Erbium(III) triflate is a highly efficient catalyst for the synthesis of β-alkoxy alcohols, 1,2-diols and β-hydroxy sulfides by ring opening of epoxides

Article abstract of DOI:10.1055/s-0029-1216956

Chemo- and stereoselectivity in the ring-opening reaction of epoxides with erbium(III) triflate are described. Epoxides can be cleaved under neutral conditions with alcohols and thiols in the presence of catalytic amounts of Lewis acid, affording the corresponding β-alkoxy alcohols and β-hydroxy sulfides in high yields. In water, epoxide ring opening occurs to produce the corresponding diols in good yields.

Full text of DOI:10.1055/s-0029-1216956

PAPER
3433
Erbium(III) Triflate is a Highly Efficient Catalyst for the Synthesis of
b-Alkoxy Alcohols, 1,2-Diols and b-Hydroxy Sulfides by Ring Opening of
Epoxides
E
r(OTf) for the
S
e
ynthesis
o
n
f
b
-Alkoxy
A
a
lcohols, an
t
d
b
-Hy
o
droxy Sulfides Dalpozzo,a Monica Nardi,*a Manuela Oliverio,b Rosina Paonessa,b Antonio Procopiob
3
a
Dipartimento di Chimica, Università della Calabria, ponte Bucci cubo 12/c, 87030 Arcavacata di Rende (Cs), Italy
Fax +39(0984)493077; E-mail: nardi@unical.it
Dipartimento Farmacobiologico, Università della Magna Graecia, Complesso Ninì Barbieri, 88021 Roccelletta Di Borgia (CZ), Italy
b
Received 25 May 2009; revised 19 June 2009
Dedicated to Professor Giovanni Sindona on the occasion of his 60th birthday
under solvent-free conditions is an ideal green methodol-
Abstract: Chemo- and stereoselectivity in the ring-opening reac-
tion of epoxides with erbium(III) triflate are described. Epoxides
can be cleaved under neutral conditions with alcohols and thiols in
the presence of catalytic amounts of Lewis acid, affording the cor-
responding b-alkoxy alcohols and b-hydroxy sulfides in high
yields. In water, epoxide ring opening occurs to produce the corre-
sponding diols in good yields
ogy.10
In the course of our research program on Lewis acid cata-
lyzed reactions, we found that erbium triflate is a very
useful, environmentally friendly catalyst for several acid-
catalyzed reactions.11 Moreover, erbium(III) triflate
works under almost neutral conditions,12 and is therefore
tolerant towards many organic functional groups.
Key words: epoxides, Lewis acids, nucleophilic additions, ring
opening, green chemistry
Owing to its unique qualities, erbium triflate has already
proven to be a highly efficient and regioselective catalyst
for many reactions involving epoxides, such as the rear-
rangement to carbonyl compounds,13 the synthesis of ace-
tonides,14 the conversion into 1,2-diacetates,15 and the
preparation of b-amino alcohols.16
Epoxides play an increasingly pivotal role in organic syn-
thesis as versatile synthetic intermediates. Their ring-
opening reaction is an important process in organic trans-
formations that is widely applied in pharmaceutical1 and
natural product chemistry.2 The inherent polarity and
strain of the three-membered oxirane ring make them sus-
ceptible to reaction with a wide number of reagents, in-
cluding nucleophiles, acids, bases, reducing and oxidizing
agents.3
In this paper, we wish to report that erbium(III) triflate
[Er(OTf)3] can act as a mild and efficient Lewis acid cat-
alyst for the regio- and stereoselective ring opening of ep-
oxides with both oxygen and sulfur nucleophiles such as
water, primary, secondary, tertiary or aromatic alcohols
and thiols.
Epoxide ring-opening reactions to give b-amino alco-
hols,4 1,2-diacetates,5 and carbonyl compounds,6 as well
as hydrolysis,7 alcoholysis,8 and thiolysis9 are convenient,
practical and widely employed strategies for the synthesis
of important classes of intermediates in organic chemis-
try.
The reaction of styrene oxide (1a) with methanol in the
presence of only 0.1 mol% Er(OTf)3 proceeded smoothly
under mild conditions with excellent conversion in a short
reaction time. When the reaction was performed in the ab-
sence of Er(OTf)3, 1a was recovered entirely unreacted,
whereas higher catalyst amounts (1 mol%) allowed 1a to
rearrange to the carbonyl compound.13 Almost equimo-
lecular amounts of reagents or slight excess of alcohol
form a homogeneous mixture, so the reaction can be con-
sidered to be solvent-free.
