A reagent for selective deprotection of alkyl acetates

Article abstract of DOI:10.1021/jo961257b

The use of magnesium methoxide for selective deprotection of alkyl esters is described. By adjusting the equivalents of the magnesium methoxide reagent, it is possible to selectively cleave primary acetate in the presence of secondary and tertiary acetate and to cleave secondary acetate in the presence of tertiary acetate. A high selectivity can also be obtained for the same primary acetates if the β-positions of the acetates render a different steric bulkiness. This mild reagent has been successfully applied to the selective deprotection of many natural-occurring molecules including hydroxycitronnellol diacetate, trans-sobrerol diacetate, betulin diacetate, and baccatin III.

Full text of DOI:10.1021/jo961257b

9086
J . Org. Chem. 1996, 61, 9086-9089
Articles
A Rea gen t for Selective Dep r otection of Alk yl Aceta tes
Yao-Chang Xu,* Amsalu Bizuneh, and Clint Walker
CNS Division, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285
Received J uly 3, 1996X
The use of magnesium methoxide for selective deprotection of alkyl esters is described. By adjusting
the equivalents of the magnesium methoxide reagent, it is possible to selectively cleave primary
acetate in the presence of secondary and tertiary acetate and to cleave secondary acetate in the
presence of tertiary acetate. A high selectivity can also be obtained for the same primary acetates
if the â-positions of the acetates render a different steric bulkiness. This mild reagent has been
successfully applied to the selective deprotection of many natural-occurring molecules including
hydroxycitronnellol diacetate, trans-sobrerol diacetate, betulin diacetate, and baccatin III.
In tr od u ction
example, primary acetates vs secondary acetates, etc.
Deprotection agents with such selectivity are more
practically useful because initial protection can be carried
out in a single step. Several agents with moderate
selectivity have been reported. BF3‚Et2O in wet aceto-
nitrile8 and Bu3SnOMe in ClCH2CH2Cl9 have been found
to cleave anomeric acetates in the presence of alkyl
acetates. Lipase from Candida cylindracea10 and Al2O3
in benzene11 are also reported to be effective agents for
deacylation of primary acetates. Other conditions for
selectively removing primary acetates include KCN in
EtOH,12 5% KOH in methanol,13 and K2CO3 in methanol
and water.14 It should be noted that most of these
conditions can work only for a specific set of substrates.
There is no single agent reported that can effectively
differentiate among primary, secondary, and tertiary
acetates. In connection with our recent interest in
selective deprotection agents,7 we report our new findings
that magnesium methoxide is a selective agent for
effective differentiation of various acetates and it is
widely applicable to many organic substrates.
Of the many methods available for hydroxy group
protection, esters have still retained a position of promi-
nence due to their ease of formation and cleavage as well
as their rich choices of a whole array of different esters
such as acetate, benzoate, pivaloate, etc.1 The acetate
esters are among the most popular protecting groups for
hydroxy functions in synthetic chemistry as they are
readily introduced and removed by a variety of reaction
conditions.
One of the common practices encountered in the
organic chemistry laboratory is the use of a reagent to
selectively remove a protecting group. Selective depro-
tecting agents are particularly important and beneficial
in complex synthetic sequences in which two protected
functional groups must be unmasked at different stages
of a synthesis. A great deal of effort has been devoted to
develop deprotection conditions to remove one ester in
the presence of other esters. DBU in benzene,2 for
example, has been reported to cleave acetates only,
without affecting benzoates. Guanidine in ethanol and
dichloromethane has also been found to selectively
remove acetates in the presence of benzoates, pivaloates,
and acetamides.3 There are many other deprotection
protocols reported, including 50% NH3 in methanol,4 NH2-
NH2 in acetic acid and pyridine,5 and Mg metal in
methanol.6 Recently, magnesium methoxide in methanol
has been reported to be a selective ester deprotection
agent and allows for an effective differentiation among
p-nitrobenzoates, acetates, benzoates, pivaloates, and
acetamides.7
Resu lts a n d Discu ssion
During our recent studies of selective deprotection of
different esters using magnesium methoxide in metha-
nol,7 it was found that the amount of the reagent is
essential to obtain a high selectivity. It was our expecta-
tion that the steric unlikeness of various acetates result-
ing from primary, secondary, and tertiary alcohols could
also be differentiated by controlling the amount of
magnesium methoxide reagent. For this purpose, a
competitive deacylation reaction from a primary acetate
and a tertiary acetate was set out to test this hypothesis.
