Domino multicomponent michael - Michael - Aldol reactions under phase-transfer catalysis: Diastereoselective synthesis of pentasubstituted cyclohexanes

Article abstract of DOI:10.1055/s-0029-1218523

A simple, efficient, and environmental friendly domino multicomponent reaction to construct new cyclohexane derivatives with five new stereocenters, one of them quaternary, under phasetransfer catalysis is reported. This novel one-pot reaction allows the

Full text of DOI:10.1055/s-0029-1218523

LETTER
115
Domino Multicomponent Michael–Michael–Aldol Reactions under
Phase-Transfer Catalysis: Diastereoselective Synthesis of Pentasubstituted
Cyclohexanes
S
ynthesis of Penta
i
substitu
a
ted
C
ycloh
n
exanes a I. S. P. Resende,a Cristina G. Oliva,a Artur M. S. Silva,*a Filipe A. Almeida Paz,b José A. S. Cavaleiroa
a
QOPNA, Departamento de Química, Universidade de Aveiro, 3810-193 Aveiro, Portugal
Fax +351(234)370084; E-mail: artur.silva@ua.pt
CICECO, Departamento de Química, Universidade de Aveiro, 3810-193 Aveiro, Portugal
b
Received 8 October 2009
other hand, the development of structures including a ste-
reogenic quaternary carbon is an important task in organic
synthesis since the number of natural products and phar-
maceutical agents possessing quaternary centers is grow-
Abstract: A simple, efficient, and environmental friendly domino
multicomponent reaction to construct new cyclohexane derivatives
with five new stereocenters, one of them quaternary, under phase-
transfer catalysis is reported. This novel one-pot reaction allows the
transformation of very simple starting materials into pentasubstitut- ing.11
ed cyclohexane derivatives bearing hydroxy, nitro, and ketone moi-
Herein we report the development of new methodology
eties and involving the formation of three new C–C bonds. All
compounds have been formed in a completely diastereoselective
way and have been isolated in high yields.
involving domino multicomponent Michael–Michael–
aldol reactions from (E,E)-1,5-diarylpenta-2,4-dien-1-one
(cinnamylideneacetophenones) and nitromethane under
PTC.
Key words: domino reaction, multicomponent reaction, phase-
transfer catalysis, diastereoselectivity
In our initial studies, we initiated the reaction between
cinnamylideneacetophenone 1a and nitromethane
(Table 1) with DBU as base at room temperature. The
synthesis of (E,E,1R*,2S*,3S*,4S*,5S*)-2-benzoyl-1-
hydroxy-4-nitro-1-phenyl-3,5-distyrylcyclohexane (2a)
took place with total diastereoselectivity in all solvents
(entries 1–7), with acetonitrile (entry 1) attending the
highest yield.
Discovery of rapid, efficient, and low-cost methods to
construct cyclohexanes with multiple stereogenic centers
has been an important goal in organic chemistry1 because
these ring systems are common structures in natural
products2 and biologically significant molecules.3 Domi-
no multicomponent reactions4 have emerged as a power-
ful tool in organic synthesis and have received
considerable attention due to their advantages over con-
ventional synthesis. Most important features are the gen-
eration of multiple C–C bonds in a multistep reaction
concomitant with the creation of many stereocenters from
simple precursors. These allow a rapid construction of
structurally complex molecules from cheap and easily
available starting materials in a simple operation, thereby
minimizing the cost, waste, and manual efforts and avoid-
ing the need to protect groups and isolate intermediates.
Table 1 Domino Multicomponent Reaction of 1a with
Nitromethane Using DBU as Basea
Ph
O
O
NO2
MeNO2
DBU
Ph
HO
Ph
Ph
1a
(E,E,1R*,2S*,3S*,4S*,5S*)-2a
Phase-transfer catalysis (PTC) has long been recognized
as a versatile methodology for synthesis,5 featuring simple
experimental operations, mild reaction conditions, inex-
pensive and environmentally benign reagents and sol-
vents, and the possibility to conduct large-scale
preparations. Combining the advantages of domino multi-
component reactions with those from PTC is an important
target in green chemistry.6
The synthesis of cyclohexanes with two,7 three,8 or
four1,3a,9 stereogenic centers from a domino multicompo-
nent reaction is known, although pentasubstituted cyclo-
hexanes have only been generated by two routes.10 On the
Entry
Solvent
MeCN
EtOH
Yield (%)b
dr (%)c
>99
1
2
3
4
5
6
7
63
52
33
23
26
36
24
>99
MeOH
CHCl3
toluene
CH2Cl2
THF
>99
>99
>99
>99
>99
a Reactions were carried out at 0.2 M solution of 1a (20.0 mg, 0.085
mmol) in solvent (0.43 mL), and it was added DBU (14 mL, 0.094
mmol) and MeNO2 (2.8 mL, 0.051 mmol) at r.t. for 7 d. DBU: 1,8-
diazabicyclo[5.4.0]undec-7-ene.
