Bridging Fluorine and Aryne Chemistry: Vicinal Difunctionalization of Arynes Involving Nucleophilic Fluorination, Trifluoromethylation, or Trifluoromethylthiolation

Abstract

Multi-functionalized fluorinated arenes, especially those that are transformable fluorinated building blocks, are intriguing compounds in synthetic chemistry and for life science related applications. The development of straightforward and efficient approaches to these compounds is of significant importance and has, therefore, attracted much attention. This short review presents our recent progress on the fluoro-difunctionalization of arynes, which allows facile construction of a series of fluorinated arene building blocks bearing an ortho-iodine substituent as a coupling handle for further elaboration.

1 Introduction

2 Silver-Mediated Trifluoromethylation–Iodination of Arynes

3 Silver-Catalyzed Insertion of Aryne into R_f–I Bonds

4 Diphenyliodonium-Catalyzed Fluorination of Arynes

5 Silver-Mediated Trifluoromethylthiolation–Iodination of Arynes

6 Summary and Outlook

Keywords

aryne - fluorine - trifluoromethylation - fluorination - trifluoromethylthiolation - iodination

• References

• 1a Kirsch P. Modern Organofluorine Chemistry . Wiley-VCH; Weinheim: 2004
• 1b Uneyama K. Organofluorine Chemistry . Wiley-Blackwell; Oxford: 2008
• 1c Yamazaki T, Taguchi T, Ojima I In Fluorine in Medicinal Chemistry and Chemical Biology . Ojima I. Wiley-Blackwell; Oxford: 2009. Chap. 1

For recent reviews, see:
• 2a Jeschke P. ChemBioChem 2004; 5: 570
• 2b Purser S, Moore PR, Swallow S, Gouverneur V. Chem. Soc. Rev. 2008; 37: 320
• 2c Hagmann WK. J. Med. Chem. 2008; 51: 4359
• 2d O’Hagan D. Chem. Soc. Rev. 2008; 37: 308
• 2e Cametti M, Crousse B, Metrangolo P, Milani R, Resnati G. Chem. Soc. Rev. 2012; 41: 31
• 2f Wang J, Sanchez-Rosello M, Acena JL, del Pozo C, Sorochinsky AE, Fustero S, Soloshonok VA, Liu H. Chem. Rev. 2014; 114: 2432

For recent examples for aromatic trifluoromethylation, see:
• 3a Oishi M, Kondo H, Amii H. Chem. Commun. 2009; 1909
• 3b Koller R, Huchet Q, Battaglia P, Welch JM, Togni A. Chem. Commun. 2009; 5993
• 3c Cho EJ, Senecal TD, Kinzel T, Zhang Y, Watson DA, Buchwald SL. Science (Washington, D. C.) 2010; 328: 1679
• 3d Chu L.-L, Qing F.-L. Org. Lett. 2010; 12: 5060
• 3e Ball ND, Kampf JW, Sanford MS. J. Am. Chem. Soc. 2010; 132: 2878
• 3f Wang X, Truesdale L, Yu J.-Q. J. Am. Chem. Soc. 2010; 132: 3648
• 3g Zhang C.-P, Wang Z.-L, Chen Q.-Y, Zhang C.-T, Gu Y.-C, Xiao J.-C. Angew. Chem. Int. Ed. 2011; 50: 1896
• 3h Ji YN, Brueckl T, Baxter RD, Fujiwara Y, Seiple IB, Su S, Blackmond DG, Baran PS. Proc. Natl. Acad. Sci. U.S.A. 2011; 108: 14411
• 3i Nagib DA, MacMillan DW. C. Nature (London) 2011; 480: 224
• 3j Litvinas ND, Fier PS, Hartwig JF. Angew. Chem. Int. Ed. 2012; 51: 536
• 3k Dai J.-J, Fang C, Xiao B, Yi J, Xu J, Liu Z.-J, Lu X, Liu L, Fu Y. J. Am. Chem. Soc. 2013; 135: 8436
• 3l Wang X, Xu Y, Mo F, Ji G, Qiu D, Feng J, Ye Y, Zhang S, Zhang Y, Wang J. J. Am. Chem. Soc. 2013; 135: 10330
• 3m Seo S, Taylor JB, Greaney MF. Chem. Commun. 2013; 49: 6385

