none 10.1021/acsomega.7b00482 American Chemical Society (ACS) American Chemical Society 316 91490630 300900 2026090209090523000 10.1021 2026-09-02T13:09:13Z 2017-07-07T08:48:15Z 10 ACS Omega 2470-1343 07 07 2017 07 31 2017 2 7 Joshua Almond-Thynne Imperial College London , , , London, England, SW7 2AZ Andrew J. P. White Imperial College London , , , London, England, SW7 2AZ Anastasios Polyzos CSIRO Manufacturing , , , Clayton, Victoria, Australia, 3169 University of Melbourne , , Parkville , , , Melbourne, Victoria, Australia, 3010 http://orcid.org/0000-0003-1063-4990 Henry S. Rzepa Imperial College London , , , London, England, SW7 2AZ Philip J. Parsons Imperial College London , , , London, England, SW7 2AZ Anthony G. M. Barrett Imperial College London , , , London, England, SW7 2AZ Abstract An efficient two-step synthesis of symmetrical and unsymmetrical tetrahydrospirobiquinolines from o-azidobenzaldehydes is reported. A novel series of tetrahydrospirobiquinolines was prepared by sequential double-aldol condensation with acetone, cyclopentanone, and cyclohexanone to form the corresponding o,o′-diazido-dibenzylidene-acetone, -cyclopentanone, and -cyclohexanone derivatives, respectively, and hydrogenation–spirocyclization. The spirodiamines were further derivatized by electrophilic aromatic bromination, Suzuki coupling, and N-alkylation, all of which proceeded with preservation of the spirocyclic core. 07 07 2017 07 31 2017 3241 3249 GlaxoSmithKline http://dx.doi.org/10.13039/100004330 NA Commonwealth Scientific and Industrial Research Organisation http://dx.doi.org/10.13039/501100000943 NA https://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html 10.1021/acsomega.7b00482 https://pubs.acs.org/acsodf/article/2/7/3241/751008/Synthesis-and-Reactions-of-Benzannulated https://pubs.acs.org/acsodf/article-pdf/2/7/3241/67756059/acsomega.7b00482.pdf https://pubs.acs.org/acsodf/article-pdf/2/7/3241/67756059/acsomega.7b00482.pdf https://pubs.acs.org/doi/pdf/10.1021/acsomega.7b00482 Curr. Opin. Chem. Biol. Welsch 14 347 2010 10.1016/j.cbpa.2010.02.018 J. Med. Chem. Lovering 52 6752 2009 10.1021/jm901241e Nat. Prod. Rep. Sperry 27 1117 2010 10.1039/b911514p Weingarten, D. M.; Ni, L.; Ye, Z.; Meng, C. Q.; Ng, R.; Sikorski, J. A. Spiro Compounds for Treatment of Inflammatory Disorders. U.S. Patent 2008/0280974 A1, Nov 13, 2008. Angew. Chem., Int. Ed. Freixa 42 1284 2003 10.1002/anie.200390330 Eur. J. Org. Chem. Sala 2008 6197 2008 10.1002/ejoc.200800913 Tetrahedron: Asymmetry Jacquet 22 1490 2011 10.1016/j.tetasy.2011.08.023 Org. Lett. Wang 16 22 2014 10.1021/ol4033286 ACS Catal. Huang 6 5747 2016 10.1021/acscatal.6b01725 Org. Lett. Cordes 15 4992 2013 10.1021/ol402301g Eur. J. Org. Chem. Loerbroks 2014 5476 2014 10.1002/ejoc.201402576 J. Mol. Struct. Nycz 1106 416 2016 10.1016/j.molstruc.2015.11.011 Angew. Chem., Int. Ed. Denisenko 28 1381 1989 10.1002/anie.198913811 Org. Lett. Hubbs 1 1315 1999 10.1021/ol9902632 J. Am. Chem. Soc. Miura 134 11995 2012 10.1021/ja305856q Angew. Chem., Int. Ed. Xu 54 14937 2015 10.1002/anie.201508150 Phytochem. Lett. Atilaw 10 28 2014 10.1016/j.phytol.2014.07.003 Org. Lett. Umehara 16 2526 2014 10.1021/ol500903e J. Nat. Prod. Feng 73 22 2010 10.1021/np900595v J. Am. Chem. Soc. Xu 137 6712 2015 10.1021/jacs.5b03619 Org. Lett. Wang 17 3458 2015 10.1021/acs.orglett.5b01503 Angew. Chem., Int. Ed. Wang 51 936 2012 10.1002/anie.201106488 Angew. Chem., Int. Ed. Wang 51 9276 2012 10.1002/anie.201204925 Adv. Synth. Catal. Wang 355 2900 2013 10.1002/adsc.201300380 J. Am. Chem. Soc. Cao 135 8197 2013 10.1021/ja4040895 Org. Lett. Stokes 12 2884 2010 10.1021/ol101040p J. Am. Chem. Soc. Stokes 133 4702 2011 10.1021/ja111060q Imp. Coll. Comput. Serv. Data Repository Almond-Thynne 2017 10.14469/hpc/2099 Angew. Chem., Int. Ed. Shibuguchi 45 4635 2006 10.1002/anie.200601722 J. Org. Chem. Irvine 37 2033 1972 10.1021/jo00977a037 Eur. J. Med. Chem. Li 93 461 2015 10.1016/j.ejmech.2015.02.005 J. Org. Chem. Boswell 60 6592 1995 10.1021/jo00125a055 Eur. J. Org. Chem. Leroux 2005 5049 2005 10.1002/ejoc.200500514 J. Org. Chem. Riesgo 61 3017 1996 10.1021/jo952164h Org. Process Res. Dev. Zhou 16 204 2012 10.1021/op200271b Supplemental Information for 10.1021/acsomega.7b00482 10.1021/acsomega.7b00482.s001 https://pubs.acs.org/doi/suppl/10.1021/acsomega.7b00482/suppl_file/ao7b00482_si_001.pdf