Fluorous distannoxane-catalyzed acetylation of alcohols in heterogeneous single fluorous solvent system

Article abstract of DOI:10.1016/j.tetlet.2005.03.055

Acetylation of alcohols with an equivalent amount of acetic anhydride is feasible in the presence of fluorous distannoxane catalyst in heterogeneous single fluorous system. The fluorous layer containing catalyst can be recycled and reused at least 10 times.

Full text of DOI:10.1016/j.tetlet.2005.03.055

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 3187–3189
Fluorous distannoxane-catalyzed acetylation of alcohols
in heterogeneous single fluorous solvent system
Zhihong Peng,a,b Akihiro Orita,b Delie Ana,* and Junzo Oterab,*
aDepartment of Chemistry, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China
bDepartment of Applied Chemistry, Okayama University of Science, Ridai-cho, Okayama 700-0005, Japan
Received 27 January 2005; revised 4 March 2005; accepted 10 March 2005
Available online 25 March 2005
Abstract—Acetylation of alcohols with an equivalent amount of acetic anhydride is feasible in the presence of fluorous distannoxane
catalyst in heterogeneous single fluorous system. The fluorous layer containing catalyst can be recycled and reused at least 10 times.
ꢀ 2005 Elsevier Ltd. All rights reserved.
The last decade has witnessed great advance in fluorous
biphase technology, which has now been modified into
several variations.1 The original protocol has its found-
ation on the thermomorphic nature of fluorous solvents.2
That is, innately immiscible fluorous and organic sol-
vents become homogeneous upon elevation of reaction
temperature so that the desired reaction could readily
proceed. Cooling the reaction mixture restores the two
phases, and the fluorous phase containing a fluorous
catalyst can be easily separated from the organic phase.
Thus, the key to smooth reaction is attainment of homo-
geneous conditions. However, it turned out recently that
heterogeneous conditions are also employable. For
instance, fluorous rhodium-catalyzed hydroboration
can be best performed in CF3C6F11 without the second
organic solvent.3 The mixture of substrate and borane
was not soluble in the fluorous phase during the reaction
at 40 ꢁC. We report herein that highly efficient and con-
venient acetylation of alcohols is feasible with fluorous
distannoxane catalyst 1 in a heterogeneous single fluor-
ous solvent system, which offers a novel means to immo-
bilize catalysts.4
techniques for removing the alcohol or water co-
product.
Rf Rf
Cl
Rf
Sn
Cl
O
Sn
Sn
O
Cl
Sn
Cl
Rf
Rf
Rf
Rf Rf
Rf = C6F13C2H4
1
In this protocol, reaction at 150 ꢁC under homogeneous
conditions is crucial for biasing the equilibrium in favor
of the products.6 Then, we were intrigued by applying
this technology to synthetically important acetylation
of alcohols. We expected that the reaction would
smoothly occur with an equivalent amount of acetic
anhydride even in a biphase system without elevation
of the reaction temperature because this reaction is a
non-equilibrium process. Thus, acetylation of 2-phenyl-
ethanol was attempted in the presence of 1 (5 mol %) in
FC-72/toluene or FC-72/CH2Cl2 (Table 1). The reaction
mixture was stirred at room temperature for 6 h while a
biphasic system was maintained. Unfortunately, how-
ever, yields of the desired acetate were only 72% and
56%, respectively. With these unsatisfactory results in
hand, we turned our attention to the single fluorous
solvent system without the second organic solvent. An
equimolar mixture of 2-phenylethanol and acetic anhy-
dride was added to an FC-72 solution of 1 (5 mol %).
The resulting heterogeneous mixture was stirred for
We earlier disclosed that fluorous distannoxane 1 effi-
ciently catalyzed (trans)esterification in a single fluorous
solvent.5 The perfect conversion was achieved using
reactants in a strict 1:1 ratio without recourse to any
Keywords: Fluorous distannoxane; Acetylation; Heterogeneous
catalysis.
*
Corresponding authors. Tel.: +81 86 256 9525; fax: +81 86 256
4292; e-mail: otera@high.ous.ac.jp
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.03.055

