One-Pot Enol Silane Formation–Allylation of Ketones Promoted by Trimethylsilyl Trifluoromethanesulfonate

In memory of Professor David A. Evans

Abstract

Ketones and related substrate classes undergo enol silane formation in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and triethylamine, reaction conditions that also promote the in situ ionization of allyl propionates. When these two processes are performed in one pot, allylation of the ketone is observed in high yields. Aldehydes, esters, and thioesters also serve as enol silane precursors under these conditions. When unsymmetrical allyl cations are employed, regioselectivity depends upon the electronic and steric properties of the substituents.

Key words

allylation - enol silane - one pot - alkylation - silyl triflates - Lewis acid catalysis - regioselectivity

• References

• 1a Matsuda I, Wakamatsu S, Komori K, Makino T, Itoh K. Tetrahedron Lett. 2002; 43: 1043
• 1b Tandiary MA, Asano M, Hattori T, Takehira S, Masui Y, Onaka M. Tetrahedron Lett. 2017; 58: 1925
• 2 Umeda R, Takahashi Y, Yamamoto T, Iseki H, Osaka I, Nishiyama Y. J. Organomet. Chem. 2018; 877: 92
• 3a Zhang G.-M, Zhang H, Wang B, Wang J.-Y. RSC Adv. 2021; 11: 17025
• 3b Cheng H.-G, Feng B, Chen L.-Y, Guo W, Yu X.-Y, Lu L.-Q, Chen J.-R, Xiao W.-J. Chem. Commun. 2014; 50: 2873
• 4a Koppolu SR, Naveen N, Balamurugan R. J. Org. Chem. 2014; 79: 6069
• 4b Naveen N, Koppolu SR, Balamurugan R. Adv. Synth. Catal. 2015; 357: 1463
• 4c Perez JM, Maquilon C, Ramon DJ, Baeza A. Asian J. Org. Chem. 2017; 6: 1440
• 5a Fereyduni E, Sanders JN, Gonzalez G, Houk KN, Grenning AJ. Chem. Sci. 2018; 9: 8760
• 5b Sebesta R, Skvorcova A, Horvath B. Tetrahedron: Asymmetry 2010; 21: 1910
• 5c Jayakumar S, Prakash M, Balaraman K, Kesavan V. Eur. J. Org. Chem. 2014; 606
• 5d Le H, Batten A, Morken JP. Org. Lett. 2014; 16: 2096
• 5e Sobie KM, Albritton M, Yang Y, Alves MM, Roitberg A, Grenning AJ. Chem. Sci. 2022; 13: 1951
• 5f Wang W, Xiong Q, Gong L, Wang Y, Liu J, Lan Y, Zhang X. Org. Lett. 2020; 22: 5479
• 6 Wang J, Huang W, Zhang Z, Xiang X, Liu R, Zhou X. J. Org. Chem. 2009; 74: 3299
• 7 Yang H, Fang L, Zhang M, Zhu C. Eur. J. Org. Chem. 2009; 666
• 8 Umeda R, Jikyo T, Toda K, Osaka I, Nishiyama Y. Tetrahedron Lett. 2018; 59: 1121
• 9a Downey CW, Confair DN, Liu Y, Heafner ED. J. Org. Chem. 2018; 83: 12931
• 9b Sklar DE, Helbling AV, Liu Y, Downey CW. Tetrahedron Lett. 2021; 87: 153424
• 10 Similar biases have been observed in related systems. See references 5–8.
• 11 In cases of 1,3-diaryl-substituted electrophiles the identity of the major regioisomer was established unambiguously by NOESY.
• 12 For the use of a related methyl ether as an alkylating agent under similar conditions see: Downey CW, Covington SE, Obenschain DE, Halliday E, Rague JT, Confair DN. Tetrahedron Lett. 2014; 55: 5213

For the reduction of acetals by i-Pr₂NEt in the presence of TMSOTf, see:
• 13a Downey CW, Fleisher AS, Rague JT, Safran CL, Venable ME, Pike RD. Tetrahedron Lett. 2011; 52: 4756

For the reduction of nitrones by i-Pr₂NEt in the presence of TMSOTf, see:
• 13b Downey CW, Dombrowski CM, Maxwell EN, Safran CL, Akomah OA. Eur. J. Org. Chem. 2013; 5716
• 13c For the deoxygenation of β-silyloxy aldehydes by i-Pr₂NEt in the presence of TMSOTf, see: Dixon, G. J.; Rodriguez, M. R.; Chong, T. G.; Kim, K. Y.; Downey, C. W. J. Org. Chem. 2022, 87, 14846.
• 14 Pangborn AB, Giardello MA, Grubbs RH, Rosen RK, Timmers FJ. Organometallics 1996; 15: 1518
• 15 For a synthesis of this compound and accompanying spectra, see: Thompson BB, Montgomery J. Org. Lett. 2011; 13: 3289
• 16 For a synthesis of this compound and accompanying spectra, see ref. 4a.
• 17 For a synthesis of this compound and accompanying spectra, see: Gan K, Ng JS, Sadeer A, Pullarkat SA. Synlett 2016; 27: 254
• 18 For a synthesis of this compound and accompanying spectra, see: Doerr AA, Lubell WD. Can. J. Chem. 2007; 85: 1006
• 19 A search of the literature revealed no previous syntheses of this compound.
• 20 For a synthesis of this compound and accompanying spectra, see: Li C, Xing J, Zhao J, Huynh P, Zhang W, Jiang P, Zhang YJ. Org. Lett. 2012; 14: 390
• 21 For a synthesis and accompanying spectra of one unidentified diastereomer, see: Huang, X.-F.; Salman, M.; Huang, Z.-Z. Chem. Eur. J. 2014, 20, 6618. While the ¹³C NMR spectrum in this report matches our experimental results, the ¹H NMR data recorded do not align perfectly with our data, most notably the methyl doublet reported by Huang et al. at δ = 0.95.
• 22 For a synthesis of this compound and accompanying spectra, see: Xu L.-W, Gao G, Gu F.-L, Sheng H, Li L, Lai G.-Q, Jiang J.-X. Adv. Synth. Catal. 2010; 352: 1441
• 23 For a synthesis of this compound and accompanying spectra, see: Roscales S, Rincon A, Buxaderas E, Csaky AG. Tetrahedron Lett. 2012; 53: 4721
• 24 For a synthesis of this compound and accompanying spectra, see: Sugiura M, Tokudomi M, Nakajima M. Chem. Commun. 2010; 46: 7799
• 25 For a synthesis of this compound and accompanying spectra, see: Magrez-Chiquet M, Morin MS. T, Wencel-Delord J, Drissi Amraoui S, Basle O, Alexakis A, Crevisy C, Mauduit M. Chem. Eur. J. 2013; 19: 13663
• 26 Tao J.-J, Tang J.-D, Hong T, Ye J.-W, Chen J.-Y, Xie C, Zhang Z, Li S. ACS Omega 2021; 6: 35093