Bi(OTf)3-catalyzed regioselective ring opening of epoxides with phenols: Facile synthesis of 1,3-diaryloxy-2-propanols

Article abstract of DOI:10.1246/cl.2005.1142

Substituted aryl oxiranes undergo the facile ring opening with phenols in the presence of catalytic amount of bismuth(III) triflate to afford 1,3-diaryloxy-2-propanols in excellent yields under mild conditions. Bismuth(III) triflate is relatively non-toxic, easy to handle and inexpensive, which makes this procedure particularly attractive for large scale synthesis. Copyright

Full text of DOI:10.1246/cl.2005.1142

1142
Chemistry Letters Vol.34, No.8 (2005)
Bi(OTf)3-catalyzed Regioselective Ring Opening of Epoxides with Phenols:
Facile Synthesis of 1,3-Diaryloxy-2-propanols
Ahmed Kamal,ꢀ Syed Kaleem Ahmed, Mahendra Sandbhor, Mohammed Naseer Ahmed Khan, and Mohammed Arifuddin
Biotransformation Laboratory, Division of Organic Chemistry, Indian Institute of Chemical Technology,
Hyderabad 500 007, India
(Received March 18, 2005; CL-050363)
Substituted aryl oxiranes undergo the facile ring opening
OH
OH
Bi(OTf)3
(10 mol %)
O
with phenols in the presence of catalytic amount of bismuth(III)
triflate to afford 1,3-diaryloxy-2-propanols in excellent yields
under mild conditions. Bismuth(III) triflate is relatively non-
toxic, easy to handle and inexpensive, which makes this proce-
dure particularly attractive for large scale synthesis.
O
O
O
R1
R1
R2
R2
+
CH2Cl2, 2h, rt
3
1
2
Scheme 1.
sponding aryl ether 3m in good yield (75%).
The high regioselectivity in the epoxide ring opening with
bismuth(III) triflate can be explained by the in situ formation
of complex between epoxide and bismuth(III) triflate, which un-
dergoes SN2 attack of phenols at less hindered C-3 carbon to
give secondary alcohol exclusively (Scheme 2). In the present
investigation among the various solvents examined for the epox-
ide ring opening with phenols, dichloromethane gave good re-
sults under these conditions. However, in the absence of bismu-
th(III) triflate the reaction did not proceed even under reflux con-
ditions and prolonged reaction time (1 to 2 d).
The regioselective ring opening of oxiranes with various nu-
cleophiles is an important transformation and has wide applica-
tions in organic synthesis.1 The chemo- and regioselectivity in
the nucleophilic ring opening of oxirane depends on intrinsic
and environmental factors.2 The ring opening of terminal epox-
ides with phenols is the direct method for the synthesis of ꢀ-aryl-
oxy alcohols, which are key intermediates in a variety of phar-
maceutically important compounds.3 However, it is believed that
reaction of epoxides with oxygen nucleophile are rather difficult
and therefore the epoxide ring opening with phenol is quite chal-
lenging. Although the reaction of oxiranes with aliphatic alco-
hols appears well documented in the literature, but oxirane ring
opening with phenols has not been extensively studied.4 Some of
the known methods employ chiral metal complexes such as
(Salen)–Co(III) complex,5a,5b (Salen)–Ti(IV) complex,5c and
gallium heterobimetalic complexes5d but these methods have
certain disadvantages viz. longer reaction time and employ ex-
pensive reagents. Epoxides have also been regioselectively
opened with phenoxide ion under biomimetic conditions
employing ꢀ-cyclodextrin in aqueous media5e and by using
Ce(OTf)45f in micellar media. The ring opening of chiral glyci-
dols with phenol was also reported using 5 mol % triethylamine
in refluxing ethanol without serious racemization.5g
Bi(III)
OH
O
O
O
O
Bi(OTf)3
R1
R1
R2
-
+
O
1
2
R2
C-2 attack
C-3 attack
R2
OH
O
O
O
R1
R2
O
OH
R1
3
Not found
In recent years, bismuth(III) triflate attracted researchers for
its wide range of applications for different type of transforma-
tions in organic synthesis.6,7 Recently, bismuth(III) triflate was
employed for the preparation of ꢀ-amino alcohols by epoxide
ring opening with anilines.6g Bismuth(III) triflate is not available
commercially but easily prepared in large quantity at a relatively
lower cost.7 In continuation to our ongoing research on the epox-
ide ring opening by different nucleophiles particularly through
biocatalytic and biomimetic methods,8 herein we wish to report
the use of Bi(OTf)3 as an efficient Lewis acid catalyst for the re-
gioselective oxirane opening with different substituted phenols
to obtain the corresponding 1,3-diaryloxy-2-propanols under
mild reaction conditions (Scheme 1). Treatment of epoxide 1a
with phenol in the presence of catalytic amount of Bi(OTf)3 in
dichloromethane afforded the corresponding 1,3-diphenoxy-2-
propanol 3a in 96% yield. In a similar fashion, various aryl sub-
stituted oxiranes reacted smoothly with substituted phenols and
gave corresponding 1,3-diaryloxy-2-propanols in excellent
yields (Table 1). The aliphatic epoxide 1f also gave the corre-
Scheme 2.
