Synthesis of 2,3,5,6-tetrahydro-1-alkyl/aryl-1H-benzo[f]chromen-3-ol derivatives from β-tetralones and α,β-unsaturated aldehydes

Article abstract of DOI:10.1039/c1ob05966a

Organocatalytic domino Michael-hemiacetalization of β-tetralones with α,β-unsaturated aldehydes is presented. Treatment of β-tetralones with α,β-unsaturated aldehydes in the presence of diphenylprolinol silyl ether gave 2,3,5,6-tetrahydro-1-alkyl/aryl-1H-

Full text of DOI:10.1039/c1ob05966a

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PAPER
Synthesis of 2,3,5,6-tetrahydro-1-alkyl/aryl-1H-benzo[f ]chromen-3-ol
derivatives from b-tetralones and a,b-unsaturated aldehydes†
Jung-Hsuan Chen, Chihliang Chang, Hui-Ju Chang and Kwunmin Chen*
Received 15th June 2011, Accepted 5th August 2011
DOI: 10.1039/c1ob05966a
Organocatalytic domino Michael–hemiacetalization of b-tetralones with a,b-unsaturated aldehydes is
presented. Treatment of b-tetralones with a,b-unsaturated aldehydes in the presence of
diphenylprolinol silyl ether gave 2,3,5,6-tetrahydro-1-alkyl/aryl-1H-benzo[f ]chromen-3-ol derivatives
with high to excellent chemical yields (50–99%) and high levels of enantioselectivities (up to 96% ee).
Introduction
Six-membered oxygenated benzopyrans such as chromans,
chromenes, and flavanones exhibit one of the most important
structural motifs in natural products total synthesis.1 The syn-
thesis of functionalized derivatives for the study of diverse
biological profiles has attracted attention in both academia
and the pharmaceutical industry.2 Asymmetric organocatalysis
has proven to be a highly effective means of developing novel
Results and discussion
methodologies in organic synthesis.3 In recent years, the scope of
this field has been expanded to include multicomponent domino
reactions for the preparation of complex molecules with more
than one stereogenic center.4 An organocatalytic cascade reaction
of a,b-unsaturated aldehydes with various enolizable carbonyl
compounds has been utilized to synthesize 3,4-dihydropyran,5
hydroxyquinone,6 3,4-dihydropyranones,7 chromene derivatives8
and many other intermediates.9 Benzochromenes are found in
numerous natural products and are important pharmacophores
of many biologically active compounds.10
Functionalization of b-tetralone at the benzylic position has
been documented.11 For example, treatment of cinnamalde-
hyde with b-tetralone under acidic conditions affords Michael–
dehydration conjugate products.12 To the best of our knowl-
edge, the asymmetric synthesis of multifunctionalized 2,3,5,6-
tetrahydro-1H-benzo[f ]chromen-3-ol derivatives from b-tetralone
and a,b-unsaturated aldehydes catalyzed by an organocatalyst
has not been reported. This work describes the first organocat-
alytic reaction of b-tetralones with a,b-unsaturated aldehydes
to construct optically enriched 2,3,5,6-tetrahydro-1-substituent-
1H-benzo[f ]chromen-3-ol derivatives through a domino Michael–
hemiacetalization sequence.
Investigations were begun using b-tetralone (1a) and trans-
cinnamaldehyde (2a) as model substrates in the presence of a
catalytic amount of diphenylprolinol silyl ether I.13 The corre-
sponding benzochromene product 3aa was obtained under neat
conditions with moderate stereoselectivity and low chemical yield
(Table 1, entry 1). We next studied the solvent effects of the
sequential process. No improvement was observed when weakly
polar organic solvents were used (Table 1, entries 2–4). Both the
reactivity and stereoselectivity of the products decreased when
protic methanol was used (Table 1, entry 5). The reactivity was
enhanced when the reaction was conducted in CH3CN and further
improved when DMSO was used (Table 1, entries 6–7). These
effects may have been caused by the stabilization of the reaction
intermediate by the polar aprotic solvents. Various L-proline
derived organocatalysts were tested in the domino reaction.
The incorporation of the sterically encumbered naphthalene
group into organocatalysts II–IV resulted in high chemical yields
and low enantioselectivities of the desired product 3aa (Table
1, entries 8–10). Interestingly, the opposite enantiomer of 3aa
dominated when catalyst II was adopted (Table 1, entry 8).14
The use of the camphor–pyrrolidine derived organocatalysts
V–VII15 failed to improve the stereoselectivity of the domino
Michael–hemiacetalization reaction (Table 1, entries 11–13). The
structure of benzo[f ]chromenol 3aa was characterized by IR,
1H, 13C NMR and DEPT NMR spectroscopy. The diastereo-
/enantioselectivities were determined by chiral HPLC analyses.
The ratio of the hemiacetal anomers typically ranges from 5 : 1 to
7 : 1. Organocatalyst I was the catalyst of choice for the process.
The reaction conditions were fine-tuned by examining the effects
of additives. Various acidic and basic additives were studied.
Department of Chemistry, National Taiwan Normal University, 88 Sec. 4,
TingChow Road, Taipei, Taiwan 116, ROC. E-mail: kchen@ntnu.edu.tw;
Fax: (+886)2-29324249
† Electronic supplementary information (ESI) available. CCDC reference
numbers 824118 and 824119. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c1ob05966a
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Table 1 Domino Michael–hemiacetalization: solvents and catalysts
proceeded rapidly to give the corresponding 3aa in 97% yield and
88% ee after 24 h (Table 2, entry 7).
surveya
Variations of catalyst loading were investigated to optimize the
reaction conditions. Comparable stereoselectivity with decreased
chemical yield was obtained when the reaction were carried out in
the presence of 25 and 5 mol% of catalyst, respectively (Table 2,
entries 8 and 10). The chemical yield was regained with comparable
selectivity when 10 mol% of the catalyst was used (Table 2, entry 9).
The selectivity was slightly improved by performing the reaction
at 0 ◦C. Finally, the optimal reaction conditions were realized by
using 10 mol% of catalyst I and 20 mol% of DABCO at 0 ◦C (Table
2, entry 12).
The scope and general utility of the organocatalytic Michael–
hemiacetalization were exploited using various b-tetralones 1a–
f and a,b-unsaturated aldehydes 2a–g (Table 3). Substituted b-
tetralones reacted efficiently with 2a to generate the corresponding
products with excellent chemical yields and high enantioselectivi-
ties (Table 3, entries 1, 3–5). The use of 6-methoxy-b-tetralone 1c
resulted in a low chemical yield owing to the ready decomposition
of the starting substrate (Table 3, entry 2).
