Low-Temperature Intermolecular Addition of RCF₂Li Compounds to Various Carbonyl Electrophiles for a Practical Synthesis of CF₂-Containing Building Blocks

This article is dedicated to the memory of Prof. Jean F. Normant and in tribute to his outstanding contribution to the field of organometallic chemistry.

Abstract

The addition of various RCF₂Li compounds to a wide range of carbonyl electrophiles (aldehydes, ketones, acylsilanes, esters, and lactones) is reported. The reaction proceeds at very low temperature under Barbier conditions through a Br/Li exchange from the corresponding RCF₂Br compounds. In contrast with existing methods that use more stable, but less reactive, organometallic species, there is efficient addition to esters, lactones and poorly reactive ketones.

Key words

fluorine - organolithium - carbenoid - acylsilanes - ketones - esters - lactones

• References

• 1a Kokotos CG, Baskakis C, Kokotos G. J. Org. Chem. 2008; 73: 8623
• 1b Cregge RJ, Curran TT, Metz WA. J. Fluorine Chem. 1998; 88: 71
• 1c Uno H, Shiraishi Y, Matsushima Y, Yayama A, Suzuki H. Bull. Chem. Soc. Jpn. 1991; 64: 842
• 1d Stahly GP, Jackson A. J. Org. Chem. 1991; 56: 5472
• 1e Uno H, Shiraishi Y, Suzuki H. Bull. Chem. Soc. Jpn. 1989; 62: 2636
• 1f Gassman PG, O’Reilly NJ. J. Org. Chem. 1987; 52: 2481
• 1g Uno H, Shiraishi Y, Simokawa K, Suzuki H. Chem. Lett. 1987; 1153
• 1h Gassman PG, O’Reilly NJ. Tetrahedron Lett. 1985; 26: 5243
• 2a Xue C, He G, Fu C, Xue L, Lin Z, Ma S. Eur. J. Org. Chem. 2010; 7012
• 2b Kvicala J, Mouyrin J.-C, Paleta O. J. Fluorine Chem. 2002; 113: 195
• 2c Moreau P, Naji N, Commeyras A. J. Fluorine Chem. 1987; 34: 421
• 2d Chen LS, Chen GJ, Ryan MT, Tamborski C. J. Fluorine Chem. 1987; 34: 299
• 2e Chemn LS, Chen GJ, Tamborski C. J. Fluorine Chem. 1984; 26: 341
• 2f Henne AL, Francis WC. J. Am. Chem. Soc. 1953; 75: 992
• 3a Wang Z, Hammond GB. Tetrahedron Lett. 2000; 41: 2339
• 3b Shen Y, Qi M. J. Fluorine Chem. 1994; 66: 175
• 3c Yang Z.-Y, Burton DJ. J. Org. Chem. 1991; 56: 1037
• 3d Yang Z.-Y, Burton DJ. J. Fluorine Chem. 1989; 44: 339
• 3e Kitazume T, Ikeya T. J. Org. Chem. 1988; 53: 2349
• 3f Hanzawa Y, Inazawa K, Kon A, Aoki H, Kobayashi Y. Tetrahedron Lett. 1987; 28: 659
• 3g Kitazume T, Ishikawa N. J. Am. Chem. Soc. 1985; 107: 5186
• 3h O’Reilly NJ, Maruta M, Ishikawa N. Chem. Lett. 1984; 517
• 4a Fujiu M, Nakamura Y, Serizawa H, Aikawa K, Ito S, Mikami K. Eur. J. Org. Chem. 2012; 7043
• 4b Arimitsu S, Jacobsen JM, Hammond GB. Tetrahedron Lett. 2007; 48: 1625
• 4c Xu B, Mashuta MS, Hammond GB. Angew. Chem. Int. Ed. 2006; 45: 7265
• 4d Arimitsu S, Hammond GB. J. Org. Chem. 2006; 71: 8665
• 4e Kirihara M, Takuwa T, Takizawa S, Momose T, Nemoto H. Tetrahedron 2000; 56: 8275
• 4f Wang Z, Hammond GB. J. Org. Chem. 2000; 65: 6547
• 4g Wang Z, Hammond GB. Chem. Commun. 1999; 2545
• 4h Qing F.-L, Wan D.-P. Tetrahedron 1998; 54: 14189
• 4i Kirihara M, Takuwa T, Takizawa S, Momose T. Tetrahedron Lett. 1997; 38: 2853

