Gold-catalyzed oxa-povarov reactions for the synthesis of highly substituted dihydrobenzopyrans from diaryloxymethylarenes and olefins

Article abstract of DOI:10.1002/chem.201403285

Oxa-Povarov reactions involving readily available diaryloxymethylarenes and aryl-substituted alkenes are reported. Their [4+2] cycloadditions were efficiently catalyzed by IPrAuSbF₆ (IPr=1,3-bis(diisopropylphenyl) imidazol-2-ylidene) with high diastereoselectivity. Product analysis revealed that the reactions likely proceed by a stepwise ionic mechanism, because both E- and Z-configured β-methylstyrene gave the same cycloadducts in the same proportions.

Full text of DOI:10.1002/chem.201403285

DOI: 10.1002/chem.201403285
Full Paper
&
Synthetic Methods
Gold-Catalyzed Oxa-Povarov Reactions for the Synthesis of Highly
Substituted Dihydrobenzopyrans from Diaryloxymethylarenes
and Olefins
Vinayak Vishnu Pagar, Chang-Chin Tseng, and Rai-Shung Liu*[a]
Abstract: Oxa-Povarov reactions involving readily available
diaryloxymethylarenes and aryl-substituted alkenes are re-
ported. Their [4+2] cycloadditions were efficiently catalyzed
by IPrAuSbF6 (IPr=1,3-bis(diisopropylphenyl)imidazol-2-yli-
dene) with high diastereoselectivity. Product analysis re-
vealed that the reactions likely proceed by a stepwise ionic
mechanism, because both E- and Z-configured b-methylstyr-
ene gave the same cycloadducts in the same proportions.
Introduction
(Scheme 1). Their specific biological activities are well docu-
mented.[7,8]
Povarov reactions are formal [4+2] cycloadditions of
N-aryl imines with electron-rich olefins, catalyzed by
a Lewis acid (L.A.). Such reactions are powerful tools
to construct tetrahydroquinoline cores [Eq. (1)],
which are important skeletons for many bioactive
molecules.[1,2] In contrast to this nitrogen system,
metal-catalyzed oxa-Povarov reactions have remained
largely unexplored, although the resulting dihydro-
benzopyrans are also useful structural motifs. Batey
and co-workers reported the first oxa-Povarov reac-
tions involving [4+2] cycloadditions of alkenes with
the oxonium intermediates A.[3] The reactions re-
quired the use of SnCl4 (2.0 equiv) in stoichiometric
proportions with special substrates such as aryl pico-
linates 1 [Eq. (2)]. We reported Povarov reactions of
alkenyldiazocarbonyl compounds with diphenoxyme-
thylbenzene, notably in a catalytic process using
small amounts (2–3 mol%) of HOTf and a-phenyle-
thylamine [Eq. (3)].[4] The examples in Equations (2)
and (3) are not typical of oxa-Povarov reactions, be-
cause only special types of substrates and alkenes
can be used. We report herein a logical extension of our pre-
ceding work to include diverse aryl acetals and commonly
used alkenes with a suitable gold catalyst [Eq. (4)]. The impor-
tance of this new synthetic method is to provide a rapid
access to the dihydrobenzopyran core, which is commonly
found in numerous biologically active natural compounds in-
cluding (+)-brazilane,[5] (+)-haematoxylane,[5] and flavan[6]
Scheme 1. Representative bioactive compounds.
[a] V. V. Pagar, C.-C. Tseng, Prof. Dr. R.-S. Liu
Department of Chemistry
National Tsing Hua University
Hsinchu, 30013 (Taiwan)
Fax: (+886)3-5711082
E-mail: rsliu@mx.nthu.edu.tw
Results and Discussion
We tested the reactions of diphenoxymethylbenzene (3a) with
styrene (5a) in the presence of various Lewis acid catalysts
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201403285.
