An improved method for the synthesis of allylic gem-diacetates from α, β-unsaturated aldehydes catalyzed by lithium tetrafluoroborate

Article abstract of DOI:10.1246/cl.2008.1248

An improved method for the synthesis of allylic gem-diace-tates (acylals) is described. The desired acylals are obtained by the reaction of α, β-unsaturated aldehydes with acetic anhydride using a catalytic amount of lithium tetrafluoroborate in diethyl ether at room temperature. Copyright

Full text of DOI:10.1246/cl.2008.1248

1248
Chemistry Letters Vol.37, No.12 (2008)
An Improved Method for the Synthesis of Allylic gem-Diacetates from ꢀ,ꢁ-Unsaturated
Aldehydes Catalyzed by Lithium Tetrafluoroborate
Fumiaki Ono, Kuniaki Nishioka, Shirou Itami, Hirotaka Takenaka, and Tsuneo SatoÃ
Department of Life Science, Kurashiki University of Science and the Arts, Kurashiki 712-8505
(Received September 1, 2008; CL-080825; E-mail: sato@chem.kusa.ac.jp)
An improved method for the synthesis of allylic gem-diace-
Table 1. Preparation of allylic gem-diacetates from ꢀ,ꢁ-unsat-
urated aldehydes using LiBF4
a
tates (acylals) is described. The desired acylals are obtained by
the reaction of ꢀ,ꢁ-unsaturated aldehydes with acetic anhydride
using a catalytic amount of lithium tetrafluoroborate in diethyl
ether at room temperature.
R2
R2 OAc
Ac2O
CHO
R1
R1
OAc
LiBF4
R3
R3
Yield
/%b
Time
/h
Entry
Substrate
Allylic gem-diacetates (acylals) have demonstrated a wide
range of applicability in directing organometallic transforma-
tions.1 The allylic diacetates are generally prepared by reaction
of ꢀ,ꢁ-unsaturated aldehydes and acetic anhydride catalyzed
by a variety of acid catalysts. However, significant amounts of
rearranged products (vinyl acetates) are also produced under
these conditions (Scheme 1). Although Trost et al. recently
reported that iron(III) chloride was the best catalyst for this
reaction among the various acid catalysts they tested,1h,1l this in-
volves some annoying problems. (1) Because iron(III) chloride
catalyzes not only the acylal formation but also its rearrange-
ment, it is necessary to quench the reaction before the complete
consumption of the starting aldehyde in order to obtain the de-
sired product with highly isomeric purity. (2) Aldehydes with
a tertiary alkyl ether functional group, which is readily cleaved
by iron(III) chloride, cannot be used. Thus, development of more
efficient catalysts for this reaction is still actively pursued by
synthetic chemists. As part of our ongoing program in develop-
ing new synthetic methods using lithium salts as mild Lewis acid
catalysts,2 we wish to report our findings wherein lithium tetra-
fluoroborate has been identified as a mild and effective acid cat-
alyst for this transformation.
1c
2c
CHO
CHO
22
22
83
87
CHO
CHO
88d
91d
3
4
2
n-C3H7
1.5
5
6
2
4
100
78d
CHO
CHO
CHO
R
R
OMe
7c
8c
R = R = n-C3H7
5
4
76
78
R−R = (CH2)5
CHO
9c
8
79
OCH2Ph
OR
Initially, (E)-2-hexenal was treated with 2.0 equiv of acetic
anhydride in the presence of 10 mol % of LiBF4 in diethyl ether
at room temperature for 2 h. After completion of the reaction
(monitored by GLC), the usual work-up of the reaction mixture
afforded crude product. GLC analysis of the crude product
showed the formation of (E)-2-hexene-1,1-diyl diacetate and
1-hexene-1,3-diyl diacetate in 93.4% and 1.5% yields, respec-
tively. Short column chromatography on silica gel provided iso-
merically pure (E)-2-hexene-1,1-diyl diacetate in 88% yield
(Table 1, Entry 3).3 Because of the low acidity of LiBF4, rear-
rangement was almost completely suppressed and the acylal for-
mation mainly proceeded. A screening of solvents revealed that
diethyl ether as a solvent gave the best result.4 Iron(III) chloride
protocol gave the product in 67% yield and with 96% isomeric
purity after silica gel flash chromatography.1h
CHO
Ph
10c
11c
12c
6.5
89
80
89
R = Ac
R = CH2OMe
0.25
8.5
R = SiMe2-t-C4H9
*
CHOe
13c
14
12
23
4
80
O
Ph
CHO
90
Ph
CHOf
15c
79f
n-C5H11
aConditions: substrate (2.0 mmol), Ac2O (4.0 mmol), LiBF4 (0.20
mmol), Et2O (2 mL), rt (15–25 ꢀC), unless otherwise noted. bIsolated
yield of isomerically pure product. cLiBF4 (0.60 mmol) was used. dTrace
amount of vinyl acetate (1.5–3.5% checked by GLC) was detected in the
R2
R2 OAc
OAc
R3
crude product. eAsterisk signifies the reactive site. E/Z = 90/10.
f
OAc
R2
R1
Ac2O
CHO
+
R1
R1
OAc
cat. acid catalyst
The scope and generality of the present method was then
tested by converting various other ꢀ,ꢁ-unsaturated aldehydes
into the corresponding gem-diacetates and the results are sum-
R3
R3
Scheme 1.
Copyright Ó 2008 The Chemical Society of Japan