In spite of their respective features, the reported methods
for the preparation of 1,2-diol, b-alkoxy alcohols and b-
hydroxy sulfides, in particular, suffer from drawbacks in
one way or another. The widespread applicability of such
reactions in most cases is, however, restricted by the
handling of toxic and/or expensive reagents, intolerance
to highly sensitive groups, the formation of unwanted by-
products and, for thiolysis in particular, the need to adopt
an appropriate pH value that ensures good regioselectivity
and minimizes the formation of side-products.
It is noteworthy that 2-methoxy-2-phenylethanol (3aa)
was almost exclusively obtained, proving the high degree
of regioselectivity achieved in this reaction (Table 1). On
the other hand, upon the addition of amines to 1a, a mix-
ture of regioisomers was generally obtained where the for-
mation of either isomer could prevail depending from the
nature of the amine.16
Recently, organic reactions using reusable and water-
tolerant catalysts have received much attention. Further-
more, employing simple catalysts with high activity,
δ–
Er(OTf)3
(TfO)3Er–
Ph
OMe
δ+
O
O+
OH
Ph
Ph
SYNTHESIS 2009, No. 20, pp 3433–3438
x
x.
x
x
.
2
0
0
9
MeOH
Advanced online publication: 21.08.2009
DOI: 10.1055/s-0029-1216956; Art ID: Z11109SS
A
© Georg Thieme Verlag Stuttgart · New York
Scheme 1

3434
R. Dalpozzo et al.
PAPER
Table 1 Alcoholysis and Hydrolysis of Epoxides by Er(OTf)3 at Room Temperaturea
OR3
OH
O
OR3
OH
R3OH
+
R1
R1
+
R1
R2
R2
R2
1
2
a
a: R1 = Ph, R2 = H
: R3 = Me
3
4
b: R1–R2= -(CH2)4-
b: R3 = Et
c: R1 = PhOCH2, R2 = H c: R3 = i-Pr
d: R1 = AllOCH2, R2 = H d: R3 = t-Bu
e: R1 = Bu, R2 = H
e: R3 = C6H11
f: R3 = Ph
g: R3 = Bn
h: R3 = H
Entry
Epoxide
R3OHb
Product
Time (min)
Yield (%)c
3/4
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
2a
2b
2c
aa
ab
ac
ad
ae
af
30
45
90
90
180
1440
60
100
100
100
80
100
100
75
100:0
100:0
100:0
100:0
100:0
100:0
100:0
–
2d
2e
2fd
2g
2he
ag
ah
30
100
9
10
11
12
13
14
15
16
2a
2b
2c
ba
bb
bc
bd
be
bf
45
45
60
120
360
2880
60
100
100
100
67
95
80
2d
2e
2fd
2g
2he
bg
bh
100
100
60
17
18
19
20
21
22
23
24
2a
2b
2c
ca
cb
cc
cd
ce
cf
30
45
60
150
580
2880
90
100
90
90
59
85
70
70
100
0:100
0:100
0:100
0:100
0:100
0:100
0:100
–
2d
2e
2fd
2g
2he
cg
ch
60
25
26
27
28
29
30
31
32
2a
2b
2c
da
db
dc
dd
de
df
90
90
90
220
120
1440
90
75
70
70
76
80
70
70
75
0:100
0:100
0:100
0:100
0:100
0:100
0:100
–
2d
2e
2fd
2g
2he
dg
dh
90
33
34
35
36
37
38
39
40
2a
2b
2c
ea
eb
ec
ed
ee
ef
90
90
90
180
120
1440
120
60
75
70
70
65
90
90
70
100
0:100
0:100
0:100
0:100
0:100
0:100
0:100
–
2d
2e
2fd
2g
2he
eg
eh
a Catalyst: 0.1 mol% (entries 1–8) or 1 mol% (entries 9–40).
b Alcohol: 1.2 mol per mole of 1. Solvent-free.
c Isolated yield based on epoxides.
d Et2O as solvent.
e H2O–MeCN mixture.
