Controlled Generation of 3-Triflyloxyarynes

Abstract

The efficient generation of 3-triflyloxyarynes, including those bearing a transformable group, through an iodine–magnesium exchange reaction of 1,3-bis(triflyloxy)-2-iodoarenes was achieved by using finely tuned reaction conditions that efficiently suppressed the competing thia-Fries rearrangement. The method enabled the facile synthesis of a wide range of multisubstituted arenes.

Key words

benzyne - arynes - Grignard reagent - halogen–metal exchange - thia-Fries rearrangement

• References

• 1 Hoffmann RW. Dehydrobenzene and Cycloalkynes . Academic Press; New York: 1967

For some recent reviews on arynes, see:
• 2a Dyke AM, Hester AJ, Lloyd-Jones GC. Synthesis 2006; 4093
• 2b Bronner SM, Goetz AE, Garg NK. Synlett 2011; 2599
• 2c Yoshida H, Takaki K. Synlett 2012; 1725
• 2d Bhunia A, Yetra SR, Biju AT. Chem. Soc. Rev. 2012; 41: 3140
• 2e Gampe CM, Carreira EM. Angew. Chem. Int. Ed. 2012; 51: 3766
• 2f Tadross PM, Stoltz BM. Chem. Rev. 2012; 112: 3550
• 2g Pérez D, Peña D, Guitián E. Eur. J. Org. Chem. 2013; 5981
• 2h Dubrovskiy AV, Markina NA, Larock RC. Org. Biomol. Chem. 2013; 11: 191
• 2i Goetz AE, Garg NK. J. Org. Chem. 2014; 79: 846
• 2j Goetz AE, Shah TK, Garg NK. Chem. Commun. 2015; 51: 34
• 2k Miyabe H. Molecules 2015; 20: 12558
• 2l Yoshida S, Hosoya T. Chem. Lett. 2015; 44: 1450

