Synthesis 2018; 50(09): 1820-1826
DOI: 10.1055/s-0036-1591920
paper
© Georg Thieme Verlag Stuttgart · New York

Expedient Entry to 1-Aminoadamantane Derivatives via Aza-Prins Cyclization of 7-Methylenebicyclo[3.3.1]nonan-3-one Oximes

Tetsuya Kuga
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan   Email: y-iwabuchi@m.tohoku.ac.jp
,
Yusuke Sasano
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan   Email: y-iwabuchi@m.tohoku.ac.jp
,
Masaki Tomizawa
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan   Email: y-iwabuchi@m.tohoku.ac.jp
,
,
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan   Email: y-iwabuchi@m.tohoku.ac.jp
› Author Affiliations
This work was partly supported by a Grant-in-Aid for Scientific Research on Innovative Areas ‘Advanced Molecular Transformations by Organocatalysis’ (No. 23105011) from MEXT, ‘Precisely Designed Catalysts with Customized Scaffolding’ (No. JP16H00998) from JSPS, and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science) from the Japan Agency for Medical Research and Development (AMED), Japan.
Further Information

Publication History

Received: 05 December 2017

Accepted after revision: 05 January 2018

Publication Date:
05 February 2018 (online)


Abstract

An efficient synthesis of 1-aminoadamantane (amantadine) derivatives is described. This synthesis features acid-promoted aza-Prins cyclization of 7-methylenebicyclo[3.3.1]nonan-3-one oximes, which are readily prepared from 1,3-adamantanediol via a Grob fragmentation and the subsequent oximation, to give various 3-substituted 1-(alkoxyamino)adamantanes. After the reduction of alkoxyamines, not only 3-substituted 1-aminoadamantanes, but also chiral 2,5-disubstituted derivatives were obtained in good yields.

Supporting Information

 
  • References

  • 1 New address: Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
    • 2a Lenda S. Mackaek V. Collect. Czech. Chem. Commun. 1933; 5: 1
    • 2b Fort RC. Schleyer P. vR. Chem. Rev. 1964; 64: 277
    • 2c Gunawan MA. Hierso J.-C. Poinsot D. Fokin AA. Folina NA. Trachenko BA. Schreiner PR. New J. Chem. 2014; 38: 28
    • 3a Wanka L. Iqbal K. Schreiner PR. Chem. Rev. 2013; 113: 3516
    • 3b Liu J. Obando D. Liao V. Lifa T. Codd R. Eur. J. Med. Chem. 2011; 46: 1949
    • 3c Lamoureux G. Artavia G. Curr. Med. Chem. 2010; 17: 2967
    • 3d Spasov AA. Khamidova TV. Bugaeva LI. Morozov IS. Pharm. Chem. J. 2000; 34: 1
  • 4 Davis WL. Grunert RR. Haff RF. McGahen JW. Neumayer EM. Paulshock M. Watts JC. Wood TR. Hermann EC. Hoffmann CE. Science 1964; 144: 862
    • 5a Gerzon K. Krumkalns EV. Brindle RL. Marshall FJ. Root MA. J. Med. Chem. 1963; 6: 760
    • 5b Witt A. Macdonald N. Kirkpatric P. Nat. Rev. Drug Discovery 2004; 3: 109
    • 5c Alam S. Lingenfelter KS. Bender AM. Lindsley CW. ACS Chem. Neurosci. 2017; 8: 1823
    • 6a Villhauer EB. Brinkman JA. Naderi GB. Burkey BF. Dunning BE. Prasad K. Mangold BL. Russell ME. Hughes TE. J. Med. Chem. 2006; 46: 2774
    • 6b Keating GM. Drugs 2014; 74: 587

      For selected examples, see:
    • 7a Jasys VJ. Lombardo F. Applenton TA. Bordner J. Ziliox M. Volkmann RA. J. Am. Chem. Soc. 2000; 122: 466
    • 7b Jirgensons A. Kauss V. Kalvinsh I. Gold MR. Synthesis 2000; 1709
    • 7c Forkin AA. Merz AM. Schwertfeger H. Liu SL. Dahl JE. P. Carlson RK. M. Schreiner PR. Synthesis 2009; 909

      Recently, few examples of palladium-catalyzed adamantane methylene C–H functionalization have been reported, see:
    • 8a Lao Y.-X. Wu J.-Q. Chen Y. Zhang S.-S. Li Q. Wang H. Org. Chem. Front. 2015; 2: 1374
    • 8b Fan Z. Shu S. Ni J. Yao Q. Zhang A. ACS Catal. 2016; 6: 769
    • 8c Larrosa M. Heiles S. Becker J. Spengler B. Hrdina R. Adv. Synth. Catal. 2016; 358: 2163
  • 9 Torres E. Fernández R. Miquet S. Font-Bardia M. Vanderlinden E. Naesens L. Vázquez S. ACS Med. Chem. Lett. 2012; 3: 1065
    • 10a Shibuya M. Tomizawa M. Suzuki I. Iwabuchi Y. J. Am. Chem. Soc. 2006; 128: 8412
    • 10b Shibuya M. Sasano Y. Tomizawa M. Hamada T. Kozawa M. Nagahama N. Iwabuchi Y. Synthesis 2011; 3418
    • 10c Iwabuchi Y. Chem. Pharm. Bull. 2013; 61: 1197
    • 11a Olah GA. Krishnamurti R. Prakash GK. S. Synthesis 1990; 646
    • 11b Messmer A. Glléri D.-CA. Angew. Chem. 1965; 77: 171
    • 11c Stetter H. Gärtner J. Chem. Ber. 1966; 99: 925
    • 11d Serguchev YA. Ponomarenko MV. Lourie LF. Chenega AN. J. Fluorine Chem. 2013; 123: 207
    • 11e Jung ME. Lee GS. J. Org. Chem. 2014; 79: 10544
  • 12 The Ts- and Bz-esters of oxime 1 underwent Beckmann rearrangement without acids.
  • 13 Shibuya M. Taniguchi T. Takahashi M. Ogasawara K. Tetrahedron Lett. 2002; 43: 4145