CuI/l-proline-catalyzed selective one-step mono-acylation of styrenes and stilbenes

Article abstract of DOI:10.1016/j.tetlet.2010.08.084

Vicinal di-oxygenation of styrene-type olefins was achieved with cheaper, less toxic CuI in the presence of l-proline as ligand and NaIO₄ as the oxidant. This approach provides a straightforward and efficient access to mono-acylated diols from both styrene and stilbene derivatives with good to excellent yields and diastereoselectivity.

Full text of DOI:10.1016/j.tetlet.2010.08.084

Tetrahedron Letters 51 (2010) 5771–5774
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
CuI/L-proline-catalyzed selective one-step mono-acylation of styrenes
and stilbenes
⇑
P. Sai Prathima, C. Uma Maheswari, K. Srinivas, M. Mohan Rao
Inorganic and Physical Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Vicinal di-oxygenation of styrene-type olefins was achieved with cheaper, less toxic CuI in the presence
Received 8 April 2010
Revised 24 August 2010
Accepted 27 August 2010
Available online 6 September 2010
of L-proline as ligand and NaIO4 as the oxidant. This approach provides a straightforward and efficient
access to mono-acylated diols from both styrene and stilbene derivatives with good to excellent yields
and diastereoselectivity.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Styrene
Copper iodide
L
-Proline
Mono-acylated diols
Di-oxygenation
Vicinal di-functionalizations are attractive synthetic tools as
they can be used to transform simple and readily available alkenes
into value added products. Transition metal-catalyzed vicinal di-
functionalizations of alkenes are among the most powerful tech-
niques for the synthesis of several organic building blocks.1 By
employing this strategy, in one-step, functionalized molecules
can be generated by methods such as di-amination, amino-oxygen-
ation, di-oxygenation, and di-methoxylation of olefins in a highly
regio- and enantio-selective manner.2 Among them, di-oxygena-
tion of alkenes gains its importance with the development of the
Sharpless asymmetric di-hydroxylation (ADH), where both enanti-
omers of the syn di-oxygenated products could selectively be ac-
cessed.3 The main disadvantage of the Sharpless procedure is the
toxicity associated with the osmium metal and its expensive
nature.
Recently, there has been a surge in reports of organic transfor-
mations catalyzed by cheaper and more benign metals such as
copper and iron that are predominantly found in metallo-enzymes
which play important roles in biological di-oxygen metabolism.8
The low cost, ample supply of Cu salts combined with their envi-
ronmentally benign nature and lack of toxicity make them ideal
for an industrial scale synthesis of specialty chemicals.9 Amin-
ohydroxylation of styrenes and activated olefins by Cu(TFA)2,10
copper-catalyzed allylic oxidation of olefins with peresters,11 and
copper-catalyzed enantio-selective intramolecular amino-oxygen-
ation of olefins12 were a few notable olefin oxidations mediated
by Copper. Till recently, di-oxygenation of olefins with Cu proved
to be of great challenge.13
Herein, we report a facile and highly selective synthesis of
mono-acylated diols from styrenes and stilbenes using inexpensive
This led to the development of alternate routes for di-oxygena-
tion, employing cheaper and environmentally benign catalytic sys-
tems. Several groups have reported Pd-catalyzed di-oxygenation of
alkenes, viz., hydroxyl acetoxylation of alkenes using cationic Pd
catalyst,4 Pd(II)-catalyzed aerobic di-alkoxylation of styrene deriv-
atives containing an o-phenol5 and aerobic di-acetoxylation of
alkenes with Pd(II) catalyst6 to name a few. A conceptually differ-
ent approach, where a metal-free di-hydroxylation of alkenes
employing LiBr as the catalyst in presence of commercially avail-
able NaIO4 or PhI(OAc)2 as oxidants has also been reported.7
CuI/L-proline catalytic system. This strategy represents an efficient,
convenient, and direct one-pot synthesis of mono-acylated diols
from styrene-type olefins.
Our initial aim was to develop a simple catalytic system for di-
hydroxylation of stilbenes with Cu salts. For the optimization stud-
ies, trans-stilbene was taken as the model substrate in presence of
NaIO4 as the oxidant. With various non-polar solvents, we could
not observe the desired product and polar solvents such as AcOH,
DMSO, and DMF were also screened. Among them AcOH proved
to be the best solvent and the analysis of final product revealed
that one of the hydroxyl group was selectively converted into –
OAc in the presence of AcOH. Inspired by this result, we optimized
the conditions for selective one-pot mono-acylation of stilbenes
and styrenes by treating trans-stilbene with several oxidants and
⇑
Corresponding author. Tel.: +91 40 27193510; fax: +91 40 27160921.
E-mail address: mandapati@iict.res.in (M.M. Rao).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.08.084

