Ruthenium-catalyzed rearrangement of cis-1-ethynyl-2-vinyloxiranes to substituted phenols

Article abstract of DOI:10.1055/s-2006-926255

Catalytic cyclization of cis-1-ethynyl-2-vinyloxiranes was implemented with TpRuPPh₃(CH₃CN)₂PF₆ catalyst (10 mol%), to give 2,6-disubstituted phenols in reasonable yields. Under similar conditions, 1,1,2,2-tetrasubstituted oxirane gave the 2,3,6-trisubstituted phenol with skeleton reorganization. On the basis of ²H- and ^l3C-labeling results, we propose that the reaction mechanism involves electrocyclization of ruthenium-vinylidene intermediate with cleavage of the carbon-oxygen bond of the epoxide. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-926255

LETTER
1173
Ruthenium-Catalyzed Rearrangement of cis-1-Ethynyl-2-vinyloxiranes to
Substituted Phenols
R
earrangemen
h
t
of
c
i s -1-Eth
a
ynyl-2-vin
m
yloxirane
s
to Subst
b
d
Phenol
a
s
bu Joseph Maddirala, Arjan Odedra, Bhanu Pratap Taduri, Rai-Shung Liu*
Department of Chemistry, National Tsing-Hua University, Hsinchu, Taiwan
E-mail: rsliu@mx.nthu.edu.tw
Received 19 August 2005
R
R
R
Abstract: Catalytic cyclization of cis-1-ethynyl-2-vinyloxiranes
X
X
R
was implemented with TpRuPPh3(CH3CN)2PF6 catalyst (10 mol%),
to give 2,6-disubstituted phenols in reasonable yields. Under similar
conditions, 1,1,2,2-tetrasubstituted oxirane gave the 2,3,6-trisubsti-
tuted phenol with skeleton reorganization. On the basis of 2H- and
13C-labeling results, we propose that the reaction mechanism in-
volves electrocyclization of ruthenium-vinylidene intermediate
with cleavage of the carbon–oxygen bond of the epoxide.
X
M
M
M
R
M
R
X = CH2
X = O
X
OH
Key words: cis-1-ethynyl-2-vinyloxiranes, 2,6-disubstituted phe-
nols, TpRuPPh3(CH3CN)2PF6, ruthenium-vinylidine intermediate,
endo-dig cyclization, 1,2-hydrogen shift
Scheme 2 Metal-catalyzed reaction of cis-1-acyl- or 1-vinyl-2-
ethynylcyclopropanes
was generated from thermal [3,3]-sigmatropic electrocy-
clization of the initial cis-1-ethynyl-2-vinyloxiranes.
Transition metal complexes can improve the efficiency
and chemoselectivity of an electrocyclization reaction un-
der mild conditions.1,2 Metal-catalyzed cyclization of
enediynes1 and 3,5-dien-1-ynes2 represents interesting
examples, and in such cases terminal alkynes are trans-
formed into metal-vinylidene intermediates3 to facilitate
catalytic aromatization under mild conditions, as shown in
Scheme 1. Uemura and co-workers4 reported metal-cata-
lyzed [3,3]-sigmatropy of cis-1-acyl- or 1-vinyl-2-ethyn-
ylcyclopropanes via a cyclopropyl vinylidene species,
which ultimately gave 2-substituted phenols (X = O) and
cycloheptatrienes (X = CH2), respectively (Scheme 2).
