Organocatalyzed Friedel-Craft-type reaction of 2-naphthol with β,γ-unsaturated α-keto ester to form novel optically active naphthopyran derivatives

Article abstract of DOI:10.1016/j.tetasy.2008.11.025

A novel bifunctional thiourea-tertiary-amine-catalyzed enantioselective Friedel-Craft-type addition reaction of 2-naphthol with β,γ-unsaturated α-keto ester was developed. Subsequent dehydration of the reaction adducts with a catalytic amount of concentrated H₂SO₄ in a one-pot fashion readily afforded a series of new optically active naphthopyran derivatives with moderate to good yields (up to 91%) and enantioselectivities (up to 90%).

Full text of DOI:10.1016/j.tetasy.2008.11.025

Tetrahedron: Asymmetry 19 (2008) 2699–2704
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Tetrahedron: Asymmetry
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Organocatalyzed Friedel–Craft-type reaction of 2-naphthol with b,c-unsaturated
a-keto ester to form novel optically active naphthopyran derivatives
b,
Xiao-Sheng Wang b, Chang-Wu Zheng a, Sheng-Li Zhao c, Zhuo Chai a, Gang Zhao a, , Gao-Sheng Yang
*
*
a Laboratory of Modern Synthetic Organic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
b Anhui Key Laboratory of Functional Molecular Solids, Institute of Organic Chemistry, School of Chemistry and Materials Science, Anhui Normal University,
Wuhu, Anhui 241000, China
c Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel bifunctional thiourea–tertiary-amine-catalyzed enantioselective Friedel–Craft-type addition
reaction of 2-naphthol with b, -unsaturated -keto ester was developed. Subsequent dehydration of
the reaction adducts with a catalytic amount of concentrated H2SO4 in a one-pot fashion readily afforded
a series of new optically active naphthopyran derivatives with moderate to good yields (up to 91%) and
enantioselectivities (up to 90%).
Received 26 October 2008
Accepted 18 November 2008
Available online 10 January 2009
c
a
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
the cinchona alkaloid-derived thiourea catalyst 1a to furnish a Fri-
edel–Craft-type addition adduct 4a. Since compound 4a is in rapid
Naphthopyran derivatives are an important class of compounds
with excellent photochromic properties,1 some of which are also
structural motifs present in many biologically active compounds.2
For instance, some naphthopyran derivatives could have potential
applications in biochemical research as photoswitch tag com-
pounds.1d Therefore, the synthesis of such compounds has at-
tracted strong interest.3 Although several methods have been
successfully developed for this purpose, the enantioselective syn-
thesis of naphthopyran derivatives has scarcely been reported.3
Recently, we have disclosed an efficient bifunctional thiourea-
equilibrium with the cyclic hemiketal 5a,6i it was dehydrated with
3a
a catalytic amount of concentrated H2SO4 in a one-pot fashion
after completion of the Friedel–Craft-type addition step, which
provided the naphthopyran derivative 6a in 79% yield (over two
steps) and 57% ee (Scheme 1).
Subsequently, we decided to optimize the reaction conditions,
and the results were summarized in Table 1. Firstly, a dramatic sol-
vent effect on both the yield and enantioselectivity was observed,
and CH2Cl2 was found to be the solvent of choice, giving the de-
sired product 6a in 73% ee and 82% yield (entry 2). Next, a series
of thiourea and tertiary amine-based bifunctional catalysts were
screened at room temperature in CH2Cl2 (entries 7–11). Interest-
ingly, of all the catalysts examined, the (R,R)-1,2-cyclohexyldi-
amine-derived catalyst 1c was again found to exhibit the best
catalytic effect as shown in our previous work4 (entry 8). Changing
the trifluoromethyl phenyl group in 1c to 4-fluorophenyl 1d, 4-tri-
fluorophenyl 1e, or cyclohexyl 1f groups led to inferior chemical
yields and enantioselectivities. Further optimization with 1c re-
vealed that no beneficial effect on the enantioselectivity could be
observed when lowering the reaction temperature to ꢀ25 °C (entry
12, 76% ee), while a slightly better enantioselectivity was obtained
when 20 mol % of 1c was used (entry 14, 87% ee).
catalyzed addition–cyclization reaction of 2-naphthol with
a,a-
dicyanoolefins affording the corresponding naphthopyran
derivatives in high yields and moderate enantioselectivities.4 As
an extension of this work,5 we then wondered if other electro-
philes, such as b,
stead of -dicyanoolefins. Compound 2 was also found to be a
c-unsaturated a
-keto esters 26 could be used in-
a,a
suitable reaction component in this reaction system to provide a
series of novel optically active naphthopyran derivatives with
moderate to good yields and enantioselectivities after a simple
conversion step. Herein, we report the details of this study (Fig. 1).