Synthesis 2009, No. 20, 3433–3438 © Thieme Stuttgart · New York

PAPER
Er(OTf)3 for the Synthesis of b-Alkoxy Alcohols and b-Hydroxy Sulfides
3435
The present results appear to have come about as an obvi- on the other hand, crowded amines did not decrease yield
ous consequence of the involvement of a carbonium ion but inverted the regiochemistry.16
intermediate that is formed by a Lewis acid assisted ring-
In addition, an electronic effect seemed to affect epoxide
opening reaction.17 The Er(OTf)3-catalyzed ring opening
ring opening. In fact, attack of the less nucleophilic phe-
of an unsymmetrically polarized epoxide proceeds via
cleavage of the C–O bond in a manner that gives the best
nol (2f) produced the b-hydroxy ether (3af) after very
long reaction times (Table 1, entry 6). However, this reac-
stabilization of the developing positive charge (structure
tion was carried out in ethereal solution, because the re-
A, Scheme 1). Thus, the benzylic position is the favored
agents did not dissolve each other, so the influence of
solvent could be invoked to explain this behavior.
site for the nucleophilic attack of methanol (2a), which
gives rise to the formation of 2-methoxy-2-phenylethan-
1-ol (3aa) with essentially complete regioselectivity.
In order to increase the merit of the present method, the
procedure was then applied successfully to various 1,2-
epoxides (1b–e) and, as expected because of the mild con-
ditions employed, it was found to be compatible with sub-
In order to extend this simple procedure, we decided to in-
vestigate the ring-opening reaction of styrene oxide (1a)
using several other alcohols (2b–g) and water (2h)
strates containing delicate functionalities (Table 1, entries
(Table 1, entries 2–8). Among the tested compounds,
9–40). Yields and reaction times followed a trend similar
small alcohols and water generally gave the best yields
to those obtained with styrene oxide.
and the shortest reaction times. As the alkyl group of the
In these reactions 1 mol% of catalyst was employed in
order to ensure comparable reaction times and yields. It is
alcohol became bulkier, the reaction times increased, thus,
the ring-opening reaction with tert-butanol produced b-
hydroxy ether (3ad) in only low yield (Table 1, entry 4).
well-established that rearrangement is much slower with
aliphatic epoxides.13
Nucleophilic attack of the alcohol on the benzylic site of
As expected, the aliphatic oxiranes gave major products
the epoxide might be controlled by steric constraints and
with the opposite regiochemistry to those obtained from
it is quite clear that a bulky alkyl group on the alcohol re-
aromatic epoxides: in the former, steric factors predomi-
tards the reaction due to bulkiness. It is worth noting that,
nate over electronic effects.
Table 2 Thiolysis of Epoxides in Acetonitrile Using 1 mol% of Er(OTf)3 at Room Temperature
SR3
OH
OH
SR3
1a–c + R3SH
R1
R1
+
R2
R2
5
a: R3 = C6H11
7
6
b: R3 = Ph
c: R3 = Bn
d: R3 = 4-MeC6H4
e: R3 = C8H17
f: R3 = C6H13
Entry
Epoxide
R2SHa
Product
Time (min)
Yield (%)b
6/7
1
2
3
4
5
6
1a
1b
1c
5a
5bc
5c
5d
5e
5f
aa
ab
ac
ad
ae
af
30
1220
45
560
60
30
98
100:0
100:0
98:2
100:0
45:55
43:57
100
100
100
100
100
7
8
9
10
11
12
5a
5bc
5c
5d
5e
5f
ba
bc
bd
be
bf
120
90
90
560
120
120
65
70
70
86
75
60
13
14
15
16
17
18
5a
5bc
5c
5d
5e
5f
ca
cb
cc
cd
ce
cf
90
90
98
560
120
120
75
68
78
83
85
85
0:100
0:100
0:100
0:100
0:100
0:100
a Thiol: 1.1 mol per mole of 1.
b Isolated yield based on epoxides.
Synthesis 2009, No. 20, 3433–3438 © Thieme Stuttgart · New York

3436
R. Dalpozzo et al.
PAPER
All known products were identified by comparison of their EI-MS
The same reaction was then extended to ring opening of
epoxides with thiols to produce b-hydroxysulfides. Reac-
tion conditions ware slightly modified in order to ensure
homogeneity of the mixture, by adding a little acetonitrile
as solvent.
1
and H NMR spectral data with literature reported data: 3aa,8d
3ab,8d 3ac,8d 3ad,8d 3ae,17c 3af,17c 3ag,17c 3ba,8d 3bb,8d 3bc,8d 3bd,8d
3be,17c 3bf,17c 3bg,17c 4ca,8d 4cb,8d 4cc,8d 4cd,8d 4ce,17c 4cf,17c 4cg,17c
4da,8d 4db,8d 4dc,8d 4dd,8d 4de,17c 4df,17c 4dg,17c 4ea,17c 4eb,17c
4ec,17c 4ed,17c 4ee,17c 4ef,17c 4eg,17c 6aa,18 6ab,9i 6ac,9j 7ac,9j 6ad,9j
6ba,18 6bb,9j 6bc,9j 6bd,9j 6be,19 6bf,19 7cb,9j 7cc,9j and 7cd.9j
Significantly, the reaction with 1a did not show rearrange-
ment to the carbonyl compound with 1 mol% of catalyst.