For some recent aryne chemistries, see:
• 3a Smith III AB, Kim W.-S. Proc. Natl. Acad. Sci. U.S.A. 2011; 108: 6787
• 3b Allan KM, Gilmore CD, Stoltz BM. Angew. Chem. Int. Ed. 2011; 50: 4488
• 3c Candito DA, Dobrovolsky D, Lautens M. J. Am. Chem. Soc. 2012; 134: 15572
• 3d Hamura T, Chuda Y, Nakatsuji Y, Suzuki K. Angew. Chem. Int. Ed. 2012; 51: 3368
• 3e Hoye TR, Baire B, Niu D, Willoughby PH, Woods BP. Nature 2012; 490: 208
• 3f Yoshida S, Hosoya T. Chem. Lett. 2013; 42: 583
• 3g Yun SY, Wang K.-P, Lee N.-K, Mamidipalli P, Lee D. J. Am. Chem. Soc. 2013; 135: 4668
• 3h Yoshida H, Yoshida R, Takaki K. Angew. Chem. Int. Ed. 2013; 52: 8629
• 3i Sumida Y, Kato T, Hosoya T. Org. Lett. 2013; 15: 2806
• 3j Bhojgude SS, Thangaraj M, Suresh E, Biju AT. Org. Lett. 2014; 16: 3576
• 3k Liu F.-L, Chen J.-R, Zou Y.-Q, Wei Q, Xiao W.-J. Org. Lett. 2014; 16: 3768
• 3l Yoshida S, Uchida K, Hosoya T. Chem. Lett. 2014; 43: 116
• 3m Pandya VG, Mhaske SB. Org. Lett. 2014; 16: 3836
• 3n Sumida Y, Harada R, Kato-Sumida T, Johmoto K, Uekusa H, Hosoya T. Org. Lett. 2014; 16: 6240
• 3o Mizukoshi Y, Mikami K, Uchiyama M. J. Am. Chem. Soc. 2015; 137: 74
• 3p Yoshida S, Karaki F, Uchida K, Hosoya T. Chem. Commun. 2015; 51: 8745
• 3q Li H.-Y, Xing L.-J, Lou M.-M, Wang H, Liu R.-H, Wang B. Org. Lett. 2015; 17: 1098
• 3r Pawliczek M, Garve LK. B, Werz DB. Org. Lett. 2015; 17: 1716
• 3s Chen Y, Willis MC. Org. Lett. 2015; 17: 4786
• 3t Yoshida S, Hazama Y, Sumida Y, Yano T, Hosoya T. Molecules 2015; 20: 10131
• 3u Yoshida S, Shimomori K, Nonaka T, Hosoya T. Chem. Lett. 2015; 44: 1324
• 3v Yoshida S, Yano T, Misawa Y, Sugimura Y, Igawa K, Shimizu S, Tomooka K, Hosoya T. J. Am. Chem. Soc. 2015; 137: 14071
• 3w Demory E, Devaraj K, Orthaber A, Gates PJ, Pilarski LT. Angew. Chem. Int. Ed. 2015; 54: 11765
• 3x Holden CM, Sohel SM. A, Greaney MF. Angew. Chem. Int. Ed. 2016; 55: 2450
• 4a Matsumoto T, Sohma T, Hatazaki S, Suzuki K. Synlett 1993; 843
• 4b Akai S, Ikawa T, Takayanagi S, Morikawa Y, Mohri S, Tsubakiyama M, Egi M, Wada Y, Kita Y. Angew. Chem. Int. Ed. 2008; 47: 7673
• 4c 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: 5674
• 4d Bronner SM, Mackey JL, Houk KN, Garg NK. J. Am. Chem. Soc. 2012; 134: 13966
• 4e Ikawa T, Takagi A, Goto M, Aoyama Y, Ishikawa Y, Itoh Y, Fujii S, Tokiwa H, Akai S. J. Org. Chem. 2013; 78: 2965
• 4f Ikawa T, Urata H, Fukumoto Y, Sumii Y, Nishiyama T, Akai S. Chem. Eur. J. 2014; 20: 16228
• 4g Ikawa T, Masuda S, Takagi A, Akai S. Chem. Sci. 2016; 7: 5206
• 5a Ikawa T, Takagi A, Kurita Y, Saito K, Azechi K, Egi M, Kakiguchi K, Kita Y, Akai S. Angew. Chem. Int. Ed. 2010; 49: 5563
• 5b Takagi A, Ikawa T, Saito K, Masuda S, Itoh T, Akai S. Org. Biomol. Chem. 2013; 11: 8145
• 6a Leroux F, Schlosser M. Angew. Chem. Int. Ed. 2002; 41: 4272
• 6b Charmant JP, Dyke AM, Lloyd-Jones GC. Chem. Commun. 2003; 39: 380
• 6c Ramúez A, Candler J, Bashore CG, Wirtz MC, Coe JW, Collum DB. J. Am. Chem. Soc. 2004; 126: 14700
• 6d Rao UN, Maguire J, Biehl E. ARKIVOC 2004; (i): 88
• 6e Hamura T, Arisawa T, Matsumoto T, Suzuki K. Angew. Chem. Int. Ed. 2006; 45: 6842
• 6f Arisawa T, Uekusa H, Hamura T, Matsumoto T, Suzuki K. Synlett 2008; 1179
• 6g Dyke FA. M, Gill DM, Harvey JN, Hester AJ, Lloyd-Jones GC, Muñoz MP, Shepperson IR. Angew. Chem. Int. Ed. 2008; 47: 5067
• 6h Nagashima Y, Takita R, Yoshida K, Hirano K, Uchiyama M. J. Am. Chem. Soc. 2013; 135: 18730
• 6i Hall C, Henderson JL, Ernouf G, Greaney MF. Chem. Commun. 2013; 49: 7602
• 6j Medina JM, Mackey JL, Garg NK, Houk KN. J. Am. Chem. Soc. 2014; 136: 15798
• 6k Riggs JC, Ramirez A, Cremeens ME, Bashore CG, Candler J, Wirtz MC, Coe JW, Collum DB, Picazo E, Houk KN, Garg NK. Tetrahedron Lett. 2015; 56: 3511
• 7a Yoshida S, Uchida K, Igawa K, Tomooka K, Hosoya T. Chem. Commun. 2014; 50: 15059
• 7b Shi J, Qiu D, Wang J, Xu H, Li Y. J. Am. Chem. Soc. 2015; 137: 5670
• 7c Ikawa T, Kaneko H, Masuda S, Ishitsubo E, Tokiwa H, Akai S. Org. Biomol. Chem. 2015; 13: 520
• 8a Yoshida S, Nonaka T, Morita T, Hosoya T. Org. Biomol. Chem. 2014; 12: 7489
• 8b Yoshida S, Uchida K, Hosoya T. Chem. Lett. 2015; 44: 691
• 8c Yoshida S, Morita T, Hosoya T. Chem. Lett. 2016; 45: 726
• 9 NBO analyses of 3-methoxybenzyne 2b-B and 3-triflyloxybenzyne 2a-A were also performed in reference 7c, indicating the higher electron-deficient nature of 3-triflyloxybenzyne (2a) compared with 3-methoxybenzyne (2b).
• 10 A suspension of (trimethylsilylmethyl)magnesium chloride–lithium chloride complex was prepared by adding an equimolar amount of (trimethylsilylmethyl)lithium (pentane solution) to a suspension of magnesium chloride in a solvent at 0 °C and the mixture was stirred for 30 min.
• 11 Treatment of 4,6-di(tert-butyl)-substituted substrate 3f with a silylmethyl Grignard reagent resulted in thia-Fries rearrangement reaction along with the desired aryne generation, suggesting that the bulky tert-butyl group adjacent to the triflyloxy group facilitated the thia-Fries rearrangement.
• 12 Bozzo C, Pujol MD. Synlett 2000; 550
• 13a Littke AF, Dai C, Fu GC. J. Am. Chem. Soc. 2000; 122: 4020
• 13b Espino G, Kurbangalieva A, Brown JM. Chem. Commun. 2007; 1742