Radical Alkylations of Alkyl Halides and Unactivated C-H Bonds Using Vinyl Triflates

Abstract

Radical alkylations of activated alkyl iodides and bromides were achieved using vinyl triflates in the presence of hexadimethyltin, whereas those of unactivated C-H bonds using vinyl triflates proceeded cleanly under tin-free conditions.

Key words

alkylation - radical reaction - ketone - vinyl triflate

References and Notes

• 1a House HO. Modern Synthetic Reactions   Benjamin WA. Menlo Park; CA: 1972.  Chap. 9.
• 1b Caine D. In Comprehensive Organic Synthesis   Trost BM. Fleming I. Pattenden G. Pergamon; Oxford: 1991.  Vol. 3. p.1-63  
• 1c Seebach D. Angew. Chem. Int. Ed.  1988,  27:  1624 
• 2 Kim S. In Radicals in Organic Synthesis   Vol 2.:  Renaud P. Sibi M. Wiley-VCH; Weinheim: 2001.  p.1-21  
• 3a Watanabe Y. Yoneda T. Ueno Y. Toru T. Tetrahedron Lett.  1990,  31:  6669 
• 3b Miura K. Fujisawa H. Saito D. Hosomi A. Org. Lett.  2001,  3:  2591 
• 4 Roepel MG. Tetrahedron Lett.  2002,  43:  1973 
• 5a Perkins MJ. Roberts BP. J. Chem. Soc., Perkin Trans.  1975,  2:  77 
• 5b Dang H.-S. Franchi P. Roberts BP. Chem. Commun.  2000,  499 
• 5c Fielding AJ. Franchi P. Roberts BP. Smits TM. J. Chem. Soc., Perkin Trans.  2002,  2:  155 
• 6a Kim S. Lim CJ. Song C. Chung W.-j. J. Am. Chem. Soc.  2002,  124:  14306 
• 6b Kim S. Lim CJ. Angew. Chem. Int. Ed.  2004,  43:  5378 
• 6c Song H.-J. Lim CJ. Lee S. Kim S. Chem. Commun.  2006,  2893 
• 7 Kim S. Lee JY. Synlett  2008,  49 
• 8a Ritter K. Synthesis  1993,  735 
• 8b Roth GP. Fuller CE. J. Org. Chem.  1989,  54:  4899 
• 8c Pridgen LN. Huang GK. Tetrahedron Lett.  1998,  39:  8421 
• 8d Limmert ME. Roy AH. Hartwig JF. J. Org. Chem.  2005,  70:  9364 
• 9a Huffman MA. Yasuda N. Synlett  1999,  471 
• 9b Baxter JM. Steinhubel D. Palucki M. Davies IW. Org. Lett.  2005,  7:  215 
• 10 Cui D.-M. Meng Q. Zheng J.-Z. Zhang C. Chem. Commun.  2009,  1577 
• 11a Wille U. J. Am. Chem. Soc.  2002,  124:  14 
• 11b Wille U. Org. Lett.  2000,  2:  3485 
• 12a Kim S. Kim S. Bull. Chem. Soc. Jpn.  2007,  80:  809 
• 12b Kim S. Kim S. Otsuka N. Ryu I. Angew. Chem. Int. Ed.  2005,  44:  6183 
• 12c Kim S. Lim CJ. Angew. Chem. Int. Ed.  2002,  41:  3265 
• For alkynylations, see:
• 13a Gong J. Fuchs PL. J. Am. Chem. Soc.  1996,  118:  4486 
• 13b Gong J. Fuchs PL. Tetrahedron Lett.  1997,  38:  787 
• For alkenylations, see:
• 13c Xiang J. Fuchs PL. J. Am. Chem. Soc.  1996,  118:  11986 
• 13d Xiang J. Jiang W. Gong J. Fuchs PL. J. Am. Chem. Soc.  1997,  119:  4123 
• 13e For allylation, see: Xiang J. Evarts J. Rivkin A. Curran DP. Fuchs PL. Tetrahedron Lett.  1998,  39:  4163 
• 14a Kharasch MS. Brown HC. J. Am. Chem. Soc.  1942,  64:  329 
• 14b Tabushi I. Hamuro J. Oda R. J. Org. Chem.  1968,  33:  2108 
• 15a Bentrude WG. Darnall KR. J. Am. Chem. Soc.  1968,  90:  3588 
• 15b Citterio A. Filippini L. Synthesis  1986,  473 
• 15c Kim S. Kim N. Chung W.-j. Cho CH. Synlett  2001,  937 
• 16 Akindele T. Yamada K.-I. Tomioka K. Acc. Chem. Res.  2009,  42:  345 ; and references cited therein

17

Typical procedure for radical alkylation of a carbonyl compound: A solution of iodomethyl phenylsulfone (56 mg, 0.2 mmol), vinyl triflate 7 (76 mg, 0.3 mmol), and hexamethylditin (33 mg, 0.1 mmol) in benzene (1 mL; 0.2 M in iodide) was degassed with nitrogen for 10 min, and the solution was then irradiated in a photochemical reactor (300 nm) for 5 h. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (EtOAc-hexane, 1:10) to give 1-phenyl-3-(phenylsulfonyl)propan-1-one (38 mg, 69%) as a colorless oil. ^¹H NMR (CDCl₃, 400 MHz): δ = 3.45-3.49 (m, 2 H), 3.52-3.56 (m, 2 H), 7.42-7.46 (m, 2 H), 7.55-7.57 (m, 3 H), 7.63-7.64 (m, 1 H), 7.88-7.94 (m, 4 H); ^¹³C NMR (CDCl₃, 100 MHz): δ = 31.3, 51.0, 127.9 (C2), 128.0 (C2), 128.7 (C2), 129.4 (C2), 133.7, 133.9, 135.8, 139.0, 195.3

18

Typical procedure for radical alkylation of an unactivated C-H bond: A solution of vinyl triflate 9 (76 mg, 0.3 mmol) and AIBN (5 mg, 0.03 mmol) in THF (1 mL) was degassed with nitrogen for 10 min, and the solution was heated at reflux (80 ˚C) for 9 h under nitrogen. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (EtOAc-hexane, 1:50) to give 16 (41 mg, 65%) as a colorless oil. ^¹H NMR (CDCl₃, 400 MHz): δ = 1.33 (t, J = 7.2 Hz, 3 H), 1.48-1.55 (m, 1 H), 1.84-1.92 (m, 2 H), 2.06-2.14 (m, 1 H), 2.94 (dd, J = 16.5, 5.7 Hz, 1 H), 3.10 (dd, J = 16.5, 7.1 Hz, 1 H), 3.67-3.73 (m, 1 H), 3.80-3.85 (m, 1 H), 4.29 (q, J = 7.2 Hz, 2 H), 4.26-4.32 (m, 1 H); ^¹³C NMR (CDCl₃, 100 MHz): δ = 13.9, 25.4, 31.4, 45.1, 62.4, 67.9, 74.3, 160.8, 192.6