Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000084.xml
Synthesis 2015; 47(03): 367
DOI: 10.1055/s-0034-1379456
DOI: 10.1055/s-0034-1379456
paper
An Expedient and Practical Approach to Functionalized 3-Aza-, 3-Oxa-, and 3-Thiabicyclo[3.3.1]nonane Systems
Further Information
Publication History
Received: 02 August 2014
Accepted after revision: 22 October 2014
Publication Date:
14 November 2014 (online)
![](https://www.thieme-connect.de/media/synthesis/201503/lookinside/thumbnails/10.1055-s-0034-1379456-1.jpg)
Abstract
The synthesis of a number of heterobicyclo[3.3.1]nonane derivatives possessing carbonyl, amino, or carboxyl groups is reported. The synthetic scheme is concise and practical, based on optimized reaction conditions for each step and an orthogonal protection group strategy. Procedures for the key synthetic steps (double annulation of α-bromomethyl acrylates to enamines and a Caglioti reaction) were improved significantly. This makes the compounds attractive for medicinal chemistry as potential chemically diverse 3D-scaffolds applicable in drug design.
Key words
bicyclic compounds - annulation - Caglioti reaction - diversity-oriented synthesis - medicinal chemistrySupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0034-1379456.
- Supporting Information
-
References
- 1 Lovering F, Bikker J, Humblet C. J. Med. Chem. 2009; 52: 6752
- 2a Ruiz M, López-Alvarado P, Giorgi G, Menéndez JC. Chem. Soc. Rev. 2011; 40: 3445
- 2b Grygorenko OO, Radchenko DS, Volochnyuk DM, Tolmachev AA, Komarov IV. Chem. Rev. 2011; 111: 5506
- 2c Burkhard JA, Wagner B, Fischer H, Schuler F, Müller K, Carreira EM. Angew. Chem. Int. Ed. 2010; 49: 3524
- 2d Trabocchi A, Scarpi D, Guarna A. Amino Acids 2008; 34: 1
- 2e Horton DA, Bourne GT, Smythe ML. Chem. Rev. 2003; 103: 893
- 3 Kumar K, Wetzel S, Waldmann H In Practice of Medicinal Chemistry . 3rd ed.; Wermuth CG. Academic/Elsevier; Amsterdam: 2008: 187-209
- 4a Burke MD, Schreiber SL. Angew. Chem. Int. Ed. 2004; 43: 46
- 4b Spring DR. Org. Biomol. Chem. 2003; 1: 3867
- 5 Thomas GL, Wyatt EE, Spring DR. Curr. Opin. Drug Discov. Dev. 2006; 9: 700
- 6a Nelson RP, Lawton RG. J. Am. Chem. Soc. 1966; 88: 2884
- 6b Nelson RP, McEuten JM, Lawton RG. J. Org. Chem. 1969; 34: 1225
- 6c McEuten JM, Nelson RP, Lawton RG. J. Org. Chem. 1970; 35: 690
- 7a Dekkers AW. J. D, Speckamp WN, Huisman HO. Tetrahedron Lett. 1971; 489
- 7b Stetter H, Reinartz W. Chem. Ber. 1972; 105: 2773
- 7c Mazurov AA, Kombo DC, Akireddy S, Murthy S, Hauser TA, Jordan KG, Gatto GJ, Yohannes D. Bioorg. Med. Chem. Lett. 2013; 23: 3927
- 8a Yeh VS. C, Kurukulasuriya R, Madar D, Patel JR, Fung S, Monzon K, Chiou W, Wang J, Jacobson P, Sham HL, Link JT. Bioorg. Med. Chem. Lett. 2006; 16: 5408
- 8b Yu J, Liu H, Xia G, Liu L, Xu Zh, Chen Q, Ma C, Sun X, Xu J, Li H, Li P, Shi Y, Xiong B, Liu X, Shen J. ACS Med. Chem. Lett. 2012; 3: 793
- 9a Meeuwissen HJ, van der Knaap TA, Bickelhaupt F. Phosphorus Sulfur 1983; 18: 109
- 9b Meeuwissen HJ, van der Knaap TA, Bickelhaupt F. Tetrahedron 1983; 39: 4225
- 10 Cao C.-L, Sun X.-L, Kang Y.-B, Tang Y. Org. Lett. 2007; 9: 4151
- 11 Plettenburg O, Lorenz K, Loehn M, Duclos O, Biscarrat S. PCT Int. Appl. WO 2009/156092 A2, 2009 ; Chem. Abstr. 2009, 146, 350380.
- 12a Peters JA, van der Toorn JM, van Bekkum H. Tetrahedron 1974; 30: 633
- 12b Renzoni GE, Borden WT. J. Org. Chem. 1983; 48: 5231
- 13 Pautigny C, Jeulin S, Ayad T, Zhang Zh, Genêt J.-P, Ratovelomanana-Vidal V. Adv. Synth. Catal. 2008; 350: 2525
- 14 Grange RL, Ziogas J, North AJ, Angusc JA, Schiesser CH. Bioorg. Med. Chem. Lett. 2008; 18: 1241
- 15a Hutchins RO, Hutchins MK In Comprehensive Organic Synthesis . Vol. 8. Trost BM, Fleming I. Pergamon Press; Oxford: 1991: 343-362
- 15b Lane CF. Synthesis 1975; 135
- 16 Komarov IV, Grigorenko AO, Turov AV, Khilya VP. Russ. Chem. Rev. 2004; 73: 785
- 17 Perrin DD, Armarego WL. F. Purification of Laboratory Chemicals . Pergamon; Oxford: 1988. 3rd ed.
- 18 Pittelkow M, Christensen JB. Org. Lett. 2005; 7: 1295
- 19 O’Leary BM, Szabo T, Svenstrup N, Schalley CA, Lützen A, Schäfer M, Rebek JJr. J. Am. Chem. Soc. 2001; 123: 11519
- 20 Tsunoda T, Suzuki M, Noyori R. Tetrahedron Lett. 1980; 21: 1357
- 21 Ninomiya K, Shioiri T, Yamada S. Tetrahedron 1974; 30: 2151
- 22 CCDC-1009296 and 1009297 contain the supplementary crystallographic data of compounds 11a·HCl and 10a, respectively, reported in this paper. These data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336033; E-mail: deposit@ccdc.cam.ac.uk.
- 23 Sheldrick GM. Acta Crystallogr., Sect. A 2008; 64: 112
For some representative reviews, see: