Notes
J . Org. Chem., Vol. 63, No. 7, 1998 2361
Sch em e 1
were consistent with literature spectral data. 2-Hexyltetrahy-
drofuran was also characterized by elemental analysis (E & R
Analytical Laboratory, Inc.). References to known products are
given in Table 1. 1H NMR and 13C NMR were taken in CDCl3
at 300 and 75 MHz, respectively.
reported several times for the cyclic ether (-)-ambroxide
(Table 1, entry d) derived from the corresponding lactone
using LiAlH4 followed by treatment with POCl3, TsOH,
or TsCl in overall yields of 88-90%;6 a comparable yield
is obtained using our system. Using the DIBAL-H/
BF3‚OEt2/HSiEt3 method, Kraus prepared 2-phenyltet-
rahydrofuran in 75% yield;2a using our procedure, a 90%
yield is realized (Table 1, entry b).
In conclusion, we have developed a simple and practical
method for the conversion of lactones into cyclic ethers.
The first step reduces the lactone to the lactol using a
readily available titanocene complex and an inexpensive
stoichiometric reducing agent. After a brief workup,
crude product can be further transformed into the cor-
responding cyclic ether using Amberlyst 15 and trieth-
ylsilane. The yields for this two-step procedure are good
to excellent.
Gen er a l P r oced u r e. Titanocene difluoride (10.8 mg, 0.05
mmol) and dry THF (3 mL) are added to an oven-dried Schlenk
flask under an argon atmosphere. To the yellow solution was
added PMHS (0.75 mL, 12.5 mmol) via syringe. The reaction
vessel was placed in a hot water bath (ca. 60 °C) for 0.5-2 min,
resulting in a color change from yellow to dark blue, which was
accompanied by bubbling. The flask was cooled in an ice bath,
and lactone (2.5 mmol) was added dropwise via syringe. The
reaction mixture was stirred at room temperature and monitored
by TLC. After consumption of the starting material (0.1-6 h),
the catalyst was deactivated by exposure to air. The reaction
mixture was diluted with THF (10 mL), transferred to a 100
mL round-bottom flask, and treated with 1 M NaOH (15 mL).
[CAUTION: vigorous bubbling!]. The two-phase mixture was
stirred for 1 h or until the organic layer became clear. The
organic phase was diluted with ether (20 mL), washed twice with
1 M NaOH (10 mL), washed with a saturated brine solution (10
mL), dried (MgSO4), and concentrated in vacuo. Amberlyst 15
ion-exchange resin (1.25 g) was added to a stirred solution of
dichloromethane (10 mL), triethylsilane (0.8 mL, 5 mmol), and
the crude lactol product. The reaction was stirred at room
temperature open to the air until TLC analysis indicated the
reaction was complete (0.5-5 h). The Amberlyst 15 was
removed by filtration and washed with CH2Cl2. The resulting
solution was concentrated in vacuo. Flash column chromatog-
raphy was performed.
Exp er im en ta l Section
Gen er a l Meth od s. The titanocene bisphenoxide 1a and the
lactones used in entries a and g (Table 1) were prepared as
previously described.1a Tetrahydrofuran was distilled under
argon from sodium/benzophenone ketyl before use. Titanocene
difluoride was prepared via the literature procedure.7 All other
compounds are commercially available and were used as pur-
chased. All products were previously known (except 2-hexyltet-
rahydrofuran), and their 1H NMR, 13C NMR, and IR spectra
2-Hexyltetr a h yd r ofu r a n (En tr y c). The general procedure
was used to convert 0.45 mL (2.5 mmol) of δ-decanolactone to
the corresponding cyclic ether. The ether was purified via flash
chromatography (SiO2, 2% ether in pentane) to give 0.74 g (94%)
of a clear liquid. IR (film, cm-1) νmax: 2957, 2927, 2857, 1459,
1378, 1068. 1H NMR (300 MHz, CDCl3): δ 3.66-3.91 (m, 3H),
1.8-2.01 (m, 3H), 1.2-1.67 (m, 11H), 0.88 (t, 3H J ) 7 Hz). 13C
NMR (75 MHz, CDCl3): δ 79.4, 67.5, 35.7, 31.8, 31.3, 29.4, 26.3,
(6) (a) Teresa, J . d. P.; Urones, J . G.; Pedrero, A. M.; Barcala, P. B.
Tetrahedron Lett. 1985, 26, 5717. (b) Coste-Maniere, I. C.; Zahra, J .
P.; Waegell, B. Tetrahedron Lett. 1988, 29, 1017. (c) Ohloff, G.; Giersch,
W.; Pickenhagen, W.; Furrer, A.; Frei, B. Helv. Chim. Acta 1985, 68,
2022. (d) Martres, P.; Perfetti, P.; Zahra, J .-P.; Waegell, B.; Giraudi,
E.; Petrzilka, M. Tetrahedron Lett. 1993, 34, 629.
(7) Druce, P. M.; Kingston, B. M.; Lappert, M. F.; Spalding, T. R.;
Srivastava, R. C. J . Chem. Soc. A 1969, 2106.
(8) Deady, L. W.; Topsom, R. D.; Vaughan, J . J . Chem. Soc. 1965,
5718.
(9) Hashmi, M.; Khan, M.; Ahmad, M. S., J r.; Ahmad, F.; Osman,
S. M. J . Am. Oil Chem. Soc. 1984, 61, 1024.
(10) Hanson, R. L.; Banerjee, A.; Comezoglu, F. T.; Mirfakhrae, K.
D.; Patel, R. N.; Szarka, L. J . Tetrahedron: Asymmetry 1994, 5, 1925.
(11) Ahmad-J unan, S. A.; Walkington, A. J .; Whiting, D. A. J . Chem.
Soc., Perkins Trans. 1 1992, 2313.
22.5, 14.0. Anal. Calcd for
Found: C, 76.83; H, 12.84.
C10H20O: C, 76.86; H, 12.90.
Ack n ow led gm en t. This work was supported by the
National Institutes of Health, Pfizer, and Dow Chemi-
cal. X.V. thanks the Spanish Ministry of Education and
Science for a postdoctoral fellowship.
(12) Arnold, D. R.; Fahie, B. J .; Lamont, L. J .; Wierzchowski, J .;
Young, K. M. Can. J . Chem. 1987, 65, 2734.
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