Diols 3ah–eh were identical to authentic compounds.
Yields were always found to be good to excellent and
regioselectivity was complete in the aliphatic epoxide 1c.
In contrast, styrene oxide (1a) showed significant loss of
selectivity with long-chain thiols (Table 2, entries 5–6).
2-(Octylthio)-2-phenylethanol (6ae)
Colorless oil.
1H NMR (CDCl3): d = 0.83–0.92 (m, 3 H), 1.18–1.29 (m, 8 H),
1.32–1.40 (m, 2 H), 1.45–1.65 (m, 2 H), 2.53 (t, J = 7.27 Hz, 2 H),
3.80–3.88 (m, 2 H), 3.93 (dd, J = 8.07, 6.06 Hz, 1 H), 7.25–7.31 (m,
5 H).
In conclusion, erbium(III) triflate provides a genuinely
‘green’, economically convenient, practical and regiose-
lective method for alcoholysis of epoxides under solvent- 13C NMR (CDCl3): d = 140.80 (C), 130.40 (2 × CH), 128.34 (CH),
125.49 (2 × CH), 66.39 (CH2), 53.10 (CH), 32.56 (CH2), 31.97
(CH2), 29.88 (CH2), 28.18 (CH2), 24.97 (CH2), 23.37 (CH2), 21.75
(CH2), 14.80 (CH3).
MS (EI): m/z (%) = 266 (1) [M+], 145 (68), 107 (100), 103 (20), 91
free conditions. Hydrolysis and thiolysis need low
amounts of solvent, without diminishing the merit of the
protocol. The present procedure does not need sophisticat-
ed equipment, and uses a non-toxic catalyst. The catalyst
can be easily and consistently recovered,13–16 so signifi-
cant release into the environment can be avoided.
(14), 79 (58), 77 (32).
2-(Hexylthio)-2-phenylethanol (6af)
Colorless oil.
1H NMR and 13C NMR spectra were recorded with a Bruker
WM300 instrument operating at 300 MHz and 75 MHz, respective-
ly. Chemical shift (d) are given in ppm from TMS as internal stan-
dard, coupling constants (J) are given in Hertz. Reactions were
monitored by a GC-MS Shimadzu workstation fitted with a GC
2010 (30 m, QUADREX 007-5MS capillary column, operating in
splitless mode; 1 mL/min flow of He as carrier gas) and a 2010 qua-
drupole mass-detector. Commercial reagents (Aldrich or Fluka)
were used without further purification.
1H NMR (CDCl3): d = 0.81–0.92 (m, 3 H), 1.20–1.40 (m, 6 H),
1.45–1.65 (m, 2 H), 2.40 (t, J = 7.27 Hz, 2 H), 3.80–3.88 (m, 2 H),
3.95 (dd, J = 7.67, 6.06 Hz, 1 H), 7.23–7.25 (m, 5 H).
13C NMR (CDCl3): d = 140.59 (C), 129.80 (2 × CH), 128.22 (CH),
125.51 (2 × CH), 71.50 (CH2), 53.00 (CH), 32.95 (CH2), 32.05
(CH2), 30.58 (CH2), 29.24 (CH2), 23.26 (CH2), 15.00 (CH3).
MS (EI): m/z (%) = 238 (1) [M+], 132 (74), 117 (61), 107 (100), 84
(43), 79 (71).
2-(Octylthio)-1-phenylethanol (7ae)
Colorless oil.
b-Hydroxy Ether Synthesis; General Procedure
To a solution of epoxide 1a–e (1 mmol) in the appropriate alcohol
2a–d or 2f,g (1.2 mmol), Er(OTf)3 (0.1 mmol) was added and the
mixture was stirred at 25 °C (reaction was monitored by TLC). Sat.
NaHCO3 (30 mL) was added and the mixture was extracted with
CH2Cl2 (3 × 15 mL). The organic layer was separated and dried
with Na2SO4. Evaporation of the solvent followed by chromatogra-
phy on a short silica gel column gave the corresponding product.