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Table 2 assesses the generality of the oxa-Povarov
reactions of diphenoxymethylbenzene (3a) with vari-
ous alkenes (2 equiv) catalyzed by IPrAuSbF6
(5 mol%); complete consumption of starting acetal
3a was attained in all cases. Low temperatures
(À208C) were maintained in CH2Cl2 to optimize the
d.r. values. In entries 2–4, 6, 7, 9, and 10 of Table 2,
the two diastereomeric products 6 and 6’ were sepa-
rable on silica columns. These cycloadditions worked
well with various styrene derivatives 5b–5d bearing
4-methoxy, 4-chloro, and 4-bromo substituents to
give the corresponding cycloadducts 6b–6d in good
yields (68–78%) and high diastereoselectivities (d.r.>
6.1:1; Table 2, entries 1–3). The reaction was extendi-
ble to phenyl vinyl sulfide (5e) to afford cycloadducts
6e and 6e’ in 76 and 8% yield, respectively. The cy-
cloaddition of a-methylstyrene (5 f) proceeded highly
stereoselectively to give dihydrobenzopyran 6 f ex-
clusively (Table 2, entry 5). We prepared (E)- and (Z)-
b-methylstyrene (5g and 5h) to test the diastereose-
lectivity of the reaction, but both olefins gave prod-
ucts 6g and 6g’ with the same composition
(6g:6g’=4:1; Table 2, entries 6 and 7). The molecular
Table 1. Catalyst screening and product stereoselectivity in the reaction of 3a
(1.0 equiv,
0.40m)
with
5a
(2 equiv).
Entry
Catalyst[a] (mol%)
Solvent
T [8C] t [h] d.r.
Yield [%][b]
6a
6a’
1
2
3
4
5
6
7
8
TfOH (3)/PhCH(NH2)Me (2) DCE
À20
À20
28
À20
À20
28
À20
À20
2.4
2.4
1.1
3.0
3.5
0.2
2.0
2.0
2.0
2.0
2.2
1.8:1 43
23
21
–
TfOH (3)
LAuCl/AgNTf2 (5)
SnCl4 (5)
DCE
DCE
DCE
DCE
DCE
DCE
1.8:1 37
[c]
–
–
1.5:1 40
3:1 42
1.2:1 48
27
14
40
22
10
12
13
21
BF3(Et2O) (5)
IPrAuCl/AgSbF6 (5)
IPrAuCl/AgSbF6 (5)
IPrAuCl/AgSbF6 (5)
IPrAuCl/AgSbF6 (5)
IPrAuCl/AgSbF6 (5)
IPrAuCl/AgOTf (5)
3:1
8.1:1
66
81
CH2Cl2
9
10
11
toluene À20
5.2:1 63
CHCl3
À20
À20
5:1
1:1.2
67
17
CH2Cl2
[a] IPr=1,3-bis(diisopropy phenyl)imidazol-2-ylidene, L=P(tBu)2(o-biphenyl). [b] Prod-
uct yields are given after purification on a silica column. [c] Benzaldehyde and phenol
were formed.
under optimized conditions (Table 1). In a typical reaction, 3a
(1 equiv) and 5a (2 equiv) were mixed in a suitable solvent
and then added slowly to a solution of the catalyst by using
a syringe pump (ca. 0.2–1.0 h). The initial reaction was per-
formed with 3a and 5a (2 equiv) in cold and dry dichloro-
ethane (DCE, À208C) by using our previously reported combi-
nation of TfOH (3 mol%) and a-phenylethylamine (2 mol%).