Entry
Catalyst
Solvent
Yield (%)b
ee (%)c
1
2
3
4
5
6
7
8
I
neat
41
34
59
49
39
70
91
81
99
98
93
79
94
63
35
60
42
17
69
72
-40
-2
15
-4
15
33
I
toluene
CH2Cl2
CHCl3
MeOH
CH3CN
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
I
I
I
I
I
Various a,b-unsaturated aldehydes were also tolerated with
1a under the reaction conditions (Table 3, entries 7–11). How-
ever, 1,2-addition–dehydration products were observed when
specific substrates were adopted.16 Therefore, the use of trans-4-
bromocinnamaldehyde with b-tetralone gave the desired product
with 60% chemical yield together with 25% of the 1,2-addition–
dehydration product (Table 3, entry 7).17 The reaction was carried
II
III
IV
V
VI
VII
9
10
11
12
13
a Reaction conditions: 1a (0.20 mmol) and catalyst (20 mol%) were
dissolved in the solvent (0.5 mL) indicated at 23 ◦C, then 2a (0.80 mmol)
was added. b Isolated yield. c Determined by chiral HPLC analysis.
◦
out at -20 C to avoid the side reaction and failed. Comparable
results were obtained when the starting enals 2d–e were used with
isolated yields of 15 and 40%, respectively (Table 3, entries 8, 9).
The aliphatic a,b-unsaturated aldehydes were excellent substrates
High enantioselectivities with low chemical yields were obtained
when an acidic additive was employed in the reaction (Table 2,
entries 1–3). Both the reactivity and the enantioselectivity dropped
considerably when DBU was used but rebounded when DMAP
was used instead (Table 2, entries 5 and 6). The reactivity increased
when DABCO was used and the product was obtained with high
stereoselectivity. Thus, in the presence of DABCO, the reaction
Table 3 The scope of the domino Michael–hemiacetalizationa
Table 2 Optimization of the domino reactiona
Entry R1
R2
Time (d) Yield (%)c d.r. ee (%)d
1
2
3
4
5-OMe C6H5
6-OMe C6H5
3ba
3ca
3da
3ea
3fa
1
1
1
1
1
1
2
2
1
1
2
1
1
1
1
92
77
95
99
99
99
6 : 1 89
5 : 1 88
4 : 1 90
4 : 1 91
5 : 1 93
6 : 1 86
4 : 1 80
3 : 1 95
9 : 1 83
2 : 1 93
3 : 1 93
3 : 1 94
3 : 1 95
3 : 1 95
3 : 1 96
Entry
Cat. I (mol%)
Additive
Time (d)
Yieldb
ee (%)c
6-Cl
6-Br
C6H5
C6H5
1
2
3
4
5
6
7
8
20
20
20
20
20
20
20
25
10
5
NH4Cl
PhCOOH
AcOH
TsOH
DBU
DMAP
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
3
3
3
3
1.5
1.5
1
1
1
39
66
66
trace
27
74
97
80
94
81
74
71
—
0
88
88
84
88
89
88
90
5
7-OMe C6H5
6
H
H
H
H
H
H
4-OMeC6H4 3ab
4-BrC6H4 3ac
4-NO2C6H4 3ad
2-furyl
Me
7b
8b
9
60 (25)e
67 (15)e
50 (40)e
99
3ae
3af
3ag
3bf
3df
3ef
3ff
10
11b
12
13
14
15
Et
62
67
80
99
5-OMe Me
9
6-Cl
6-Br
Me
Me
10
11d
12d
1
1
1
73
99
97
20
10
7-OMe Me
77
a Reaction conditions: 1 (0.2 mmol), Cat. I (10 mol%) and DABCO (20
mol %) were dissolved in DMSO (0.5 mL) at 0 ◦C, then enals 2 (0.8 mmol)
were added. b The reaction was carried out at -20 ◦C. c Isolated yield.
d Determined by HPLC. e Yield of 1,2-addition–dehydration product (4).
a Unless otherwise noted, the reaction was performed using 1a (0.20 mmol),
Cat. I, additive (20 mol%) and 2a (0.80 mmol) in DMSO (0.5 mL) at 23 ◦C.
b Isolated yield. c Determined by chiral HPLC analysis. d The reaction was
carried out at 0 ◦C.
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for use in the reaction. High enantioselectivities were observed
when (E)-2-butenal and (E)-2-pentenal were used (Table 3, entries
10–11). (E)-2-Butenal also reacted smoothly with substituted b-
tetralones. The corresponding benzochromene products 3bf–3ff
were achieved with good to excellent chemical yields and excellent
levels of enantioselectivities (Table 3, entries 12–15).
A reasonable mechanism is proposed in Scheme 1. a,b-
Unsaturated aldehydes 2 reacted with amine catalyst I to form
the intermediary iminium ion (A). The enol derived from the b-
tetralone 1a attacked the iminium ion on the less hindered side
to give the Michael adduct. Protonation and hydrolysis of the
intermediate produced keto aldehyde B. This process was followed
by hemiacetalization to complete the domino sequence. The amine
catalyst I was regenerated and participated in the next catalytic
cycle.
Experimental
Measurement: 1H and 13C NMR spectra were measured, and
spectral data are reported in ppm relative to tetramethylsilane
(TMS) as an internal standard using CDCl3 as solvent; stereos-
electivities were determined by chiral High-Performance Liquid
Chromatography analysis; optical rotation was measured on a
polarimeter.
Typical procedure
To a stirred solution of catalyst I (0.02 mmol) and DABCO
(0.04 mmol) in DMSO (0.5 mL) was added b-tetralone 1a–f
(0.21 mmol) at appropriate temperature (0 ◦C or -20 ◦C). The
mixture was stirred for 5 min and then a,b-unsaturated aldehydes
2a–g (0.85 mmol) were added slowly. Stirring was continued until
the starting material had completely disappeared, as determined
by TLC. The reaction mixture was quenched with H2O (3 mL) and
extracted with dichloromethane (5 mL). The combined organic
layer was washed with brine and dried over MgSO4. After removal
of the solvent, a crude residue was purified by flash column
chromatography on silica gel (eluted with hexanes–ethyl acetate =
4 : 1 ~ 6 : 1) to give the corresponding benzo[f ]chromen-3-ol (3).