SYNLETT 2010, No. 1, pp 0115–0118
x
x.
x
x.
2
0
0
9
Advanced online publication: 20.11.2009
DOI: 10.1055/s-0029-1218523; Art ID: D28809ST
© Georg Thieme Verlag Stuttgart · New York
b Isolated yield after chromatography.
c Diastereomeric ratio based on 1H NMR analyses.

116
D. I. S. P. Resende et al.
LETTER
After selecting acetonitrile as the most efficient solvent, stereoselectivity, independently of the nature and position
we proceeded to explore the reaction under PTC condi- of the substituents in good isolated yield (45–97%). When
tions (Table 2). We began with 0.5 mol equivalents of the ketone aryl group possessed ortho substitution
Cs2CO3 and nitromethane (entry 1), with 2a being ob- (Table 3, entry 1) the yield decreased significantly proba-
tained in a moderate yield. Next we increased the mol bly because the OH most likely forms an intramolecular
equivalents of base to 0.85 and of TBAB to 0.2 (entries 2– hydrogen bond with the carbonyl group and the a,b,d,g-
4) and varied the reaction time. We found that the best system of 1b is less reactive. Derivatives with either elec-
yield was obtained when the reaction took place over 20 tron-donating or electron-withdrawing groups at the para
hours (entry 3). Yields stayed good when the mol equiva- position on the a-aryl group of cinnamylideneacetophe-
lents of catalyst was increased to 0.3 (entry 5) for 20 hours nones afforded the corresponding cyclohexanes in good to
of reaction time, but longer reaction times resulted in low- high yields (entries 2–6). In addition, we explored the
er yields (entry 6). With 1 mol equivalent of Cs2CO3 (en- reaction with a methoxy substitution in the d-aryl group of
tries 7–9), we found that the best conditions were 0.5 mol the system which also led to high isolated yields (entry 7).
equivalents of nitromethane, 0.3 mol equivalents of
TBAB and 20 hours reaction time (entry 8) which led to a
The relative stereochemistry of compounds 2a–h was as-
signed by analysis of 1H–1H coupling constants of the cy-
79% yield. The increase to 0.7 mol equivalents of nitro-
clohexane ring and of the NOESY spectrum of derivative
methane did not improve the yield (entry 9). Notably,
2a, which confirmed the relative configuration of all
neighboring substitution (Figure 1). This was also con-
complete diastereoselectivity was obtained in all reac-
tions.
firmed by the single-crystal X-ray diffraction studies of 2a
(Figure 2)15 which clearly show that the 1-OH group is en-
Table 2 Domino Multicomponent Reaction of 1a with
gaged in an intramolecular hydrogen bond with the C=O
of the benzoyl group.
Nitromethane under PTCa
Ph
The mechanism proposed for the formation of compounds
2 is depicted in Scheme 1. It starts with the formation of
O
O
MeNO2
Cs2CO3
NO2
Ph
Table 3 Scope of the Domino Multicomponent Reactiona
TBAB
MeCN, r.t.
HO
Ph
1a
R3
Ph
R2
(E,E,1R*,2S*,3S*,4S*,5S*)-2a
R1
O
Entry
Cs2CO3
(mol equiv) (mol equiv) (h)
TBAB
Time
Yield
(%)b
dr
(%)c
R1
O
1
2
3
4
5
6
7
8
9d
0.50
0.85
0.85
0.85
0.85
0.85
1.0
0.1
0.2
0.2
0.2
0.3
0.3
0.2
0.3
0.3
20
3
59
21
62
54
60
48
58
79
53
>99
>99
>99
>99
>99
>99
>99
>99
>99
MeCN, r.t.