We sought to achieve this cyclization with suitable metal
catalyst via generation of a metal-vinylidene intermediate,
envisaging that cyclization of this vinylidene intermediate
may proceed via cleavage of either the C–C7 or the C–O8
bond of the epoxide as depicted in Scheme 4. This new
pathway may improve the cyclization chemoselectivity
because it avoids formation of the cyclic allene intermedi-
ate (Scheme 3). Electrocyclization of (o-ethynyl)phenyl
9
epoxides9a catalyzed by TpRuPPh3(CH3CN)2PF6
[Tp = tris(1-pyrazolyl)borate] has been shown to proceed
via cleavage of the epoxide C–O bond. Here, we report the
ruthenium-catalyzed cyclization of cis-1-ethynyl-2-
vinyloxiranes, which leads to formation of substituted
M
2 [H]
M
M
M
[3,3]
[1,3]-H
O
O
O
R
R'
M
R'
R
R'
R
M
[3,3]
HO
Ph
O
R = R' = H
Scheme 1 Metal-mediated cyclization of endiynes and dienynes
CHO
R'
R''
R' = H
R = Ph
R' = H, TMS
R = CH2R''
R'' = CnH2n+1, n = 1–3
Thermal rearrangement of cis-1-vinyl-2-ethynylcyclopro-
panes may lead to various products including 1-formyl-2-
ethynylcyclopropanes, 2-alkylidene-2,3-dihydrooxepins
or phenols (130–150 °C), depending on the nature of R
and R¢ substituents as shown in Scheme 3. These products
are given from the [3,3]-sigmatropy and 1,3-hydrogen
shift of a cyclic allene intermediate, respectively, which
Scheme 3 Thermal rearrangement of cis-1-ethynyl-2-vinyloxiranes
O
b
O
a
or
O
O
M
path b
M
M
path a
SYNLETT 2006, No. 8, pp 1173–1176
Advanced online publication: 10.03.2006
DOI: 10.1055/s-2006-926255; Art ID: W30505ST
© Georg Thieme Verlag Stuttgart · New York
1
5.
0
5.
2
0
0
6
Scheme 4 Metal-catalyzed rearrangement of cis-1-ethynyl-2-vinyl-
oxiranes

1174
S. J. Maddirala et al.
LETTER
Table 1 Ruthenium-Catalyzed Cyclization of Ethynyl-2-vinylox-
iranes
phenols. The mechanism has been elucidated by experi-
ments including 2H- and 13C-labeling studies.
In Scheme 5 is shown a new synthetic procedure for cis-
1-ethynyl-2-vinyloxiranes; the literature method6 pro-
vides the cis- and trans-epoxides in a mixture that requires
chromatographic separation. Treatment of allylic alcohol
110 with m-chloroperbenzoic acid produced a-hydroxyl
epoxide 2 in 60% yield. Swern oxidation of this epoxide
followed by Wittig reaction and desilylation gave the de-
Entries
Epoxidea
Phenol (yield, %)b
13 (57)
1
2
3
4
5
6
R1 = n-Bu, R2 = Et (7)
R1 = n-Pr, R2 = i-Bu (8)
R1 = n-C6H13, R2 = Me (9)
R1 = t-C4H9, R2 = Me (10)
R1 = t-C4H9, R2 = Et (11)
R1 = Ph, R2 = Me (12)
14 (50)
15 (40)
16 (64)
9
sired cis-epoxide 5. We selected TpRuPPh3(CH3CN)2PF6
17 (56)
as the catalyst because it reacts readily with terminal
alkynes to give ruthenium-vinylidene species.9 Treatment
of epoxide 5 with this catalyst (10 mol%) in hot toluene
(100 °C, 12 h) gave 2,6-disubstituted phenol 6 in 57%
yield. We observed no 2-propylidene-2,3-dihydrooxepin,
a typical product resulting from thermal rearrangement5,6
as shown in Scheme 3.
18 (48)
a TpRuPPh3(CH3CN)2PF6, [substrate] = 0.60 M, toluene, 100 °C,
12 h.
b Yields were calculated after separation on silica gel.
Elucidation of the reaction mechanism relies on the cy-
clization of 1,1,2,2-tetrasubstituted 1-ethynyl-2-vinylox-
iranes such as species 19 (Scheme 7). Under the same
condition, epoxide 19 gave 2,3,6-trisubstituted phenol 20
in 48% yield. We prepared 13C-labeled 19 that transfers
We prepared various epoxides 7–12 to examine the gener-
ality of this cyclization. Entries 1–3 show alternations of
the R1 and R2 epoxide substituents with various aliphatic
groups including ethyl, n-propyl, n-butyl, isobutyl and n-
hexyl groups, for which yields of phenols 13–15 were 40–
57%. This method is notably applicable to epoxides 10
and 11 bearing a tert-butyl group and gave highly sterical-
ly crowded phenols 16 and 17 in 56–64% yields. The
cyclization also works for epoxide 12, bearing a phenyl
group, that gave phenol 18 in 48% yield.
