Synthesis of Enantiomerically Pure 1,5,7-Trimethyl-3-azabicyclo[3.3.1]nonan-2-ones as Chiral Host Compounds for Enantioselective Photochemical Reactions in Solution

Abstract

The synthesis of the title compounds is described. As common starting material, 1,5,7-trimethyl-2,4-dioxo-3-azabicyclo[3.3.1]-nonan-7-carboxylic acid chloride (4) was employed which is in turn available from cis,cis-1,3,5-trimethylcyclohexane-1,3,5-tricarboxylic acid (Kemp’s triacid). For the synthesis of the diastereomeric menthyl esters 1 and 2, the chloride 4 was initially substituted by (-)-menthol and its imide part was subsequently reduced to an amide by consecutive treatment with sodium borohydride and triethylsilane. The enantiomerically pure hosts 3a and 3b were obtained from the racemate by resolution of their N-menthoxycarbonyl derivatives. The racemic compounds rac-3a and rac-3b were prepared from the acid chloride 4 and the ortho-hydroxyanilines 9a and 9b via amide formation, condensation to the oxazole and reduction. Structural data are provided which prove the absolute configuration of compound ent-3b and the relative configuration of compound rac-3a.

Key words

supramolecular chemistry - amides - enantiomeric resolution - reductions - photochemistry

References

• 1a

  To whom inquiries about the X-ray analyses of compound 5 and rac-3a should be addressed at the Philipps-Universität, Marburg

• 1b

  To whom inquiries about the X-ray analysis of compound ent-3b should be addressed at the Technische Universität München

• 2a Helmchen G. Hoffmann RW. Mulzer J. Schaumann E. Houben-Weyl, 4th ed.   Vol. E21:  Thieme; Stuttgart: 1995. 
• 2b Winterfeldt E. Prinzipien und Methoden der stereoselektiven Synthese   Vieweg; Braunschweig: 1988. 
• Reviews:
• 3a Everitt SRL. Inoue Y. In Molecular and Supramolecular Photochemistry: Organic Molecular Photochemistry   Vol. 3:  Ramamurthy V. Schanze KS. Dekker; New York: 1999.  p.71 
• 3b Inoue Y. Chem. Rev.  1992,  92:  741 
• 3c Rau H. Chem. Rev.  1983,  83:  535 
• 4 Kemp DS. Petrakis KS. J. Org. Chem.  1981,  46:  5140 
• 5a Rebek J. Pure Appl. Chem.  1989,  61:  1517 
• 5b Rebek J. Angew. Chem. Int. Ed. Engl.  1990,  29:  245 
• 5c Jeong K.-S. Tjivikua T. Rebek J. J. Am. Chem. Soc.  1990,  112:  3215 
• 5d Park TK. Schroeder J. Rebek J. Tetrahedron  1991,  47:  2507 
• 5e Jeong KS. Tjivikua T. Muehldorf A. Deslongchamps G. Famulok M. Rebek J. J. Am. Chem. Soc.  1991,  113:  201 
• 6a Potin D. Williams K. Rebek J. Angew. Chem. Int. Ed. Engl.  1990,  29:  1420 
• 6b Yanagisawa A. Kikuchi T. Watanabe T. Yamamoto H. Bull. Chem. Soc. Jpn.  1999,  72:  2337 
• 7a Curran DP. Jeong K.-S. Heffner TA. Rebek J. J. Am. Chem. Soc.  1989,  111:  9238 
• 7b Jeong K.-S. Parris K. Ballester P. Rebek J. Angew. Chem., Int. Ed. Engl.  1990,  29:  555 
• 7c Stack JG. Curran DP. Rebek J. Ballester P. J. Am. Chem. Soc.  1991,  113:  5918 
• 7d Stack JG. Curran DP. Geib SV. Rebek J. Ballester P. J. Am. Chem. Soc.  1992,  114:  7007 
• 7e Curran DP. Yoon M.-H. Tetrahedron  1997,  53:  1971 
• 8 Bergmann H. Ph. D. Thesis   Universität Marburg; Marburg: 2001. 
• 9a Bach T. Bergmann H. Harms K. Angew. Chem., Int. Ed.  2000,  39:  2302 
• 9b Bach T., Bergmann H.; J. Am. Chem. Soc.; 2000, 122: 11525
• 9c Bach T. Bergmann H. Harms K. J. Org. Lett.  2001,  3:  601-603  
• 12a Wijnberg JBPA. Schoemaker HE. Speckamp WN. Tetrahedron  1978,  34:  179 
• 12b Rosenfield RE. Dunitz JD. Helv. Chim. Acta  1978,  61:  2176 
• 12c Nagasaka T. Esumi S. Ozawa N. Kosugi Y. Hamaguchi F. Heterocycles  1981,  16:  1987 
• 12d Weinreb SM. Kim MY. Starret JE. J. Org. Chem.  1981,  46:  5383 
• 13a Dockner M. Meyer T. Nemes P. Otten MG. Winterfeldt E. Bull Soc. Chim Belg.  1994,  103:  379 
• 13b Winterfeldt E. Chem. Rev.  1993,  93:  827 
• 13c Hungate RW. Chen JL. Starbuck KE. Macaluso SA. Rubino RS. Tetrahedron Lett.  1996,  37:  4113 
• 14a Wanner MJ. Koomen G.-J. J. Org. Chem.  1994,  59:  7479 
• 14b Adams DJ. Simpkins NS. Smith TJN. Chem. Commun.  1998,  1605 
• 15a Goto T. Konno M. Saito M. Sato R. Bull. Chem. Soc. Jpn.  1989,  62:  1205 
• 15b Koot W.-J. Hiemstra H. Speckamp WN. J. Org. Chem.  1992,  57:  1059 
• 16 Ducrot P. Thal C. Tetrahedron Lett.  1999,  40:  9037 
• 17a Ballester P. Tadayoni M. Branda N. Rebek J. J. Am. Chem. Soc.  1990,  112:  3685 
• 17b Kirby AJ. Komarov IV. Feeder N. J. Am. Chem. Soc.  1998,  120:  7101 
• 18 Kajino M. Shibouta Y. Nishikawa K. Meguro K. Chem. Pharm. Bull. Jpn.  1991,  39:  2896 
• 19a