This gave desired cycloadducts 6a and 6a’ in 43 and 23%
yield, respectively (d.r.=1.8:1; Table 1, entry 1). Hereby, hydrol-
ysis of diphenoxymethylbenzene 3a occurred to produce ben-
zaldehyde and phenol in small amounts. For HOTf alone
(3 mol%), the same reaction in cold DCE gave 6a and 6a’ in
lower yields with d.r.=1.8:1. The use of P(tBu)2(o-bipheny-
l)AuCl/AgNTf2 gave only benzaldehyde and phenol in DCE
(288C, 1.1 h; Table 1, entry 3). Highly acidic catalysts such as
SnCl4 and BF3·Et2O gave 6a and 6a’ in 40–42 and 14–27%
yield, respectively (Table 1, entries 4 and 5). When less acidic
IPrAuCl/AgSbF6 (IPr=1,3-bis(diisopropylphenyl)imidazol-2-yli-
dene) was employed in DCE at 288C, the respective yields of
6a and 6a’ were 48 and 40%, albeit with a low d.r. of 1.2:1. At
À208C, the diastereoselectivity improved to 6a:6a’=3:1 with
a satisfactory product yield of 66% (Table 1, entry 7). The d.r.
value and product yield improved significantly to 6a:6a’=
8.1:1 and 81% in dichloromethane at À208C (Table 1, entry 8).
The use of toluene and chloroform gave d.r. values of about
6a:6a’=5.2:1 and 5:1, respectively (Table 1, entries 9 and 10).
We then tested the reaction with IPrAuOTf, which is less acidic
than IPrAuSbF6, but the yields of 6a (17%) and 6a’ (21%) were
poor in this case (Table 1, entry 11). The molecular structure of
the major diastereomer 6a was confirmed by X-ray diffrac-
tion.[9] The stereochemistry of compound 6a is also readily
structure of the major diastereomer 6g was determined by X-
ray crystallography.[9] We observed excellent diastereoselectiv-
ity for (E)-1-phenylbuta-1,3-diene (5i) to afford compound 6i
exclusively in 87% yield (Table 2, entry 8). By using indene 5j
and dihydronaphthalene 5k, this new method provides access
to polycyclic products 6j,6k and 6j’,6k’ in 60–61 and 8–10%
yield respectively (Table 2, entries 9 and 10). The reactions of 2-
vinylbenzothiophene (5l) and 2-vinylbenzofuran (5m) with
acetal 3a also proceeded smoothly to give highly substituted
cycloadducts 6l and 6m (d.r.>20:1) in 75 and 58% yield, re-
spectively (Table 2, entries 11 and 12). The reactions of their a-
methylvinyl derivatives 5n and 5o provided only single diaste-
reomers 6n and 6o in 67 and 55% yield, respectively (Table 2,
entries 13 and 14). We also prepared substrates 5p and 5q
with E:Z ratios of about 2:1; their reactions with acetal 3a pro-
vided only dihydrobenzopyran derivatives 6p and 6q (Table 2,
entries 15 and 16) in 78 and 55% yield, respectively, whereby
the Z forms of the substrates remained predominantly in the
reaction mixture, as revealed by 1H NMR spectroscopy. For
compounds 6p and 6q, the 1H NMR spectra of their crude
products showed the presence of a single resonance in the
region 4.5–5.5 ppm, assignable to the OCHPh protons. The re-
actions of acetal 3a with cyclic or acyclic enol ethers such as
2,3-dihydrofuran and ethoxyethene were unsuccessful: only
phenol and benzaldehydes were obtained.
We expanded the scope of this gold-catalyzed oxa-Povarov
reaction with various acetals 3b–3g (Table 3). We selected sty-
rene (5a) and 2-vinylbenzothiophene (5p, 2.0 equiv, E:Z=2:1)
as the test alkenes to achieve both carbo- and heterocyclic
frameworks. For acetals 3b and 3c containing 4-methoxy and
4-chloro substituents at their phenoxyl rings, the correspond-
ing dihydrobenzopyran products 7b,7c and 7b’,7c’ were ob-
tained in good yields (>66%) with d.r.>6.1:1. The reactions
were extendable to acetals 3d and 3e bearing 4-chloro and 4-
1
identifiable from the H NMR spectrum, in which one of the
methylene protons has a coupling constant of 10–11 Hz, indi-
cative of vicinal axial–axial coupling.