OH
O
10% [Ru]
1
3
Y
X
Formation of substituted phenols (Table 1, entries 1–3)
rather than the 2-propylidene-2,3-dihydrooxepins sug-
gests the influence of ruthenium catalyst on the course of
Y = 0.60 D (d-16)
X = 0.96 D (d-10)
Scheme 6 Ruthenium-catalyzed rearrangement of 2H-labeled
ethynyl-2-vinyloxiranes (d-10)
2
cyclization. We performed experiments involving H-la-
beling to confirm that the preceding phenols 13–18 are
truly produced from ruthenium-catalyzed reactions rather
than a thermal rearrangement. As shown in Scheme 6, we
prepared epoxide d-10, bearing an alkynyl deuterium,
which was transferred regioselectively to the phenyl C3
carbon of phenol d-16, indicative of a 1,2-hydrogen shift.
In this case, we observed a 35% loss of deuterium content,
which is attributed to the exchange of external water with
alkynylruthenium hydride intermediate.3c This ruthenium
hydride is thought to be the intermediate for transforma-
OH
(1)
(2)
Me
Me
*
*
O
*C = 8%13C
20 (48%)
19
OH
X
X
Me
Me
X
O
d-19
(1) X = D, Y = D
X = H, Y = 0.94D
d-20
1
tion of metal-p-alkyne into metal-vinylidene. The H
X = D, Y = H
X = Y = H
NMR signals of product 16 are assigned on the basis of 1H
NOE effect. This character strongly supports a ruthenium-
vinylidene pathway.3
d-20
d-19
Y
Y
(2)
Scheme 7 2H- and 13C-labeling experiments
nPr
O
nPr
O
nPr
Swern
92%
MCPBA
60%
OH
O
OH
3
2
1
TMS
TMS
(1) PPh3CH3Br
(2) n-BuLi
TMS
70%
nPr
OH
O
nPr
O
nPr
Bu4NF
93%
10% [Ru]
57%
4
5
TMS
6
Scheme 5 Preparation of cis-1-ethynyl-2-vinloxiranes
Synlett 2006, No. 8, 1173–1176 © Thieme Stuttgart · New York

LETTER
Rearrangement of cis-1-Ethynyl-2-vinyloxiranes to Substituted Phenols
1175
the vinyl 13C(1¢) atom to the phenyl C(6) carbon of prod- ketones E¢ and E¢¢ and ultimately forms two phenol
uct 20, consistent with our expectation. We also prepared products K and d2-20 according to the dienone–phenol re-
epoxides d-19 containing deuterium at the vinyl and ter- arrangement.12 But we only obtained phenol 20. The deu-
minal alkyne, respectively. As shown in Scheme 7 (eq. 2), terium labeling experiment are also strongly inconsistent
we observed the loss of one deuterium for both the vinyl with this mechanism because the resulting phenol d2-20
and alkynyl groups, whereas the other vinyl deuterium would be expected to bear one deuterium at each of the
remains at the phenyl C(5) carbon of phenol 20. This phenyl C(4) and C(5) carbons if the starting epoxide 19
phenomenon suggests that these two deuterium atoms are bears a =CD2 group. However, we only observed a deute-
transformed into free protons, which then exchange with rium located only at the C(5) carbon (Scheme 7, entry 1).
residual water.
In a separate experiment, treatment of undeuterated phe-
nol 20 with CD3OD (2.5 equiv) in presence of ruthenium
catalyst (10 mol%) in hot toluene (100 °C, 12 h) did not
lead to deuterium enrichment at the phenyl C(4) and C(5)
carbons.
The preceding observation with epoxide 19 is valuable to
characterize the reaction mechanism: the cyclization like-
ly begins with cleavage of the epoxide C–O bond rather
than the C–C bond. As shown in Scheme 8, cyclization of
ruthenium-vinylidene species A leads to formation of car-
benium B, which undergoes a subsequent epoxide open-
ing to form 1,4-dien-3-ol C and its demetallation species
E. The cyclopenta-2,4-dien-1-one E was easily trans-
formed into phenol 20 by free proton according to di-
enone-phenol rearrangement.11 This proposed mechanism
rationalizes well our 2H- and 13C-labeling experiments in
Scheme 7. In this mechanism, the alkynyl and one vinyl
hydrogen of starting epoxide 19 are transformed into two
free protons, resulting in the loss of their deuterium
contents.
