J . Org. Chem. 2000, 65, 4729-4731
4729
Notes
Sch em e 1
A Sin gle Step Con ver sion of
Tetr a h yd r op yr a n yl Eth er s to Aceta tes†
S. Chandrasekhar,* T. Ramachandar,
M. Venkat Reddy, and Mohamed Takhi
Indian Institute of Chemical Technology,
Hyderabad, 500 007, India
instance, the THP ether of 3-phenyl-1-propanol 1a (entry
1) was treated with 20 mol % of TiCl4 and Ac2O in
anhydrous CH2Cl2 at ambient temperature for 6 h to
obtain the corresponding acetate 1b in 78% yield. This
prompted us to study the conversion of the THP ether of
benzyl alcohol 2a (entry 2) and 2-phenylethanol 3a (entry
3), which proceeded efficiently with 80% and 85% yields,
respectively. The bis THP ether derivative 4a (entry 4)
also underwent smooth conversion; however, the isopro-
pylidine group was also displaced to yield tetra acetate
derivative 4b in 80% yield. Another bis OTHP ether 5a
was converted to the diacetate derivative 5b in 90% yield.
The terpenyl derivative having an allyl alcohol 6a (entry
6), the steroidal derivative 9a (entry 9), and the bromo
THP ether 10a (entry 10) were also effectively converted
to corresponding acetates. The tricyclic sertraline inter-
mediate10 8a (entry 8), enyne derivative 12a (entry 12,
pheromone components of Spodoptera litura), and the
7-ene derivative 14a (entry 14, pheromone component of
Aproaerema modicella) are other representative examples
studied having biological importance. Entry 13 describes
the mildness of the protocol, wherein silyl ether stability
is demonstrated.
srivaric@iict.ap.nic.in, srivaric@hotmail.com.
Received October 13, 1999
The acetylation of alcohols is a useful transformation,
as the resulting acetate group serves as an effective
blocking group that is stable to acidic conditions.1 Also,
acetates of natural products show biological profiles
different from those of the parent compounds (morphine
to heroin and salicylic acid to aspirin serve as excellent
examples). With its importance in mind, several useful
methods have been reported2 for the conversion of alco-
hols to acetates, under both acidic and basic conditions.
Development of new methods for the direct conversion
of one protective group to an other has been gaining
importance in recent times. Methods are now available
for the one-step conversion of silyl ethers to acetates,3
tetrahydropyranyl ethers to silyl-protected alcohols,4
p-methoxy benzyl ethers to p-methoxymethyl ethers,5 or
benzyl ethers to acetates.6 Surprisingly however, there
is only one report that deals with the direct conversion
of a tetrahydropyranyl (OTHP) ether to an acetate
(AcOH/AcCl).7 These conditions, being harsh, have not
found wide applicability. While working toward the
In conclusion, an efficient one-step conversion of THP
ethers to acetates is described that has direct applications
in the total synthesis of biologically active natural
product derivatives and pheromones.
synthesis of pheromone components of Aproaerema mod-
8
icella
and Spodoptera litura,9 we desired a direct
method for this transformation to improve the overall
synthetic efficiency. Toward this goal, herein we report
a mild method for direct conversion of THP ethers to
acetates (Scheme 1). After screening various Lewis acid
catalysts, it was concluded that 20 mol % of TiCl4 and
1.2 equiv of Ac2O were effective for this transformation.
Importantly, this protocol installs a base-labile protective
group in place of an acid-labile protective group in one
step.
Exp er im en ta l Section
Gen er a l Meth od s. Crude products were purified by column
chromatography on silica gel of 60-120 mesh. 1H NMR spectra
are obtained in CDCl3 at 200 MHz. Chemical shifts are given in
ppm with respect to internal TMS, and J values are quoted in
Hz. Infrared spectra were obtained neat, and only the most
significant absorptions are indicated, in cm-1. Dichloromethane
was distilled over CaH2 prior to use. All reactions were carried
out under an atmosphere of nitrogen using dry glassware. TiCl4
(1 M in CH2Cl2) was obtained from Aldrich Chemical Co. and
was used as received.
Gen er a l P r oced u r e for th e On e-Step Con ver sion of
Tetr a h yd r op yr a n yl Eth er s to Aceta tes As Descr ibed for
1a . First, 20 mol % of TiCl4 (1 M in CH2Cl2, 84 mg, 0.45 mmol)
was added dropwise to a solution of 2-(3-phenylpropoxy) tet-
rahydro-2H-pyran 1a (0.5 g, 2.27 mmol) and acetic anhydride
(0.27 mL, 2.72 mmol) in dichloromethane(10 mL) at 0 °C under
a nitrogen atmosphere. The resulting mixture was stirred at
ambient temperature for 6 h, and the mixture was diluted with
water, extracted with dichloromethane, and washed with brine
solution. Evaporation of the volatiles followed by chromatogra-
phy furnished 0.31 g of corresponding acetate (1b, 78%).
Representative examples of direct conversions of THP
ethers to acetates are shown in Table 1. In the first
† IICT Communication no. 4317.
(1) Greene, T. W.; Wuts, P. G. M. In Protective Groups in Organic
Synthesis, 2nd ed.; J ohn Wiley & Sons: New York, 1991.
(2) Oriyama, T.; Kimura, M.; Oda, M.; Koga, G. Syn. Lett. 1993, 437.
(3) Oriyama, T.; Oda, M.; Gono, J .; Koga, G. Tetrahedron Lett. 1994,
35, 2027.
(4) Oriyama, T.; Yatabe, K.; Sugawara, S.; Machiguchi, Y.; Koga,
G. Syn Lett. 1996, 523.
(5) Oriyama, T.; Kimura, M.; Koga, G. Bull. Chem. Soc. J pn. 1994,
67, 885.
(6) Yang, G.; Ding, X.; Kong, F. Tetrahedron Lett. 1997, 37, 6725.
(b) Ganem, B.; Small, V. R., J r. J . Org. Chem. 1974, 39, 3728-3730.
(7) Schwarz, M.; Waters, R. M. Synthesis 1972, 567.
(8) Yadav, J . S.; Chandrasekhar, S.; Rajashaker, K. Synth. Commun.
1995, 25, 4305.
(10) Qualich, G. J .; Woodall, T. M. Tetrahedron 1992, 48, 10239.
(b) Lautens, M.; Rovis, T. J . Org. Chem. 1997, 62, 5246. (c) Chan-
drasekhar, S.; Reddy, M. V. Tetrahedron 2000, 56, 1111-1114.
(11) Entries 2 and 9 were comparable with literature values, J . Org.
Chem. 1992, 57, 2001.
(9) Bestman, H. J .; Sub, J .; Vostrowsky, O. Liebigs Ann. Chemie
1981, 2117.
10.1021/jo991594v CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/21/2000