2. Results and discussion
With the optimized reaction conditions in hand, we then exam-
ined a range of b,
plore the generality of this reaction, and the results are
c-unsaturated a-keto esters and naphthols to ex-
As a starting point, the reaction of b,c-unsaturated a-keto ester
2a with 2-naphthol was chosen as a model reaction to investigate.
The reaction proceeded well at room temperature in toluene with
summarized in Table 2. Firstly, several b,c-unsaturated a-keto es-
ters 2a–e bearing different R3 substituents were tested in the reac-
tion (Table 2, entries 1–5). It was found that variation of the R3
groups had a greater influence on the chemical yield of the reaction
* Corresponding authors. Fax: +86 21 64166128.
E-mail addresses: zhaog@mail.sioc.ac.cn (G. Zhao), gshyang@mail.ahnu.edu.cn
(G.-S. Yang).
than on the enantioselectivity. Next, a series of a-keto esters with
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.11.025

2700
X.-S. Wang et al. / Tetrahedron: Asymmetry 19 (2008) 2699–2704
CF3
CF3
S
OMe
N
N
N
CF3
NH
N
CF3
H
NH
NH
N
N
S
N
CF3
S
N
H
CF3
H
1c
1b
1a
S
S
R
NH
N
NH
N
H
H
N
N
1d: R=F
1e: R=CF3
1f
Figure 1. Thiourea–tertiary amine catalysts used in the study.
O
OH
1a (5 mol %)
toluene, r.t.
OMe
+
Ph
O
2a
3a
COOMe
OH
O
COOMe
Ph
COOMe
Ph
Ph
OH
O
H2SO4(cat.)
r.t.
O
6a
Yield: 79%, ee: 57%
4a
5a
Scheme 1. The one-pot two-step enantioselective synthesis of 6a.
differently substituted phenyl rings having the same R3 = Me were
also examined (Table 2, entries 6–13). It seems that the electronic
nature of the substituents on the phenyl ring has a dramatic effect
on this reaction. With the exception of the ortho-Br-substituted
substrate 2l (Table 2, entry 12), substrates bearing para- or meta-
electron-withdrawing groups on the phenyl ring provided much
better results than those bearing electron-donating groups in
terms of both yield and enantioselectivity. Moreover, two substi-
tuted 2-naphthols were also reacted with ketoester 2a to study
the influence of the structure of the naphthol component on the
reaction (Table 2, entries 14 and 15). In both cases, comparable
enantioselectivities to those of the unsubstituted 2-naphthol were
obtained, albeit with lower yields. The absolute configuration of
the product 6n was determined to have an (S)-configuration by
X-ray crystallographic analysis (Fig. 2).7
3. Conclusions
In conclusion, we have reported the enantioselective synthesis
of a series of novel naphthopyran derivatives based on an asym-
metric Friedel–Craft-type addition reaction of 2-naphthol with
b,c-unsaturated a-keto ester catalyzed by bifunctional thiourea–
tertiary amines. With this procedure, the desired naphthopyran
derivatives 6 could be obtained with moderate to good yields
and enantioselectivities (51–91% yield and 57–90% ee) under mild
conditions.
H
COOMe
O
Br
6n
Figure 2. X-ray structure of compound 6n.

X.-S. Wang et al. / Tetrahedron: Asymmetry 19 (2008) 2699–2704
2701
1178, 1141, 1060, 812, 750, 760, 697 cmꢀ1
;
1H NMR (300 MHz,
4. Experimental
4.1. General
CDCl3) d 7.79–7.71 (m, 2H), 7.38–7.09 (m, 9H), 4.83–4.72 (m,
1H), 4.19 (s, 0.60H), 3.98 (s, 0.40H), 3.87 (s, 1.18H), 3.82 (s,
1.82H), 2.93–2.86 (m, 0.37H), 2.66–2.53 (m, 1.63H); 13C NMR
(75 MHz, CDCl3) d 170.1, 150.3, 149.9, 145.7, 143.9, 132.4, 132.1,
130.3, 129.8, 129.3, 129.2, 128.8, 128.4, 128.3, 128.234, 128.197,
127.6, 126.5, 126.3, 125.7, 125.2, 123.7, 123.4, 119.0, 118.9,
116.0, 114.0, 94.6, 93.9, 53.4, 39.9, 36.6, 35.7, 35.0; LRMS (EI): m/
e 231 (M+, 100), 257 (81), 77 (65), 44 (64), 131 (64), 103 (64), 51
(63), 239 (62). Anal. Calcd for C21H18O4: C, 75.43; H, 5.43. Found:
C, 75.05; H, 5.41.