For recent examples of aromatic perfluoroalkylation, see:
• 3n Loy RN, Sanford MS. Org. Lett. 2011; 13: 2548
• 3o Qi Q, Shen Q, Lu L. J. Am. Chem. Soc. 2012; 134: 6548
• 3p Lishchynskyi A, Grushin VV. J. Am. Chem. Soc. 2013; 135: 12584

For an excellent review on aromatic fluorination, see:
• 4a Campbell MG, Ritter T. Chem. Rev. 2015; 115: 612

For transition-metal-free nucleophilic fluorination, see:
• 4b Balz G, Schiemann G. Ber. Dtsch. Chem. Ges. 1927; 60: 1186
• 4c Gottlieb HB. J. Am. Chem. Soc. 1936; 58: 532
• 4d Tang P, Wang W, Ritter T. J. Am. Chem. Soc. 2011; 133: 11482

For transition-metal-free electrophilic fluorination, see:
• 4e Deyoung J, Kawa H, Lagow RJ. J. Chem. Soc., Chem. Commun. 1992; 811
• 4f Yamada S, Gavryushin A, Knochel P. Angew. Chem. Int. Ed. 2010; 49: 2215

For selected examples by transition-metal-mediated fluorination, see:
• 4g Hull KL, Anani WQ, Sanford MS. J. Am. Chem. Soc. 2006; 128: 7134
• 4h Watson DA, Su MJ, Teverovskiy G, Zhang Y, Garcia-Fortanet J, Kinzel T, Buchwald SL. Science (Washington, D. C.) 2009; 325: 1661
• 4i Tang P, Furuya T, Ritter T. J. Am. Chem. Soc. 2010; 132: 12150
• 4j Casitas A, Canta M, Sola M, Costas M, Ribas X. J. Am. Chem. Soc. 2011; 133: 19386
• 4k Fier PS, Hartwig JF. J. Am. Chem. Soc. 2012; 134: 10795
• 4l Liu W, Huang XY, Cheng MJ, Nielsen RJ, Goddard WA, Groves JT. Science (Washington, D. C.) 2012; 337: 1322
• 4m Lee E, Hooker JM, Ritter T. J. Am. Chem. Soc. 2012; 134: 17456
• 4n Fier PS, Luo JW, Hartwig JF. J. Am. Chem. Soc. 2013; 135: 2552
• 4o Ye YD, Schimler SD, Hanley PS, Sanford MS. J. Am. Chem. Soc. 2013; 135: 16292
• 4p Fier PS, Hartwig JF. Science (Washington, D. C.) 2013; 342: 956

For recent reviews on the synthesis of ArSCF₃, see:
• 5a Boiko VN. Beilstein J. Org. Chem. 2010; 6: 880
• 5b Tlili A, Billard T. Angew. Chem. Int. Ed. 2013; 52: 6818
• 5c Toulgoat F, Alazet S, Billard T. Eur. J. Org. Chem. 2014; 2415
• 6a Roberts JD, Simmons HE, Carlsmith LA, Vaughan CW. J. Am. Chem. Soc. 1953; 75: 3290
• 6b Himeshima Y, Sonoda T, Kobayashi H. Chem. Lett. 1983; 1211

