Synlett, Table of Contents Synlett DOI: 10.1055/a-2720-9227 Letter Intramolecular Hydride Shift-Mediated Double C(sp3)–H Bond Functionalization of Conformationally Flexible Aliphatic Alkenylidene Malonates Authors Author Affiliations Sosuke Ando 1 Graduate School of Engineering, Department of Applied Chemistry, Tokyo University of Agriculture and Technology, Tokyo, Japan Masahiro Anada 2 Faculty of Pharmacy, Musashino University, Tokyo, Japan 3 Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan Shunsuke Sueki 2 Faculty of Pharmacy, Musashino University, Tokyo, Japan 3 Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan Kosho Makino 2 Faculty of Pharmacy, Musashino University, Tokyo, Japan 3 Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan Tomoko Kawasaki-Takasuka 1 Graduate School of Engineering, Department of Applied Chemistry, Tokyo University of Agriculture and Technology, Tokyo, Japan Keiji Mori 1 Graduate School of Engineering, Department of Applied Chemistry, Tokyo University of Agriculture and Technology, Tokyo, Japan Recommend Article Abstract Buy Article(opens in new window) All articles of this category(opens in new window) Abstract We report on a double C(sp3)–H bond functionalization from a substrate that has no conformational bias, an indispensable factor for achieving the sequential hydride shift process. By employing ZnBr2 as a promoter and low concentration conditions (0.025 M), the sequential hydride shift/cyclization process from alkenylidene malonates with no substituents on the linker proceeded smoothly, affording dicyclic piperidine derivatives in moderate to good chemical yields with excellent diastereoselectivities. Keywords KeywordsC–H bond functionalization - Redox process - Heterocycles - Hydride shift - Sequential reaction - Stereoselective reaction Full Text References References For recent reviews on C–H activation, see: 1a Godula K, Sames D. Science 2006; 312: 67 1b Bergman RG. Nature 2007; 446: 391 1c Alberico D, Scott ME, Lautens M. Chem Rev 2007; 107: 174 1d Davies HML, Manning JR. Nature 2008; 451: 417 1e Chen X, Engle KM, Wang D-H, Yu J-Q. Angew Chem Int Ed 2009; 48: 5094 1f Jazzar R, Hitce J, Renaudat A, Sofack-Kreutzer J, Baudoin O. Chem Eur J 2010; 16: 2654 1g Lyons TW, Sanford MS. Chem Rev 2010; 110: 1147 1h Davies HML, Du Bois J, Yu J-Q. Chem Soc Rev 2011; 40: 1855 1i Brückl T, Baxter RD, Ishihara Y, Baran PS. Acc Chem Res 2012; 45: 826 1j Qin Y, Lv J, Luo S. Tetrahedron Lett 2014; 55: 551 1k Davies HML, Morton D. J Org Chem 2016; 81: 343 See also, highlight on visible-light photocatalysis: 1l Hu X-Q, Chen J-R, Xiao W-J. Angew Chem Int Ed 2017; 56: 1960 For recent reviews on internal redox process, see: 2a Tobisu M, Chatani N. Angew Chem Int Ed 2006; 45: 1683 2b Peng B, Maulide N. Chem Eur J 2013; 19: 13274 2c Wang L, Xiao J. Adv Synth Catal 2014; 356: 1137 2d Haibach MC, Seidel D. Angew Chem Int Ed 2014; 53: 5010 2e Kwon SJ, Kim DY. Chem Rec 2016; 16: 1191 2f An X-D, Xiao J. Org Chem Front 2021; 8: 1364 2g Mori K. Bull Chem Soc Jpn 2022; 95: 296 2h Wang L, Xiao J. Org Chem Front 2022; 9: 5041 2i Mori K, Okawa H. Tetrahedron Lett 2022; 110: 154178 2j Shen Y-B, Hu F, Li S-S. Tetrahedron 2022; 127: 133089 For selected recent examples of internal redox reaction developed by our group, see: 3a Yoshida T, Mori K. Chem Commun 2018; 54: 12686 3b Tamura R, Kitamura E, Tustsumi R, Yamanaka M, Akiyama T, Mori K. Org Lett 2019; 21: 2383 3c Otawa Y, Mori K. Chem Commun 2019; 55: 13856 3d Yokoo K, Mori K. Org Lett 2020; 22: 244 3e Hoshino D, Mori K. Org Lett 2021; 23: 9403 3f Okawa H, Kawasaki-Takasuka T, Mori K. Org Lett 