Me
Me
Me
Ru+
D
CD2
Ru+
CD2
Ru+
O
O
O
D
A
I
H
D
Me
Me
Me
D
O
D
D
D
D
+
O
H+
J
O
E''
H+
OH
Me
Me
D
D
1
Me
Me
O
5
3
4
H
Ru+
D
H
Ru+
K
D
O
d2-20
19
OH
Ru+
A
B
Scheme 9 A reaction mechanism for the cyclization of cis-1-
ethynyl-2-vinyloxiranes via cleavage of the epoxide C–C bond
Me
OH
Me
Me
H+
H
O
O
H
H
In summary, we report a new ruthenium-catalyzed
cyclization of cis-1-ethynyl-2-vinyl-oxiranes13–15 that
produces substituted phenols in reasonable yields. On the
+
Ru
Ru H+
Ru+
C
H
E
D
2
basis of H- and 13C-labeling experiments, a reaction
H+
mechanism is proposed to involve 6-endo-dig cyclization
of ruthenium-vinylidene intermediate with cleavage of
the epoxide C–O bond.
Me
Me
H+
HO
H
HO
H
20
+
H
H
H
Acknowledgment
F
The authors wish to thank the National Science Council, Taiwan for
supporting this work.
Scheme 8 Plausible reaction mechanism for the cyclization of cis-
1-ethynyl-2-vinyloxiranes via cleavage of the epoxide C–O bond
References and Notes
The electrocyclization via cleavage of the epoxide C–C
bond pathway is less compatible with our experimental
data This mechanism inevitably involves formation of
oxepine species I, which equilibrates with arene oxide J12
as shown in Scheme 9. Arene oxide J is thermally stable
in neutral reaction conditions. We do not preclude the
(1) (a) Wang, Y.; Finn, M. G. J. Am. Chem. Soc. 1995, 117,
8045. (b) O’Connor, J. M.; Friese, S. J.; Tichenor, M. J. Am.
Chem. Soc. 2002, 124, 3506. (c) Rawat, D. S.; Zaleski, J. M.
J. Am. Chem. Soc. 2001, 123, 9675. (d) Warner, B. P.;
Millar, S. P.; Broene, R. D.; Buchwald, S. L. Science 1995,
269, 814. (e) Ohe, K.; Kojima, M.-a.; Yonehara, K.;
Uemura, S. Angew. Chem., Int. Ed. Engl. 1996, 35, 1823.
(f) Manabe, T.; Yanagi, S.-I.; Ohe, K.; Uemura, S.
Organometallics 1998, 17, 2942.
possibility
that
residual
water
reacts
with
TpRuPPh3(CH3CN)2PF6 catalyst to release free proton,
and triggers the rearrangement of arene oxide J to phenol
products. In the presence of proton catalyst, arene epoxide
J undergoes rearrangement to give two possible spiro
(2) (a) Merlic, C. A.; Pauly, M. E. J. Am. Chem. Soc. 1996, 118,
11319. (b) Maeyama, K.; Iwasawa, N. J. Org. Chem. 1999,
64, 1344.
Synlett 2006, No. 8, 1173–1176 © Thieme Stuttgart · New York

1176
S. J. Maddirala et al.
LETTER
(3) (a) Bruce, M. I. Chem. Rev. 1991, 91, 197. (b) Bruneau, C.;
Dixneuf, P. H. Acc. Chem. Res. 1999, 32, 311.
hexanes, 1:20) to get the epoxy ketone 3 as a colorless oil
(1.55 g, 6.91 mmol, 92%).
(c) McDonald, F. E. Chem. Eur. J. 1999, 5, 3103.
(d) Puerta, M. C.; Valerga, P. Coord. Chem. Rev. 1999, 193-
195, 977. (e) Trost, B. M.; Flygare, J. A. J. Am. Chem. Soc.
1992, 114, 5476.
To a solution of methyltriphenylphosphonium bromide
(3.66 g, 10.24 mmol) in THF (45 mL) at –20 °C was added
n-BuLi (3.77 mL, 9.42 mmol), and the mixture was stirred at
that temperature for 1 h and then cooled to –78 °C. To the
resulting solution was added a solution of 3 (1.15 g, 5.12
mmol) in THF (5 mL) over 10 min and the resulting reaction
mixture was allowed to warm to –30 °C over 2 h. The
reaction was quenched with sat. aq NH4Cl and concentrated
in vacuo. The organic mass was extracted into Et2O. The
ether layer was washed with brine, dried over MgSO4 and
concentrated in vacuo. The residue was purified by column
chromatography over a Et3N-pretreated silica column
(hexane) to get the olefination product 4 as a colorless oil
(0.80 g, 3.60 mmol, 70%).
To a solution of this silyl compound 4 in THF (5 mL) was
added Bu4NF (1 M, 3.6 mL, 3.6 mmol) under ice conditions
and allowed the resulting solution to warm to 26 °C over
4 h. Then, H2O (5 mL) was added and the solution was
concentrated, extracted with Et2O. The ether layer was dried
over MgSO4 and concentrated in vacuo. Elution of the crude
enyne through a Et3N-pretreated silica column (hexane)
gave 5 (0.50 g, 3.33 mmol, 93%).
(4) Ohe, K.; Yokoi, T.; Miki, K.; Nishino, F.; Uemura, S. J. Am.
Chem. Soc. 2002, 124, 526.
(5) (a) Manisse, N.; Chuche, J. J. Am. Chem. Soc. 1977, 99,
1272. (b) Manisse, N.; Chuche, J. Tetrahedron 1977, 33,
2399. (c) Bourelle-Wargnier, F.; Vincent, M.; Chuche, J.
Tetrahedron Lett. 1978, 19, 283.
(6) Bourelle-Wargnier, F.; Vincent, M.; Chuche, J. J. Org.
Chem. 1980, 45, 428.
(7) (a) Chou, W.-N.; White, J. B. Tetrahedron Lett. 1991, 32,
7637. (b) Gaebert, C.; Mattay, J. Tetrahedron 1997, 53,
14297. (c) Palomino, E.; Schaap, A. P.; Heeg, M. J.
Tetrahedron Lett. 1989, 30, 6801.
(8) (a) McDonald, F. E.; Schultz, C. C. J. Am. Chem. Soc. 1994,
116, 9363. (b) Madhushaw, R. J.; Lin, M.-Y.; Abu Sohel, S.
M.; Liu, R.-S. J. Am. Chem. Soc. 2004, 126, 6895. (c) Lo,
C.-Y.; Guo, H.; Lian, J.-J.; Shen, F.-M.; Liu, R.-S. J. Org.
Chem. 2002, 67, 3930.
(9) For catalytic reactions using TpRuPPh3(CH3CN)2PF6, see
selected examples: (a) Yeh, K.-L.; Liu, B.; Lo, C.-Y.;
Huang, H.-L.; Liu, R.-S. J. Am. Chem. Soc. 2002, 124,
6510. (b) Datta, S.; Chang, C.-L.; Yeh, K.-L.; Liu, R.-S. J.
Am. Chem. Soc. 2003, 125, 9294. (c) Shen, H.-C.; Pal, S.;
Lian, J.-J.; Liu, R.-S. J. Am. Chem. Soc. 2003, 125, 15762.
(d) Lian, J.-J.; Odedra, A.; Wu, C.-J.; Liu, R.-S. J. Am.
Chem. Soc. 2005, 127, 4186. (e) Datta, S.; Odedra, A.; Liu,
R.-S. J. Am. Chem. Soc. 2005, 127, 11606. (f) Odedra, A.;
Wu, C.-J.; Pratap, T. B.; Huang, C.-W.; Ran, Y.-F.; Liu, R.-
S. J. Am. Chem. Soc. 2005, 127, 3406.
(14) Typical Procedure for Cyclization of 2-Ethynyl-3-
isopropenyl-2-propyl Oxirane (5) to 2-Methyl-6-
propylphenol (6).
A long tube containing TpRu(PPh3)(CH3CN)2PF6 (50.7 mg,
0.067 mmol) was dried in vacuo for 2 h. It was then charged
with epoxide 5 (100 mg, 0.67 mmol) and freshly distilled
toluene (0.6 mL). The mixture was heated at 100 °C for 16 h
and then cooled to r.t. Concentration of the solution followed
by elution through a silica column (hexane–Et2O = 5:1)
afforded the phenol 6 (57 mg, 0.38 mmol, 57%) as a pale-
yellow oil.
(10) Odedra, A.; Wu, C.-J.; Madhushaw, R. J.; Wang, S.-L.; Liu,
R.-S. J. Am. Chem. Soc. 2003, 125, 9610.