Chemistry Letters Vol.37, No.12 (2008)
1249
marized in Table 1. A wide range of mono-, di-, and trisubstitut-
ed substrates underwent smooth diacetylation without any trace
of by-products arising from rearrangement (Entries 1, 2 and 5,
and 7–15). The case of (E)-4-methyl-2-pentenal (Entry 4) and
1-cyclohexene-1-carboxaldehyde (Entry 6) is worth mentioning
as these gave the desired acylals in 91% and 78% yields by our
method, in contrast to relatively moderate yields (64% and 50%)
of products by the FeCl3 protocol.1l Notably, aldehydes with a
tertiary alkyl ether functional group, which undergoes acylal for-
mation by the Trost method with difficulty,1l could easily be
converted into the corresponding gem-diacetates in good yields
(Entries 7–9).5 A variety of functional groups such as benzyloxy
(Entry 9), acetoxy (Entry 10), methoxymethoxy (Entry 11), tert-
butyldimethylsiloxy (Entry 12), and ketone (Entry 13) remained
intact under our reaction conditions. Exposure of ꢀ,ꢂ-dienal
(Entry 14) and ꢀ,ꢂ-enynal (Entry 15) to LiBF4/Ac2O furnished
the corresponding gem-diacetates in 90% and 79% yields,
respectively. These results clearly indicate the mildness and
the versatility of the present protocol.6
M. L. Crawley, Chem. Rev. 2003, 103, 2921. k) M. B.
Deshmukh, S. D. Jadhav, A. R. Mali, A. W. Suryawanshi,
P. V. Anbhule, S. S. Jagtap, S. A. Deshmukh, Synth. Com-
mun. 2005, 35, 2967. l) B. M. Trost, M. L. Crawley, C. B.
Lee, Chem.—Eur. J. 2006, 12, 2171. m) M. S. Reddy, M.
Narender, Y. V. D. Nageswar, K. R. Rao, Synth. Commun.
2007, 37, 1983.
a) F. Ono, R. Negoro, T. Sato, Synlett 2001, 1581. b) Y.
Nakae, I. Kusaki, T. Sato, Synlett 2001, 1584. c) N. Sumida,
K. Nishioka, T. Sato, Synlett 2001, 1921. d) N. Hamada, K.
Kazahaya, H. Shimizu, T. Sato, Synlett 2004, 1074. e) K.
Kazahaya, S. Tsuji, T. Sato, Synlett 2004, 1640. f) N.
Hamada, T. Sato, Synlett 2004, 1802.
LiBF4 was the best catalyst among the lithium salts exam-
ined under identical conditions: LiBr (0%), LiNTf2 (0%),
LiOTf (0%), and LiClO4 (0%).
Hexane (80%), THF (0%), EtOAc (0%), and CH3CN (0%).
When iron(III) chloride was used as catalyst in the reaction
of (2E)-4-methoxy-4-propyl-2-heptenal (neat, rt), a complex
mixture was obtained as indicated by TLC, and the desired
acylal was isolated in 35% yield.
Typical procedure (Table 1, Entry 3): A mixture of (E)-
2-hexenal (197 mg, 2.0 mmol), Ac2O (409 mg, 4.0 mmol),
LiBF4 (18.8 mg, 0.20 mmol), and Et2O (2 mL) was stirred
at room temperature for 2 h (monitored by GLC). After the
reaction was quenched with sat. NaHCO3 (2 mL), the result-
ing mixture was extracted with EtOAc (20 mL Â 2). The
combined extracts were successively washed with sat.
NaHCO3 (10 mL) and with sat. NaCl (10 mL). The organic
layer was dried (Na2SO4) and concentrated. GLC analysis
of the crude product indicated the formation of (E)-2-
hexene-1,1-diyl diacetate and 1-hexene-1,3-diyl diacetate
in 93.4% and 1.5% yields relative to n-C15H32 as an internal
standard. The crude product was purified by short column
chromatography on silica gel (3% EtOAc–hexane) affording
isomerically pure (checked by GLC and 500 MHz 1H NMR)
(E)-2-hexene-1,1-diyl diacetate (353 mg, 88%).
2
3
4
5
In conclusion, we have developed a mild and efficient meth-
od by which allylic gem-diacetates can be prepared from ꢀ,ꢁ-
unsaturated aldehydes and acetic anhydride in the presence of
catalytic of lithium tetrafluoroborate in good to high yields.
6
References and Notes
1
For example, see: a) A. Ghribi, A. Alexakis, J. F. Normant,
Tetrahedron Lett. 1984, 25, 3079. b) X. Lu, Y. Huang, J.
Organomet. Chem. 1984, 268, 185. c) B. M. Trost, J.
Vercauteren, Tetrahedron Lett. 1985, 26, 131. d) B. M.
Trost, C. B. Lee, J. M. Weiss, J. Am. Chem. Soc. 1995,
117, 7247. e) C. W. Holzapfel, L. Marais, Tetrahedron Lett.
1998, 39, 2179. f) F. R. van Heerden, J. J. Huyser, D.
Bradley, G. Williams, C. W. Holzapfel, Tetrahedron Lett.
1998, 39, 5281. g) J. S. Yadav, B. V. S. Reddy, G. S. K. K.
Reddy, Tetrahedron Lett. 2000, 41, 2695. h) B. M. Trost,
C. B. Lee, J. Am. Chem. Soc. 2001, 123, 3671. i) B. M. Trost,
C. B. Lee, J. Am. Chem. Soc. 2001, 123, 3687. j) B. M. Trost,
Published on the web (Advance View) November 8, 2008; doi:10.1246/cl.2008.1248