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

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.

Key words

1-aminoadamantanes - amantadine - 1-(alkoxyamino)-adamantanes­ - aza-Prins reaction - oxime

• 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