Spectral Data for 2-Ethynyl-3-(prop-1-en-2-yl)-2-
propyloxirane (5).
(11) (a) Pilkington, J. W.; Waring, A. J. J. Chem. Soc., Perkin
Trans. 2 1976, 1349. (b) Palmer, J. D.; Warling, A. J. J.
Chem. Soc., Perkin Trans. 2 1979, 1089. (c) Lukac, J.;
Heimgartner, H. Helv. Chim. Acta 1985, 68, 355.
(d) Warling, A. J.; Zaidi, J. H.; Pilkington, J. W. J. Chem.
Soc., Perkin Trans. 1 1981, 1454.
(12) (a) Vogel, E.; Gunther, H. Angew. Chem., Int. Ed. Engl.
1967, 6, 385. (b) Bruice, T. C.; Bruice, P. Y. Acc. Chem.
Res. 1976, 9, 378.
(13) Procedure for the Synthesis of Epoxide 5.
To a CH2Cl2 solution (60 mL) of species 1 (2.87 g, 13.64
mmol) was added MCPBA and the mixture was stirred at
28 °C for 4 h. The resulting suspension was quenched with
H2O. The aqueous layer was extracted with CH2Cl2 twice.
The combined organic layer was washed with H2O, dried
over MgSO4 and the solvent was removed in vacuo. The
resulting mass was eluted through a Et3N-pretreated silica
column (EtOAc–hexane, 1:20) to get the epoxide 2 as a
colorless oil (1.86 g, 8.22 mmol, 60%).
IR (nujol): 3300 (m), 2235 (w), 1645 (w), 1210 (m) cm–1. 1H
NMR (600 MHz, CDCl3): d = 5.05 (dd, J = 2.98, 1.64 Hz, 2
H), 3.24 (s, 1 H), 2.29 (s, 1 H), 1.80 (s, 3 H), 1.61–1.58 (m,
1 H), 1.56–1.55 (m, 3 H), 0.96 (t, J = 7.0 Hz, 3 H). 13C NMR
(150 MHz, CDCl3): d = 138.6, 113.1, 80.1, 73.2, 65.7, 57.1,
38.9, 19.1, 18.8, 13.7. MS (75 eV): m/z = 150 [M+]. HRMS:
m/z calcd for C10H14O: 150.1045; found: 150.1049.
Spectral Data for 2-Methyl-6-propylphenol (6).
IR (nujol): 3416 (s), 1620 (s), 1585 (m), 1230 (s) cm–1. 1H
NMR (600 MHz, CDCl3): d = 6.95 (d, J = 6.8 Hz, 2 H), 6.76
(t, J = 7.5 Hz, 1 H), 4.61 (s, 1 H), 2.55 (t, J = 7.6 Hz, 2 H),
2.23 (s, 3 H), 1.64–1.61 (m, 2 H), 0.96 (t, J = 7.4 Hz, 3 H).
13C NMR (150 MHz, CDCl3): d = 151.8, 128.5, 127.9, 127.6,
123.0, 120.2, 32.1, 22.9, 15.9, 14.1. MS (75 eV): m/z = 150
[M+]. HRMS: m/z calcd for C10H14O: 150.1045; found:
150.1043.
(15) In a separate experiment, epoxide 12 (0.6 M) was heated
alone in toluene (100 °C, 12 h), and we isolated the phenol
18 and aldehyde 21 in 4% and 10%, respectively, whereas
the starting epoxide 12 was recovered in 51% (Scheme 10).
To a solution of oxalyl chloride (1.26 mL, 14.57 mmol) in
CH2Cl2 (40 mL) maintained at –60 °C was added DMSO
(2.09 mL, 29.14 mmol) with stirring. After 15 min a solution
of 2 (1.65g, 7.30 mmol) in CH2Cl2 (5 mL) was added and the
stirring continued for 1 h at –60 °C. Then, Et3N (8.83 mL,
63.35 mmol) was added and the reaction mixture was
allowed to attain 28 °C over 2 h. Afterwards, H2O was added
and the organic layer was separated. It was washed with
brine, dried over MgSO4 and concentrated. The crude mass
was eluted through Et3N-pretreated silica column (EtOAc–
OH
O
Ph
Me
Ph
Me
Ph
+
Me
CHO
12
18
21
Scheme 10
Synlett 2006, No. 8, 1173–1176 © Thieme Stuttgart · New York