PAPER
Synthesis of a Novel Chiral Cubane-Based Schiff Base Ligand
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evaporated to afford 4-methoxycarbonyl cubane carboxylic acid
in EtOH (1.1 mL) at r.t. and stirred for 30 min. The mixture was
(6).
evaporated to dryness, affording an off-white solid. The solid was
collected and washed with cold EtOH under vacuum filtration,
yielding 10.
Yield: 1.70 g (73.0%); mp 181–183 °C (Lit.22a 182–183 °C).
1H NMR (400 MHz, CD3OD): d = 3.71 (s, 3 H, CH3), 4.20 (s, 6 H,
cubyl H).
Yield: 195 mg (75.0%); white solid; mp 95–97 °C.
1H NMR (400 MHz, CDCl3): d = 1.36–1.40 (m, 2 H), 1.61–1.84 (m,
6 H) 3.06–3.09 (m, 2 H), 4.21–4.32 (m, 6 H), 7.66 (s, 2 H).
4-Iodocubanecarboxylic Acid (7)
A suspension of 4-methoxycarbonyl-cubanecarboxylic acid (6;
1.94 g, 9.38 mmol) was prepared in anhydrous benzene (150 mL)
under argon. To it, iodobenzenediacetate (9.06 g, 28.1 mmol) and I2
(7.14 g, 28.1 mmol) were added and the mixture was refluxed for 7
h. The mixture was then cooled to r.t. and hexanes (75 mL) was add-
ed. The solution was washed with sat. Na2SO3 (2 × 25 mL), H2O (25
mL), and brine (25 mL), dried with MgSO4, filtered, and evaporated
to near dryness. The resulting red-brown liquid was dissolved in
THF (50 mL) and a mixture of NaOH (3.75 g, 93.8 mmol) dissolved
in MeOH (40 mL) and H2O (15 mL) was added. The mixture was
stirred overnight then the solution was evaporated to near dryness.
The residue was dissolved in H2O (25 mL), and acidified with concd
HCl to pH <1, whereby a white precipitate formed which was col-
lected under vacuum filtration, yielding 4-iodocubanecarboxylic
acid (7).
13C NMR (100 MHz, CDCl3): d = 162.0, 73.7, 59.0, 54.7, 49.9, 37.5,
32.6, 24.4.
HRMS (ESI): m/z [M + H+] calcd for C24H25N2I2: 595.0102; found:
595.01074.
General Procedure for Henry Reaction
To the solvent (1.5 mL) at r.t., 4 Å molecular sieves (20 mg), the
copper salt (0.00841 mmol), and cube ligand 10 (10 mg, 0.0168
mmol) were added and the mixture was stirred for 10 min. 4-Ni-
trobenzaldehyde (25.4 mg, 0.168mmol) and excess MeNO2 (1 mL)
were added and the reaction was stirred for 48 h. The mixture was
evaporated to near dryness, dissolved in CH2Cl2 (10 mL) and 1 M
HCl (10 mL) was added until the mixture became clear. Work-up
with CH2Cl2 (2 × 10 mL), washing with H2O (2 × 10 mL) and brine
(10 mL), drying with MgSO4, filtering and evaporating to dryness
afforded the dark-yellow glutinous product which was used directly
to determine conversion and enantioselectivity.
Yield: 1.91 g (74.3%); mp 212 °C (dec.) [Lit.22a 215 °C (dec.)].
1H NMR (400 MHz, CD3OD): d = 4.24 (m, 3 H, cubyl H), 4.36 (m,
3 H, cubyl H).
1H NMR (400 MHz, CDCl3): d = 4.49–4.60 (m, 2 H, CH2), 5.62 (dd,
J = 4.4, 8.0 Hz, 1 H, CH), 7.63 (d, J = 9.2 Hz, 2 H, Ar), 8.28 (d,
J = 9.2 Hz, 2 H, Ar).
1-Iodo-4-(hydroxymethyl)cubane (8)
4-Iodocubanecarboxylic acid (7; 676 mg, 2.46 mmol) was dissolved
in anhydrous THF (25 mL) under argon and cooled to 0 °C. To it,
borane dimethyl sulfide complex (0.78 mL, 3.91 mmol) was added
and the mixture was stirred for 20 min at 0 °C, then at r.t. for 4 h.
The reaction was quenched with H2O (20 mL) and stirred overnight.
After adding EtOAc (20 mL), the solution was washed with H2O
(2 × 15 mL) and brine (20 mL), dried with MgSO4, filtered, and
evaporated to dryness. Column chromatography (CHCl3–EtOAc,
1:1) afforded 1-iodo-4-(hydroxymethyl)cubane (8).