For recent reviews, see:
• 7a Pellissier H, Santelli M. Tetrahedron 2003; 59: 701
• 7b Wenk HH, Winkler M, Sander W. Angew. Chem. Int. Ed. 2003; 42: 502
• 7c Dyke AM, Hester AJ, Lloyd-Jones GC. Synthesis 2006; 4093
• 7d Pena D, Perez D, Guitian E. Angew. Chem. Int. Ed. 2006; 45: 3579
• 7e Gampe CM, Carreira EM. Angew. Chem. Int. Ed. 2012; 51: 3766
• 7f Tadross PM, Stoltz BM. Chem. Rev. 2012; 112: 3550
• 8a Brown RD, Godfrey PD, Rodler M. J. Am. Chem. Soc. 1986; 108: 1296
• 8b Radziszewski JG, Hess BA, Zahradnik R. J. Am. Chem. Soc. 1992; 114: 52
• 8c Warmuth R. Angew. Chem. Int. Ed. 1997; 36: 1347
• 8d Hoye TR, Baire B, Niu DW, Willoughby PH, Woods BP. Nature (London) 2012; 490: 208
• 8e Hoffmann RW, Suzuki K. Angew. Chem. Int. Ed. 2013; 52: 2655
• 8f Medina JM, Mackey JL, Garg NK, Houk KN. J. Am. Chem. Soc. 2014; 136: 15798
• 9 Zeng Y, Zhang L, Zhao Y, Ni C, Zhao J, Hu J. J. Am. Chem. Soc. 2013; 135: 2955
• 10 Zeng Y, Hu J. Chem. Eur. J. 2014; 20: 6866
• 11 Zeng Y, Li G, Hu J. Angew. Chem. Int. Ed. 2015; 54: 10773
• 12 Zeng Y, Hu J. Org. Lett. 2016; 18: 856
• 13 Ni C, Zhang L, Hu J. J. Org. Chem. 2008; 73: 5699
• 14 Zhang W, Ni C, Hu J. Top. Curr. Chem. 2012; 308: 25
• 15a Prakash GK. S, Wang F, Zhang Z, Haiges R, Rahm M, Christe KO, Mathew T, Olah GA. Angew. Chem. Int. Ed. 2014; 53: 11575
• 15b Lishchynskyi A, Miloserdov FM, Martin E, Benet-Buchholz J, Escudero-Adán EC, Konovalov AI, Grushin VV. Angew. Chem. Int. Ed. 2015; 54: 15289

For the preparation and reactivity of AgCF₃, see:
• 16a Nair HK, Morrison JA. J. Organomet. Chem. 1989; 376: 149
• 16b Naumann D, Wessel W, Hahn J, Tyrra W. J. Organomet. Chem. 1997; 547: 79
• 16c Tyrra WE. J. Fluorine Chem. 2001; 112: 149
• 16d Wessel W, Tyrra W, Naumann D. Z. Anorg. Allg. Chem. 2001; 627: 1264
• 16e Tyrra W. Heteroat. Chem. 2002; 13: 561