Unless otherwise indicated, chemicals and solvents were pur-
chased from commercial suppliers and purified by standard tech-
niques. Flash column chromatography was performed using silica
gel. For thin-layer chromatography (TLC), silica gel plates (HSGF
254) were used, and compounds were visualized by irradiation
with UV light or by treatment with a solution of phosphomolybdic
acid in ethanol followed by heating. The 1H NMR spectra were re-
corded on a DPX-300 or Varian EM-360 (300 MHz). All chemical
shifts (d) are given in ppm. Data are reported as follows: chemical
shift, multiplicity (s = single, d = doublet, t = triplet, q = quartet,
br = broad, and m = multiplet) and coupling constants (Hz), inte-
gration. 13C NMR spectra were recorded on a DPX-300 (75 MHz).
Analytical high performance liquid chromatography (HPLC) was
carried out on WATERS equipment using a chiral column. Melting
points were determined on a SGW X-4 apparatus and were/are
uncorrected. Optical rotations were measured on a JASCO P-1030
Polarimeter at k = 589 nm. IR spectra were recorded on a Perkin–
Elmer 983G instrument. Elementary analysis was taken on a Vario
EL III elementary analysis instrument. Mass spectra analysis was
performed on API 200 LC/MS system (Applied Biosystems Co. Ltd).
4.1.1.2. Methyl 1-phenyl-1H-benzo[f]chromene-3-carboxylate
6a.
CHCl3); IR (KBr): 1725, 1674, 1622, 1599, 1516, 1434, 1335,
1262, 1231, 1190, 1113, 1070, 1037, 764, 748, 705 cmꢀ1 1H
White solid. Mp 176–177 °C;
½
a 2D2
ꢁ
¼ ꢀ341:6 (c 0.50,
;
NMR (300 MHz, CDCl3) d 7.79 (d, J = 8.4 Hz, 2H), 7.66–7.64 (m,
1H), 7.42–7.35 (m, 3H), 7.29–7.17 (m, 5H), 6.46 (d, J = 4.8 Hz,
1H), 5.35 (d, J = 4.8 Hz, 1H), 3.85 (s, 3H); 13C NMR (75 MHz, CDCl3)
d 162.2, 148.9, 144.3, 138.9, 131.3, 131.2, 129.4, 128.9, 128.4,
127.7, 126.8, 126.7, 124.4, 123.5, 117.9, 114.9, 113.0, 52.3, 39.0;
LRMS (EI): m/e 239 (M+, 100), 257 (65), 315 (44), 240 (19), 258
(13), 317 (10), 226 (7), 316 (7). Anal. Calcd for C21H16O3: C,
79.73; H, 5.10. Found: C, 79.69; H, 5.22. The enantiomeric ratio
was determined by HPLC analysis, using a Chiracel OD-H column
4.1.1. General procedure for the asymmetric synthesis of
naphthopyran derivatives 6a–6o
(25 °C, 254 nm, 9:1, hexane/2-propanol, 1.0 mL/min); tmajor
14.24 min, tminor = 17.79 min.
=
A solution of 0.1 mmol of 2-naphthol, 0.1 mmol of b,
c-unsatu-
rated -keto ester, and 0.02 mmol of 1c in 1.0 mL of DCM was stir-
a
4.1.1.3. (S)-Ethyl 1-phenyl-1H-benzo[f]chromene-3-carboxylate
6b.
White solid. Mp 155–156 °C; ½a D20
¼ 290:5 (c 0.50, CHCl3);
ꢁ
red at room temperature for 6–48 h (monitored by TLC). Then a
drop of concentrated H2SO4 (98%) was added directly and stirring
was continued for 30 min at room temperature. The crude reaction
mixture was directly purified by column chromatography on silica
gel to afford the corresponding products.
IR (KBr): 1719, 1672, 1597, 1516, 1400, 1371, 1331, 1264, 1228,
1108, 1073, 820, 763, 704 cmꢀ1 1H NMR (300 MHz, CDCl3): d
;
7.78 (d, J = 8.1 Hz, 2H), 7.66–7.64 (m, 1H), 7.42–7.17 (m, 8H),
6.45 (d, J = 4.8 Hz, 1H), 5.35 (d, J = 4.8 Hz, 1H), 4.31 (q, J = 6.5 Hz,
2H), 1.34 (t, J = 6.5 Hz, 3H); 13C NMR (75 MHz, CDCl3): d 161.8,
149.0, 144.4, 139.1, 131.3, 131.2, 129.3, 128.9, 128.4, 127.8,
126.8, 126.7, 124.4, 123.5, 118.0, 114.6, 113.1, 61.5, 39.0, 14.1;
LRMS (EI): m/e 253 (M+, 100), 257 (86), 225 (59), 330 (39), 226
4.1.1.1. (S)-Methyl 4-(2-hydroxynaphthalen-1-yl)-2-oxo-4-phe-
nylbutanoate 4a.