For fluoroalkylzincate and cuprate additions, see:
• 5a Wang X, Hirano K, Kurauchi D, Kato H, Toriumi N, Takita R, Uchiyama M. Chem. Eur. J. 2015; 21: 10993
• 5b Kosobokov MD, Levin VV, Zemtsov AA, Struchkova MI, Korlyukov AA, Arkhipov DE, Dilman AD. Org. Lett. 2014; 16: 1438
• 6 In contrast, Professor Normant demonstrated the synthetic utility of α-fluorovinyllithium reagents, despite stability issues as well, see: Normant J.-F. J. Organomet. Chem. 1990; 400: 19
• 7a Chen Z.-H, Wang B.-L, Kale AJ, Moore BS, Wang R.-W, Qing F.-L. J. Fluorine Chem. 2012; 136: 13
• 7b Jiang S, Singh G, Batsanov AS. Tetrahedron: Asymmetry 2000; 11: 3873
• 7c Seyferth D, Simon RM, Sepelak DJ, Klein HA. J. Am. Chem. Soc. 1983; 105: 4634
• 7d Seyferth D, Simon RM, Sepelak DJ. J. Org. Chem. 1980; 45: 2273
• 7e Seyferth D, Wursthorn KR. J. Organomet. Chem. 1979; 182: 455
• 7f Seyferth D, Wursthorn KR. J. Organomet. Chem. 1977; 137: C17
• 8a Konno T, Takano S, Takahashi Y, Konishi H, Tanaka Y, Ishihara T. Synthesis 2011; 33
• 8b Bonnac L, Lee SE, Giuffredi GT, Elphick LM, Anderson AA, Child ES, Mann DJ, Gouverneur V. Org. Biomol. Chem. 2010; 8: 1445
• 8c Linclau B, Boydell AJ, Timofte RS, Brown KJ, Vinader V, Weymouth-Wilson AC. Org. Biomol. Chem. 2009; 7: 803
• 8d Timofte RS, Linclau B. Org. Lett. 2008; 10: 3673
• 9 For the stabilization of perfluoroalkyllithium reagents thanks to flow chemistry conditions, see: Nagaki A, Tokuoka S, Yamada S, Tomida Y, Oshiro K, Amii H, Yoshida J.-I. Org. Biomol. Chem. 2011; 9: 7559
• 10 Shimizu M, Yamada N, Takebe Y, Hata T, Kuroboshi M, Hiyama T. Bull. Chem. Soc. Jpn. 1998; 71: 2903
• 11 Shimizu M, Takebe Y, Kuroboshi M, Hiyama T. Tetrahedron Lett. 1996; 37: 7387
• 12 Köbrich G, Akhtar A, Ansari F, Breckoff WE, Büttner H, Drischel W, Fischer RH, Flory K, Fröhlich H, Goyert W, Heinemann H, Hornke I, Merkle HR, Trapp H, Zündorf W. Angew. Chem. Int. Ed. 1967; 6: 41
• 13a Saadi J, Akakura M, Yamamoto H. J. Am. Chem. Soc. 2011; 133: 14248
• 13b Nakagawa M, Saito A, Soga A, Yamamoto N, Taguchi T. Tetrahedron Lett. 2005; 46: 5257
• 13c Shinokubo H, Oshima K, Utimoto K. Tetrahedron Lett. 1993; 34: 4985
• 14 Kelly CB, Mercadante MA, Leadbeater NE. Chem. Commun. 2013; 49: 11133
• 15 Bégué J.-P, Bonnet-Delpon D. Bioorganic and Medicinal Chemistry of Fluorine . John Wiley & Sons; Hoboken: 2008
• 16 Doussot P, Portella C. J. Org. Chem. 1993; 58: 6675
• 17 Dondy B, Doussot P, Portella C. Synthesis 1992; 995
• 18 Decostanzi M, Van Der Lee A, Campagne J.-M, Leclerc E. Adv. Synth. Catal. 2015; 357: 3091