Various substituents in the phenyl ring did not effect the ep-
oxide ring opening as both the electron donating and electron
withdrawing substituents provided the secondary alcohols in
good yields. In all the cases, the reaction proceeds spontaneously
at room temperature giving only one regioisomers whereas the
earlier reported methods afforded both the regioisomers employ-
ing Ce(OTf)4 in micellar media.5e Interestingly, no rearranged
products were formed under these conditions as reported in the
earlier methods.6c Various substituted aryl oxiranes (1a–1f) were
prepared quantitatively by treating corresponding phenols with
epichlorohydrin in sodium hydroxide with the reported meth-
od.8d
In conjunction with our earlier studies10 on the enzymatic
resolution of various biologically important compounds includ-
ing secondary alcohols employing different lipases, it was con-
sidered worthwhile, to attempt the resolution of 1,3-diaryloxy-
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.8 (2005)
1143
4
5
S. Jost, L. Venbellinghen, P. Henderson, and J. Merchand-Brynaert,
Org. Prep. Proced. Int., 31, 193 (1999), and references cited there in.
a) J. Ready and E. Jacobsen, J. Am. Chem. Soc., 121, 6086 (1999).
b) J. Reddy and E. Jacobsen, J. Am. Chem. Soc., 123, 2687 (2001).
c) J. Wu, X.-L. Hou, L.-X. Dai, L.-J. Xia, and M.-H. Tang, Tetrahe-
dron: Asymmetry, 9, 3431 (1998). d) S. Matsunaga, J. Das, J. Roels,
E. Vogel, N. Yamamoto, T. Iida, K. Yamaguchi, and M. Shibasaki,
J. Am. Chem. Soc., 122, 2252 (2000). e) K. Surendra, N. Krishnaveni,
Y. Nageshwar, and K. Rao, J. Org. Chem., 68, 4994 (2003). f) N.
Iranpoor, H. Firouzabadi, A. Safavi, and M. Shekarriz, Synth. Com-
mun., 32, 2287 (2002). g) J. Chen and W. Shum, Tetrahedron Lett.,
36, 2379 (1995).
a) S. Repichet, C. Roux, P. Hernandez, and J. Dubac, J. Org. Chem.,
64, 6479 (1999). b) B. Garrigues, F. Gonzaga, H. Robert, and J.
Dubac, J. Org. Chem., 62, 4880 (1997). c) K. Bhatia, K. Eash, N.
Leonard, M. Oswald, and R. Mohan, Tetrahedron Lett., 42, 8129
(2001). d) J. Yadav, B. Reddy, and G. Satheesh, Tetrahedron Lett.,
44, 6501 (2003), and references cited there in. e) L. Wieland, M.