20 h, 0.2 M
NO2
1 equiv Cs2CO3
0.3 equiv TBAB
0.5 equiv MeNO2
R2
HO
20
74
20
48
20
20
20
R1
R3
R3
R2
(E,E,1R*,2S*,3S*,4S*,5S*)-2
1
Entry
1
R1
R2
R3
Time
(h)
2
dr
(%)b
(%)c
>99
>99
>99
>99
>99
>99
>99
1.0
1
2
3
4
5
6
7
1b
1c
1d
1e
1f
OH
H
H
H
60
60
40
40
20
60
20
2b (45)
2c (70)
2d (58)
2e (91)
2f (90)
2g (97)
2h (81)
1.0
Me
OMe
Br
H
a Reactions were carried out at 0.2 M solution of 1a (20.0 mg, 0.085
mmol) in MeCN (0.43 mL), and it was added TBAB, Cs2CO3, and 0.5
mol equiv of MeNO2 (2.3 mL, 0.043 mmol) at r.t. TBAB: tetrabuty-
lammonium bromide.
H
H
H
H
b Isolated yield after chromatography.
H
CN
Cl
H
c Diastereomeric ratio based on 1H NMR analyses.
d Reaction was carried out with 0.7 mol equiv of MeNO2 (3.2 mL,
0.060 mmol).
1g
1h
H
H
H
H
OCH3
a Reactions were carried out at 0.2 M solution of 1b–h (0.085 mmol)
in MeCN (0.43 mL), and it was added TBAB (9.2 mg, 0.028 mmol),
Cs2CO3 (27.7 mg, 0.085 mmol), and MeNO2 (2.3 mL, 0.043 mmol)
for 20 h at r.t. TBAB: tetrabutylammonium bromide.
b Isolated yield after chromatography.
After establishing optimal reaction conditions, the scope
of the reaction for different cinnamylideneacetophenones
1b–h12,13 was investigated (Table 3). The synthesis of new
cyclohexane derivatives 2b–h14 took place with total dia-
c Diastereomeric ratio based on 1H NMR analyses.
Synlett 2010, No. 1, 115–118 © Thieme Stuttgart · New York

LETTER
Synthesis of Pentasubstituted Cyclohexanes
117
nitromethane anion I following by a 1,4-Michael addition
to 1 providing the intermediate II, which can be isolated
and identified. Next, anion III17 is involved in a 1,4-
Michael addition to 1 leading to the intermediate IV. Fi-
nally, an intramolecular aldol reaction takes place to af-
ford the cyclohexane derivatives 2. According to the
proposed mechanism for the formation of 2, it is easy to
understand that the relative configuration of C3 and C5
dictate those of the remaining stereocenters. Furthermore,
the relative C1/C2 stereochemistry is ruled by the steric
hindrance originating from the two aryl groups.
H
Ph
J6B-5 = 12.2 Hz
6B-OH = 2.6 Hz
J6A-5 = 4.1 Hz
H
HB
J
O
4NO2
2
3
6
Ph
Ph
J4-5 = 11.1 Hz
J4-3 = 11.1 Hz
J2-3 = 11.6 Hz
5
1
Ph
HA
H
OH
H
Figure 1 Main NOE effects and J values of 2a
In conclusion, we have described a very simple, efficient,
and environmentally friendly domino multicomponent re-
action for the synthesis of pentasubstituted cyclohexane
derivatives in high yield and in a completely regio- and
diastereoselective manner under PTC. This novel trans-
formation allows the generation of three new C–C bonds
and five new stereocenters, which contain hydroxy, nitro,
and ketone functional groups and also include a stereo-
genic quaternary carbon.
Acknowledgment
Thanks are due to the University of Aveiro, to ‘Fundação para a
Ciência e a Tecnologia’ and FEDER for funding the Organic Che-
mistry Research Unit and for the financial support towards the
purchase of the single-crystal diffractometer.
Figure 2 Schematic representation of the (E,E,1R,2S,3S,4S,5S)-2a
molecular unit present in the crystal structure16
References and Notes
Ar
MeNO2
(1) Enders, D.; Huttl, M. R. M.; Grondal, C.; Raabe, G. Nature
(London) 2006, 441, 861.
(2) Ho, T. L. Carbocycle Construction in Terpene Synthesis;
Wiley-VCH: Weinheim, 1988.
(3) For examples, see: (a) Ramachary, D. B.; Reddy, Y. V.;
Prakash, B. V. Org. Biomol. Chem. 2008, 6, 719.