The other important aspect of selective ester depro-
tection is to differentiate the same type of esters, for
X Abstract published in Advance ACS Abstracts, December 1, 1996.
(1) Green, T. W.; Wuts, P. G. M. Protective Groups In Organic
Synthesis; Wiley & Sons: New York, 1991.
(2) Baptistella, L. H. B.; Dos Santos, J . F.; Ballabio, K. C.; Marsaioli,
A. J . Synthesis 1989, 436.
(3) Kunesch, N.; Meit, C.; Poisson, J . Tetrahedron Lett. 1987, 28,
3569.
(4) Neilson, T.; Werstiuk, E. S. Can. J . Chem. 1971, 49, 493.
(5) Ishido, Y.; Nakazaki, N.; Sakairi, N. J . Chem. Soc., Perkin Trans.
I 1979, 2088.
(8) Askin, D.; Angst, C.; Danishefsky, S. J . Org. Chem. 1987, 52,
622.
(9) Nudelman, A.; Herzig, J .; Gottlieb, H. E.; Keinan, E.; Sterling,
J . Carbohydr. Res. 1987, 162, 145.
(10) (a) Sweers, H. M.; Wong, C-H. J . Am. Chem. Soc. 1986, 108,
6421. (b) Kloosterman, M.; Mosuller, E. W. J .; Schoemaker, H. E.;
Meijer, E. M. Tetrahedron Lett. 1987, 28, 2989. (c) Chang, K. Y.; Wang,
K. T.; Wu, S. H. Carbohydr. Res. 1991, 222, 121.
(11) J ohns, W. F.; J erina, D. M. J . Org. Chem. 1963, 28, 2922.
(12) Herzig, J .; Nudelman, A.; Gottlieb H. E.; Fischer, B. J . Org.
Chem. 1986, 51, 727.
(6) Xu, Y. C.; Lebeau, E.; Walker, C. Tetrahedron Lett. 1994, 35,
6207.
(7) Xu, Y. C.; Bizuneh, A.; Walker, C. Tetrahedron Lett. 1996, 37,
455.
(13) Kato, K.; Hirata, Y.; Yamamura, S. Tetrahedron 1971, 27, 5987.
(14) Barua, N. C.; Schmidt, R. R. Synthesis 1986, 11, 891.
S0022-3263(96)01257-1 CCC: $12.00 © 1996 American Chemical Society

Selective Deprotection of Alkyl Acetates
J . Org. Chem., Vol. 61, No. 26, 1996 9087
Sch em e 1
Sch em e 2
As shown in Scheme 1, a mixture of primary acetate 1
(1.0 mmol) and tertiary acetate 2 (1.0 mmol) in methanol
was treated with 4.0 equiv of magnesium methoxide
under nitrogen at rt. The reaction was worked up after
6 h when acetate 1 was all consumed. A primary alcohol
3, resulting from deacylation of 1, was isolated in 94%
yield. Tertiary alcohol 4 was not detected from the
reaction mixture; instead, the tertiary acetate 2 was
recovered in 94% yield. Treatment of 2 with 15 equiv of
magnesium methoxide afforded 4 in 95% yield. These
experiments clearly indicate that it is possible to control
the rate of cleavage of primary acetate 1 and tertiary
acetate 2 by adjusting the amount of magnesium meth-
oxide.
Encouraged by this data, we decided to study system-
atically the selective deacylation reaction on a set of
substrates bearing two sterically different acetate func-
tionalities. Therefore, a series of diacetates 5, 8, and 11
was prepared from their corresponding diols 7 (hydroxy-
citronnellol), 10 (trans-sobrerol), and 13 (betulin), re-
spectively. The choice to prepare these diacetates for the
selective deacylation study is mainly due to the com-
mercial availability of the starting diols.
As indicated in Scheme 2, treatment of hydroxycitron-
nellol diacetate 5 with 4.0 equiv of magnesium methoxide
in methanol at rt for 14 h resulted in the formation of
monoacetate product 6 in 98% isolated yield. Only a
trace amount of hydroxycitronnellol (7) was observed on
TLC but could not be isolated due to the small quantity
of the material. The reaction is very selective with
deacylation occurring predominantly at the primary
acetate.
We next examined the selective deacylation reaction
on (()-trans-sobrerol diacetate (8), which bears two
acetates resulting from secondary and tertiary alcohols.