  The structure was resolved by direct methods, carbon bound hydrogen atoms and N-H atom were refined. Further details regarding the crystal structure determination are provided in the Experimental section.

• 19b

  Straver, L. Enraf-Nonius CAD4 Operating System Unix Version, B. V. Enraf-Nonius, Delft, The Netherlands, 1997.

• 19c

  IPDS Operating System Version 2.8., Stoe&Cie. GmbH, Darmstadt, Germany, 1997.

• 19d Müller U. Schmidt RE. Massa W. Herdtweck E. CADLP: A Program to Correct X-Ray Raw Data for LP-Terms and Decay   University of Marburg and TU München; München, Germany: 1986. 
• 19e Altomare A. Cascarano G. Giacovazzo C. Guagliardi A. Burla MC. Polidori G. Camalli M. SIR92 J. Appl. Cryst.  1994,  27:  435 
• 19f International Tables for Crystallography   C: Tables 6.1.1.4 (pp. 500-502), 4.2.6.8 (pp. 219-222), and 4.2.4.2 (pp. 193-199) Wilson AJC. Kluwer Academic Publishers; Dordrecht, The Netherlands: 1992. 
• 19g

  Sheldrick, G. M. SHELXL-97, University of Göttingen, Göttingen, Germany, 1998.

• 19h

  Spek, A. L. PLATON: A Multipurpose Crystallographic Tool, Utrecht University, Utrecht, The Netherlands, 2000.

• 21 Still WC. Kahn M. Mitra AJ. J. Org. Chem.  1978,  43:  2923 

11

5: C₂₂H₃₅NO₄; Crystal Data: colorless prism; rhombohedral, R3, a = b = 2822.4(1)pm, c = 1526.2(1)pm; Z = 6; R = 5.16%; GOF = 1.034. Data collection: Data were collected on an Enraf Nonius CAD4 instrument at 293 K employing Cu Kα irradiation (154.178 pm). ω-scan, 6287 reflections (-h, +k, ±l), Θ_max = 65°, 5754 independent and 4128 observed reflections [F ≥ 4σ(F)], 521 refined parameters, wR2 = 0.1373, residual electron density 0.174 eÅ^-3, direct methods, hydrogen atoms calculated. Further details of the crystal structure investigations related to this compound may be obtained from the Director of the Cambridge Crystallographic Data Centre, 12 Union Road, GB-Cambridge CB2 1EZ, on quoting the full literature citation (CCDC-157021)

20

rac-3a: C₂₂H₂₄N₂O₂; Crystal Data: yellowish prism; monoclinic, P2₁/c, a = 1137.2(2)pm, b = 1491.2(1)pm, c = 1154.5(3)pm; β = 111.7(2)°; Z = 4; R = 6.49%; GOF = 1.044. Data collection: Data were collected on an Enraf Nonius CAD4 instrument at 223 K employing Cu Kα irradiation (154.178 pm), ω-scan, 2410 reflections (±h, +k, ±l), Θ_max = 55°, 2276 independent and 1659 observed reflections [F ≥ 4σ(F)], 242 refined parameters, wR2 = 0.2057, residual electron density 0.225 eÅ^-3. The structure was resolved by direct methods with carbon bound hydrogen atoms calculated and N-H atom refined. Further details of the crystal structure investigations related to this compound may be obtained from the Director of the Cambridge Crystallographic Data Centre, 12 Union Road, GB-Cambridge CB2 1EZ, on quoting the full literature citation (CCDC-157022)