(1S)-2,3,5,6-Tetrahydro-1-phenyl-1H -benzo[f ]chromen-3-ol
(3aa). 90% ee, [a]2D0 = +80.6 (c = 1.0 in CHCl3); colorless
oil; Rf 0.25 (4 : 1 Hex–EtOAc); 1H NMR (400 MHz, CDCl3):
d 7.29–7.24 (m, 4H, both diastereomers), 7.20–7.15 (m, 1H,
both diastereomers), 7.08–7.06 (m, 1H, both diastereomers),
6.95–6.89 (m, 2H, both diastereomers), 6.70–6.65 (m, 1H, both
diastereomers), 5.38 (br s, 1H, minor), 5.28 (d, J = 7.4 Hz, 1H,
major), 4.06 (t, J = 7.0 Hz, 1H, minor), 4.01 (t, J = 5.1 Hz,
1H, major), 3.03–2.86 (m, 3H, both diastereomers), 2.56–2.47
(m, 2H, both diastereomers), 2.25 (ddd, J = 16.4, 7.8, 5.9 Hz,
1H, both diastereomers), 2.17 (ddd, J = 16.4, 4.4, 2.6 Hz, 1H,
both diastereomers); 13C NMR (100 MHz, CDCl3): d 152.7, 152.3,
144.4, 143.7, 134.9, 134.6, 133.0, 132.8, 128.8, 128.6, 127.9, 127.3,
126.9 (¥2), 126.4, 126.3, 126.2, 126.1, 124.3 (¥2), 122.9, 122.7,
106.7, 105.6, 93.5, 91.3, 39.3, 38.3, 36.6, 36.4, 28.5 (¥2), 27.4,
27.1 ppm; FTIR (n/cm-1): 3404, 3061, 3026, 2936, 1646, 1601,
1488, 1451, 1240, 1115, 1040; HRMS (EI) m/z calcd. for C19H18O2
278.1307; found 278.1302.
Scheme 1 The proposed mechanism of the domino Michael–hemia-
cetalization.
To determine the absolute stereochemistry of the newly gen-
erated stereogenic centers, several attempts to derivatize the
products were made and unsuccessful. Finally, treatment of
benzochromene acetal 3aa with IBX gave 2,3,5,6-tetrahydro-
1-phenyl-1H-benzo[f ]chromen-3-one (5) with excellent optical
purity (Scheme 2). The structure of compound 5 was verified by
X-ray analysis.17
(1S)-2,3,5,6-Tetrahydro-7-methoxy-1-phenyl-1H-benzo[f ]chro-
men-3-ol (3ba). 89% ee, [a]1D8 = +105.3 (c = 1.0 in CHCl3); yellow
oil; Rf 0.28 (3 : 1 Hex–EtOAc); H NMR (500 MHz, CDCl3): d
Scheme
2 The synthesis of 2,3,5,6-tetrahydro-1-phenyl-1H-benzo-
1
[f ]chromen-3-one (5) and its X-ray crystal structure (30% probability).18
7.28–7.19 (m, 4H, both diastereomers), 7.19–7.11 (m, 1H, both
diastereomers), 6.87 (t, J = 8.0 Hz, 1H, both diastereomers),
6.57 (d, J = 8.2 Hz, 1H, both diastereomers), 6.36 (d, J =
7.9 Hz, 1H, major), 6.33 (d, J = 7.8 Hz, 1H, minor), 5.36 (dd,
J = 5.9, 2.5 Hz, 1H, minor), 5.24 (dd, J = 8.4, 2.5 Hz, 1H,
major), 4.04 (t, J = 6.7 Hz, 1H, minor), 3.98 (t, J = 4.5 Hz, 1H,
major), 3.79 (s, 3H, both diastereomers), 3.16–2.75 (m, 2H, both
diastereomers), 2.53–2.41 (m, 3H, both diastereomers), 2.25–2.18
(m, 1H, both diastereomers), 2.15 (ddd, J = 13.1, 4.2, 2.7 Hz, 1H,
both diastereomers); 13C NMR (125 MHz, CDCl3): d 155.8 (¥2),
152.8, 152.6, 144.7, 143.9, 136.3, 136.1, 128.9, 128.6, 127.9, 127.4,
126.5 (¥2), 126.4, 126.3, 120.7, 120.5, 116.1, 116.0, 107.4 (¥2),
106.1, 105.3, 93.4, 91.3, 55.4 (¥2), 39.0, 38.4, 37.0, 36.2, 26.8, 26.5,
20.6, 20.4 ppm; FTIR (n/cm-1): 3417, 2960, 2930, 2898, 2834,
Conclusions
In summary, the organocatalytic enantioselective domino
Michael–hemiacetalization of b-tetralones with a,b-unsaturated
aldehydes
to
give
2,3,5,6-tetrahydro-1-alkyl/aryl-1H-
benzo[f ]chromen-3-ol derivatives has been presented. The
functionalized products were obtained with high to excellent
chemical yields and good to high enantioselectivities. This process
provides a useful synthesis for the preparation of important
benzo[f ]chromenols and their derivatives. Further exploration is
underway.
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1649, 1598, 1572, 1470, 1439, 1261, 1153, 1122, 1054; HRMS (EI)
m/z calcd. for C20H20O3 308.1412; found 308.1414.
(1S)-2,3,5,6-Tetrahydro-9-methoxy-1-phenyl-1H-benzo[f ]chro-
men-3-ol (3fa). 93% ee, [a]2D0 = +48.2 (c = 1.0 in CHCl3); yellow
oil; Rf 0.25 (3 : 1 Hex–EtOAc); H NMR (500 MHz, CDCl3): d
1
(1S)-2,3,5,6-Tetrahydro-8-methoxy-1-phenyl-1H-benzo[f ]chro-
men-3-ol (3ca). 88% ee, [a]2D0 = +46.2 (c = 1.0 in CHCl3); yellow
oil; Rf 0.20 (4 : 1 Hex–EtOAc); H NMR (400 MHz, CDCl3): d
7.27–7.22 (m, 4H, both diastereomers), 7.18–7.11 (m, 1H, both
diastereomers), 6.97 (d, J = 8.1 Hz, 1H, minor), 6.96 (d, J = 8.2 Hz,
1H, major), 6.46 (dd, J = 8.2, 2.6 Hz, 1H, both diastereomers),
6.27 (d, J = 2.6 Hz, 1H, major), 6.24 (d, J = 2.6 Hz, 1H, minor),
5.34 (d, J = 4.7 Hz, 1H, minor), 5.28 (dd, J = 7.9, 2.0 Hz, 1H,
major), 4.02 (td, J = 7.0, 1.8 Hz, 1H, minor), 3.96 (td, J = 4.8,
1.0 Hz, 1H, major), 3.51 (s, 3H, minor), 3.50 (s, 3H, major), 3.39–
3.26 (br s, 1H, major), 3.26–3.16 (br s, 1H, minor), 2.98–2.77 (m,
2H, both diastereomers), 2.50–2.45 (m, 2H, both diastereomers),
2.26–2.20 (m, 1H, both diastereomers), 2.18–2.10 (m, 1H, both
diastereomers); 13C NMR (125 MHz, CDCl3): d 158.2, 158.1,
153.3, 153.0, 144.4, 143.6, 136.2, 136.0, 128.9, 128.7, 127.9, 127.5,
127.4, 127.3, 126.6, 126.4, 125.4, 125.2, 109.8, 109.6, 109.0, 108.9,
106.7, 105.7, 93.5, 91.3, 55.0 (¥2), 39.3, 38.3, 36.7, 36.5, 27.8, 27.7,
27.6, 27.5 ppm; FTIR (n/cm-1): 3426, 3023, 2932, 2835, 1646,
1606, 1575, 1493, 1453, 1244, 1215, 1150, 1122, 1045; HRMS (EI)
m/z calcd. for C20H20O3 308.1412; found 308.1404.