Upon treatment of compound 8 with 8.0 equiv of mag-
nesium methoxide at rt for 48h, sobrerol monoacetate (9)
was isolated in 94% yield. Diol 10 was only detected by
TLC and could not be isolated. In comparison with the
previous deacylation reaction (substrate 5), it has been
noted that more equivalents of reagents were required
for the substrate 8. The selective deacylation of 8 with
only 4 equiv of magnesium methoxide is too slow to be
practically useful. Although the steric difference between
the secondary acetate and the tertiary acetate in struc-
ture 8 is less than that of the primary acetate and the
tertiary acetate in structure 5, a very good selectivity for
diacetate 8 was still obtained.
these acetates. There was very little reaction observed
after compound 11 was treated with 4.0 equiv of mag-
nesium methoxide in methanol for 14 h. The deacylation
reaction began to proceed when 14.0 equiv of magnesium
methoxide was employed. The reaction mixture was
stirred at rt for 3 days before it was worked up, affording
81% yield of betulin monoacetate (12) along with only
14% of betulin (13). Although the selectivity has dropped
in comparison with the previous two cases, a syntheti-
cally useful yield of monoacetate 12 was obtained.
In order to compare magnesium methoxide with other
commonly used reagents for selective ester cleavage, we
tested the selective ester hydrolysis of betulin diacetate
(11) with sodium methoxide in methanol and THF. The
reaction progressed very slowly with up to 3.0 equiv of
sodium methoxide. With 5.0 equiv of the reagent, the
starting material was consumed in 2 days and betulin
monoacetate (12) and betulin (13) were isolated in 43%
and 53% yield, respectively. The selectivity is clearly
deteriorated in comparison with the previous reaction
using magnesium methoxide.
The requirement of 14.0 equiv of magnesium methox-
ide to cleave the primary acetate from compound 11 was
a little surprising because primary acetates of both
compounds 1 and 5 were removed cleanly with only 4.0
equiv of the reagent. Looking into the structure differ-
ences of these compounds, it was noted that compound
11 possesses a quaternary carbon R to the primary
acetate. In light of the changes of the reactivity (4.0
We then examined the selectivity among a primary
acetate and a secondary acetate for betulin diacetate (11).
It should be noted that both the primary acetate and the
secondary acetate in compound 11 have a similar qua-
ternary carbon residing next to them. This, however, is
not expected to influence the absolute difference between

9088 J . Org. Chem., Vol. 61, No. 26, 1996
Xu et al.
Sch em e 3
Sch em e 4
equiv vs 14.0 equiv) reflected by this steric difference, it
is envisioned that it might be possible to differentiate
two primary acetates by magnesium methoxide if â-posi-
tions of the primary acetates render a steric difference.
In order to test this hypothesis, a competitive deacylation
reaction of primary acetate 1 and primary acetate 11 was
carried out (Scheme 3). Upon treatment of the mixture
of compound 1 (0.5 mmol) and betulin diacetate (11) (0.5
mmol) with 4.0 equiv of magnesium methoxide at rt for
4 h, a primary alcohol 3, resulting from acetate 1, was
isolated in 96% yield. Betulin diacetate (11), intact under
these conditions, was almost fully recovered (98%).
In order to demonstrate the synthetic utility of mag-
nesium methoxide as a reagent for selective deacylation
reaction, a selective cleavage of an acetate for baccatin
III was investigated. There are two major reasons for
us to study baccatin III. First, there is a great deal of
interest in taxol analogs for developing potent anticancer
agents.15 Baccatin III, being a late stage intermediate,
has been used for the synthesis of taxol and taxol
analogs.16 Secondly, baccatin III, possessing three ac-
etates and one benzoate, is an ideal substrate to test the
selectivity of magnesium methoxide in the ester hydroly-
sis reaction.
As shown in Scheme 4, the reaction of 14 with 2.4 equiv
of magnesium methoxide in methanol at rt for 16 h
afforded a mixture of 10-deacetylbaccatin III (15) and 10-
deacetylbaccatin V (16) in 92% overall yield. The deacy-
lation occurred exclusively at the C-10 secondary acetate.