5772
P. S. Prathima et al. / Tetrahedron Letters 51 (2010) 5771–5774
Table 1
afforded improved yield compared to that of ligand-free condition
(entry 4). Varying different ligands does not produce any apprecia-
ble increase in the yield. Thus the optimized reaction condition for
Optimization conditions for mono-acylation of trans-stilbenea
mono-acylation of olefins was fixed and CuI/L-proline system was
proved to be the suitable catalytic system for this reaction.
Catalyst (10 mol %),
Oxidant (0.5 eq)
OH
With the optimized reaction condition in hand, the general
applicability of this reaction was tested with substituted styrenes,
di-substituted alkenes (trans-stilbenes), and a tri-substituted al-
kene and the results are summarized in Table 3. As expected, the
reaction was found to be faster with styrenes compared to stilb-
enes, which can be explained in terms of steric factors. In case of
styrenes, we focused our attention on the regioisomeric distribu-
tion of monoesters and found that acetylation was more favorable
at the least hindered site. Thus mono-acylation preferably occurs
at the primary carbon rather than at the sterically crowded second-
ary position (Scheme 1). Irrespective of the electronic nature of the
substituted styrenes, the reaction proceeds smoothly to give the
desired product in good to excellent yields (Table 3, entries 1–8).
When stilbene derivatives were taken as the substrates, there is
slight decrease in yield and the rate of the reaction (Table 4).
AcOH, 80 oC
OAc
1j
2j
Entry
Oxidantb
Catalyst
Yield (%)
GCc
Isolatedd
1
2
3
4
5
6
7
8
9
NaIO4
NaIO4
NaIO4
NaIO4
NaIO4
NaIO4
NaOCl
mCPBA
Oxone
PhI(OAc)2
H2O2
—
NRe
45
29
40
50
60
—
—
35
15
25
35
45
—
CuCl
CuSO4
Cu(OAc)2
CuBr
CuI
CuI
CuI
CuI
CuI
NRe
10
38
43
—
5
10
11
25
30
CuI
a
Reaction conditions: substrate 1j (1 mmol), oxidant (0.5–1 equiv), catalyst
(10 mol %), AcOH (3 mL), 80 °C, 18 h.
Table 3
b
CuI/L-proline-catalyzed mono-acylation of terminal olefinsa
NaIO4 = 0.5 equiv; NaOCl or oxone or mCPBA or PhI(OAc)2 or H2O2 = 1.0 equiv.
Determined by GC integration of crude product.
Isolated yield of 2j.
c
Entry
1
Olefin
Product
Yieldb (%)
79
d
e
Benzaldehyde was observed as the major product.
OH
OAc
2a
1a
copper salts and the results are summarized in Table 1. The reac-
tion fails to yield the desired product in the absence of copper (en-
try 1). Screening of various copper salts shows that CuI was the
suitable catalyst for this reaction in terms of both conversion and
selectivity (entries 2–6). Several oxidants were screened and
among them NaOCl and mCPBA do not afford the desired product
(entries 7 and 8). With oxone as the oxidant, only oxidatively
cleaved product, that is, benzaldehyde was observed as the major
product (entry 9). When PhI(OAc)2 and H2O2 were taken as the oxi-
dants, the yield and selectivity were appreciable (entries 10 and
11) but lower than that of NaIO4 (entry 6). Thus we can conclude
that CuI acts as the best catalyst and NaIO4 as the best oxidant
for this selective mono-acylation of olefins.
OH
Br
Cl
Br
Cl
2
3
4
5
85
82
80
79
OAc
1b
1c
2b
OH
OAc
2c
OH
F
F
OAc
2d
1d
OH
Despite the moderate conversion and selectivity for mono-acyl-
ation of trans-stilbene with CuI/NaIO4, the yields were very low. To
improve the over-all conversion and yield, we have screened sev-
OAc
O2N
Me
O2N
Me
1e
2e
OH
eral ligands for this reaction (Table 2). Among them, L-proline
6
7
75
72
OAc
2f
1f
Table 2
OH
Effect of ligands on mono-acylation of trans-stilbenea
MeO
MeO
OAc
1g
2g
CuI (10 mol%)
Ligand (10 mol%)
OAc
Ph
OH
Ph
Ph
Ph
OAc
NaIO4 (0.5 eq)
AcOH
8
76
OH
1h
1j
2j
2h
a
All reactions were carried out in 1 mmol scale in acetic acid solvent system at
Entry
Ligand
—
Time (h)
Yieldb (%)
80 °C, NaIO4 (0.5 equiv), CuI (10 mol %),
L
-proline (10 mol %), 18 h.
1
2
24
24
45
15
b
Isolated yield.
L
-Valine
Diaminocyclohexane
-Proline
3
4
72
18
5
74
L
OH
5
6
7
8
Picolinic acid
24
24
24
24
8
10
20
7
OAc
CuI/L-Proline
NaIO4
Ethylene diamine
2-Amino pyridine
1,2-Diamino benzene
OAc
+
OH
AcOH, 80 oC
R
R
R
a
All reactions were carried out on a 1 mmol reaction scale of (1j) using NaIO4
(0.5 equiv), CuI (10 mol %), AcOH (3 mL) at 80 °C.
5-6%
>90%
b
Isolated yield.
Scheme 1. Cu-catalyzed mono-acylation of styrenes.

