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.

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

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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)

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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)

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