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termediate in an endo conformation to generate
a chairlike transition state B with two bulky phenyl
groups located in the equatorial positions, which
thus gives the observed major product 6a. In Table 2,
entries 6 and 7, both cis- and trans-b- methylstyrenes
5g and 5h gave cycloadducts with the same compo-
sition (6g:6g’=4:1). We postulate that the E-config-
ured olefin 5g reacts with this oxonium intermediate
via an antiperiplanar[10] conformation A’, which leads
to an anti orientation between the bulky phenyl and
PhCH=C moieties and thus generates a six-mem-
bered transition state B’ bearing the three protons in
the axial positions; this stereochemical course yields
the observed major diastereomer 6g. For the cis-con-
figured b-methylstyrene, its antiperiplanar[10] confor-
mation A’’ generates a six-membered transition state
B’’ that has a bulky phenyl group at the axial position
and thus suffer a 1,3-axial steric interaction. Inter-
mediate B“ thus undergoes a rearrangement to
attain a more stable conformation B’ that gives the
observed major diastereomer 6g.
Table 2. Oxa-Povarov reactions of 3a (0.40m) with various alkenes (2 equiv).
Entry
Alkene
6 (Yield [%])[a]
6’ (Yield [%])[a]
d.r.
1
2
3
5b (Ar=4-MeOC6H4)
5c (Ar=4-ClC6H4)
5d (Ar=4-BrC6H4)
6b (78)
6c (71)
6d (68)
6b’ (trace)
6c’ (10)
6d’ (11)
>20:1
7.1:1
6.1:1
4
5
9.3:1
>20:1
6
7
4:1
4:1
6g (57)
6g’ (14)
8
>20:1
Conclusion
We have reported gold-catalyzed[11–12] oxa-Povarov re-
actions involving readily available diaryloxymethyl
arenes and aryl-substituted alkenes to give dihydro-
benzopyrans;[13] their [4+2] cycloadditions are effi-
ciently catalyzed by IPrAuSbF6 with high diastereose-
lectivity. The cycloadditions were applicable to a rea-
sonable range of substrates under ambient condi-
tions. Our product analysis revealed that the reaction
likely proceeds via a stepwise ionic mechanism, be-
cause both E- and Z-configured b-methylstyrene
gave the same cycloadducts in the same proportions.
9
10
5j (n=1)
5k (n=2)
6j (n=1, 61)
6k (n=2, 60)
6j’ (n=1, 10)
6k’ (n=2, 8)
6.1:1
7.3:1
11
12
5l (X=S)
5m (X=O)
6l (Ar=2-benzothienyl, 75)
6m (Ar=2-benzofuryl, 58)
>20:1
>20:1
13
14
5n (X=S)
5o (X=O)
6n (Ar=2-benzothienyl, 67)
6o (Ar=2-benzofuryl, 55)
>20:1
>20:1
Experimental Section
(E/z)=2 :1
5p (R=Me)
5q (R=Et)
(Ar=2-benzothienyl)
6p (78)
6q (55)
General
15
16
>20:1
>20:1
Unless otherwise noted, the preparations of the sub-
strates were performed in oven-dried glassware under
nitrogen atmosphere with freshly distilled solvents. Cata-
lytic reactions were performed under argon atmosphere.
DCE and CH2Cl2 were distilled from CaH2 under nitrogen.
THF and toluene were distilled from Na metal under ni-
[a] Product yields are given after purification from a silica column.
bromo substituents at the phenylmethylacetal moiety to give
desired 7d,7e and 7d’,7e’ in 51–53 and 10% yield, respective-
ly (Table 3, entries 3 and 4). Gold-catalyzed reactions of acetals
3 f and 3g bearing a 2- or 4-methoxyphenylmethylacetal sub-
stituent with alkene 5p yielded cycloadducts 7 f and 7g in 73
and 41% yield, respectively. The gold-catalyzed reactions be-
tween alkene 5p and acetals 3b–3d delivered desired cycload-
ducts 7h–7j with excellent yields (81–85%) and excellent
d.r.>20:1 (Table 3, entries 7–9).
trogen. Commercial reagents were used without further purifica-
tion. 1H NMR and 13C NMR spectra were recorded on Varian
400 MHz or Bruker 400, 500, 600 MHz spectrometers with CDCl3 as
internal standard.