White solid. Mp 127–128 °C; IR (KBr):
3476, 3432, 1752, 1729, 1622, 1589, 1451, 1433, 1263, 1224,
Table 1
Screen of the optimal reaction conditions for the reaction of 2a and 3aa
Ph
COOMe
O
OH
O
1) 1a, Solvent
OMe
+
Ph
2) H2SO4(cat.)
O
2a
3a
6a
Entry
Solvent
Catalyst
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
10
11
12d
13e
14f
Toulene
CH2Cl2
n-Hexane
CH2ClCH2Cl
Et2O
MeOH
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
1a
1a
1a
1a
1a
1a
1b
1c
1d
1e
1f
79
82
66
63
47
60
70
83
82
71
63
73
84
84
57
73
42
35
30
8
66
80
72
75
37
76
83
87
1c
1c
1c
a
Unless otherwise noted, the reaction was conducted with 0.1 mmol of 2a and 0.1 mmol of 3a in the presence of 5 mol % of 1 in 1.0 mL of solvent at room temperature.
b
c
d
e
f
Isolated yields.
Determined by chiral HPLC analysis on a chiral OD-H column.
The reaction was conducted at ꢀ25 °C.
10 mol % of 1c was used.
20 mol % of 1c was used.

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X.-S. Wang et al. / Tetrahedron: Asymmetry 19 (2008) 2699–2704
(21), 258 (20), 152 (20), 254 (18). Anal. Calcd for C22H18O3: C,
79.98; H, 5.49. Found: C, 79.79; H, 5.58. The enantiomeric ratio
was determined by HPLC analysis, using a Chiracel OD-H column
(25 °C, 254 nm, 9:1, hexane/2-propanol, 1.0 mL/min); tma-
jor = 13.04 min, tminor = 15.07 min.
4.1.1.6. (S)-Benzyl 1-phenyl-1H-benzo[f]chromene-3-carboxyl-
ate 6e.
White solid. Mp 136–137 °C; ½a D22
¼ 147:4 (c 0.50,
ꢁ
CHCl3); IR (KBr): 1732, 1668, 1622, 1598, 1515, 1454, 1330,
1261, 1185, 1119, 820, 747, 698 cmꢀ1 1H NMR (300 MHz, CDCl3):
;
d 7.70 (d, J = 8.2 Hz, 2H), 7.40–7.62 (m, 1H), 7.39–7.34 (m, 8H);
7.25–7.16 (m, 5H), 6.47 (d, J = 4.8 Hz, 1H), 5.34 (d, J = 12.2 Hz,
2H), 5.20 (d, J = 12.4 Hz, 1H); 13C NMR (75 MHz, CDCl3): d 161.6,
149.0, 144.3, 139.0, 135.3, 131.3, 131.2, 129.4, 129.0, 128.6,
128.5, 128.4, 127.8, 126.9, 126.7, 124.4, 123.5, 118.0, 115.1,
113.1, 67.1, 39.1; LRMS (EI): m/e 315 (M+, 100), 257 (89), 69 (56),
91 (55), 57 (54), 392 (43), 55 (42), 97 (39). Anal. Calcd for
C27H20O3: C, 82.63; H, 5.14. Found: C, 82.65; H, 5.13. The enantio-
meric ratio was determined by HPLC analysis, using a Chiracel OD
column (25 °C, 254 nm, 9:1, hexane/2-propanol, 1.0 mL/min);
tmajor = 11.61 min, tminor = 12.76 min.
4.1.1.4. (S)-Isopropyl
boxylate 6c.
1-phenyl-1H-benzo[f]chromene-3-car-
White solid. Mp 111–112 °C; ½a D21
¼ ꢀ182:9 (c
ꢁ
0.50, CHCl3); IR (KBr): 1723, 1666, 1621, 1599, 1516, 1488, 1264,
1252, 1190, 1127, 1104, 821, 750, 700 cmꢀ1 1H NMR (300 MHz,
;
CDCl3): d 7.70 (d, J = 7.6 Hz, 2H), 7.55 (s, 1H), 7.35–7.16 (m, 8H),
6.33 (d, J = 4.8 Hz, 1H), 5.26 (d, J = 4.8 Hz, 1H), 5.10–5.07 (m, 1H),
1.24 (s, 6H); 13C NMR (75 MHz, CDCl3): d 161.3, 149.1, 144.5,
139.4, 131.3, 131.2, 129.3, 128.9, 128.4, 127.8, 126.8, 126.6,
124.3, 123.5, 118.1, 114.3, 113.1, 69.3, 39.1, 21.73, 21.70; LRMS
(EI): m/e 225 (M+, 100), 257 (90), 267 (50), 344 (33), 226 (28),
258 (18), 152 (18), 228 (13). Anal. Calcd for C23H20O3: C, 80.21;
H, 5.85. Found: C, 80.27; H, 5.95. The enantiomeric ratio was deter-
mined by HPLC analysis, using a Chiracel OD-H column (25 °C,
254 nm, 9:1, hexane/2-propanol, 1.0 mL/min); tmajor = 10.27 min,
tminor = 11.60 min.