1
7.29–7.23 (m, 4H, both diastereomers), 7.22–7.16 (m, 1H, both
diastereomers), 6.67–6.66 (m, 1H, both diastereomers), 6.60–6.56
(m, 1H, both diastereomers), 6.46 (dd, J = 8.5, 2.7 Hz, 1H,
both diastereomers), 5.39–5.33 (m, 1H, minor), 5.31–5.20 (m,
1H, major), 4.04–4.01 (m, 1H, minor), 3.98–3.95 (m, 1H, major),
3.72 (s, 3H, minor), 3.70 (s, 3H, major), 3.05–2.81 (m, 3H, both
diastereomers), 2.50 (td, J = 7.6, 1.4 Hz, 2H, both diastereomers),
2.27–2.12 (m, 2H, both diastereomers); 13C NMR (125 MHz,
CDCl3): d 156.7 (¥2), 150.7, 150.5, 144.6, 143.8, 134.8, 134.7,
128.9, 128.6, 128.0, 127.8, 127.6, 127.4, 126.5, 126.4, 123.8, 123.7,
113.7, 113.6, 110.8, 110.7, 106.1, 105.2, 93.4, 91.2, 55.2 (¥2), 39.2,
38.5, 36.8, 36.3, 29.0, 28.9, 27.3, 27.0 ppm; FTIR (n/cm-1): 3420,
3057, 3023, 2932, 2835, 1649, 1609, 1572, 1499, 1453, 1252, 1119,
1054.
(1S)-2,3,5,6-Tetrahydro-1-(4-methoxyphenyl)-1H-benzo[f ]chro-
men-3-ol (3ab). 86% ee, [a]2D1 = +59.9 (c = 1.0 in CHCl3);
yellow oil; Rf 0.23 (3 : 1 Hex–EtOAc); 1H NMR (400 MHz,
CDCl3): d 7.18–7.14 (m, 2H, both diastereomers), 7.08–7.06 (m,
1H, both diastereomers), 6.95–6.90 (m, 2H, both diastereomers),
6.82–6.79 (m, 2H, both diastereomers), 6.73–6.67 (m, 1H, both
diastereomers), 5.38 (tt, J = 5.8, 2.8 Hz, 1H, minor), 5.26 (tt, J =
5.9, 2.5 Hz, 1H, major), 4.00 (t, J = 6.5 Hz, 1H, minor), 3.95 (t,
J = 4.7 Hz, 1H, major), 3.76 (s, 3H, major), 3.74 (s, 3H, minor),
3.01–2.87 (m, 3H, both diastereomers), 2.56–2.43 (m, 2H, both
diastereomers), 2.25–2.18 (m, 1H, both diastereomers), 2.14 (ddd,
J = 13.0, 4.0, 2.8 Hz, 1H, both diastereomers); 13C NMR (125
MHz, CDCl3): d 158.2, 158.1, 152.4, 152.3, 136.5 (¥2), 135.3,
135.0, 133.1, 132.9, 128.9, 128.4, 127.0 (¥2), 126.3, 126.2, 124.4,
124.3, 122.8 (¥2), 114.4, 114.0, 106.5, 105.8, 93.4, 91.4, 55.2 (¥2),
38.8, 38.6, 35.9, 34.8, 28.6 (¥2), 27.4, 27.1 ppm; FTIR (n/cm-1):
3420, 3063, 3017, 2932, 2835, 1646, 1609, 1510, 1487, 1453, 1246,
1178, 1116, 1059; HRMS (EI) m/z calcd. for C20H20O3 308.1412;
found 308.1406.
(1S)-2,3,5,6-Tetrahydro-8-chloro-1-phenyl-1H -benzo[f ]chro-
men-3-ol (3da). 90% ee, [a]1D8 = +60.3 (c = 1.0 in CHCl3); yellow
oil; Rf 0.28 (3 : 1 Hex–EtOAc); H NMR (500 MHz, CDCl3): d
1
7.29–7.24 (m, 2H, both diastereomers), 7.22–7.18 (m, 3H, both
diastereomers), 7.05–7.04 (m, 1H, both diastereomers), 6.86 (dd,
J = 8.4, 2.1 Hz, 1H, both diastereomers), 6.58 (d, J = 8.4 Hz, 1H,
major), 6.55 (d, J = 8.4 Hz, 1H, minor), 5.38 (ddd, J = 8.3, 6.2,
2.2 Hz, 1H, minor), 5.31–5.27 (m, 1H, major), 4.01 (td, J = 7.3,
1.8 Hz, 1H, minor), 3.96 (t, J = 5.4 Hz, 1H, major), 3.00 (d, J =
6.2 Hz, 1H, major), 3.01–2.98 (m, 1H, minor), 2.97–2.81 (m, 2H,
both diastereomers), 2.52–2.48 (m, 2H, both diastereomers), 2.26
(ddd, J = 13.6, 7.8, 6.0 Hz, 1H, both diastereomers), 2.19–2.13 (m,
1H, both diastereomers); 13C NMR (125 MHz, CDCl3): d 152.9,
152.5, 144.1, 143.3, 135.0, 134.8, 133.5, 133.3, 129.6, 129.5, 129.0,
128.7, 127.8, 127.3, 127.0 (¥2), 126.7, 126.6, 126.1, 126.0, 124.1,
124.0, 106.0, 105.3, 93.5, 91.3, 39.1, 38.3, 36.4, 36.3, 28.4 (¥2),
27.2, 27.0 ppm; FTIR (n/cm-1): 3417, 3028, 2930, 2852, 1646,
1598, 1484, 1451, 1241, 1122, 1054; HRMS (EI) m/z calcd. for
C19H17ClO2 312.0917; found 312.0912.