Cs2CO3
TBAB
O
NO2
3
6
Ar
HO
2
1
4
O–
N+
O–
Bu
5
Bu
Bu
O
Ar
N+
Bu
Ar
2
(b) Ishikawa, H.; Suzuki, T.; Hayashi, Y. Angew. Chem. Int.
Ed. 2009, 48, 1304.
I
intramolecular
aldol reaction
Ar
(4) For reviews of this concept, see: (a) Tietze, L. F. Chem.
Rev. 1996, 96, 115. (b) Nicolaou, K. C.; Montagnon, T.;
Snyder, S. A. Chem. Commun. 2003, 551. (c) Zhe, J.;
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VCH: Weinheim, 2005. (d) Ramón, D. J.; Yus, M. Angew.
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Edmonds, D. J.; Bulger, P. G. Angew. Chem. Int. Ed. 2006,
45, 7134. (f) Tietze, L. F.; Brasche, G.; Gericke, K. Domino
Reactions in Organic Synthesis; Wiley-VCH: Weinheim,
2006. (g) Guo, H. C.; Ma, J. A. Angew. Chem. Int. Ed. 2006,
45, 354. (h) Enders, D.; Grondal, C.; Huttl, M. R. M. Angew.
Chem. Int. Ed. 2007, 46, 1570. (i) Tejedor, D.; García-
Tellado, F. Chem. Soc. Rev. 2007, 36, 484. (j) Guillena, G.;
Ramón, D. J.; Yus, M. Tetrahedron: Asymmetry 2007, 18,
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(l) Yua, X. H.; Wang, W. Org. Biomol. Chem. 2008, 6, 2037.
(5) Hashimoto, T.; Maruoka, K. Chem. Rev. 2007, 107, 5656.
(6) Trost, B. M. Science 1991, 254, 1471.
1,4-Michael
addition
Bu
N+
Bu
Bu
Ar
O–
Bu
1
Ar
NO2
NO2
Ar
O
Ar
O
Ar
Ar
Ar
IV
II
1,4-Michael
addition
Bu
N+
Bu
Bu
Bu
Cs2CO3
TBAB
O–
N+
Ar
O
O
O–
Ar
Ar
III
(7) (a) Hong, B. C.; Wu, M. F.; Tseng, H. C.; Liao, J. H. Org.
Lett. 2006, 8, 2217. (b) Enders, D.; Narine, A. A.;
Benninghaus, T. R.; Raabe, G. Synlett 2007, 1667.
(c) Sridharan, V.; Menendez, J. C. Org. Lett. 2008, 10,
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Jørgensen, K. A. Angew. Chem. Int. Ed. 2008, 47, 121.
(e) Hong, B. C.; Nimje, R. Y.; Sadani, A. A.; Liao, J. H. Org.
1
Ar
Scheme 1 Mechanism proposed for the Michael–Michael–aldol
reaction
Synlett 2010, No. 1, 115–118 © Thieme Stuttgart · New York

118
D. I. S. P. Resende et al.
LETTER
and crystallized (hexane–EtOAc) to afford the desired
Lett. 2008, 10, 2345.
(8) Carlone, A.; Cabrera, S.; Marigo, M.; Jørgensen, K. A.
Angew. Chem. Int. Ed. 2007, 46, 1101.
products 2a–g as single diastereomers.
