Regiodivergent Asymmetric Conjugate Addition of 2-Furfuryl Ketones to Nitroalkenes Using Thiourea Organocatalysts

Abstract

We recently reported the asymmetric ε-regioselective conjugate addition of 2-furfuryl ketones to nitroalkenes utilizing a thiourea–pyrrolidine organocatalyst, resulting in good yields and enantioselectivities. In this study, we present a novel approach for the asymmetric α-regioselective conjugate addition of 2-furfuryl ketones to nitroalkenes using a thiourea–tertiary amine organocatalyst, which has not been previously documented. The reactions produced α-regioselective addition products in high yields and with excellent stereoselectivities. Thus, this work marks the first example of regiodivergent asymmetric conjugate addition of 2-furfuryl ketones to nitroalkenes.

Keywords

Organocatalyst - Asymmetric - Conjugate addition - Regiodivergent reaction - 2-Furfuryl ketones - Nitroalkene

Publication History

Received: 02 June 2025

Accepted after revision: 03 July 2025

Accepted Manuscript online:
03 July 2025

Article published online:
30 July 2025

• References


For reviews, see:
• 1a Ping L, Chung D-S, Bouffard J, Lee S-G. Chem Soc Rev 2017; 46: 4299
• 1b Nájera C, Beletskaya IP, Yus M. Chem Soc Rev 2019; 48: 4515
• 1c Huang H-Y, Benzai A, Shi X, Doucet H. Chem Rec 2021; 21: 343
• 1d Rodrigalvarez J, Haut FL, Martin R. JACS Au 2023; 3: 3270
• 2 For review, see: Viji M, Lanka S, Sim J. et al. Catalysts 2021; 11: 1013

For regiodivergent asymmetric reactions using metal catalysts, see:
• 3a Hénon H, Mauduit M, Alexakis A. Angew Chem Int Ed 2008; 47: 9122
• 3b Ye Y, Kim S-T, Jeong J, Baik MH, Buchwald SL. J Am Chem Soc 2019; 141: 3901
• 3c Bai X-Y, Zhao W, Sun X, Li B-J. J Am Chem Soc 2019; 141: 19870
• 3d Pan Q, Ping Y, Wang Y, Guo Y, Kong W. J Am Chem Soc 2021; 143: 10282
• 3e Yang P-F, Shu W. Angew Chem Int Ed 2022; 61: e202208018
• 3f Wang S, Shi L, Chen X-Y, Shu W. Angew Chem Int Ed 2023; 62: e202303795
• 3g Collins S, Sieber JD. Chem Commun 2023; 59: 10087

For regiodivergent asymmetric reactions using organocatalysts, see:
• 4a Zhong F, Luo J, Chen G-Y, Dou X, Lu Y. J Am Chem Soc 2012; 134: 10222
• 4b Zhan G, Du W, Chen Y-C. Chem Soc Rev 2017; 46: 1675
• 4c Liu J-Y, Yang X-C, Lu H, Gu Y-C, Xu P-F. Org Lett 2018; 20: 2190
• 4d Zhang C, Cheng Y, Li F, Luan Y, Li P, Li W. Adv Synth Catal 2020; 362: 1286
• 4e Yang W-L, Li W, Yang Z-T, Deng WP. Org Lett 2020; 22: 4026
• 4f Liu S-K, Chien P-H, Huang B-W, Han J-L. Org Biomol Chem 2023; 21: 4999
• 5 List B, Lerner RA, Barbas CF. J Am Chem Soc 2000; 122: 2395
• 6 Ahrendt KA, Borths CJ, MacMillan DWC. J Am Chem Soc 2000; 122: 4243

For reviews, see:
• 7a Dalko PI, Moisan L. Angew Chem Int Ed 2004; 43: 5138
• 7b Tsogoeva SB. Eur J Org Chem 2007; 2007: 1701
• 7c Dondoni A, Massi A. Angew Chem Int Ed 2008; 47: 4638
• 7d Lattanzi A. Chem Commun 2009; 1452
• 7e Gruttadauria M, Giacalone F, Noto R. Adv Synth Catal 2009; 351: 33
• 7f Yang H, Carter RG. Synlett 2010; 2010: 2827
• 7g Scheffler U, Mahrwald R. Chem Eur J 2013; 19: 14346
• 7h Joshi H, Singh VK, Asian J. Org Chem 2022; 11: e202100053
• 8a Okino T, Hoashi Y. Takemoto J Am Chem Soc 2003; 125: 12672
• 8b Fuerst DE, Jacobsen EN. J Am Chem Soc 2005; 127: 8964
• 8c Cao C-L, Ye M-C, Sun X-L, Tang Y. Org Lett 2006; 8: 2901
• 8d Miyabe H, Takemoto Y. Bull Chem Soc Jpn 2008; 81: 785
• 8e Yu F, Jin Z, Huang H, Ye T, Liang XY. Org Biomol Chem 2010; 8: 4767
• 8f Fang X, Wang CJ. Chem Commun 2014; 51: 1185
• 9 Li J-L, Yue C-Z, Chen P-Q, Xiao Y-C, Chen Y-C. Angew Chem Int Ed 2014; 53: 5449
• 10 Yang G-J, Du W, Chen Y-C. J Org Chem 2016; 81: 10056
• 11 Koda T, Akutsu H, Suzuki M. et al. Tetrahedron Lett 2025; 155: 155392
• 12 Hamza A, Schubert G, Pápai I. J Am Chem Soc 2006; 128: 13151