(1S)-2,3,5,6-Tetrahydro-1-(4-bromophenyl)-1H -benzo[f ]chro-
men-3-ol (3ac). 80% ee, [a]3D0 = +58.1 (c = 1.0 in CHCl3); yellow
oil; Rf 0.23 (4 : 1 Hex–EtOAc); H NMR (500 MHz, CDCl3): d
(1S)-2,3,5,6-Tetrahydro-8-bromo-1-phenyl-1H -benzo[f ]chro-
men-3-ol (3ea). 91% ee, [a]1D8 = +51.3 (c = 1.1 in CHCl3); yellow
oil; Rf 0.28 (3 : 1 Hex–EtOAc); H NMR (500 MHz, CDCl3): d
1
1
7.39 (dt, J = 8.5, 2.4 Hz, 2H, major), 7.35 (dt, J = 8.4, 2.6 Hz,
2H, minor), 7.15–7.09 (m, 2H, both diastereomers), 7.09–7.05 (m,
1H, both diastereomers), 6.97–6.89 (m, 2H, both diastereomers),
6.63 (dd, J = 6.8, 2.2 Hz, 1H, major), 6.61 (dd, J = 7.1, 1.3 Hz,
1H, minor), 5.40–5.36 (m, 1H, minor), 5.29–5.22 (m, 1H, major),
4.02 (td, J = 7.3, 2.6 Hz, 1H, minor), 3.97 (t, J = 5.2 Hz,
1H, major), 3.09 (br s, 1H, both diastereomers), 3.03–2.82 (m,
2H, both diastereomers), 2.53–2.45 (m, 2H, both diastereomers),
2.28–2.21 (m, 1H, both diastereomers), 2.13–2.05 (m, 1H, both
diastereomers); 13C NMR (125 MHz, CDCl3): d 152.9, 152.7,
143.6, 142.9, 134.6, 134.4, 133.1, 133.0, 131.9, 131.8, 129.7, 129.3,
127.1 (¥2), 126.3, 126.2, 124.6, 124.5, 122.9, 122.7, 120.2, 120.1,
106.3, 105.4, 93.3, 91.1, 39.1, 38.2, 36.0 (¥2), 28.6, 28.5, 27.4, 27.2
ppm; FTIR (n/cm-1): 3415, 3063, 3023, 2932, 2898, 2858, 1646,
1601, 1569, 1487, 1241, 1150, 1119, 1057; HRMS (EI) m/z calcd.
for C19H17BrO2 356.0412; found 356.0415.
7.28–7.23 (m, 2H, both diastereomers), 7.21–7.17 (m, 4H, both
diastereomers), 7.00 (dd, J = 8.4, 2.0 Hz, 1H, both diastereomers),
6.52 (d, J = 8.4 Hz, 1H, major), 6.49 (d, J = 8.4 Hz, 1H, minor),
5.37 (t, J = 5.6 Hz, 1H, minor), 5.30–5.26 (m, 1H, major), 4.00
(td, J = 6.9, 2.0 Hz, 1H, minor), 3.95 (t, J = 5.4 Hz, 1H, major),
3.11 (d, J = 5.3 Hz, 1H, major), 3.03 (d, J = 8.7 Hz, 1H, minor),
3.00–2.80 (m, 2H, both diastereomers), 2.51–2.46 (m, 2H, both
diastereomers), 2.27–2.22 (m, 1H, both diastereomers), 2.17–2.12
(m, 1H, both diastereomers); 13C NMR (125 MHz, CDCl3): d
153.0, 152.7, 144.1, 143.2, 135.3, 135.1, 134.0, 133.8, 129.8 (¥2),
129.1 (¥2), 129.0, 128.7, 127.8, 127.3, 126.7, 126.6, 124.4 (¥2),
117.6, 117.5, 106.1, 105.3, 93.5, 91.4, 39.1, 38.3, 36.4, 36.2, 28.3
(¥2), 27.2, 27.0 ppm; FTIR (n/cm-1): 3392, 3028, 2926, 2858, 1646,
1555, 1482, 1450, 1377, 1238, 1159, 1122, 1054; HRMS (EI) m/z
calcd. for C19H17BrO2 356.0412; found 356.0404.
This journal is
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Org. Biomol. Chem., 2011, 9, 7510–7516 | 7513
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View Article Online
(1S)-2,3,5,6-Tetrahydro-1-(4-nitrophenyl)-1H-benzo[f ]chro-
men-3-ol (3ad). 95% ee, [a]2D1 = +40.1 (c = 1.0 in CHCl3); yellow
oil; Rf 0.16 (3 : 1 Hex–EtOAc); H NMR (400 MHz, CDCl3): d
(1S )-2, 3, 5, 6-Tetrahydro-1-ethyl-1H -benzo[f ]chromen-3-
ol (3ag). 93% ee, [a]1D7 = -86.9 (c = 1.0 in CHCl3); colorless
oil; Rf 0.30 (4 : 1 Hex–EtOAc); H NMR (400 MHz, CDCl3): d
1
1
8.12 (d, J = 8.6 Hz, 2H, major), 8.08 (d, J = 8.6 Hz, 2H, minor),
7.42–7.37 (m, 2H, both diastereomers), 7.09 (d, J = 7.1 Hz, 1H,
both diastereomers), 6.94 (t, J = 7.1 Hz, 1H, both diastereomers),
6.89 (t, J = 7.5 Hz, 1H, both diastereomers), 6.54 (d, J = 7.5 Hz,
1H, both diastereomers), 5.43 (d, J = 6.2 Hz, 1H, minor), 5.30 (d,
J = 6.2 Hz, 1H, major), 4.16–4.13 (m, 1H, both diastereomers),
3.41 (br s, 1H, major), 3.26 (br s, 1H, minor), 3.07–2.84 (m,
2H, both diastereomers), 2.59–2.41 (m, 2H, both diastereomers),
2.36–2.29 (m, 1H, both diastereomers), 2.12–2.06 (m, 1H, both
diastereomers); 13C NMR (125 MHz, CDCl3): d 153.3, 153.0,
152.5, 152.2, 146.7, 146.6, 134.2, 134.1, 133.2, 133.0, 128.8, 128.6,
127.3 (¥2), 126.3 (¥2), 124.8, 124.7, 124.0, 123.9, 122.6 (¥2), 105.8,
105.1, 93.0, 90.8, 38.5, 37.9, 36.6, 36.0, 28.5 (¥2), 27.4 (¥2) ppm;
FTIR (n/cm-1): 3432, 2926, 2852, 1646, 1603, 1518, 1487, 1348,
1238, 1113, 1057; HRMS (EI) m/z calcd. for C19H17NO4 323.1158;
found 323.1150.