Acknowledgment
The authors thank the Niagara University Academic Center for
Integrated Science and the Rochester Academy of Science for their
financial support. M.L.I. would like to thank the Barbara S. Zimmer
Memorial Research Award for financial aid. R.P. would also like to
thank Dr. David Llewellyn for helpful discussions.
Yield: 438 mg (68.4%); white solid; mp 109–111 °C (Lit.22a 109–
111 °C).
1H NMR (400 MHz, CDCl3): d = 3.80 (s, 2 H, CH2), 4.07 (m, 3 H,
cubyl H), 4.23 (m, 3 H, cubyl H).
References
(1) Eaton, P. E.; Cole, T. W. Jr. J. Am. Chem. Soc. 1964, 96, 962
and 3157.
(2) (a) Service, R. F. Science 2000, 287, 564. (b)Zhang, M.-X.;
Eaton, P. E.; Gilardi, R. Angew. Chem. 2000, 39, 401.
(c) Kortus, J.; Pederson, M. R.; Richardson, S. L. Chem.
Phys. Lett. 2000, 322, 224. (d) Hrovat, D. A.; Borden, W.
T.; Eaton, P. E.; Kahr, B. J. Am. Chem. Soc. 2001, 123, 1289.
(3) Eaton, P. E. Angew. Chem., Int. Ed. Engl. 1992, 31, 1421.
(4) Priefer, R.; Lee, Y. J.; Barrios, F.; Wosnick, J. H.; Lebuis,
A.-M.; Farrell, P. G.; Harpp, D. N.; Sun, A.; Wu, S.; Snyder,
J. P. J. Am. Chem. Soc. 2002, 124, 5626.
1-Iodocubane-4-carboxaldehyde (9)
A stirring solution of oxalyl chloride (0.16 mL, 1.89 mmol) in an-
hydrous CH2Cl2 (4 mL) was prepared under argon at –78 °C. To it,
anhydrous DMSO (0.28 mL, 3,86 mmol) in anhydrous CH2Cl2 (4
mL) was added dropwise. After 20 min at –78 °C, 1-iodo-4-(hy-
droxymethyl)cubane (8; 403 mg, 1.56 mmol) dissolved in anhy-
drous CH2Cl2 (17 mL) under argon was added to the system
dropwise. The system was maintained at –78 °C for 1.5 h and anhy-
drous Et3N (7.02 mmol) was added via syringe. The mixture was
warmed to r.t. and quenched with H2O (15 mL). The aqueous layer
was extracted with CH2Cl2 (2 × 15 mL) and the organic layers were
combined and washed with H2O (15 mL) and brine (15 mL), dried
with MgSO4, filtered, and evaporated to dryness. Column chroma-
tography (CH2Cl2) afforded 1-iodocubane-4-carboxaldehyde (9).
(5) Priefer, R.; Martineau, E.; Harpp, D. N. J. Sulfur Chem.
2007, 28, 529.
(6) Cassar, L.; Eaton, P. E.; Halpern, J. J. Am. Chem. Soc. 1970,
92, 6366.
(7) Cassar, L.; Eaton, P. E.; Halpern, J. J. Am. Chem. Soc. 1970,
92, 3515.
(8) Carroll, V. M.; Harpp, D. N.; Priefer, R. Tetrahedron Lett.
2008, 49, 2677.
Yield: 326 mg (80.9%); white solid; mp 106–109 °C (Lit.27 108–
110 °C).
1H NMR (400 MHz, CDCl3): d = 4.31 (m, 3 H, cubyl H), 4.53 (m,
(9) Priefer, R.; Nguyen, S.; Farrell, P. G.; Harpp, D. N.
Macromolecules 2003, 36, 5435.
(10) McGonagle, A. E.; Savage, G. P. Aust. J. Chem. 2009, 62,
145.
(11) Henry, L. C. R. Hebd. Seances Acad. Sci. 1895, 120, 1265.
(12) Sasai, H.; Suzuki, T.; Arai, S.; Arai, T.; Shibasaki, M. J. Am.
Chem. Soc. 1992, 114, 4418.
3 H, cubyl H), 9.76 (s, 1 H, CHO).
Cubane-Based Chiral Schiff Base Ligand (10)
trans-(1R,2R)-(–)-1,2-Cyclohexanediamine (50.3 mg, 0.438 mmol)
and 1-iodocubane-4-carboxaldehyde (9; 226 mg, 0.876 mmol) and
oven-dried 4 Å molecular sieves (0.05 g) were combined together
Synthesis 2010, No. 1, 98–102 © Thieme Stuttgart · New York