1H NMR (CDCl3): d = 0.83–0.92 (m, 3 H), 1.18–1.29 (m, 8 H),
1.32–1.40 (m, 2 H), 1.45–1.65 (m, 2 H), 2.42 (t, J = 7.27 Hz, 2 H),
2.72 (dd, J = 13.72, 9.69 Hz, 1 H), 2.92 (dd, J = 13.72, 3.63 Hz,
1 H), 4.71 (ddd, J = 9.69, 3.64, 2.42 Hz, 1 H), 7.23–7.25 (m, 5 H).
13C NMR (CDCl3): d = 143.30 (C), 129.75 (2 × CH), 127.61 (CH),
125.44 (2 × CH), 71.90 (CH), 34.14 (CH2), 31.97 (CH2), 30.38,
29.88 (CH2), 28.18 (CH2), 24.97 (CH2), 23.37 (CH2), 21.75 (CH2),
14.80 (CH3).
Phenol (2e) and 1a–e gave heterogeneous mixtures, so Et2O (2 mL)
was added to ensure solubility. Upon completion, the solvent was
removed by rotary evaporation and the residue treated as above.
MS (EI): m/z (%) = 266 (6) [M+], 235 (100), 145 (3), 123 (21), 121
(21), 103 (34), 91 (84), 77 (13).
1,2-Diol Synthesis; General Procedure
To a solution of 1a–e (1 mmol) in MeCN–H2O (1:1, 2 mL),
Er(OTf)3 (0.1 mmol) was added and the mixture was stirred at 25 °C
(reaction monitored by TLC). After completion of the reaction, the
solution was extracted with EtOAc (3 × 15 mL). The organic layer
was separated and dried with Na2SO4. Evaporation of the solvent
followed by chromatography on a short silica gel column gave the
corresponding product.
2-(Hexylthio)-1-phenylethanol (7af)
Colorless oil.
1H NMR (CDCl3): d = 0.81–0.92 (m, 3 H), 1.20–1.40 (m, 6 H),
1.45–1.65 (m, 2 H), 2.52 (t, J = 7.27 Hz, 2 H), 2.70 (dd, J = 9.63,
9.29 Hz, 1 H), 2.92 (dd, J = 13.72, 3.63 Hz, 1 H), 4.73 (dd, J = 9.69,
3.63 Hz, 1 H), 7.23–7.25 (m, 5 H).
13C NMR (CDCl3): d = 143.35 (C), 130.57 (2 × CH), 127.71 (CH),
125.28 (2 × CH), 73.33 (CH), 33.05 (CH2), 32.95 (CH2), 32.05
(CH2), 30.58 (CH2), 29.24 (CH2), 23.26 (CH2), 15.00 (CH3).
MS (EI): m/z (%) = 238 (9) [M+], 207 (100), 122 (31), 117 (3), 107
(3), 103 (38), 91 (88), 77 (17).
b-Hydroxysulfide Synthesis; General Procedure
To a solution of 1a–c (1 mmol) in MeCN (2 mL), the appropriate
thiol 5a–f (1.1 mmol) and Er(OTf)3 (0.1 mmol) were added and the
mixture was stirred at 25 °C (reaction monitored by TLC). After
completion of the reaction, solvent was evaporated under reduced
pressure. Sat. NaHCO3 (30 mL) was added and the mixture was ex-
tracted with CH2Cl2 (3 × 15 mL). The organic layer was separated
and dried with Na2SO4. Evaporation of the solvent followed by
chromatography on a short silica gel column gave the correspond-
ing product.
1-(Cyclohexylthio)-3-phenoxypropan-2-ol (7ca)
Colorless oil.
1H NMR (CDCl3): d = 1.22–1.34 (m, 6 H), 1.71–1.76 (m, 4 H),
1.96–1.98 (m, 1 H), 2.73 (dd, J = 13.72, 6.86 Hz, 1 H), 2.88 (dd, J =
Synthesis 2009, No. 20, 3433–3438 © Thieme Stuttgart · New York

PAPER
Er(OTf)3 for the Synthesis of b-Alkoxy Alcohols and b-Hydroxy Sulfides
3437
13.72, 5.25 Hz, 1 H), 3.99–4.08 (m, 3 H), 6.89–6.93 (m, 3 H), 7.25–
7.29 (m, 2 H).
13C NMR (CDCl3): d = 159.31 (C), 130.05 (2 × CH), 121.99 (CH),
116.45 (2 × CH), 71.00 (CH2), 68.77 (CH), 45.65 (CH), 34.61
(CH2), 28.33 (2 × CH2), 26.50 (2 × CH2), 25.21 (CH2).
MS (EI): m/z (%) = 266 (15) [M+], 245 (25), 173 (21), 155 (100),
133 (53), 94 (61), 83 (81), 55 (63).
(4) See among others: (a) Zhao, P. Q.; Xu, L. W.; Xia, C. G.