7.17–7.14 (m, 1H, both diastereomers), 7.11–7.07 (m, 1H, both
diastereomers), 7.05–6.99 (m, 2H, both diastereomers), 5.40 (dd,
J = 8.0, 2.0 Hz, 1H, major), 5.22 (dd, J = 7.7, 1.8 Hz, 1H,
minor), 3.58–3.21 (m, 1H, both diastereomers), 2.93–2.83 (m,
1H, both diastereomers), 2.78–2.70 (m, 1H, both diastereomers),
2.68–2.63 (m, 1H, both diastereomers), 2.51–2.35 (m, 1H, both
diastereomers), 2.22 (ddd, J = 16.0, 6.9, 3.8 Hz, 1H, both
diastereomers), 2.10 (ddd, J = 13.4, 4.0, 2.6 Hz, 1H, both
diastereomers), 1.90–1.73 (m, 2H, both diastereomers), 1.44–1.22
(m, 1H, both diastereomers), 0.97 (t, J = 7.4 Hz, 3H, major), 0.90
(t, J = 7.4 Hz, 3H, minor); 13C NMR (125 MHz, CDCl3): d 150.7,
150.1, 135.0, 134.9, 133.8, 133.5, 127.3, 127.2, 126.3, 126.1, 124.3
(¥2), 122.0, 121.4, 109.8, 108.8, 94.1, 91.7, 34.6, 32.8, 31.4, 30.6,
28.6 (¥2), 27.3, 27.0, 26.8, 26.0, 11.5, 10.7 ppm; FTIR (n/cm-1):
3415, 3063, 3023, 2960, 2932, 2875, 1643, 1601, 1569, 1484, 1456,
1235, 1125, 1110, 1085, 1014; HRMS (FAB) m/z calcd. for [M -
H]+ C15H17O2 229.1229; found 229.1226.
(1R) - 2,3,5,6 - Tetrahydro - 1 - (furan - 2 - yl) - 1H - benzo[f ]chro-
men-3-ol (3ae). 83% ee, [a]1D8 = +54.8 (c = 0.36 in CHCl3); yellow
oil; Rf 0.25 (4 : 1 Hex–EtOAc); 1H NMR (500 MHz, CDCl3): d 7.37
(d, J = 1.1 Hz, 1H, minor), 7.33–7.32 (m, 1H, major), 7.11–7.07 (m,
1H, both diastereomers), 7.05–7.02 (m, 1H, both diastereomers),
7.01–6.96 (m, 1H, both diastereomers), 6.89–6.87 (m, 1H, both
diastereomers), 6.24–6.22 (m, 1H, both diastereomers), 6.00 (d,
J = 3.2 Hz, 1H, minor), 5.96 (d, J = 3.2 Hz, 1H, major), 5.44 (d,
J = 7.5 Hz, 1H, minor), 5.32 (d, J = 8.2 Hz, 1H, major), 4.10–4.04
(m, 1H, both diastereomers), 3.54 (d, J = 10.6 Hz, 1H, minor),
3.15 (br s, 1H, major), 3.02–2.86 (m, 2H, both diastereomers),
2.54 (dt, J = 14.0, 3.1 Hz, 1H, minor), 2.51–2.43 (m, 2H, both
diastereomers), 2.40 (dt, J = 13.0, 2.6 Hz, 1H, major), 2.30 (ddd,
J = 14.0, 6.8, 3.1 Hz, 1H, minor), 2.06 (ddd, J = 13.0, 9.3, 5.7 Hz,
1H, major); 13C NMR (125 MHz, CDCl3): d 156.8, 156.4, 152.3,
151.6, 142.1, 141.4, 134.8, 134.5, 132.9, 132.8, 127.2, 127.1, 126.4
(¥2), 124.7, 124.6, 121.8, 121.6, 110.6, 110.3, 107.1, 106.5, 104.0,
103.6, 92.3, 92.1, 34.7, 32.9, 31.1, 28.5, 28.3, 27.7, 27.2, 27.0 ppm;
FTIR (n/cm-1): 3415, 3063, 2932, 2892, 2852, 1646, 1601, 1504,
1487, 1453, 1272, 1241, 1150, 1119, 1057; HRMS (ESI) m/z calcd.
for C17H16O3 [M - H]- 267.1099; found 267.1090.
(1S)-2,3,5,6-Tetrahydro-7-methoxy-1-methyl-1H-benzo[f ]chro-
men-3-ol (3bf). 94% ee, [a]D24 = -45.9 (c = 1.0 in CHCl3); colorless
oil; Rf 0.23 (4 : 1 Hex–EtOAc); H NMR (500 MHz, CDCl3): d
1
7.14 (t, J = 8.0 Hz, 1H, both diastereomers), 6.78 (d, J = 7.8 Hz,
1H, major), 6.74 (d, J = 7.8 Hz, 1H, minor), 6.68 (d, J = 8.0 Hz,
1H, minor), 6.67 (d, J = 8.0 Hz, 1H, major), 5.44–5.42 (m, 1H,
major), 5.28 (dd, J = 7.1, 2.0 Hz, 1H, minor), 3.82 (s, 3H, minor),
3.82 (s, 3H, major), 3.16 (ddd, J = 15.5, 6.5, 2.6 Hz, 1H, minor),
3.09 (ddd, J = 16.0, 7.1, 4.5 Hz, 2H, major), 2.95–2.89 (m, 1H, both
diastereomers), 2.65–2.46 (m, 1H, both diastereomers), 2.44–2.27
(m, 1H, both diastereomers), 2.23 (ddd, J = 16.0, 7.3, 4.5 Hz, 1H,
both diastereomers), 2.00–1.92 (m, 2H, both diastereomers), 1.79
(dt, J = 13.5, 7.3 Hz, 1H, minor), 1.21 (d, J = 6.5 Hz, 3H, minor),
1.20 (d, J = 6.8 Hz, 3H, major); 13C NMR (125 MHz, CDCl3): d
156.1, 156.0, 150.1, 149.9, 136.4, 136.3, 126.6, 126.4, 121.4, 121.0,
115.4, 114.8, 109.4, 107.5, 93.6, 91.4, 55.5 (¥2), 38.0, 36.9, 26.5,
26.3, 25.0, 24.2, 21.2, 20.6, 20.5, 20.3 ppm; FTIR (n/cm-1): 3420,
2960, 2926, 2858, 1649, 1586, 1575, 1473, 1439, 1263, 1130, 1093,
1028; HRMS (ESI) m/z calcd. for C15H18O3 [M - H]- 245.1256;
found 245.1244.