Carrigan, D. Sarapa, R. Smith, and R. Mohan, J. Org. Chem., 67,
1027 (2002). f) A. Kamal, P. Reddy, and D. Reddy, Tetrahedron
Lett., 44, 2857 (2003). g) T. Ollevier and G. Lavie-Compin, Tetrahe-
dron Lett., 45, 49 (2004).
a) M. Labrouillere, C. Le Roux, H. Gaspard, A. Laporterie, J. Dubac,
and J. Desmuss, Tetrahedron Lett., 40, 285 (1999). b) S. Repichet,
A. Zwick, L. Vendier, C. Le Roux, and J. Dubac, Tetrahedron Lett.,
43, 993 (2002).
a) A. Kamal, A. Rao, and M. Rao, Tetrahedron Lett., 33, 4077
(1992). b) A. Kamal, Y. Damayanthi, and M. Rao, Tetrahedron:
Asymmetry, 3, 1361 (1992). c) A. Kamal and M. Rao, Tetrahedron:
Asymmetry, 5, 1881 (1994). d) A. Kamal, M. Arifuddin, and M. Rao,
Tetrahedron: Asymmetry, 10, 4261 (1999).
Table 1. Bi(OTF)3 catalyzed synthesis of 1,3-diaryloxy-2-
propanols9
Epoxide (1)
Phenol (2)
Producta (3)
Yieldb/%
O
OH
O
O
O
OAr
96
88
Ar = C H
Ar = p-Cl5-C H
Ar = p-NO -C H
3a
3b
3c
C6H5OH
6
1a
p-Cl-C6H4OH
p-NO2-C6H4OH
6
4
84
2
6 4
OH
O
O
OAr
C6H5OH
p-Cl-C6H4OH
94
86
Ar = C H
6
Ar = p-Cl5-C H
3d
3e
H3CO
Cl
H3CO
6
4
1b
O
O
OH
6
O
O
O
C6H5OH
84
3f
1c
Cl
Br
OH
O
OAr
O
C6H5OH
p-OMe-C6H4OH
α-C10H7OH
86
88
92
3g
Ar = C6H5
Br
1d
Ar = p-OMe-C H
Ar = α-C10H7
3h
6
4
3i
O
OH
O
O
OAr
OHC
91
87
85
C6H5OH
p-Cl-C6H4OH
p-NO2-C6H4OH
3j Ar = C6H5
OHC
1e
Ar = p-Cl-C H
3k
3l
Ar = p-NO2-C64H4
6
7
8
OH
O
75
3m
C6H5OH
O
1f
aAll products were characterized by 1H NMR, IR, and mass
spectroscopy. bYields refers to pure product after column
chromatography.
9
General Procedure for the Synthesis of 1,3-diaryloxy-2-propanols: A
mixture of 1-aryloxy-2,3-epoxypropane
2-propanols by employing lipases. It was observed that lipase-
mediated transesterifications employing various lipases and
solvents under different conditions offered the corresponding al-
cohols and acetates in low enantioselectivities (<40%ee). The
insignificant enantioselectivity for these substrates is probably
due to the steric factor at the asymmetric centre. However,
1,3-diaryloxypropanols 3 have been synthesized in high enantio-
purity by employing bismuth(III) triflate and the corresponding
chiral epoxide precursors 1. The chiral epoxides for this purpose
were obtained by lipase (PS-C) mediated resolution of the
corresponding chlorohydrins with 80–95%ee.11
In summary, we have described a facile and practical meth-
od for the epoxide ring opening with substituted phenols using
catalytic amount of Bi(OTf)3 under mild reaction conditions.
High regioselectivity, spontaneity, experimental simplicity,
and quantitative yields make this procedure an attractive alterna-
tive over the conventional methods for the synthesis of biologi-
cally important 1,3-diaryloxy-2-propanols.