3188
Z. Peng et al. / Tetrahedron Letters 46 (2005) 3187–3189
Table 3.
6 h at room temperature, and the acetate was obtained
in 99% yield (Table 2, entry 1). The product was formed
atop the fluorous layer and extracted with octane which
is immiscible with FC-72. This operation is necessary
simply because of the small reaction scale and otherwise
a portion of the product remains on the surface of the
fluorous layer. In larger-scale reactions, however, the
product could be directly separated by means of syringe
(vide infra). From the fluorous layer, the catalyst was
recovered almost quantitatively,7 but partially in modi-
fied structures. Such modification is reminiscent of the
actual active species and thus caused no practical prob-
lem. In fact, the catalyst could be successfully recycled as
described later. Primary alcohols provided excellent
yields (entries 2 and 3). The mild conditions allowed
substrates involving various acid-sensitive moieties like
furfuryl alcohol, geraniol, and alcohols with THP,
TBS, acetonide, or carbomethoxy groups to undergo
smooth acetylation (entries 4–9). In all cases, excellent
yields were obtained even by use of just one equivalent
of acetic anhydride concomitant with quantitative
recovery of the catalyst. On the other hand, secondary
alcohols and phenol reacted sluggishly (entries 10–12).
1
OH
OAc
+
Ac2O
Ph
Ph
FC-72
20 mmol
Entry
Run
6
1
2
3
4
5
7
8
9
10
1a,b
2c,d
96
98
96
98
94
97
93
95
91
94
88
94
84
92
82
91
78
88
73
86e
a 1 (3 mol %) Ac2O (1.0 eq.), FC-72 (10 mL), rt, 12 h.
b Isolated yield.
c 1 (5 mol %) Ac2O (1.2 eq.), FC-72 (14 mL), rt, 9 h.
d GLC yield.
e After 10th run, 83% of catalyst was recovered.
3 mol % of 1 in FC-72 (10 mL). After reaction for
12 h, the upper organic layer was separated from the
fluorous layer by means of syringe and the acetate was
isolated through column chromatography after usual
workup. The catalyst solution can be used directly for
the next reaction without isolation of the catalyst. To
the FC-72 solution was added the alcohol and acetic
anhydride again, and the reaction was repeated as
above. The yield decreased gradually down to a 73%
isolated yield (75% by GLC) in the 10th run. Next,
the reaction was conducted using 1.2 equiv of acetic
anhydride in the presence of 5 mol % of 1 in FC-72
(14 mL). After 9 h, the yield was determined by GLC.
Under these conditions the yield in the 10th run was
increased to 86%. The catalyst was recovered in 83%
by weight after the 10th run.8
Finally, the recycled use of the catalyst was performed
for acetylation of 2-phenylethanol in a larger scale
(Table 3). First, the ester (20 mmol) was exposed to
one equivalent of acetic anhydride in the presence of
Table 1.
1 (5 mol%)
OH
OAc
+
Ac2O
Ph
Ph
rt, 6 h
(1.0 eq)
In summary, a single fluorous system has proved to be
more effective than that of the conventional biphasic
system for fluorous distannoxane-catalyzed acetylation.
Excellent yields of acetates of primary alcohols with var-
ious functions are obtained using just 1 equiv of acetic
Solvents
Yield (%)
Recovered catalysta (%)
FC-72/toluene
FC-72/CH2Cl2
72
56
90
91
a Determined by weight of the recovered catalyst.
Table 2. Acetylation of alcohols in a heterogeneous single fluorous system
1 (5 mol%)
ROAc
Yielda (%)
+
ROH
Ac2O
FC-72 (2 mL), rt
Entry
ROH
Time (h)
Recovered catalystb (%)
1
2
3
4
5
6
7
PhCH2CH2OH
PhCH2OH
C8H17OH
6
6
99
98
99
99
99
94
99
95
95
95
95
96
96
96
6
Furfuryl alcohol
Geraniol
6
6
THPO(CH2)8OH
TBSO(CH2)8OH
6
10
HO
O
O
8
7
98
95
9
MeOC(O)(CH2)8OH
PhCH(OH)CH3
2-Octanol
24
6
99
25
43
63
96
93
94
92
10
11
12
6
24
PhOH
a Isolated yield.
b Determined by weight of the recovered catalyst.

Z. Peng et al. / Tetrahedron Letters 46 (2005) 3187–3189
3189
3901; Mathivet, T.; Monflier, E.; Castanet, Y.; Mortreux,
A.; Couturier, J.-L. Tetrahedron 2002, 58, 3877;
(Trans)esterification with non-fluorous catalysts in fluorous
solvents was reported Zhu, D.-W. Synthesis 1993, 953;
Gacem, B.; Jenner, G. Tetrahedron Lett. 2003, 44, 1391.
5. Otera, J. Acc. Chem. Res. 2004, 37, 288.
6. Xiang, J.; Toyoshima, S.; Orita, A.; Otera, J. Angew.
Chem., Int. Ed. 2001, 40, 3670; Xiang, J.; Orita, A.; Otera,
J. Adv. Synth. Catal. 2002, 344, 84; Xiang, J.; Orita, A.;
Otera, J. Angew. Chem., Int. Ed. 2002, 41, 4117.
anhydride. The catalyst can be recycled at least 10 times
without significant loss of catalytic activity. Neither use
of the second organic solvent nor elevation of reaction
temperature makes operations very convenient and,
hence, the heterogeneous single fluorous system will find
many applications as a useful means to immobilize
catalysts.
References and notes
7. Usually, the catalyst was recovered more than 95% by
weight. It is reasonable to assume that the recovery is
virtually perfect because a slight loss might be attributed to
the small-scale reaction.
ˆ
1. Gladysz, J. A.; Correa da Costa, R. In Handbook of
Fluorous Chemistry; Gladysz, J. A., Curran, D. P.,
´
Horvath, I. T., Eds.; Wiley-VCH: Weinheim, 2004; Chapter
4.
2. Horvath, I. T.; Rabai, J. Science 1994, 266, 72; Horvath, I.
8. Representative procedure (Table 3, entry 1, run 1): To an
FC-72 solution (10 mL) of 1 (1.03 g, 0.6 mmol) was added
2-phenylethanol (2.44 g, 20.0 mmol) and acetic anhydride
(2.04 g, 20.0 mmol), and the mixture was stirred at rt for
12 h. After the organic layer had been separated from the
fluorous layer by a syringe and transferred to a separating
funnel, the syringe was rinsed with AcOEt (1 mL · 2). After
the organic layer was washed with NaHCO3aq (10 mL), the
aqueous layer was extracted with AcOEt (10 mL · 3), dried
over MgSO4, filtered, and evaporated. The combined
organic layer was subjected to column chromatography
on silica gel to afford 2-phenylethyl acetate (3.15 g, 96%).
The recovered FC solution of catalyst 1 was reused for the
next acetylation.
´
T. Acc. Chem. Res. 1998, 31, 641.
´
´
´
3. Juliette, J. J. J.; Horvath, I. T.; Gladysz, J. A. Angew.
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´
D.; Horvath, I. T.; Gladysz, J. A. J. Am. Chem. Soc. 1999,
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4. Hydroformylation in a homogeneous single flurous phase
was reported Foster, D. F.; Adams, D. J.; Gudmunsen, D.;
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