The tertiary acetates as well as the benzoate were not
impacted under these conditions. Compound 16 was
derived from product 15 by the epimerization at the C-7
position through a retro-aldol reaction. Such an epimer-
ization process under basic and acidic conditions has been
reported in the literature.17 10-Deacetylbaccatin III (15)
has been converted to taxol analogs of 10-deacetoxytaxol
and 10-deoxytaxotere, which are more cytotoxic than
taxol.16e
Con clu sion s
From this study, it has been demonstrated that mag-
nesium methoxide is an effective and selective reagent
for deprotection of a variety of acetates. By adjusting
the equivalents of the reagent, it is possible to effectively
differentiate among a primary acetate, a secondary
acetate, and a tertiary acetate. It is also possible to
selectively hydrolyze a primary acetate in the presence
of other primary acetates if the R-positions of these
acetates have different steric environments. Due to its
high selectivity in ester deprotection, magnesium meth-
oxide will find many applications in organic synthesis.
Exp er im en ta l Section
All experiments were run under a positive pressure of dry
nitrogen. Unless otherwise indicated all common reagents and
anhydrous solvents were used as obtained from commercial
suppliers without further purification. Magnesium methoxide
was purchased from Aldrich and stored under nitrogen.
Melting points were determined in open capillary tubes using
a capillary melting point apparatus and are uncorrected.
Routine 1H NMR spectra were recorded on
a 300 MHz
spectrometer. Infrared spectra were recorded on a FT-IR
spectrometer. Field desorption mass spectroscopy (FDMS) and
elemental analysis were carried out by Physical Chemistry
Laboratory at Lilly Corporate Center.
Com p etitive Dep r otection Rea ction of P r im a r y Ac-
eta te 1 a n d Ter tia r y Aceta te 2 w ith Ma gn esiu m Meth -
oxid e. To a stirred solution of 4-methoxyphenethyl acetate
(1) (194.0 mg, 1.0 mmol) and 2-phenyl-2-propyl acetate (2)
(187.0 mg, 1.0 mmol) in 20 mL of anhydrous methanol was
added dropwise 4.1 mL of 10.3% magnesium methoxide
solution in methanol (0.973 N, 4.0 mmol) under nitrogen at
rt. The progress of the reaction was monitored by TLC. After
the mixture was stirred at rt for 6 h, starting material 1 was
all consumed. HCl solution (0.2 N) was added until the pH of
the mixture equaled 4 to 5. Part of the methanol was removed
by reduced pressure. The product was extracted with dichlo-
romethane (30 mL × 5). The combined organic layer was dried
(Na2SO4), filtered, and concentrated. Flash chromatography
of the crude residue using hexanes and ethyl acetate (7:3) gave
4-methoxyphenethyl alcohol (3) (144.0 mg, 0.94 mmol) in 94%
yield along with recovered starting material 3 (176.0 mg, 0.94
mmol) in 94% yield. No 2-phenyl-2-propanol was detected.
Compound 3 has spectral data identical to that of the com-
mercially available authentic sample from Aldrich. Anal.
Calcd for C9H12O2: C, 71.03; H, 7.95. Found: C, 71.00; H, 7.76.
Selective Dea cyla tion Rea ction of Hyd r oxycitr on ellol
Dia ceta te (5) w ith Ma gn esiu m Meth oxid e. To a stirred
solution of diacetate 5 (327.3 mg, 1.27 mmol) in 12 mL of
anhydrous methanol was added dropwise 5.2 mL of 10.3%
(15) (a) Kingston, D. G. I.; Samaranayake, G.; Ivey, C. A. J . Nat.
Prod. 1990, 53, 1. (b) Kingston, D. G. I. Pharmacol. Ther. 1991, 52, 1.
(c) Guenard, D.; Gueritte-Voegelein, F.; Potier, P. Acc. Chem. Res. 1993,
26, 160. (d) Chen, S-H.; Kadow, J . F.; Farina, V. J . Org. Chem. 1994,
59, 6156.
(16) (a)Magri, N. F.; Kingston, D. G. I.; J itrangsri, C.; Piccariello,
T. J . Org. Chem. 1986, 51, 3239. (b) Gueritte-Voegelein, F.; Guenard,
D.; Lavelle, F.; LeGoff, M.-T.; Mangatal, L.; Potier, P. J . Med. Chem.
1991, 34, 992. (c) Swindell, C. S.; Krauss, N. E.; Horwitz, S. B.; Ringel,
I. J . Med. Chem. 1991, 34, 1176. (d) Georg, G. I.; Cheruvallath, Z. S.;
Himes, R. H.; Mejillano, M. R. Bioorg. Med. Chem. Lett. 1992, 2, 295.
(e) Chaudhary, A. G.; Kingston, D. G. I. Tetrahedron Lett. 1993, 34,
4921.