Arylsilvers are known to undergo protonation readily, see:
• 17a Sun KK, Miller WT. J. Am. Chem. Soc. 1970; 92: 6985
• 17b Furuya T, Strom AE, Ritter T. J. Am. Chem. Soc. 2009; 131: 1662
• 17c Cornella J, Lahlali H, Larrosa I. Chem. Commun. 2010; 46: 8276
• 18 For more details, see: Zeng Y. Ph.D. Dissertation . Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences; P. R. of China: 2015
• 19a Ikawa T, Nishiyama T, Shigeta T, Mohri S, Morita S, Takayanagi S, Terauchi Y, Morikawa Y, Takagi A, Ishikawa Y, Fujii S, Kita Y, Akai S. Angew. Chem. Int. Ed. 2011; 50: 5673
• 19b Ikawa T, Takagi A, Goto M, Aoyama Y, Ishikawa Y, Itoh Y, Fujii S, Tokiwa H, Akai S. J. Org. Chem. 2013; 78: 2965
• 19c Takagi A, Ikawa T, Kurita Y, Saito K, Azechi K, Egi M, Itoh Y, Tokiwa H, Kita Y, Akai S. Tetrahedron 2013; 69: 4338
• 20a Laurence C, Queignec-Cabanetos M, Dziembowska T, Queignec R, Wojtkowiak B. J. Am. Chem. Soc. 1981; 103: 2567
• 20b Laurence C, Queignec-Cabanetos M, Wojtkowiak B. J. Chem. Soc., Perkin Trans. 2 1982; 1605
• 20c Rege PD, Malkina OL, Goroff NS. J. Am. Chem. Soc. 2002; 124: 370
• 20d Moss WN, Goroff NS. J. Org. Chem. 2005; 70: 802
• 21 For hydrogen bonding basicity of aliphatic amines, see: Graton J, Berthelot M, Besseau F, Laurence C. J. Org. Chem. 2005; 70: 7892
• 22a Tripathy S, Hussain H, Durst T. Tetrahedron Lett. 2000; 41: 8401
• 22b Wiberg KB, Sklenak S, Bailey WF. J. Org. Chem. 2000; 65: 2014
• 22c Hamura T, Chuda Y, Nakatsuji Y, Suzuki K. Angew. Chem. Int. Ed. 2012; 51: 3368
• 23a Dillinger S, Bertus P, Pale P. Org. Lett. 2001; 3: 1661
• 23b Yao XQ, Li CJ. Org. Lett. 2005; 7: 4395
• 24 Silver phenylacetylide is an insoluble off-white powder which was found in the reaction mixture after the reaction.
• 25a Rosevear DT, Stone FG. A. J. Chem. Soc. A 1968; 164
• 25b Mcloughlin VC. R, Thrower J. Tetrahedron 1969; 25: 5921
• 25c Mcbride DW, Stafford SL, Stone FG. A. J. Chem. Soc. 1963; 723

For SET of R_fI to give R_f radicals, see:
• 26a Nagib DA, Scott ME, MacMillan DW. C. J. Am. Chem. Soc. 2009; 131: 10875
• 26b Herrmann AT, Smith LL, Zakarian A. J. Am. Chem. Soc. 2012; 134: 6976
• 26c Ye Y, Sanford MS. J. Am. Chem. Soc. 2012; 134: 9034

For radical atom transfer of R_fI to alkenes, see:
• 27a Haszeldine RN. J. Chem. Soc. 1949; 2856
• 27b Fuchikami T, Ojima I. Tetrahedron Lett. 1984; 25: 303
• 27c Amato C, Naud C, Calas P, Commeyras A. J. Fluorine Chem. 2002; 113: 55
• 28 Luo Y.-R. Comprehensive Handbook of Chemical Bond Energies. CRC Press; Boca Raton: 2007
• 29 CF₃I was dissolved and stored in a refrigerator with the exclusion of light. This stock solution is stable and could be readily diluted in situ to the desired concentration before use.

For the synthesis and reactivity of indolyne, see:
• 30a Im GY. J, Bronner SM, Goetz AE, Paton RS, Cheong PH. Y, Houk KN, Garg NK. J. Am. Chem. Soc. 2010; 132: 17933
• 30b Bronner SM, Goetz AE, Garg NK. J. Am. Chem. Soc. 2011; 133: 3832
• 31a Ametamey SM, Honer M, Schubiger PA. Chem. Rev. 2008; 108: 1501
• 31b Littich R, Scott PJ. H. Angew. Chem. Int. Ed. 2012; 51: 1106
• 31c Tredwell M, Gouverneur V. Angew. Chem. Int. Ed. 2012; 51: 11426

For fluorination of metal–aryne complexes, see:
• 32a Wang K, Yun SY, Mamidipalli P, Lee D. Chem. Sci. 2013; 4: 3205
• 32b Milner PJ, Kinzel T, Zhang Y, Buchwald SL. J. Am. Chem. Soc. 2014; 136: 15757

For insertion of aryne into Sn–F bonds, see:
• 32c Yoshida H, Yoshida R, Takaki K. Angew. Chem. Int. Ed. 2013; 52: 8629