(1S)-2,3,5,6-Tetrahydro-8-chloro-1-methyl-1H -benzo[f ]chro-
men-3-ol (3df). 95% ee, [a]D25 = -64.6 (c = 1.0 in CHCl3); colorless
(1S)-2,3,5,6-Tetrahydro-1-methyl-1H -benzo[f ]chromen-3-ol
(3af). 93%ee, [a]2D3 = -85.9 (c = 1.0 inCHCl3); colorless oil; Rf 0.28
(4 : 1 Hex–EtOAc); 1H NMR (500 MHz, CDCl3): d 7.17–7.14 (m,
1H, both diastereomers), 7.10–7.04 (m, 2H, both diastereomers),
7.01 (qd, J = 7.4, 1.2 Hz, 1H, both diastereomers), 5.43 (d, J =
5.1 Hz, 1H, major), 5.26 (d, J = 6.5 Hz, 1H, minor), 3.40 (br s,
1H, both diastereomers), 2.95–2.85 (m, 2H, both diastereomers),
2.78–2.68 (m, 1H, both diastereomers), 2.50–2.37 (m, 1H, both
diastereomers), 2.30–2.19 (m, 1H, both diastereomers), 2.00–1.91
(m, 2H, both diastereomers), 1.78 (dt, J = 13.5, 7.6 Hz, 1H, minor),
1.22 (d, J = 5.8 Hz, 3H, minor), 1.20 (d, J = 6.9 Hz, 3H, major);
13C NMR (125 MHz, CDCl3): d 149.8, 149.7, 134.9, 134.8, 133.8,
133.4, 127.3, 127.2, 126.3, 126.1, 124.3 (¥2), 122.2, 121.6, 110.6,
109.7, 93.7, 91.4, 38.1, 36.8, 28.6, 28.5, 27.2, 26.9, 24.9, 23.8, 21.0,
20.4 ppm; FTIR (n/cm-1): 3415, 2955, 2932, 2892, 2835, 1643,
1601, 1569, 1487, 1453, 1235, 1122, 1085; HRMS (EI) m/z calcd.
for C14H16O2 216.1150; found 216.1149.
1
oil; Rf 0.18 (4 : 1 Hex–EtOAc); H NMR (500 MHz, CDCl3): d
7.14–7.11 (m, 1H, both diastereomers), 7.08 (s, 1H, minor), 7.07
(s, 1H, major), 6.99 (d, J = 8.3 Hz, 1H, major), 6.95 (d, J = 8.3 Hz,
1H, minor), 5.43 (d, J = 6.5 Hz, 1H, major), 5.28 (d, J = 6.5 Hz,
1H, minor), 3.24 (br s, 1H, both diastereomers), 2.90–2.83 (m,
2H, both diastereomers), 2.75–2.65 (m, 1H, both diastereomers),
2.48–2.35 (m, 1H, both diastereomers), 2.28 (ddd, J = 13.5, 7.2,
2.4 Hz, 1H, minor), 2.26–2.19 (m, 1H, both diastereomers), 2.01–
1.91 (m, 2H, major), 1.79 (dt, J = 13.5, 7.4 Hz, 1H, minor), 1.19
(d, J = 6.2 Hz, 3H, minor), 1.18 (d, J = 6.9 Hz, 3H, major); 13C
NMR (125 MHz, CDCl3): d 150.0, 149.9, 135.6, 135.3, 133.5,
133.4, 129.5 (¥2), 127.3, 127.2, 126.2, 126.0, 123.3, 122.7, 110.0,
109.2, 93.6, 91.4, 37.8, 36.7, 28.4, 28.3, 26.9, 26.7, 24.7, 23.7, 20.8,
20.3 ppm; FTIR (n/cm-1): 3420, 2955, 2932, 1643, 1595, 1484,
1450, 1238, 1125, 1088; HRMS (ESI) m/z calcd. for C14H15ClO2
[M - H]- 249.0761; found 249.0731.
7514 | Org. Biomol. Chem., 2011, 9, 7510–7516
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(1S)-2,3,5,6-Tetrahydro-8-bromo-1-methyl-1H -benzo[f ]chro-
men-3-ol (3ef). 95% ee, [a]D26 = -40.6 (c = 1.0 in CHCl3); colorless
oil; Rf 0.25 (4 : 1 Hex–EtOAc); H NMR (500 MHz, CDCl3): d
129.3, 127.6 (¥2), 126.8 (¥2), 126.5, 122.7, 111.9, 38.2, 37.8, 28.3,
25.4 ppm; FTIR (n/cm-1): 3063, 3028, 2949, 2892, 2841, 1771,
1669, 1601, 1490, 1450, 1244, 1178, 1130; HRMS (EI) m/z calcd.
for C19H16O2 276.1150; found 276.1144.
1
7.28–7.25 (m, 1H, both diastereomers), 7.22 (s, 1H, minor), 7.21
(s, 1H, major), 6.94 (d, J = 8.3 Hz, 1H, major), 6.89 (d, J = 8.3 Hz,
1H, minor), 5.43 (d, J = 5.7 Hz, 1H, major), 5.28 (d, J = 6.2 Hz, 1H,
minor), 3.31 (br s, 1H, both diastereomers), 2.90–2.83 (m, 2H, both
diastereomers), 2.75–2.65 (m, 1H, both diastereomers), 2.47–2.35
(m, 1H, both diastereomers), 2.27 (ddd, J = 13.5, 7.2, 2.3 Hz, 1H,
minor), 2.21 (ddd, J = 16.1, 7.0, 4.5 Hz, 1H, both diastereomers),
2.00–1.90 (m, 2H, major), 1.78 (dt, J = 13.5, 7.4 Hz, 1H, minor),
1.19 (d, J = 6.8 Hz, 3H, minor), 1.18 (d, J = 7.0 Hz, 3H, major);
13C NMR (125 MHz, CDCl3): d 150.1, 150.0, 136.0, 135.6, 134.0,
133.9, 130.1, 130.0, 129.1, 129.0, 123.7, 123.1, 117.5, 117.4, 110.1,
109.2, 93.7, 91.4, 37.7, 36.6, 28.3, 28.2, 26.9, 26.7, 24.7, 23.7, 20.8,
20.2 ppm; FTIR (n/cm-1): 3572, 2959, 2930, 2893, 2841, 1642,
1558, 1480, 1373, 1233, 1119, 1086; HRMS (ESI) m/z calcd. for
C14H15BrO2 [M+K]+ 333.0255; found 333.0176.