Standard catalytic procedure for synthesis of dihydrobenzo-
pyrans (6a):
A solution of IPrAuCl (12.3 mg, 0.02 mmol) and AgSbF6 (6.8 mg,
0.02 mmol) in dichloromethane (1 mL) was stirred under argon at-
mosphere at À208C for 10 min. To this solution a solution of di-
phenoxymethylbenzene (3a, 110 mg, 0.40 mmol) and styrene (5a,
83 mg, 0.80 mmol) in dichloromethane (2 mL) was added dropwise
In Scheme 2, we propose a plausible mechanism involving
a stepwise ionic pathway with styrene-based alkenes as nucle-
ophiles. We envisage that styrene approaches an oxonium in-
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by syringe pump (1.5 h). The resulting solution was
stirred for a further 30 min and filtered over a short
silica bed. The filtrate was concentrated and purified
on a flash silica column (hexane:ethyl acetate 9:1) to
give 6a as a white solid (91 mg, 0.31 mmol, 81%) and
6a’ as a semisolid (11 mg, 0.04 mmol, 10%).
Table 3. Oxa-Povarov reactions of various acetals 3 (0.40m) with alkenes 5 (2 equiv).
Entry Acetals
Alkene
7 (yield [%])[a]
7’ (yield [%])[a]
d.r.
2,4-Diphenylchroman (6a): White solid (92 mg, 81%),
~
m.p. 122–1248C; IR (neat): n=3024 (m), 1580 (s), 1486
1
2
3b (X=OMe)
3c (X=Cl)
5a
5a
7b (75)
7c (66)
7b’ (12)
7c’ (10)
6.1:1
6.7:1
1
(s), 1234 (m), 1061 (s), 757 cmÀ1 (s); H NMR (600 MHz,
CDCl3): d=7.46 (dd, J=8.4, 1.3 Hz, 2H), 7.37 (t, J=
7.8 Hz, 2H), 7.31–28 (m, 3H), 7.23–7.19 (m, 3H), 7.11 (t,
J=6.9 Hz, 1H), 6.93 (d, J=8.1 Hz, 1H), 6.78–6.74 (m,
2H), 5.19 (dd, J=11.4, 1.6 Hz, 1H), 4.33 (dd, J=12.1,
5.8 Hz, 1H), 2.41–2.37 (m, 1H), 2.28–2.24 ppm (m, 1H);
13C NMR (150 MHz, CDCl3): d=155.5, 144.5, 141.2,
129.8, 128.6, 128.5(CHx2), 128.0, 127.7, 126.7, 126.1,
125.7, 120.5, 117.0, 78.1, 43.5, 40.6 ppm; HRMS calcd
for C21H18O: 286.1358; found: 286.1360.
3
4
3d (X=Cl)
3e (X=Br)
5a
5a
7d (53)
7e (51)
7d’ (10)
7e’ (10)
5.3:1
5.1:1
5
>20:1
2,4-Diphenylchroman (6a’): White semisolid (11 mg,
~
10%); IR (neat): n=3014 (m), 1565 (s), 1468 (s), 1245
(m), 1059 (s), 752 cmÀ1 (s); 1H NMR (600 MHz, CDCl3):
d=7.34–7.26 (m, 7H), 7.23–7.19 (m, 2H), 7.12 (d, J=
7.3 Hz, 2H), 7.01 (dd, J=8.2, 0.9 Hz, 1H), 6.98 (dd, J=
7.6,1.5 Hz, 1H), 6.88 (t, J=7.5 Hz, 1H), 5.04 (dd, J=
10.5, 2.4 Hz, 1H), 4.22 (dd, J=5.4, 3.5 Hz, 1H), 2.46–
2.43 (m, 1H), 2.26–2.23 ppm (m, 1H); 13C NMR
(150 MHz, CDCl3): d=155.4, 146.0, 141.4, 130.7, 128.5,
128.4(CHx2), 128.1, 127.7, 126.4, 126.0, 123.1, 120.5,
117.0, 73.2, 40.2, 38.2 ppm; HRMS calcd for C21H18O:
286.1358; found: 286.1355.
