Synthesis of an Ovoid Chiral Cage

Abstract

Evidence for the formation of an ovoid chiral cage, resulting from the auto-assembly of two hexafunctional and three tetrafunctional modules reacting through dynamic covalent bond formation, is provided.

Key words

cryptands - imines - macrocycles - polycycles - chirality

References and Notes

• 1 Xuejun L. Warmuth R. J. Am. Chem. Soc.  2008,  14120 
• 2 Steinmetz V. Couty F. David ORP. Chem. Commun.  2009,  343 
• 3a For imide formation, see: Rejman D. Kočalka P. Buděšínský M. Pohl R. Rosenberg I. Tetrahedron  2007,  1243 
• 3b For LiAlH₄ reduction, see: Bridgeman E. Cavill JL. Schofield DJ. Wilkins DS. Tomkinson NCO. Tetrahedron Lett.  2005,  8521 
• 3c For mesylation, see: Nagel U. Kinzel E. Andrade J. Prescher G. Chem. Ber.  1986,  3326 
• 3d For azide substitution, see: Reddy DR. Thornton ER. J. Chem. Soc., Chem. Commun.  1992,  172 ; We experimented with the replacement of LiN₃ by a stoichiometric mixture of NaN₃ and LiCl in DMF, and found that the substitution reaction did proceed with a yield similar to the one reported in the above article (˜75%)
• 3e For azide reduction and Boc-protection, see: Ganapati Reddy P. Verabhadra Pratap T. Kishore Kumar GD. Mohanty SK. Baskaran S. Eur. J. Org. Chem.  2002,  3740 
• 3f For benzyl hydrogenolysis, see: Löwik DWPM. Weingarten MD. Broekema M. Brouwer AJ. Still WC. Liskamp RMJ. Angew. Chem. Int. Ed.  1998,  1846 
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• 4e Gawronski J. Gawronska K. Grajewski J. Kwit M. Plutecka A. Rychlewska U. Chem. Eur. J.  2006,  12:  1807 

5

Preparation of cage 11. Hexammonium 9 (39.1 mg, 36.5 µmol) was treated with NaHCO₃ (40 mg, 475 µmol, 13 equiv) in H₂O (2 mL). The water was evaporated under vacuum and the solid residue was washed with CH₂Cl₂ to extract the free amine. After evaporation of the organic solvent, the light-yellow resin was redissolved in CH₂Cl₂
(5 mL) and MeOH (0.5 mL). Tripod 4 (19.2 mg, 24.3 µmol, 0.67 equiv) was added and the mixture was stirred at r.t. for 3 d. At this time, the mixture was slightly turbid and TLC indicated complete consumption of starting tripod 4 [R _f  = 0.25 (CH₂Cl₂-MeOH, 9:1)]. The reaction mixture was filtered and the solvents were evaporated under high vacuum (in order to prevent extensive polymerization, no heating was applied) to furnish a light-yellow resin (33 mg). Compound 11 was suspended in CDCl₃ (0.5 mL), CD₃OD (0.2 mL) was added and the NMR analyses were performed. ^¹H NMR (300 MHz, CDCl₃ + CD₃OD): δ = 1.60 (m), 2.29 (m), 2.5-3.2 (m), 3.3 (d, J = 12 Hz), 3.45 (d, J = 12 Hz), 3.93 (m), 4.15 (m), 4.24 (m), 4.78 (m), 4.82 (m), 6.87 (s, 6 H), 7.24 (s, 6 H), 7.42 (s, 6 H), 7.70 (s, 6 H), 7.98 (s, 6 H), 8.03 (s, 6 H); ^¹³C NMR (75 MHz, CDCl₃ + CD₃OD): δ = 29.3, 33.7, 36.7, 48.6, 49.0, 49.5, 66.5, 124.5, 124.6, 125.2, 136.7, 143.3, 158.1, 158.2, 179.2; HRMS was obtained from the same solution. HRMS (ESI, TOF MS): m/z calcd for [M + 2Na]^²+ 1279.6372; found: 1279.6306 (-5.15 ppm).