(17) (a) McLaughlin, J . L.; Miller, R. W.; Powell, R. G.; Smith, C.
R., J r. J . Nat. Prod. 1981, 44, 312. (b) Samaranayake, G.; Magri, N.
F.; J itrangsri, C.; Kingston, D. G. I. J . Org. Chem. 1991, 56, 5114. (c)
Chen, S-H.; Huang, S.; Wei, J .; Farina, V. Tetrahedron 1993, 49, 2805.

Selective Deprotection of Alkyl Acetates
J . Org. Chem., Vol. 61, No. 26, 1996 9089
magnesium methoxide solution in methanol (0.973 N, 5.06
mmol) under nitrogen at rt. The resulting mixture was stirred
at rt for 10 h. At this point, all starting material was
consumed. Besides major product 6, there was a faint spot
on TLC from the mixture corresponding to hydroxycitronellol
(7). Workup as described in the first experiment followed by
flash chromatography of the crude residue using hexanes and
ethyl acetate (6:4) gave 7-acetoxy-3,7-dimethyl-1-octanol (6)
(269.8 mg, 1.25 mmol) in 98% yield as a clear oil. No
hydroxycitronellol (7) was isolated. Compound 6: 1H NMR
(CDCl3) δ 0.95 (d, 3H, J ) 7.2 Hz), 1.10-1.40 (m, 5H), 1.42 (s,
6H), 1.59 (m, 2H), 1.71 (t, 2H, J ) 7.3 Hz), 1.99 (s, 3H), 3.71
(pseudo q, 2H, J ) 7.2 Hz); HRMS for C12H25O3 calcd 217.1804,
found 217.1798. Anal. Calcd for C12H24O3: C, 66.63; H, 11.18.
Found: C, 66.20; H, 10.79.
diacetate 11 (129.5 mg, 0.255 mmol) in 12 mL of anhydrous
methanol and 4 mL of anhydrous THF was added sodium
methoxide solid (13.5 mg, 0.25 mmol) under nitrogen at rt.
Very little progress of the reaction was observed after 2 h.
Additional portions of sodium methoxide were added (13.5 mg,
28 mg, 12 mg), with a total of 5.0 equiv of the reagent. The
resulting mixture was stirred at rt until the starting material
was consumed (2 days). Workup as described in the first
experiment followed by flash chromatography of the crude
residue using hexanes and ethyl acetate (4:1) gave betulin
monoacetate (12) (53.6 mg, 0.11 mmol) in 43.4% yield as a
white solid, along with the isolation of betulin (13) (59.9 mg,
0.135 mmol) in 53.1% yield as a white solid.
Com p etitive Dep r otection Rea ction of P r im a r y Ac-
et a t e 1 a n d Bet u lin Dia cet a t e (11) w it h Ma gn esiu m
Meth oxid e. To a stirred solution of 4-methoxyphenethyl
acetate (1) (97.0 mg, 0.5 mmol) and betulin diacetate (11)