1 (1 mmol), Bi(OTf)3
(0.1 mmol) and phenol 2 (1.2 mmol) in dichloromethane (10 mL)
was stirred at room temperature for 2 h. After completion of the
reaction as indicated by TLC, the reaction mixture was diluted with
dichloromethane and washed with saturated NaHCO3 (10 mL)
followed by brine solution. The organic layer was separated, dried
over anhydrous Na2SO4 and the solvent was removed under reduced
pressure. The residue was purified by chromatography on silica gel
using ethyl acetate:hexane (1:9) to afford the pure 1,3-diaryloxy-2-
propanols. The spectroscopic data of all the products were identical
with data reported in literature.5e Spectral data for selected products,
3a: IR (KBr) 3490 cmꢁ1 1H NMR (CDCl3, 200 MHz): ꢁ 2.8 (1H,
;
brs), 4.0–4.2 (4H, m), 4.2–4.5 (1H, m), 6.9–7.1 (6H, m), 7.2–7.4
(4H, m); EI Mass (m=z): 244 (Mþ); Anal. Calcd for C15H16O3: C,
73.75; H, 6.60%. Found: C, 73.35; H, 6.39%. 3k: IR (KBr)
;
3450 cmꢁ1 1H NMR (CDCl3, 200 MHz): ꢁ 2.6 (1H, brs), 4.0–4.3
(4H, m), 4.4–4.5 (1H, m), 6.84 (2H, d, J ¼ 8:92 Hz), 7.0 (2H, d,
J ¼ 8:92 Hz), 7.24 (2H, d, J ¼ 8:92 Hz), 7.83 (2H, d, J ¼ 8:92
Hz), 9.9 (1H, brs); EI Mass (m=z): 306 (Mþ); Anal. Calcd for
C
16H15ClO4: C, 62.65; H, 4.93%. Found: C, 62.53; H, 4.76%.
10 a) A. Kamal, M. Sandbhor, and K. Ramana, Tetrahedron: Asymme-
try, 13, 815 (2002). b) A. Kamal, A. Shaik, M. Sandbhor, and M.
Malik, Tetrahedron Lett., 45, 8057 (2004). c) A. Kamal, K. Ramana,
and M. Rao, J. Org. Chem., 65, 997 (2001).
11 Spectral data for epoxide 1b: mp 43 ꢂC; 96%ee (S)-1b, 80%ee (R)-
1b; (HPLC analysis DAICEL CHIRALCEL OD column (0:46 ꢃ
25 cm); eluent: hexane/isopropanol = 90/10; flow rate: 0.7 mL/
Two of the authors MS and MNAK are thankful to CSIR,
New Delhi for the award of research fellowships.
References and Notes
1
J. Buachamnan and H. Sable, ‘‘Selective Organic Transformation,’’
ed. by B. Thyagarajan, Wiley, New York (1972), Vol. 1.
a) Y. Pocker, B. Ronald, and K. Anderson, J. Am. Chem. Soc., 110,
6492 (1988). b) A. Troiani, A. Filippi, and M. Speranza, Chem.—
Eur. J., 12, 2063 (1997).
25
min.; detector: 254 nm.); [ꢂ]D (S)-1b þ11:66 (c 0.6, MeOH)
2
[lit.12 þ11:04 (c 1.08, MeOH) 96%ee], [ꢂ]D (R)-1b ꢁ10:72 (c 1,
25
MeOH) [lit.12 ꢁ11:72 (c 1.06, MeOH) 100%ee] IR (Neat) 3425,
2100 cmꢁ1 1H NMR (CDCl3, 200 MHz): ꢁ 2.6–2.7 (1H, m), 2.8–
;
3
a) K. Kitori, Y. Furukawa, H. Yoshimoto, and J. Otera, Tetrahedron,
55, 14381 (1999), and references cited there in. b) S. Peukert and
E. Jacobsen, Org. Lett., 1, 1245 (1999). c) J. Wright, T. Gregory,
T. Heffner, R. MacKenzie, T. Pugsley, S. Meulen, and L. Wise,
Bioorg. Med. Chem. Lett., 7, 1377 (1997). d) N. Baker, N. Byrne,
A. Economides, and T. Javeld, Chem. Pharm. Bull., 1995, 1045.
2.9 (1H, m), 3.2–3.3 (1H, m), 3.7 (3H, s), 3.9 (1H, dd, J ¼ 10:98,
5.12 Hz), 4.1 (1H, dd, J ¼ 10:98, 3.66 Hz), 6.7–6.9 (4H, m); EI Mass
(m=z): 178 (Mþ); Anal. Calcd for C10H12O3: C, 66.65; H, 6.71%.
Found: C, 66.53; H, 6.64%.
12 S. Takano, M. Moriya, M. Suzuki, Y. Iwabuchi, T. Sugihara, and
K. Ogasawara, Heterocycles, 31, 1555 (1990).
Published on the web (Advance View) July 16, 2005; DOI 10.1246/cl.2005.1142