CuI-Catalyzed [3+2] Cycloaddition of Hindered Vinylidenebisphosphonates (VBP) with Azomethine Imines for Highly Regioselective Access to Dinitrogen-Heterobicycle-Containing Bisphosphonates

Abstract

A concise, atom-economic, and highly regioselective synthetic strategy for the construction of several dinitrogen-fused heterocycles bearing bisphosphonates by 1,3-dipolar cycloaddition reaction of azomethine imines with tetraethyl vinylidene-1,1-bisphosphonate in the presence of CuI in toluene media has been developed. The targeted compounds were obtained in good yields and with excellent regioselectivity. This method for the synthesis of gem-bisphosphonates (BPs) is particularly attractive due to features such as low cost, mild conditions, atom economy, high stereoselectivity, and potential biological activity of the product.

Key words

copper(I) catalysis - azomethine imines - 1,3-dipolar cyclo­addition - vinylidenebisphosphonate - dinitrogen-fused heterocycles - bisphosphonates

• References

• 1a Richers MT. Breugst M. Platonova AY. Ullrich A. Dieckmann A. Houk KN. Seidel D. J. Am. Chem. Soc. 2014; 136: 6123
• 1b Boomhoff M. Yadav AK. Appun J. Schneider C. Org. Lett. 2014; 16: 6236
• 2a Black DM. Delmas PD. Eastell R. Reid IR. Boonen S. Cauley JA. Cosman F. Lakatos P. Leung PC. Man Z. N. Engl. J. Med. 2007; 356: 1809
• 2b Black DM. Reid IR. Boonen S. Bucci-Rechtweg C. Cauley JA. Cosman F. Cummings SR. Hue TF. Lippuner K. Lakatos P. J. Bone Mineral Res. 2012; 27: 243
• 3a Reszka AA. Rodan GA. Mini Rev. Med. Chem. 2004; 4: 711
• 3b Schweitzer DH. Oostendorp-van de Ruit M. van der Pluijm G. Löwik CW. Papapoulos SE. J. Bone Mineral Res. 1995; 10: 956
• 4a Ebetino FH. Hogan A.-ML. Sun S. Tsoumpra MK. Duan X. Triffitt JT. Kwaasi AA. Dunford JE. Barnett BL. Oppermann U. Bone 2011; 49: 20
• 4b Kunzmann V. Bauer E. Wilhelm M. N. Engl. J. Med. 1999; 340: 737
• 5 Pazianas M. Abrahamsen B. Eiken PA. Eastell R. Russell RG. G. Osteoporosis Int. 2012; 23: 2693
• 6a Maksymowych WP. Curr. Med. Chem. Anti-Inflam. Anti-Allergy Agents 2002; 1: 15
• 6b Nugent RA. Murphy M. Schlachter ST. Dunn CJ. Smith RJ. Staite ND. Galinet LA. Shields SK. Aspar DG. Richard KA. Rohloff NA. J. Med. Chem. 1993; 36: 134
• 7a Fleisch H. Breast Cancer Res. 2001; 4: 30
• 7b Skarpos H. Osipov SN. Vorob’eva DV. Odinets IL. Lork E. Röschenthaler G.-V. Org. Biomol. Chem. 2007; 5: 2361
• 7c Drake MT. Clarke BL. Khosla S. Mayo Clin. Proc. 2008; 83: 1032
• 7d Cohen H. Alferiev IS. Mönkkönen J. Seibel MJ. Pinto T. Ezra A. Solomon V. Stepensky D. Sagi H. Ornoy A. Pharm. Res. 1999; 16: 1399
• 8 Bortolini O. Mulani I. De Nino A. Maiuolo L. Nardi M. Russo B. Avnet S. Tetrahedron 2011; 67: 5635
• 9 Chen X. Li X. Yuan J. Qu L. Wang S. Shi H. Tang Y. Duan L. Tetrahedron 2013; 69: 4047
• 10a Li G. Wu M. Kong D. Liu R. Zhou X. Liu F. New J. Chem. 2014; 38: 3350