4.1.1.7. (S)-Methyl 1-(4-bromophenyl)-1H-benzo[f]chromene-
3-carboxylate
6f.
White
solid.
Mp
141–142 °C;
½
a 2D2
ꢁ
¼ ꢀ350:9 (c 0.50, CHCl3); 1H NMR (300 MHz, CDCl3): d 7.82–
7.79 (m, 2H), 7.59–7.56 (m, 1H), 7.41–7.35 (m, 5H), 7.08 (d,
J = 8.6 Hz, 2H), 6.42 (d, J = 5.4 Hz, 1H), 5.33 (d, J = 5.4 Hz, 1H),
3.86 (s, 3H); 13C NMR (75 MHz, CDCl3): d 162.0, 148.9, 143.3,
139.1, 132.1, 131.2, 131.0, 129.6, 129.4, 128.5, 126.8, 124.5,
123.3, 120.8, 117.9, 114.1, 112.4, 52.4, 38.4; LRMS (EI): m/e 239
(M+, 100), 335 (32), 337 (30), 240 (17), 394 (15), 396 (13), 152
(13), 226 (11). Anal. Calcd for C21H15BrO3: C, 63.81; H, 3.83. Found:
C, 63.85; H, 3.96. The enantiomeric ratio was determined by HPLC
analysis, using a Chiracel OD-H column (25 °C, 254 nm, 9:1, hex-
ane/2-propanol, 1.0 mL/min); tmajor = 14.45 min, tminor = 18.06 min.
4.1.1.5. (S)-Allyl 1-phenyl-1H-benzo[f]chromene-3-carboxylate
6d.
White solid. Mp 107–108 °C; ½a D22
¼ 112:2 (c 0.50, CHCl3);
ꢁ
IR (KBr): 1732, 1668, 1621, 1598, 1512, 1302, 1260, 1249, 1120,
808, 759, 699 cmꢀ1
; d 7.78 (d,
1H NMR (300 MHz, CDCl3):
J = 8.4 Hz, 2H), 7.66–7.63 (m, 1H), 7.41–7.17 (m, 8H); 6.47 (d,
J = 5.1 Hz, 1H), 6.04–5.91 (m, 1H), 5.40–5.26 (m, 3H), 3.81–4.67
(m, 2H); 13C NMR (75 MHz, CDCl3): d 161.4, 149.0, 144.3, 138.9,
131.6, 131.3, 131.2, 129.3, 128.9, 128.4, 127.7, 126.8, 126.7,
124.4, 123.5, 119.0, 117.9, 115.0, 113.0, 66.0, 39.0; LRMS (EI): m/
e 265 (M+, 100), 257 (75), 342 (34), 225 (28), 152 (21), 266 (20),
258 (16), 69 (16). Anal. Calcd for C23H18O3: C, 80.68; H, 5.30.
Found: C, 80.67; H, 5.23. The enantiomeric ratio was determined
by HPLC analysis, using a Chiracel OD-H column (25 °C, 254 nm,
4.1.1.8. (S)-Methyl 1-(4-chlorophenyl)-1H-benzo[f]chromene-3-
carboxylate 6g.
White solid. Mp 143–144 °C; ½a D22
¼ ꢀ369:7
ꢁ
(c 0.50, CHCl3); IR (KBr): 1737, 1673, 1448, 1436, 1263, 1252,
1121, 821, 765, 748 cmꢀ1 1H NMR (300 MHz, CDCl3): d 7.81–7.78
;
(m, 2H), 7.59–7.56 (m, 1H), 7.41–7.35 (m, 3H), 7.26–7.22 (m, 2H),
7.13 (d, J = 8.1 Hz, 2H), 6.42 (d, J = 5.4 Hz, 1H), 5.33 (d, J = 5.4 Hz,
1H), 3.86 (s, 3H); 13C NMR (75 MHz, CDCl3): d 162.0, 148.9, 143.3,
9:1, hexane/2-propanol, 1.0 mL/min); tmajor = 13.25 min, tminor
=
16.11 min.
Table 2
Enantioselective synthesis of naphthopyran derivatives catalyzed by 1ca
R1
COOR3
O
1) 1c (20 mol %), DCM
OR3
OH
O
+
R2
2) H2SO4 (cat.)