Synlett 2004, 846. (b) Bartoli, G.; Bosco, M.; Carlone, A.;
Locatelli, M.; Melchiorre, P.; Sambri, L. Org. Lett. 2004, 6,
3973. (c) Mirkani, V.; Tangestaninejad, S.; Yadollahi, B.;
Alipanah, L. Catal. Lett. 2005, 101, 93. (d) Bartoli, G.;
Bosco, M.; Carlone, A.; Locatelli, M.; Melchiorre, P.;
Sambri, L. Org. Lett. 2005, 7, 1983. (e) Ertürk, E.; Demir,
A. S. ARKIVOC 2008, (ii), 160.
(5) See among others: (a) Tatarova, L. E.; Korchagina, D. V.;
Volko, K. P.; Salakhutdinov, N. F.; Barkhash, V. A. Russ. J.
Org. Chem. 2003, 39, 1076; Chem. Abstr. 2004, 140,
271015. (b) Fan, R. H.; Hou, X. L. Tetrahedron Lett. 2003,
44, 4411. (c) Fogassy, G.; Pinel, C.; Gelbard, G. Catal.
Commun. 2009, 10, 557.
(6) See among others: (a) Bathia, K. A.; Eash, K. J.; Leonard, N.
M.; Oswald, M. C.; Mohan, R. S. Tetrahedron Lett. 2001,
42, 8129. (b) Serrano, D. P.; van Grieken, R.; Melero, J. A.;
García, A. Appl. Catal., A 2007, 319, 171.
(7) See among others: (a) Reddy, M. A.; Surendra, K.;
Bhanumathi, N.; Rao, K. R. Tetrahedron 2002, 58, 6003.
(b) Boruwa, J.; Borah, J. C.; Kalita, B.; Barua, N. C.
Tetrahedron Lett. 2004, 45, 7355. (c) Salehi, P.; Dabiri, M.;
Zolfigol, M. A.; Fard, M. A. B. Phosphorus, Sulfur Silicon
Relat. Elem. 2004, 179, 1113. (d) Sengul, M. E.; Menzek,
A.; Sahin, E.; Arik, M.; Saracoglu, N. Tetrahedron 2008, 64,
7289. (e) Cavdar, H.; Saracoglu, N. Tetrahedron 2009, 65,
985.
1-(Octylthio)-3-phenoxypropan-2-ol (7ce)
Colorless oil.
1H NMR (CDCl3): d = 0.86 (t, J = 6.45 Hz, 3 H), 1.27–1.28 (m,
8 H), 1.33–1.35 (m, 2 H), 1.55–1.59 (m, 2 H), 2.54 (t, J = 7.27 Hz,
2 H), 2.73 (dd, J = 13.72, 7.27 Hz, 1 H), 2.85 (d, J = 6.06 Hz, 1 H),
4.00–4.10 (m, 3 H), 6.82–6.99 (m, 3 H), 7.22–7.32 (m, 2 H).
13C NMR (CDCl3): d = 159.12 (C), 130.15 (2 × CH), 123.20 (CH),
116.39 (2 × CH), 71.18 (CH2), 70.40 (CH), 33.44 (CH2), 32.62
(CH2), 32.01 (CH2), 29.62 (CH2), 28.13 (CH2), 25.04 (CH2), 21.75
(CH2), 15.61 (CH2), 14.00 (CH3).
MS (EI): m/z (%) = 296 (16) [M+], 278 (19), 203 (67), 185 (100),
159 (6), 145 (5), 133 (66), 107 (20), 105 (14), 94 (40), 77 (26), 69
(27), 57 (27), 43 (51).
1-(Hexylthio)-3-phenoxypropan-2-ol (7cf)
Colorless oil.
1H NMR (CDCl3): d = 0.81–0.92 (m, 3 H), 1.53–1.63 (m, 2 H), 2.54
(t, J = 7.27 Hz, 2 H), 2.71 (dd, J = 13.72, 7.27 Hz, 1 H), 2.82 (dd,
J = 13.72, 4.84 Hz, 1 H), 4.10 (m, 3 H), 6.91 (m, 3 H), 7.25 (m,
2 H).
13C NMR (CDCl3): d = 159.13 (C), 130.20 (2 × CH), 121.0 (CH),
116.36 (2 × CH), 71.14 (CH2), 68.53 (CH), 34.75 (2 × CH2), 33.76
(CH2), 30.41 (CH2), 23.28 (CH2), 15.52 (CH2), 13.97 (CH3).
(8) See among others: (a) Kantam, M. L.; Jeyalakshmi, K. A.
K.; Likhar, P. R. Catal. Lett. 2003, 89, 95. (b)Mirkhani,V.;
Tangestaninejad, S.; Yadollahi, B.; Alipanah, L.