Acknowledgements
The authors thank the National Science Council of the Republic of
China (NSC 99-2113-M-003-002-MY3 and NSC 99-2119-M-003-
001-MY2) and National Taiwan Normal University (99T3030-
5 and 99-D) for financial support of this work. Our gratitude
extends to the Academic Paper Editing Clinic at NTNU, and to the
National Center for High-Performance Computing for providing
us with computer time and facilities.
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(1S)-2,3,5,6-Tetrahydro-9-methoxy-1-methyl-1H-benzo[f ]chro-
men-3-ol (3ff). 96% ee, [a]2D7 = -73.0 (c = 1 in CHCl3); colorless
1
oil; Rf 0.18 (4 : 1 Hex–EtOAc); H NMR (500 MHz, CDCl3): d
7.02–6.99 (m, 1H, both diastereomers), 6.69 (d, J = 2.6 Hz, 1H,
major), 6.64 (d, J = 2.5 Hz, 1H, minor), 6.58–6.55 (m, 1H, both
diastereomers), 5.43 (dd, J = 6.6, 3.6 Hz, 1H, major), 5.27 (dd, J =
6.9, 1.5 Hz, 1H, minor), 3.79 (s, 3H, both diastereomers), 3.27 (br
s, 1H, both diastereomers), 2.92–2.86 (m, 1H, both diastereomers),
2.82 (td, J = 14.6, 6.8 Hz, 1H, both diastereomers), 2.74–2.64 (m,
1H, both diastereomers), 2.48–2.35 (m, 1H, both diastereomers),
2.28 (ddd, J = 13.5, 7.2, 2.3 Hz, 1H, minor), 2.24–2.18 (m, 1H,
both diastereomers), 1.99–1.92 (m, 2H, major), 1.78 (dt, J = 13.5,
7.5 Hz, 1H, minor), 1.23 (d, J = 8.1 Hz, 3H, minor), 1.21 (d, J =
7.1 Hz, 3H, major); 13C NMR (125 MHz, CDCl3): d 158.5, 158.3,
150.5 (¥2), 136.3, 136.2, 127.7, 127.6, 126.1, 125.7, 110.5, 109.6,
109.4, 108.8, 108.3, 108.2, 93.7, 91.4, 55.3 (¥2), 37.9, 36.8, 27.7,
27.6, 27.5, 27.3, 24.8, 23.9, 21.0, 20.4 ppm; FTIR (n/cm-1): 3420,
2960, 2926, 2858, 1643, 1609, 1572, 1493, 1456, 1238, 1212, 1125,
1042; HRMS (ESI) m/z calcd. for C15H18O3 [M - H]- 245.1256;
found 245.1245.
(E)-1-((E)-3-(4-Nitrophenyl)allylidene)-3,4-dihydronaphthalen-
2(1H)-one (4). yellow crystal; Rf 0.28 (6 : 1 Hex–EtOAc); mp (◦C)
190–191; 1H NMR (500 MHz, CDCl3): d 8.21 (d, J = 8.8 Hz, 2H),
7.58 (d, J = 8.8 Hz, 2H), 7.50–7.44 (m, 3H), 7.40–7.33 (m, 3H),
7.15 (ddd, J = 11.8, 10.0, 10.0 Hz, 1H), 3.01 (t, J = 6.5 Hz, 2H),
2.65 (t, J = 6.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): d 201.3,
147.5, 142.8, 139.5, 138.6, 135.8, 133.2, 133.1, 129.2, 128.9, 128.6,
128.1, 127.6, 126.9, 124.2, 37.0, 27.8 ppm; FTIR (n/cm-1): 1680,
1592, 1507, 1337, 1241, 1167, 1110; HRMS (EI) m/z calcd. for
C19H15NO3 305.1052; found 305.1059.
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(S)-1-Phenyl-5,6-dihydro-1H-benzo[f ]chromen-3(2H)-one (5).
>99% ee, [a]2D0 = +95.6 (c =◦1 in CHCl3); colorless crystal; Rf
1
0.25 (6 : 1 Hex–EtOAc); mp ( C) 159–160; H NMR (500 MHz,
CDCl3): d 7.31 (t, J = 7.2 Hz, 2H), 7.25–7.20 (m, 3H), 7.14 (d, J =
6.7 Hz, 1H), 7.10–7.03 (m, 2H), 6.93 (dd, J = 7.0, 1.5 Hz, 1H),
4.15 (d, J = 7.5 Hz, 1H), 3.14 (dd, J = 15.7, 7.5 Hz, 1H), 3.10–3.05
(m, 1H), 2.99 (dt, J = 15.7, 6.7 Hz, 1H), 2.92 (dd, J = 15.7, 1.7 Hz,
1H), 2.79 (ddd, J = 18.9, 12.4, 7.2 Hz, 1H), 2.62–2.56 (m, 1H);
13C NMR (125 MHz, CDCl3): d 167.0, 150.8, 140.3, 133.2, 132.5,
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16 P.-J. J. Huang, E. Potter and A. Jha, Mol. Diversity, 2010, 14, 393.
17 Detailed X-ray crystallographic data† for the 1,2-addition–dehydration
product
4 (CCDC 824118) and 2,3,5,6-tetrahydro-1-phenyl-1H-
benzo[f ]chromen-3-one 5 (CCDC 824119) are available from the
CCDC, 12 Union Road, Cambridge CB2, 1EZ, UK (www.ccdc.cam.ac.
uk/data_request/cif).
18 The absolute stereochemistry of the products is tentative assigned with
the Flack parameter of compound 5 is 0.47, see: H. D. Flack, Acta
Crystallogr. Sect. A, 1983, 39, 876.
12 A. Jha, J. Zhao, T. S. Cameron, E. D. Clercq, J. Balzarini, E. K.
Manavathu and J. P. Stables, Lett. Drug Des. Discovery, 2006, 3, 304.
7516 | Org. Biomol. Chem., 2011, 9, 7510–7516
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