(263.4 mg, 0.5 mmol) in 25 mL of anhydrous methanol was
added dropwise 2.0 mL of 10.3% magnesium methoxide
solution in methanol (0.973 N, 1.95 mmol) under nitrogen at
rt. The progress of the reaction was monitored by TLC. After
the mixture was stirred at rt for 4 h, starting material 1 was
all consumed. Workup as described in the first experiment
followed by flash chromatography of the crude residue using
hexanes and ethyl acetate (7:3) gave 4-methoxyphenethyl
alcohol (3) (73.1 mg, 0.48 mmol) in 96% yield along with
recovered betulin diacetate (11) (258.5 mg, 0.49 mmol) in 98%
yield. No betulin (13) was detected. Compound 3 has spectral
data identical to that of the commercially available authentic
sample from Aldrich. Anal. Calcd for C9H12O2: C, 71.03; H,
7.95. Found: C, 70.75; H, 8.09.
Selective Dea cyla tion Rea ction of (()-tr a n s-Sobr er ol
Dia ceta te (8) w ith Ma gn esiu m Meth oxid e. To a stirred
solution of diacetate 8 (344.7 mg, 1.35 mmol) in 14 mL of
anhydrous methanol was added dropwise 11.0 mL of 10.3%
magnesium methoxide solution in methanol (0.973 N, 10.70
mmol) under nitrogen at rt. The resulting mixture was stirred
at rt for 48 h. At this point, all starting material was
consumed. Besides major product 9, there was a very faint
spot on TLC from the mixture corresponding to (()-trans-
sobrerol (10). Workup as described in the first experiment
followed by flash chromatography of the crude residue using
hexanes and ethyl acetate (6:4) gave (()-trans-8-acetoxy-p-
menth-6-en-2-ol (9) (270.4 mg, 1.27 mmol) in 94% yield as a
clear oil. No (()-trans-sobrerol (10) was isolated. (()-trans-
8-Acetoxy-p-menth-6-en-2-ol (9): 1H NMR (CDCl3) δ 1.39-1.50
(m, 2H), 1.42 (s, 3H), 1.43 (s, 3H), 1.72-2.00 (m, 2H), 1.79 (br
s, 3H), 1.98 (s, 3H), 2.00-2.12 (m, 1H), 2.13-2.25 (m, 1H),
4.01 (m, 1H), 5.58 (m, 1H); FDMS 213.1 (M + H). Anal. Calcd
for C12H20O3: C, 67.89; H, 9.50. Found: C, 67.89; H, 9.66.
Selective Dea cyla tion Rea ction of Betu lin Dia ceta te
(11) w ith Ma gn esiu m Meth oxid e. To a stirred solution of
diacetate 11 (228.0 mg, 0.43 mmol) in 20 mL of anhydrous
methanol and 6 mL of anhydrous THF was added dropwise
6.4 mL of 10.3% magnesium methoxide solution in methanol
(0.973 N, 6.23 mmol) under nitrogen at rt. The resulting
mixture was stirred at rt for 3 days. At this point, all starting
material was consumed. Workup as described in the first
experiment followed by flash chromatography of the crude
residue using hexanes and ethyl acetate (4:1) gave betulin
monoacetate (12) (169.1 mg, 0.35 mmol) in 81% yield as a
white solid, along with the isolation of betulin (13) (27.4 mg,
0.06 mmol) in 14% yield as a white solid. Betulin monoacetate
(12): mp 256-258 °C; 1H NMR (CDCl3) δ 0.75-2.00 (m, 25H),
0.83 (s, 3H), 0.84 (s, 6H), 0.97 (s, 3H), 1.02 (s, 3H), 1.68 (br s,
3H), 2.04 (s, 3H), 2.31-2.42 (m, 1H), 3.32 (d, 1H, J ) 12.8
Hz), 3.80 (d, 1H, J ) 12.8 Hz), 4.41-4.51 (m, 1H), 4.58 (br s,
1H), 4.69 (br s, 1H); IR (neat) 3400 s, 2943 s, 1732 s, 1246 s,
1027 s cm-1; FDMS 484.3 (M+). Anal. Calcd for C32H52O3:
C, 79.29; H, 10.81. Found: C, 79.33; H, 10.85. Betulin (13)
has spectral data identical to that of the commercially avail-
able authentic sample from Aldrich: mp 254-256 °C (256-
257 °C was listed in Aldrich catalog).
Selective Dea cyla tion Rea ction of Ba cca tin III (14)
w ith Ma gn esiu m Meth oxid e. To a stirred solution of
baccatin III (14) (9.4 mg, 16.0 µmol) in 2 mL of anhydrous
methanol was added 40 µL of 10.3% magnesium methoxide
solution in methanol (0.973 N, 39.0 µmol) under nitrogen at
rt. The resulting mixture was stirred at rt for 16 h. At this
point, all starting material was consumed. Workup as de-
scribed in the first experiment followed by flash chromatog-
raphy of the crude residue using 10% methanol in dichlo-
romethane gave a fast-running product 16 (4.7 mg, 8.6 µmol)
in 54% yield, along with a slow-running product 15 (3.3 mg,
6.1 µmol) in 38% yield. The fast-running compound has
spectral data identical to that of the structure 16 reported in
the literature.18 Compound 16: FDMS 544 (M+, 100). The
slow-running compound has spectral data identical to the
structure 15 reported in the literature. Compound 15: FDMS
544 (M+, 100).
Ack n ow led gm en t. We thank Dr. J ohn M. Schaus
for his insightful suggestions as well as his assistance
in manuscript preparation.
J O961257B
Selective Dea cyla tion Rea ction of Betu lin Dia ceta te
(11) w ith Sod iu m Meth oxid e. To a stirred solution of
(18) Miller, R. W.; Powell, R. G.; Smith, C. R., J r.; Arnold, E.; Clardy,
J . J . Org. Chem. 1981, 46, 1469.