Tetrahedron 2003, 59, 8213. (c) Moghadam, M.;
Tangestaninejad, S.; Mirkhani, V.; Shaibani, R. Tetrahedron
2004, 60, 6105. (d) Kim, B. H.; Piao, F.; Lee, E. J.; Kim, J.
S.; Jun, Y. M.; Lee, B. M. Bull. Korean Chem. Soc. 2004, 25,
881. (e) Firouzabadi, H.; Iranpoor, N.; Jafari, A. A.;
Makarem, S. J. Mol. Catal. A: Chem. 2006, 250, 237.
(f) Robinson, M. W. C.; Buckle, R.; Mabbett, I.; Grant, G.
M.; Graham, A. E. Tetrahedron Lett. 2007, 48, 4723.
(g) Leitao, A. J. L.; Salvador, J. A. R.; Pinto, R. M. A.;
Sà e Melo, M. L. Tetrahedron Lett. 2008, 49, 1694.
(9) See among others: (a) Fringuelli, F.; Pizzo, F.; Tortoioli, S.;
Vaccaro, L. Adv. Synth. Catal. 2002, 344. (b) Fringuelli,
F.; Pizzo, F.; Tortoioli, S.; Vaccaro, L. J. Org. Chem. 2003,
68, 8248. (c) Fringuelli, F.; Pizzo, F.; Tortoioli, S.; Vaccaro,
L. Green Chem. 2003, 5, 436. (d) Fan, R.-H.; Hou, X.-L.
J. Org. Chem. 2003, 68, 726. (e) Pironti, V.; Colonna, S.
Green Chem. 2005, 7, 43. (f) Wu, J.; Xia, H.-G. Green
Chem. 2005, 7, 708. (g) Reddy, M. S.; Srinivas, B.; Sridhar,
R.; Narender, M.; Rao, K. R. J. Mol. Catal. A: Chem. 2006,
255, 180. (h) Azizi, N.; Saidi, M. R. Catal. Commun. 2006,
7, 224. (i) Su, W.; Chen, J.; Wu, H.; Jin, C. J. Org. Chem.
2007, 72, 4524. (j) Chakraborti, S. A. K. J. Mol. Catal. A:
Chem. 2007, 263, 137. (k) Gao, P.; Xu, P.-F.; Zhai, H.
Tetrahedron Lett. 2008, 49, 6536. (l) Yang, M.-H.; Yan,
G.-B.; Zheng, Y.-F. Tetrahedron Lett. 2008, 49, 6471.
(10) (a) Grieco, P. A. Organic Synthesis in Water; Blackie
Academic and Professional: London, 1998. (b) Tundo, P.;
Ananstas, P. T. Green Chemistry: Challenging
MS (EI): m/z (%) = 268 (22) [M+], 250 (29), 175 (72), 157 (100),
133 (74), 107 (24), 94 (54), 77 (43), 43 (99).
References
(1) (a) Smith, J. G. Synthesis 1984, 629. (b) Luly, J. R.; Yi, N.;
Soderquist, J.; Stein, H.; Cohen, J.; Perun, T. J.; Plattner, J.
J. J. Med. Chem. 1987, 30, 1609. (c) Corey, E. J.; Cheng,
X.-M. The Logic of Chemical Synthesis; Wiley: New York,
1989. (d) Jones, R. J.; Rapoport, H. J. Org. Chem. 1990, 55,
1144. (e) Jaramillo, C.; Chiara, J. L.; Martinlomas, M.
J. Org. Chem. 1994, 59, 3135. (f) Stead, P.; Marley, H.;
Mahmoudian, M.; Webb, G.; Noble, D.; Ip, Y. T.; Piga, E.;
Rossi, T.; Roberts, S.; Dawson, M. J. Tetrahedron:
Asymmetry 1996, 7, 2247. (g) Amantini, D.; Fringuelli, F.;
Piermatti, O.; Tortoioli, S.; Vaccaro, L. ARKIVOC 2002,
(xi), 293.
(2) (a) Corey, e. J.; Clark, D. A.; Goto, G.; Marfat, A.;
Mioskowski, C.; Samuelsson, B.; Hammarstorm, S. J. Am.
Chem. Soc. 1980, 102, 3663. (b) Corey, E. J.; Clark, D. A.;
Goto, G. Tetrahedron Lett. 1980, 21, 3143.
(3) (a) Jacobsen, E. N. Acc. Chem. Res. 2000, 33, 421.
(b) Taylor, S. K. Tetrahedron 2000, 56, 1149.