• 10b Ferrer-Casal M. Barboza AP. Szajnman SH. Rodriguez JB. Synthesis 2013; 45: 2397
• 10c Nugent RA. Murphy M. Schlachter ST. Dunn CJ. Smith RJ. Staite ND. Galinet LA. Shields SK. Aspar DG. Richard KA. J. Med. Chem. 1993; 36: 134
• 11 Wu M. Li G. Liu F. Jiang J. Synthesis 2015; 47: 3783
• 12a Li Z. Yu H. Liu H. Zhang L. Jiang H. Wang B. Guo H. Chem. Eur. J. 2014; 20: 1731
• 12b Kosower E. Radkowsky A. Fairlamb A. Croft S. Neal R. Eur. J. Med. Chem. 1995; 30: 659
• 12c Boatman PD. Ogbu CO. Eguchi M. Kim H.-O. Nakanishi H. Cao B. Shea JP. Kahn M. J. Med. Chem. 1999; 42: 1367
• 12d Gardiner J. Abell AD. Tetrahedron Lett. 2003; 44: 4227
• 12e Liu B. Brandt JD. Moeller KD. Tetrahedron 2003; 59: 8515
• 13 Rodriguez J. Synthesis 2014; 46: 1129
• 14a Liang L. Huang Y. Org. Lett. 2016; 18: 2604
• 14b Yang Z.-W. Wang J.-F. Peng L.-J. You X.-L. Cui H.-L. Tetrahedron Lett. 2016; 57: 5219
• 15a Chen W. Yuan XH. Li R. Du W. Wu Y. Ding LS. Chen YC. Adv. Synth. Catal. 2006; 348: 1818
• 15b Chen W. Du W. Duan YZ. Wu Y. Yang SY. Chen YC. Angew. Chem. Int. Ed. 2007; 119: 7811
• 15c Mei G.-J. Zhu Z.-Q. Zhao J.-J. Bian C.-Y. Chen J. Chen R.-W. Shi F. Chem. Commun. 2017; 53: 2768
• 15d Wang X. Yang P. Zhang Y. Tang CZ. Tian F. Peng L. Wang LX. Org. Lett. 2017; 19: 646
• 15e Xin Y. Zhao J. Gu J. Zhu S. J. Fluorine Chem. 2011; 132: 402
• 16a Na R. Jing C. Xu Q. Jiang H. Wu X. Shi J. Zhong J. Wang M. Benitez D. Tkatchouk E. Goddard WA. Guo H. Kwon O. J. Am. Chem. Soc. 2011; 133: 13337
• 16b Na R. Liu H. Li Z. Wang B. Liu J. Wang M.-A. Wang M. Zhong J. Guo H. Tetrahedron 2012; 68: 2349
• 17a Shao C. Zhang Q. Cheng G. Cheng C. Wang X. Hu Y. Eur. J. Org. Chem. 2013; 6443
• 17b Shintani R. Fu GC. J. Am. Chem. Soc. 2003; 125: 10778
• 17c Shintani R. Hayashi T. J. Am. Chem. Soc. 2006; 128: 6330
• 17d Yoshimura K. Oishi T. Yamaguchi K. Mizuno N. Chem. Eur. J. 2011; 17: 3827
• 18 Pleshchev MI. Gupta NV. D. Struchkova MI. Goloveshkin AS. Bushmarinov IS. Khakimov DV. Makhova NN. Mendeleev Commun. 2015; 25: 188
• 19 Fang X. Li J. Tao H.-Y. Wang C.-J. Org. Lett. 2013; 15: 5554
• 20 Liu W. Xu Y. Sun X. Lu D. Guo L. Synlett 2014; 25: 1093
• 21 Mondal M. Wheeler KA. Kerrigan NJ. Org. Lett. 2016; 18: 4108
• 22 Degenhardt CR. Burdsall DC. J. Org. Chem. 1986; 51: 3488
• 23 CCDC 1553292 (3a) contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
• 24a Hashimoto T. Maruoka K. Chem. Rev. 2015; 115: 5366
• 24b Coldham I. Hufton R. Chem. Rev. 2005; 105: 2765
• 24c Padwa A. Angew. Chem., Int. Ed. Engl. 1976; 15: 123
• 24d Carey FA. S. Sundberg RJ. Advanced Organic Chemistry, Part B, Reactions and Synthesis . Springer; Berlin: 2007: 527
• 25a Houk KN. Sims J. Duke RE. Strozier RW. George JK. J. Am. Chem. Soc. 1973; 95: 7287
• 25b Houk KN. Sims J. Watts CR. Luskus LJ. J. Am. Chem. Soc. 1973; 95: 7301
• 25c Sustmann R. Tetrahedron Lett. 1971; 2717