For fluorination of arynes using Bu₄NF(t-BuOH)₄, see:
• 32d Ikawa T, Masuda S, Nishiyama T, Takagi A, Akai S. Aust. J. Chem. 2014; 67: 475
• 33a Grushin VV, Marshall WJ. Organometallics 2008; 27: 4825
• 33b Kolomeitsev AA, Vorobyev M, Gillandt H. Tetrahedron Lett. 2008; 49: 449
• 33c Diemer V, Garcia JS, Leroux FR, Colobert F. J. Fluorine Chem. 2012; 134: 146
• 34a Jeganmohan M, Cheng CH. Chem. Commun. 2006; 2454
• 34b Yoshida H, Asatsu Y, Mimura Y, Ito Y, Ohshita J, Takaki K. Angew. Chem. Int. Ed. 2011; 50: 9676
• 34c Yoshida H, Ito Y, Ohshita J. Chem. Commun. 2011; 47: 8512
• 34d Niu D, Hoye TR. Nat. Chem. 2014; 6: 34
• 35a Wittig G, Pieper G, Fuhrmann G. Ber. Dtsch. Chem. Ges. 1940; 73: 1193
• 35b Pawlas J, Begtrup M. Org. Lett. 2002; 4: 2687
• 36 Reich HJ, Green DP, Phillips NH. J. Am. Chem. Soc. 1989; 111: 3444
• 37 The nucleophilic attack of aryne from these anions was confirmed by observing corresponding byproducts in the reaction mxture.
• 38a Friedman L. J. Am. Chem. Soc. 1967; 89: 3071
• 38b Xie C, Liu L, Zhang Y, Xu P. Org. Lett. 2008; 10: 2393
• 39a Deprez NR, Sanford MS. Inorg. Chem. 2007; 46: 1924
• 39b Zhdankin VV, Stang PJ. Chem. Rev. 2008; 108: 5299
• 39c Phipps RJ, Gaunt MJ. Science (Washington, D. C.) 2009; 323: 1593
• 40 For another recent work using diaryliodoniums as Lewis acids, see: Zhang Y , Han J, Liu Z.-J. RSC Adv. 2015; 5: 25485
• 41a Wittig G, Clauss K. Liebigs Ann. Chem. 1952; 578: 136
• 41b Beringer FM, Chang LL. J. Org. Chem. 1972; 37: 1516

Ar₂I⁺OTf^– are known to react with F^– to give corresponding ArF at elevated temperatures (typically over 50 °C), see:
• 42a Shah A, Pike VW, Widdowson DA. J. Chem. Soc., Perkin Trans. 1 1998; 2043
• 42b Ross TL, Ermert J, Hocke C, Coenen HH. J. Am. Chem. Soc. 2007; 129: 8018

For the synthesis and application of Ph₂IF, see:
• 43a Emeleus HJ, Heal HG. J. Chem. Soc. 1946; 1126
• 43b Chen KC, Koser GF. J. Org. Chem. 1991; 56: 5764
• 43c Wang BJ, Cerny RL, Uppaluri S, Kempinger JJ, DiMagno SG. J. Fluorine Chem. 2010; 131: 1113
• 44 Further analysis of this saturated solution by ¹⁹F NMR reveals that the ratio of F^– to Ph₂I⁺ is about 0.75:1.
• 45 The formation of the ate complex is very facile, even faster than intermolecular proton abstration. See: Tripathy S, LeBlanc R, Durst T. Org. Lett. 1999; 1: 1973
• 46 CH₂CN^– is known to react with MeCN to generate a dimer (trans-3-aminobut-2-enenitrile), see: Christe KO, Wilson WW, Wilson RD, Bau R, Feng JA. J. Am. Chem. Soc. 1990; 112: 7619
• 47a Hansch C, Leo A, Taft RW. Chem. Rev. 1991; 91: 165
• 47b Smart BE. J. Fluorine Chem. 2001; 109: 3