Selected Data for (E,E,1R*,2S*,3S*,4S*,5S*)-2-Benzoyl-
1-hydroxy-4-nitro-1-phenyl-3,5-distyrylcyclohexane (2a)
White solid (17.7 mg, 79% yield; Figure 3); 227–229 °C. 1H
NMR (500.13 MHz, CDCl3, 20 °C): d = 2.00 (ddd, J = 14.4,
12.2, 2.6 Hz, 1 H, H-6B), 2.20 (dd, J = 14.4, 4.1 Hz, 1 H, H-
6A), 3.72–3.84 (m, 2 H, H-3, H-5), 4.14 (d, J = 11.6 Hz, 1 H,
H-2), 4.64 (t, J = 11.1 Hz, 1 H, H-4), 5.34 (d, J = 2.6 Hz, 1
H, OH), 5.71 (dd, J = 15.7, 9.8 Hz, 1 H, H-a¢), 6.03 (dd,
J = 15.7, 8.8 Hz, 1 H, H-a¢¢), 6.36 (d, J = 15.7 Hz, 1 H, H-
b¢), 6.56 (d, J = 15.7 Hz, 1 H, H-b¢¢), 6.85–6.87 (m, 2 H, H-
2¢¢¢,6¢¢¢), 7.10–7.11 (m, 4 H, H-3¢,5¢, H-3¢¢¢,5¢¢¢), 7.20–7.31
(m, 9 H, H-2¢¢¢¢,6¢¢¢¢, H-3¢¢,5¢¢, H-3¢¢¢¢,5¢¢¢¢, H-4¢, H-4¢¢¢, H-
4¢¢¢¢), 7.42 (t, J = 8.3 Hz, 1 H, H-4¢¢), 7.45 (dd, J = 8.3, 1.0
Hz, 2 H, H-2¢,6¢), 7.56 (dd, J = 8.3, 1.2 Hz, 2 H, H-2¢¢,6¢¢)
ppm. 13C NMR (125.77 MHz, CDCl3, 20 °C): d = 40.9 (C-
5), 44.0 (C-6), 45.6 (C-3), 53.2 (C-2), 74.3 (C-1), 94.1 (C-4),
123.9 (C-a¢¢), 124.5 (C-2¢,6¢), 126.4 (CAr), 126.5 (C-2¢¢¢,6¢¢¢),
126.6 (C-a¢), 127.4 (CAr), 127.8 (CAr), 127.9 (CAr), 128.1 (C-
2¢¢,6¢¢), 128.2 (CAr), 128.4 (CAr), 128.5 (CAr), 128.6 (CAr),
133.5 (C-b¢¢), 133.6 (C-4¢¢), 135.5 (C-b¢), 135.8 (C-1¢¢¢),
136.4 (C-1¢¢¢¢), 137.8 (C-1¢¢), 144.7 (C-1¢), 205.0 (C=O)
ppm. HRMS (ESI+): m/z calcd for [C35H31NO4 + Na]+:
552.2145; found: 552.2147. Anal. Calcd: C, 79.37; H, 5.90;
N, 2.64. Found: C, 78.97; H, 5.91; N, 2.73.
(9) (a) Hayashi, Y.; Okano, T.; Aratake, S.; Hazelard, D. Angew.
Chem. Int. Ed. 2007, 46, 4922. (b) Penon, O.; Carlone, A.;
Mazzanti, A.; Locatelli, M.; Sambri, L.; Bartoli, G.;
Melchiorre, P. Chem. Eur. J. 2008, 14, 4788. (c) Tan, B.;
Chua, P. J.; Li, Y. X.; Zhong, G. F. Org. Lett. 2008, 10,
2437. (d) Enders, D.; Huttl, M. R. M.; Raabe, G.; Bats, J. W.
Adv. Synth.Catal. 2008, 350, 267. (e) Zhao, G. L.; Dziedzic,
P.; Ullah, F.; Eriksson, L.; Cordova, A. Tetrahedron Lett.
2009, 50, 3458.
(10) (a) Reyes, E.; Jiang, H.; Milelli, A.; Elsner, P.; Hazell, R. G.;
Jørgensen, K. A. Angew. Chem. Int. Ed. 2007, 46, 9202.
(b) Ruano, J. L. G.; Marcos, V.; Suanzes, J. A.; Marzo, L.;
Aleman, J. Chem. Eur. J. 2009, 15, 6576.
(11) (a) Quaternary Stereocenters. Challenges and Solutions for
Organic Synthesis; Christoffers, J.; Baro, A., Eds.; Wiley-
VCH: Weinheim, 2005. (b) Cozzi, P. G.; Hilgraf, R.;
Zimmermann, N. Eur. J. Org. Chem. 2007, 5969.
(12) (a) Synthesis of 1a,c,d: Pinto, D. C. G. A.; Silva, A. M. S.;
Levai, A.; Cavaleiro, J. A. S.; Patonay, T.; Elguero, J. Eur.
J. Org. Chem. 2000, 2593. (b) Synthesis of 1b: Silva, A. M.
S.; Pinto, D. C. G. A.; Tavares, H. R.; Cavaleiro, J. A. S.;
Jimeno, M. L.; Elguero, J. Eur. J. Org. Chem. 1998, 2031.
(c) Synthesis of 1h: Santos, C. M. M.; Silva, A. M. S.;
Cavaleiro, J. A. S.; Levai, A.; Patonay, T. Eur. J. Org. Chem.
2007, 2877.