R2
R1
O
room temperature
3a-c
R2
2a-m
6a-o
Entry
2
R1
R3
Product
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2a
2a
H
H
H
H
H 3a
H 3a
H 3a
H 3a
H 3a
H 3a
H 3a
H 3a
H 3a
H 3a
H 3a
H 3a
H 3a
6-Br 3b
7-OCH3 3c
Me
Et
iPr
Allyl
Bn
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
84
91
64
61
51
91
89
75
58
78
71
52
58
57
68
87
82
84
84
78
87
87
86
72
90
86
57
60
86
82
H
4-Br
4-Cl
4-F
4-OEt
4-NO2
3-Cl
2-Br
1,5-Di(OMe)
H
H
a
Unless otherwise noted, the reaction was conducted with 0.1 mmol of 2a and 0.1 mmol of 3a in the presence of 20 mol % of 1 in 1.0 mL of CH2Cl2 at room temperature.
Isolated yields.
Determined by chiral HPLC analysis on a chiral OD-H or OD column. The absolute configuration of product 6n was determined to be (S)-configuration by X-ray
b
c
crystallographic analysis, while the others 6a–m, 6o were assigned by assuming that a similar catalytic mechanism was taken.

X.-S. Wang et al. / Tetrahedron: Asymmetry 19 (2008) 2699–2704
2703
139.1, 132.1, 131.2, 131.0, 129.6, 129.4, 128.5, 126.8, 124.5, 123.3,
120.8, 117.9, 114.1, 112.4, 52.4, 38.4; LRMS (EI): m/e 239 (M+,
100), 291 (52), 350 (25), 57 (20), 240 (17), 293 (17), 69 (16), 71
(16). Anal. Calcd for C21H15ClO3: C, 71.90; H, 4.31. Found: C, 71.91;
H, 4.33. The enantiomeric ratio was determined by HPLC analysis,
using a Chiracel OD-H column (25 °C, 254 nm, 9:1, hexane/2-propa-
nol, 1.0 mL/min); tmajor = 14.06 min, tminor = 17.52 min.
394 (13), 226 (13), 113 (12). Anal. Calcd for C21H15BrO3: C, 63.81;
H, 3.83. Found: C, 63.98; H, 3.98. The enantiomeric ratio was deter-
mined by HPLC analysis, using a Chiracel OD-H column (25 °C,
254 nm, 9:1, hexane/2-propanol, 1.0 mL/min); tmajor = 11.94 min,
tminor = 14.10 min.
4.1.1.13. (S)-Methyl
chromene-3-carboxylate 6m.
¼ ꢀ241:4 (c 0.50, CHCl3); IR (KBr): 1729, 1669, 1598, 1500,
1442, 1257, 1243, 1210, 1182, 1125, 1105, 808, 759 cmꢀ1 1H
1-(2,5-dimethoxyphenyl)-1H-benzo[f]
White solid. Mp 203–204 °C;
4.1.1.9. (S)-Methyl 1-(4-ethoxyphenyl)-1H-benzo[f]chromene-
½ ꢁ
a 2D1
3-carboxylate 6i.
ꢀ278:6 (c 0.50, CHCl3); IR (KBr): 1735, 1672, 1607, 1597, 1508,
1339, 1301, 1252, 1228, 1116, 816, 752, 588, 522 cmꢀ1 1H NMR
White solid. Mp 155–156 °C;
½
a 2D2
ꢁ
¼
;
NMR (300 MHz, CDCl3): d 7.77 (d, J = 7.6 Hz, 2H), 7.57–7.55 (m,
1H), 7.39–7.35 (m, 3H), 6.86 (d, J = 9.0 Hz, 1H), 6.65 (d, J = 7.8 Hz,
1H), 6.49 (d, J = 4.8 Hz, 1H), 6.28 (s, 1H), 5.79 (d, J = 4.8 Hz, 1H),
3.99 (s, 3H), 3.84 (s, 3H), 3.51 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 162.4, 154.0, 149.5, 149.4, 139.5, 133.3, 131.3, 131.1, 129.1,
128.2, 126.7, 124.4, 123.3, 117.8, 116.3, 114.2, 113.0, 111.7,
111.0, 56.0, 55.3, 52.2, 31.7; LRMS (EI): m/e 57 (M+, 100), 55 (94),
97 (89), 69 (86), 83 (77), 95 (74), 71 (70), 81 (67). Anal. Calcd for
C23H20O5: C, 73.39; H, 5.36. Found: C, 72.72; H, 5.23. The enantio-
meric ratio was determined by HPLC analysis, using a Chiracel OD-
H column (25 °C, 254 nm, 9:1, hexane/2-propanol, 1.0 mL/min);
tmajor = 14.63 min, tminor = 16.58 min.