Perspectives; Oxford University Press: Oxford, 1999.
(c) Li, C.-J.; Chan, T.-H. Comprehensive Organic Reactions
in Aqueous Media, 2nd ed.; Wiley: Hoboken, 2007.
(d) Kobayashi, S.; Sugiura, M.; Kitagawa, H.; Lam,
W. W.-L. Chem. Rev. 2002, 102, 2227. (e) Kobayashi, S.;
Menabe, K. Acc. Chem. Res. 2002, 35, 209.
Synthesis 2009, No. 20, 3433–3438 © Thieme Stuttgart · New York

3438
R. Dalpozzo et al.
PAPER
(11) (a) Dalpozzo, R.; De Nino, A.; Maiuolo, L.; Nardi, M.;
Procopio, A.; Tagarelli, A. Synthesis 2004, 496.
(15) Dalpozzo, R.; De Nino, A.; Nardi, M.; Russo, B.; Procopio,
A. ARKIVOC 2006, (vi), 67.
(16) Procopio, A.; Gaspari, M.; Nardi, M.; Oliverio, M.; Rosati,
O. Tetrahedron Lett. 2008, 49, 2289.
(b) Procopio, A.; Dalpozzo, R.; De Nino, A.; Maiuolo, L.;
Nardi, M.; Romeo, G. Org. Biomol. Chem. 2005, 3, 4129.
(c) De Nino, A.; Dalpozzo, R.; Procopio, A.; Tagarelli, A.;
Nardi, M.; Russo, B. Synthesis 2006, 332. (d) Dalpozzo, R.;
De Nino, A.; Nardi, M.; Russo, B.; Procopio, A. Synthesis
2006, 1127. (e) Procopio, A.; Dalpozzo, R.; De Nino, A.;
Nardi, M.; Oliverio, M.; Russo, B. Synthesis 2006, 2608.
(f) Dalpozzo, R.; De Nino, A.; Maiuolo, L.; Nardi, M.;
Procopio, A.; Russo, B.; Tagarelli, A. ARKIVOC 2006, (vi),
181. (g) Procopio, A.; Dalpozzo, R.; De Nino, A.; Maiuolo,
L.; Nardi, M.; Oliverio, M.; Russo, B. Carbohydr. Res. 2007,
342, 2125. (h) Procopio, A.; Gaspari, M.; Nardi, M.;
Oliverio, M.; Romeo, R. Tetrahedron Lett. 2008, 49, 1961.
(12) A 0.1 M aqueous solution of Er(OTf)3 is only weakly acidic
(pH ca. 5.9), and the aqueous layer from workup is even less
acidic (pH ca. 6.6).
(17) (a) Posner, G. H.; Rogers, D. Z. J. Am. Chem. Soc. 1977, 99,
8214. (b) Otera, J.; Yoshinago, Y.; Hirakawa, K.
Tetrahedron Lett. 1985, 26, 3219. (c) Iranpoor, N.; Salehi,
P. Synthesis 1994, 1152. (d) Tokunaga, M.; Larrow, J. F.;
Kakiuchi, F.; Jacobsen, E. N. Science 1997, 277, 936.
(e) Fringuelli, F.; Piermatti, O.; Pizzo, F.; Vaccaro, L.
J. Org. Chem. 1999, 64, 6094. (f) Iranpoor, N.; Adibi, H.
Bull. Chem. Soc. Jpn. 2000, 73, 675. (g) Schaus, S. E.;
Brandes, B. D.; Larrow, J. F.; Tokunaga, M.; Hansen, K. B.;
Gould, A. E.; Furrow, M. E.; Jacobsen, E. N. J. Am. Chem.
Soc. 2002, 124, 1307. (h) Schneider, C.; Sreekanth, A. R.;
Mai, E. Angew. Chem. Int. Ed. 2004, 43, 5691.
(18) Iranpoor, N.; Mohammadpour Baltork, I.; Shiriny Zardaloo,
F. Tetrahedron 1991, 47, 9861.
(13) Procopio, A.; Dalpozzo, R.; De Nino, A.; Nardi, M.;
(19) Yadav, J. S.; Reddy, B. V. S.; Bayshya, G. Chem. Lett. 2002,
906.
Sindona, G.; Tagarelli, A. Synlett 2004, 2633.
(14) Procopio, A.; Dalpozzo, R.; De Nino, A.; Maiuolo, L.;
Nardi, M.; Russo, B. Adv. Synth. Catal. 2005, 347, 1447.
Synthesis 2009, No. 20, 3433–3438 © Thieme Stuttgart · New York