For electrophilic trifluoromethylthiolation of arenes, see:
• 48a Sheppard WA. J. Org. Chem. 1964; 29: 895
• 48b Andreades S, Sheppard WA, Harris JF. J. Org. Chem. 1964; 29: 898
• 48c Scribner RM. J. Org. Chem. 1966; 31: 3671
• 48d Croft TS, Mcbrady JJ. J. Heterocycl. Chem. 1975; 12: 845
• 48e Haas A, Niemann U. Chem. Ber. 1977; 110: 67
• 48f Gerstenberger MR. C, Haas A. J. Fluorine Chem. 1983; 23: 525
• 48g Baert F, Colomb J, Billard T. Angew. Chem. Int. Ed. 2012; 51: 10382

For nucleophilic trifluoromethylthiolation of arenes, see:
• 48h Tavener SJ, Adams DJ, Clark JH. J. Fluorine Chem. 1999; 95: 171
• 48i Kolomeitsev A, Medebielle M, Kirsch P, Lork E, Roschenthaler GV. J. Chem. Soc., Perkin Trans. 1 2000; 2183

For recent examples of transition-metal-mediated Ar–SCF₃ bond formation, see:
• 49a Teverovskiy G, Surry DS, Buchwald SL. Angew. Chem. Int. Ed. 2011; 50: 7312
• 49b Chen C, Xie Y, Chu LL, Wang RW, Zhang XG, Qing FL. Angew. Chem. Int. Ed. 2012; 51: 2492
• 49c Tran LD, Popov I, Daugulis O. J. Am. Chem. Soc. 2012; 134: 18237
• 49d Zhang C.-P, Vicic DA. J. Am. Chem. Soc. 2012; 134: 183
• 49e Shao X, Wang X, Yang T, Lu L, Shen Q. Angew. Chem. Int. Ed. 2013; 52: 3457
• 49f Weng Z, He W, Chen C, Lee R, Tan D, Lai Z, Kong D, Yuan Y, Huang KW. Angew. Chem. Int. Ed. 2013; 52: 1548
• 49g Yang YD, Azuma A, Tokunaga E, Yamasaki M, Shiro M, Shibata N. J. Am. Chem. Soc. 2013; 135: 8782
• 49h Pluta R, Nikolaienko P, Rueping M. Angew. Chem. Int. Ed. 2014; 53: 1650
• 49i Vinogradova EV, Muller P, Buchwald SL. Angew. Chem. Int. Ed. 2014; 53: 3125
• 49j Xu C, Shen Q. Org. Lett. 2014; 16: 2046
• 49k Jiang L, Qian J, Yi W, Lu G, Cai C, Zhang W. Angew. Chem. Int. Ed. 2015; 54: 14965

For the preparation and synthetic application of AgSCF₃, see:
• 50a Emeléus HJ, MacDuffie DE. J. Chem. Soc. 1961; 2597
• 50b Adams DJ, Tavener SJ, Clark JH. J. Fluorine Chem. 1998; 90: 87
• 50c Adams DJ, Clark JH. J. Org. Chem. 2000; 65: 1456
• 51 For the monotrifluoromethylthiolation of arynes, see: refs 32a and 33b.
• 52 Matsnev A, Noritake S, Nomura Y, Tokunaga E, Nakamura S, Shibata N. Angew. Chem. Int. Ed. 2010; 49: 572

For recent examples on electrophilic trifluoromethylation reagents, see:
• 53a Umemoto T, Ishihara S. J. Am. Chem. Soc. 1993; 115: 2156
• 53b Magnier E, Blazejewski JC, Tordeux M, Wakselman C. Angew. Chem. Int. Ed. 2006; 45: 1279
• 53c Noritake S, Shibata N, Nakamura S, Toru T, Shiro M. Eur. J. Org. Chem. 2008; 3465