;
(300 MHz, CDCl3): d 7.77 (d, J = 7.8 Hz, 2H), 7.66 (s, 1H), 7.40–
7.36 (m, 3H), 7.10 (d, J = 7.9 Hz, 2H), 6.78 (d, J = 7.9 Hz, 2H), 6.45
(d, J = 4.5 Hz, 1H), 5.29 (d, J = 4.5 Hz, 1H), 3.95–3.80 (m, 2H), 3.85
(s, 3H), 1.35 (t, J = 6.5 Hz, 3H); 13C NMR (75 MHz, CDCl3): d 162.2,
157.7, 148.8, 138.7, 136.4, 131.3, 131.2, 129.2, 128.7, 128.4,
126.6, 124.4, 123.5, 117.9, 115.2, 114.8, 113.3, 63.3, 52.3, 38.1,
14.7; LRMS (EI): m/e 301 (M+, 100), 239 (35), 302 (24), 273 (13),
152 (8), 360 (7), 168 (6), 240 (5). Anal. Calcd for C23H20O4: C,
76.65; H, 5.59. Found: C, 76.65; H, 5.62. The enantiomeric ratio
was determined by HPLC analysis, using a Chiracel OD-H column
(25 °C, 254 nm, 9:1, hexane/2-propanol, 1.0 mL/min); tmajor
15.64 min, tminor = 17.23 min.
=
4.1.1.14. (S)-Methyl 8-bromo-1-phenyl-1H-benzo[f]chromene-
3-carboxylate 6n.
White solid. Mp 224–225 °C;
½
a 2D3
ꢁ
¼
4.1.1.10. (S)-Methyl 1-(4-nitrophenyl)-1H-benzo[f]chromene-3-
ꢀ273:1 (c 0.50, CHCl3); IR (KBr): 1722, 1676, 1590, 1501, 1433,
1335, 1267, 1235, 1118, 762, 700 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d 7.93 (s, 1H), 7.69 (d, J = 8.6 Hz, 1H), 7.50 (d, J = 8.6 Hz, 1H), 7.43–
7.38 (m, 2H), 7.29–7.16 (m, 5H), 6.45 (d, J = 4.8 Hz, 1H), 5.31 (d,
J = 4.8 Hz, 1H), 3.85 (s, 3H); 13C NMR (75 MHz, CDCl3): d 162.0,
149.0, 143.9, 138.8, 132.4, 130.3, 129.9, 129.8, 129.0, 128.4,
127.6, 127.0, 125.2, 119.1, 118.3, 114.7, 113.3, 52.4, 38.9; LRMS
(EI): m/e 319 (M+, 100), 317 (100), 335 (50), 337 (49), 396 (32),
394 (31), 226 (23), 151 (23). Anal. Calcd for C21H15BrO3: C, 63.81;
H, 3.83. Found: C, 63.84; H, 4.03. The enantiomeric ratio was deter-
mined by HPLC analysis, using a Chiracel OD-H column (25 °C,
254 nm, 9:1, hexane/2-propanol, 1.0 mL/min); tmajor = 13.34 min,
tminor = 16.87 min.
carboxylate 6j.
White solid. Mp 156–157 °C; ½a D22
¼ ꢀ417:2
ꢁ
(c 0.50, CHCl3); IR (KBr): 1738, 1675, 1596, 1518, 1349, 1301,
1263, 1253, 1123, 848, 821, 749 cmꢀ1 1H NMR (300 MHz, CDCl3):
;
d 8.12 (d, J = 8.0 Hz, 2H), 7.85–7.82 (m, 2H), 7.49–7.35 (m, 6H); 6.40
(d, J = 5.2 Hz, 1H), 5.48 (d, J = 5.2 Hz, 1H), 3.86 (s, 1H); 13C NMR
(75 MHz, CDCl3): d 161.8, 151.2, 148.9, 146.7, 139.8, 131.3, 130.8,
130.0, 128.7, 128.5, 127.1, 124.8, 124.3, 122.9, 117.9, 112.9,
111.6, 52.5, 38.8; LRMS (EI): m/e 239 (M+, 100), 361 (19), 302
(18), 240 (17), 152 (9), 226 (7), 168 (7), 256 (6). Anal. Calcd for
C21H15NO5: C, 69.80; H, 4.18; N, 3.88. Found: C, 69.89; H, 4.38;
N, 3.73. The enantiomeric ratio was determined by HPLC analysis,
using a Chiracel OD-H column (25 °C, 254 nm, 9:1, hexane/2-pro-
panol, 1.0 mL/min); tmajor = 31.23 min, tminor = 44.24 min.