P. S. Prathima et al. / Tetrahedron Letters 51 (2010) 5771–5774
5773
Table 4
CuI/L-proline-catalyzed mono-acylation of internal olefinsa
Entry
Olefin
Product
Yieldb (%)
72
OH
AcO
OH
AcO
1
1i
2i
2
3
4
74
75
76
1j
2j
OH
OAc
HO
Me
Me
Me
+
AcO
1k
1l
2k'
2k
2l
OAc
OH
AcO
OH
AcO
MeO
MeO
O2N
MeO
O2N
+
HO
OAc
2l
O2N
5
6
70
62
1m
+
HO
2m
2m'
Ph
Ph
OH
OAc
1n
2n
a
All reactions were carried out in 1 mmol scale in acetic acid solvent system at 80 °C, NaIO4 (0.5 equiv), CuI (10 mol %), L-proline (10 mol %).
Isolated yield.
b
C1
OAc
OH
CuI/L-Proline
NaIO4
+
OH
50
Scheme 2. Cu-catalyzed mono-acylation of stilbenes.
AcOH, 80 oC
OAc
50
R
C2
R
R
:
Remarkably, in the case of stilbenes, anti-isomers of the corre-
sponding mono-acetylated derivatives with dr >90% (entries 1–6)
were obtained exclusively. Both cis- and trans-stilbene gave the
anti-product in moderate yield (Table 4, entries 1 and 2). In case
of substituted stilbenes, mono-acylation can be possible at both
the position; C1 and C2, leading to two different regio-isomers.
In our case, we observed an inseparable mixture of both the iso-
mers in equal ratio (Table 4, entries 3–5 and Scheme 2). When a
tri-substituted olefin was taken, the reaction followed the similar
trend leading to the anti-product, but with lesser yield (Table 4,
entry 6).
The mono-acylated product thus obtained can be easily con-
verted into their respective diols in good yields by treatment with
simple base, that is, KOH in MeOH. The yields were good for both
styrene and stilbene derivatives (Scheme 3).
OH
i) CuI , L-Proline
NaIO4 , AcOH, 80oC
R2
R2
R1
R1
ii) KOH , MeOH, rt, 24 h
OH
Yield (%)b
R1 = Ph
R2 = H
75
In summary we have developed a straightforward and efficient
method to generate mono-acylated diols from styrenes and stilb-
enes using a simple, eco-economically friendly catalytic system,
R2 = H
R2 = H
R1
R1
=
=
Br
Cl
81
79
that is, CuI/L-proline and a cheap oxidant NaIO4. Structurally di-
verse styrenes and stilbenes were selectively converted into
mono-acylated product with good to excellent yields, and excellent
diastereoselectivity. Finally, the mono-acylated products, thus ob-
tained, can be easily converted into their corresponding diols by a
simple base treatment.
R1
=
R2 = H
70
72
R1 = Ph
R2 = Ph
Acknowledgment
Scheme 3. CuI/L
-proline catalyzed di-hydroxylation of styrenes and trans-stilbenea.
S.P. thanks Department of Biotechnology (DBT), New Delhi for
research fellowship.
Reagents: All reactions were carried out in 1 mmol scale in acetic acid at 80 °C,
NaIO4 (0.5 equiv), CuI (10 mol %),
L
-proline (10 mol %), 24 h. bIsolated yield.

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P. S. Prathima et al. / Tetrahedron Letters 51 (2010) 5771–5774
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