2024; 26: 1662 3g Amano K, Kawasaki-Takasuka T, Mori K. Org Lett 1824; 2024: 26 3h Koyama R, Anada M, Sueki S. et al. Chem Commun 2024; 60: 3822 3i Matsui W, Matsuno T, Takiguchi I. et al. Org Lett 2025; 27: 6198 For selected examples of the internal redox reactions, see: 4a Pastine SJ, McQuaid KM, Sames D. J Am Chem Soc 2005; 127: 12180 4b Zhang C, Kanta De C, Mal R, Seidel D. J Am Chem Soc 2008; 130: 416 4c McQuaid KM, Sames D. J Am Chem Soc 2009; 131: 402 4d Shinkai D, Murase H, Hata T, Urabe H. J Am Chem Soc 2009; 131: 3166 4e Vadola PA, Sames D. J Am Chem Soc 2009; 131: 16525 4f Zhou G, Zhang J. Chem Commun 2010; 46: 6593 4g Jurberg ID, Peng B, Wöstefeld E, Wasserloos M, Maulide N. Angew Chem Int Ed 2012; 51: 1950 4h Sugiishi T, Nakamura H. J Am Chem Soc 2012; 134: 2504 4i Vadola PA, Carrea I, Sames D. J Org Chem 2012; 77: 6689 4j Alajarin M, Bonillo B, Marin-Luna M, Sanchez-Andrada P, Vidal A. Chem Eur J 2013; 19: 16093 4k Richer MT, Breugst M, Platonova AY. et al. J Am Chem Soc 2014; 136: 6123 4l Shen Y-B, Li L-F, Xiao M-Y, Yang J-M, Liu Q, Xiao J. J Org Chem 2019; 84: 13935 4m Shen Y-B, Wang L-X, Sun Y-M. et al. J Org Chem 2020; 85: 1915 4n Hu F, Li X, Ding Z. et al. ACS Catal 2022; 12: 943 4o An X-D, Shao D-Y, Qiu B, Xiao J. Org Lett 2023; 25: 2432 4p Hu F, Sun Z, Pan M. et al. Green Chem 2023; 25: 5134 4q An X-D, Shao D-Y, Qiu B, Xiao J. Org Lett 2023; 25: 2432 4r Hu F, Sun Z, Pan M. et al. Green Chem 2023; 25: 5134 4s Dong Y, Hu F, Wu H. et al. Org Lett 2024; 26: 332 4t Shen Y-B, Zhuang Q-H, Wang X-L. et al. Green Chem 2024; 26: 11899 4u Shen Y-B, Wang X-L, Zhuang Q-H. et al. Org Chem Front 2025; 12: 591 For examples of the enantioselective internal redox reactions, see: 5a Murarka S, Deb I, Zhang C, Seidel D. J Am Chem Soc 2009; 131: 13226 5b Kang YK, Kim SM, Kim DY. J Am Chem Soc 2010; 132: 11847 5c Cao W, Liu X, Wang W, Lin L, Feng X. Org Lett 2011; 13: 600 5d Zhou G, Liu F, Zhang J. Chem Eur J 2011; 17: 3101 5e He Y-P, Du Y-L, Luo S-W, Gong LZ. Tetrahedron Lett 2011; 52: 7064 5f Chen L, Zhang L, Lv Z, Cheng J-P, Luo S. Chem Eur J 2012; 18: 8891 5g Zhang L, Chen L, Lv Z, Cheng J-P, Luo S. Chem Asian J 2012; 7: 2569 5h Jiao Z-W, Zhang S-Y, He C. et al. Angew Chem Int Ed 2012; 51: 8811 5i Kang YK, Kim DY. Adv Synth Catal 2013; 355: 3131 5j Suh CW, Woo SB, Kim DY, Asian J. Org Chem 2014; 3: 399 5k Kang YK, Kim DY. Chem Commun 2014; 50: 222 5l Suh CW, Kim DY. Org Lett 2014; 16: 5374 5m Yu J, Li N, Chen D-F, Luo S-W. Tetrahedron Lett 2014; 55: 2859 5n Cao W, Liu X, Guo J, Lin L, Feng X. Chem Eur J 2015; 21: 1632 5o Li J, Preinfalk A, Malide N. J Am Chem Soc 2019; 141: 143 See also, ref 6b For the double C(sp3)–H bond functionalization by sequential utilization of the internal redox reaction see: 6a Mori K, Kurihara K, Yabe S, Yamanaka M, Akiyama T. J Am Chem Soc 2014; 136: 3744 6b Mori K, Isogai R, Kamei Y, Yamanaka M, Akiyama T. J Am Chem Soc 2018; 140: 6203 6c Mori K, Umehara N, Akiyama T. Chem Sci 2018; 9: 7327 6d Kataoka M, Otawa Y, Ido N, Mori K. Org Lett 2019; 21: 9334 6e Yokoo K, Sakai D, Mori K. Org Lett 2020; 22: 5801 6f Nakamura I, Anada M, Sueki S, Makino K, Mori K. Adv Synth Catal 2023; 365: 502 6g See, also: Yamagishi R, Anada M, Sueki S. et al. Org Lett 2025; 27: 1961 7 Alkenylidene barbiturate having dimethyl groups at the allylic position, suitable for this study, could be synthesized (See, SI) 8a Matthews WS, Bares JE, Bartmess JE. et al. J Am Chem Soc 1975; 97: 7006 8b Arnett ED, Maroldo SG, Schilling SL, Harrelson JA. J Am Chem Soc 1984; 106: 6759 Supplementary Material Supplementary Material Supplementary Material (PDF) (opens in new window)