4.1.1.15. (S)-Methyl
9-methoxy-1-phenyl-1H-benzo[f]chro-
White solid. Mp 193–194 °C;
4.1.1.11. (S)-Methyl 1-(3-chlorophenyl)-1H-benzo[f]chromene-
mene-3-carboxylate 6o.
3-carboxylate 6k.
ꢀ341:0 (c 0.34, CHCl3); IR (KBr): 1734, 1724, 1677, 1598, 1436,
1337, 1264, 1233, 1117, 1037, 815, 764, 748 cmꢀ1 1H NMR
White solid. Mp 218–219 °C;
½
a 2D3
ꢁ
¼
½
a 2D3
ꢁ
¼ ꢀ325:5 (c 0.50, CHCl3); IR (KBr): 1737, 1668, 1621, 1513,
1254, 1221, 1205, 1123, 834, 757, 700 cmꢀ1 1H NMR (300 MHz,
;
;
CDCl3): d 7.68 (d, J = 10.1 Hz, 2H), 7.27–7.18 (m, 6H), 6.98 (dd,
J = 2.0, 8.6 Hz, 1H), 6.89 (s, 1H), 6.44 (d, J = 5.1 Hz, 1H), 5.24 (d,
J = 5.1 Hz, 1H), 3.85 (s, 3H), 3.65 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 162.2, 158.1, 149.4, 144.3, 138.8, 132.6, 129.8, 129.0, 128.9,
127.8, 126.9, 126.4, 116.4, 115.3, 114.7, 112.1, 103.1, 54.9, 52.3,
39.4; LRMS (EI): m/e 269 (M+, 100), 287 (44), 346 (30), 270 (19),
226 (16), 288 (11), 69 (9), 55 (8). Anal. Calcd for C22H18O4: C,
76.29; H, 5.24. Found: C, 76.25; H, 5.04; The enantiomeric ratio
was determined by HPLC analysis, using a Chiracel OD-H column
(300 MHz, CDCl3): d 7.80 (d, J = 8.0 Hz, 2H), 7.58 (s, 1H), 7.41–
7.38 (m, 3H); 7.19–7.07 (m, 4H), 6.42 (d, J = 4.5 Hz, 1H), 5.32 (d,
J = 4.5 Hz, 1H), 3.86 (s, 3H); 13C NMR (75 MHz, CDCl3): d 162.0,
148.9, 146.2, 139.2, 134.8, 131.2, 131.0, 130.2, 129.7, 128.5,
127.8, 127.1, 126.9, 125.8, 124.6, 123.2, 117.9, 114.0, 112.2, 52.4,
38.7; LRMS (EI): m/e 57 (M+, 100), 69 (87), 55 (85), 97 (79), 239
(71), 71 (70), 83 (70), 95 (66). Anal. Calcd for C21H15ClO3: C,
71.90; H, 4.31. Found: C, 71.76; H, 4.41. The enantiomeric ratio
was determined by HPLC analysis, using a Chiracel OD-H column
(25 °C, 254 nm, 9:1, hexane/2-propanol, 1.0 mL/min); tma-
jor = 15.52 min, tminor = 18.66 min.
(25 °C,
254 nm,
9:1,
hexane/2-propanol,
1.0 mL/min);
tmajor = 13.27 min, tminor = 17.50 min.
Acknowledgments
4.1.1.12. (R)-Methyl 1-(2-bromophenyl)-1H-benzo[f]chromene-
White solid. Mp 203–204 °C; ½a D23
¼ ꢀ102:3
ꢁ
The generous financial support from the National Natural Sci-
ence Foundation of China, QT Program, Shanghai Natural Science
Council, and Excellent Young Scholars Foundation of NNSF is grate-
fully acknowledged.
3-carboxylate 6l.
(c 0.50, CHCl3); IR (KBr): 1727, 1676, 1622, 1599, 1465, 1434, 1336,
1263, 1234, 1120, 1120, 821, 752 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d 7.82–7.80 (m, 2H), 7.61 (d, J = 3.3 Hz, 1H), 7.42–7.38 (m, 4H); 7.04
(s, 2H), 6.78–6.76 (m, 1H), 6.52 (d, J = 3.6 Hz, 1H), 5.84 (d,
J = 3.6 Hz, 1H), 3.86 (s, 3H); 13C NMR (75 MHz, CDCl3): d 162.1,
149.4, 142.7, 139.6, 132.7, 131.2, 131.0, 130.7, 129.6, 128.4,
127.0, 124.6, 123.3, 122.0, 117.7, 112.6, 112.5, 52.4, 38.1; LRMS
(EI): m/e 239 (M+, 100), 240 (17), 335 (16), 337 (16), 396 (13),
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