6
7
8
5p
5p
5p
>20:1
>20:1
>20:1
3b
3c
4-(4-Methoxyphenyl)-2-phenylchroman (6b): White
~
solid (98 mg, 78%), m.p. 130–1328C; IR (neat): n=2998
(m), 1587 (s), 1490 (s), 1208 (m), 1059 (s), 751 cmÀ1 (s);
1H NMR (600 MHz, CDCl3): d=7.48–7.47 (m, 2H), 7.38
(t, J=7.5 Hz, 2H), 7.32 (t, J=7.2 Hz, 1H), 7.14–7.11 (m,
3H), 6.94 (dd, J=7.9, 0.3 Hz, 1H), 6.87–6.83 (m, 2H),
6.79–6.77 (m, 2H), 5.20 (dd, J=11.4,1.5 Hz, 1H), 4.31
(dd, J=12.2, 5.7 Hz, 1H), 3.79 (s, 3H), 2.39–2.36 (m,
1H), 2.27–2.23 ppm (m, 1H); 13C NMR (150 MHz,
CDCl3): d=158.4, 155.4, 141.2, 136.5, 129.7, 129.5,
128.5, 128.0, 127.7 (CHꢁ2), 126.0,
9
3d
5p
>20:1
[a] Product yields are given after purification from a silica column. [b] Ar=2-benzothien-
yl.
120.5, 116.9, 114.0, 78.1, 55.2, 42.6,
40.7 ppm;
C22H20O2:
316.1468.
HRMS
316.1463;
calcd
for
found:
4-(4-Chlorophenyl)-2-phenylchro-
man (6c): White solid (90 mg,
71%), m.p. 127–1298C; IR (neat):
~
n=3034 (m), 1580 (s), 1485 (s),
1265 (m), 737 cmÀ1 (s); 1H NMR
(600 MHz, CDCl3): d=7.47 (d, J=
7.4 Hz, 2H), 7.40 (t, J=7.6 Hz, 2H),
7.32 (t, J=6.6 Hz, 1H), 7.29 (d, J=
8.3 Hz, 2H), 7.15 (d, J=8.2 Hz, 3H),
6.97 (d, J=8.1 Hz, 1H), 6.81 (t, J=
7.6 Hz, 1H), 6.74 (d, J=7.6 Hz, 1H),
5.20 (d, J=11.1 Hz, 1H), 4.34 (dd,
J=12.1, 5.7 Hz, 1H), 2.40–2.37 (m,
1H), 2.25–2.19 ppm (m, 1H);
13C NMR (150 MHz, CDCl3): d=
155.4, 143.0, 140.9, 132.4, 129.9,
129.6, 128.8, 128.6, 128.1, 127.9,
126.0, 125.0, 120.6, 117.1, 77.9,
Scheme 2. Stereochemical course of cycloadditions.
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42.8, 40.5 ppm; HRMS calcd for C21H17ClO: 320.0968; found:
320.0961.
