukumoto H, Kurokawa H, Oka M, Saijo N. Jpn. J. Cancer Res. 1996; 87: 1086
  • 173 Nakanishi T, Suzuki M, Mashiba A, Ishikawa K, Yokotsuka T. J. Org. Chem. 1998; 63: 4235
  • 174 Wang G.-W, Yuan T.-T, Li D.-D. Angew. Chem. Int. Ed. 2011; 50: 1380

    • For directed ortho-arylation of benzamides in an acidic solvent, see:
    • 175a Daugulis O, Zaitsev VG. Angew. Chem. Int. Ed. 2005; 44: 4046
    • 175b Shabashov D, Daugulis O. Org. Lett. 2006; 8: 4947
    • 176a Garcia Soriano F, Virág L, Jagtap P, Szabó É, Mabley JG, Liaudet L, Marton A, Hoyt DG, Murthy KG, Salzman AL, Southan GJ, Szabó C. Nat. Med. 2001; 7: 108
    • 176b Tu Z, Chu W, Zhang J, Dence CS, Welch MJ, Mach RH. Nucl. Med. Biol. 2005; 32: 437
  • 177 Huang S.-H, Xiong M, Chen X.-P, Xiao Z.-Y, Zhao Y.-F, Huang Z.-Y. Oncol. Rep. 2008; 20: 567

    • For recent examples of direct arylation reaction which have been carried out using a low catalyst loading, see ref. 60d and:
    • 178a Grosse S, Pillard C, Massip S, Marchivie M, Jarry C, Bernard P, Guillaumet G. J. Org. Chem. 2015; 80: 8539
    • 178b Conde N, Churruca F, SanMartin R, Herrero MT, Domínguez E. Adv. Synth. Catal. 2015; 357: 1525
    • 178c Churruca F, Hernández S, Perea M, SanMartin R, Domínguez E. Chem. Commun. 2013; 49: 1413
    • 178d Fu HY, Chen L, Doucet H. J. Org. Chem. 2012; 77: 4473

      For recent examples of direct arylation reactions carried out using new catalyst systems, see ref. 127c and:
    • 179a Pandev DK, Khake SM, Gonnade RG, Punji B. RSC Adv. 2015; 5: 81502
    • 179b Luo B.-T, Liu H, Lin Z.-J, Jiang J, Shen D.-S, Liu R.-Z, Ke Z, Liu F.-S. Organometallics 2015; 34: 4881
    • 179c Zhou Q, Wang Y.-N, Guo X.-Q, Zhu X.-H, Li Z.-M, Hou X.-F. Organometallics 2015; 34: 1021
    • 179d Jakab A, Dalicsek Z, Soós T. Eur. J. Org. Chem. 2015; 56
    • 179e Li Y, Wang J, Huang M, Wang Z, Wu Y, Wu Y. Tetrahedron 2015; 71: 2729
    • 179f Yuen OY, Charoensak M, So CM, Kuhakam C, Kwong FY. Chem. Asian J. 2015; 10: 857
    • 179g Kim D, Yoo K, Kim SE, Cho HJ, Lee J, Kim Y, Kim M. J. Org. Chem. 2015; 80: 3670
    • 179h Shen P.-X, Wang X.-C, Wang P, Zhu R.-Y, Yu J.-Q. J. Am. Chem. Soc. 2015; 137: 11574
    • 179i Satish G, Vardhan Reddy H, Anil BS. P, Ramesh K, Kumar RU, Nageswar YV. D. Tetrahedron Lett. 2015; 56: 4950
    • 179j Hubrich J, Himmler T, Rodefeld L, Ackermann L. ACS Catal. 2015; 5: 4089
    • 179k Li Y, Wang J, Huang M, Wang Z, Wu Y, Wu Y. J. Org. Chem. 2014; 79: 2890
    • 179l Khake SM, Soni V, Gonnade RG, Punji B. Dalton Trans. 2014; 14: 16084
    • 179m Özdemir I, Gürbuz N, Kaloglu N, Dogan Ö, Kaloglu M, Bruneau C, Doucet H. Beilstein J. Org. Chem. 2013; 9: 303

      For typical examples, see:
    • 180a (Poly)halobenzenesulfonyl chlorides: Skhiri A, Beladhria A, Yuan K, Soulé J.-F, Bensalem R, Doucet H. Eur. J. Org. Chem. 2015; 4428
    • 180b Arylsulfonyl chlorides: Zhang W, Liu F, Zhao B. Appl. Organomet. Chem. 2015; 29: 524
    • 180c Sodium arenesulfinates: Zhu J, Chen Y, Lin F, Wang B, Huang Q, Liu L. Synlett 2015; 26: 1124
    • 180d Aryldiazonium salts: Shin K, Park S.-W, Chang S. J. Am. Chem. Soc. 2015; 137: 8584
    • 180e Aryltrimethylammonium triflates: Zhu F, Tao J.-L, Wang Z.-X. Org. Lett. 2015; 17: 4926
    • 180f Benzenesulfonyl chlorides: Hfaiedh A, Yuan K, Ben Ammar H, Ben Hassine B, Soulé F, Doucet H. ChemSusChem 2015; 8: 1794
    • 180g 2-Thiophenecarboxylic acids: Zhao S, Liu Y.-J, Yan S.-Y, Chen F.-J, Zhang Z.-Z, Shi B.-F. Org. Lett. 2015; 17: 3338
    • 180h 2-Methoxybenzoic acids: Zhang Y, Zhao H, Zhang M, Su W. Angew. Chem. Int. Ed. 2015; 54: 3817
    • 180i Diversely substituted aryl carboxylic acids: Zhang L, Xue X, Xu C, Pan Y, Zhang G, Xu L, Li H, Shi Z. ChemCatChem 2014; 6: 3069

      For recent examples of C–H direct (hetero)arylation reactions carried out in or on water, see refs. 88a–d,f,g and:
    • 181a Zhu Y, Bauer M, Ackermann L. Chem. Eur. J. 2015; 21: 9980
    • 181b Singh KS, Dixneuf PH. ChemCatChem 2013; 5: 1313
    • 181c Ackermann L, Mulzer M. Org. Lett. 2008; 10: 5043