4'''
(13) General Procedure for the Syntheses of 1e–g
An aqueous solution of NaOH (60%, 25 mL) was slowly
added to a methanolic solution (30 mL) of appropiate
acetophenone (5.0 mmol). After cooling the solution to r.t.,
cinnamaldehyde (792 mg, 6.0 mmol) was added. The
mixture was stirred at r.t. for 20 h, and then it was poured
into H2O (100 mL), ice (100 g), and HCl (pH adjusted to ca.
2). The solid obtained was removed by filtration, dissolved
in CHCl3 (50 mL), and washed with an aq solution of
NaHCO3 (5%, 30 mL). The organic layer was collected,
dried over anhyd Na2SO4, and the solution evaporated to
dryness. The residue was purified by silica gel column
chromatography using CH2Cl2 as eluent. Finally, the isolated
compounds were recrystallized from EtOH.
3'''
2'''
5'''
6'''
1'''
β'
α'
O
2''
1''
6''
NO2
3
6
3''
4''
2
1
4
5
2''''
β''
1''''
HO
3''''
4''''
α''
5''
3'
2'
1'
HB
HA
6''''
6'
5''''
5'
4'
Figure 3
Selected Data for 1g
Yellow solid (1.13 g, 84% yield); 143–144 °C. 1H NMR
(300.13 MHz, CDCl3, 20 °C): d = 7.04–7.01 (m, 2 H, H-4,
H-5), 7.05 (d, 3Jtrans = 15.0 Hz, 1 H, H-2), 7.41–7.30 (m, 3 H,
H-3¢¢,5¢¢, H-4¢¢), 7.52–7.44 (m, 4 H, H-2¢¢,6¢¢, H-3¢,5¢), 7.65–
7.57 (m, 1 H, H-3), 7.92 (AA¢BB ¢, 3JAB = 8.6, Hz,
4JAA¢ = 2.2 Hz, 5JAB¢ = 1.9 Hz, 2 H, H-2¢,6¢) ppm. 13C NMR
(125.77 MHz, CDCl3, 20 °C): d = 124.8 (C-2), 126.7 (C-5),
127.4 (C-2¢¢,6¢¢), 128.9 (C-3¢,5¢, C-3¢¢,5¢¢), 129.4 (C-4¢¢),
129.8 (C-2¢,6¢), 136.0 (C-1¢¢), 136.5 (C-1¢), 139.1 (C-4¢),
142.4 (C-4), 145.4 (C-3), 189.1 (C-1) ppm. Anal. Calcd: C,
75.98; H, 4.88. Found: C, 75.92; H, 4.86.
(15) Crystal Data
C35H31NO4, M = 529.61, monoclinic, space group P21/n,
Z = 4, a = 5.6904 (2) Å, b = 15.8717 (5) Å, c = 31.4292 (9)
Å, b = 91.793 (2)°, V = 2837.18 (16) Å3, colorless needles
with crystal size of 0.20 × 0.08 × 0.06 mm3. Of a total of
34281 reflections collected, 7584 were independent
(Rint = 0.0843). Final R1 = 0.0588 [I > 2s(I)] and
wR2 = 0.1497 (all data). CCDC-743412 contains the
supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data
request/cif.
(14) General Procedure for the Synthesis of 2a–g
To a stirred 0.2 M solution of the appropriate 1,5-diaryl-
penta-2,4-dien-1-ones 1 (0.085 mmol) in MeCN (0.43 mL)
was added TBAB (9.2 mg, 0.028 mmol), Cs2CO3 (27.7 mg,
0.085), and MeNO2 (2.3 mL, 0.043 mmol). The mixture was
stirred at r.t. for 20 h, quenched with H2O (5 mL), and
extracted with CH2Cl2 (3 × 5 mL). The combined organic
extracts were dried over MgSO4. Evaporation of the solvent
under reduced pressure afforded an oil, which was purified
by column chromatography (hexane–EtOAc = 9:1 as eluent)
(16) Nonhydrogen atoms are represented as thermal ellipsoids
drawn at the 50% probability level and hydrogen atoms as
small spheres with arbitrary radii. For simplicity only one
position of the disordered phenyl group is represented.
Hydrogen-bonding geometry details of the intramolecular
O–H···O interaction (dashed green line): dO···O = 2.6726 (19)
Å and <(DHA) = 141.3°.
(17) Park, D. Y.; Gowrisankar, S.; Kim, N. Tetrahedron Lett.
2006, 47, 6641.
Synlett 2010, No. 1, 115–118 © Thieme Stuttgart · New York

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