3-Methyl-2,4-diphenylchroman (6g): White solid (68 mg, 57%),
~
m.p. 117–1208C; IR (neat): n=3016 (m), 1571 (s), 1492 (s), 1256
(m), 1082 (s), 767 cmÀ1 (s); 1H NMR (600 MHz, CDCl3): d=7.44 (d,
J=7.6 Hz, 2H), 7.39 (t, J=7.2 Hz, 2H), 7.35–7.30 (m, 3H), 7.25 (t,
J=6.6 Hz, 1H), 7.19 (dd, J=8.4, 1.3 Hz, 2H), 7.06 (t, J=7.2 Hz, 1H),
6.89 (d, J=8.2 Hz, 1H), 6.76 (t, J=8.4 Hz, 1H), 6.65 (d, J=7.7 Hz,
1H), 4.75 (d, J=10.1 Hz, 1H), 3.80 (d, J=10.8 Hz, 1H), 2.32–2.27 (m,
1H), 0.59 ppm (d, J=6.6 Hz, 3H); 13C NMR (150 MHz, CDCl3): d=
155.3, 143.8, 139.9, 130.1, 129.4, 128.5, 128.5, 128.4, 127.5, 127.4,
126.7, 126.4, 120.6, 116.6, 84.3, 51.1, 40.9, 15.7 ppm; HRMS calcd
for C22H20O: 300.1514; found: 300.1521.
4-(4-Chlorophenyl)-2-phenylchroman (6c’): White semisolid
~
(13 mg, 10%); IR (neat): n=3024 (m), 1570 (s), 1491 (s), 1234 (m),
1
732 cmÀ1 (s); H NMR (600 MHz, CDCl3): d=7.33–726 (m, 7H), 7.19
(t, J=8.3 Hz, 1H), 7.05 (d, J=6.6 Hz, 2H), 7.00 (d, J=8.2 Hz, 1H),
6.93 (d, J=7.7 Hz, 1H), 6.87 (t, J=7.3 Hz, 1H), 4.97 (dd, J=10.5,
2.3 Hz, 1H), 4.18 (dd, J=5.4, 3.5 Hz, 1H), 2.46–2.41 (m, 1H), 2.20–
2.17 ppm (m, 1H); 13C NMR (150 MHz, CDCl3): d=155.3, 144.5,
141.1, 132.3, 130.6, 129.9, 128.6, 128.5, 128.3, 127.8, 125.9, 122.5,
120.6, 117.2, 73.1, 39.6, 38.2 ppm; HRMS calcd for C21H17ClO:
320.0968; found: 320.0961.
3-Methyl-2,4-diphenylchroman (6g’): White semisolid (17 mg,
~
14%); IR (neat): n=3022 (m), 1573 (s), 1461 (s), 1229 (m), 1048 (s),
4-(4-Bromophenyl)-2-phenylchroman (6d): Light yellow solid
1
782 cmÀ1 (s); H NMR (600 MHz, CDCl3): d=7.30 (t, J=7.3 Hz, 4H),
~
(99 mg, 68%), m.p. 149–1538C; IR (neat): n=3049 (m), 1712 (s),
7.24–7.20 (m, 5H), 7.11–7.09 (m, 2H), 7.03 (dd, J=8.2, 0.8 Hz, 1H),
6.98 (dd, J=7.6, 1.3 Hz, 1H), 6.89 (t, J=7.3 Hz, 1H), 5.10 (d, J=
2.1 Hz, 1H), 3.98 (d, J=2.3 Hz, 1H), 2.31–2.28 (m, 1H), 0.86 ppm (d,
J=7.0 Hz, 3H); 13C NMR (150 MHz, CDCl3): d=154.9, 146.4, 140.1,
131.6, 128.8, 128.4, 128.0, 127.9, 127.0, 126.4, 125.8, 121.8, 120.7,
116.7, 74.6, 48.3, 40.6, 13.3 ppm; HRMS calcd for C22H20O: 300.1514;
found: 300.1517.
1
1473 (s), 1263 (m), 1059 (s), 739 cmÀ1 (s); H NMR (600 MHz, CDCl3):
d=7.46 (d, J=7.5 Hz, 2H), 7.43 (d, J=8.2 Hz, 2H), 7.39 (t, J=
7.5 Hz, 2H), 7.32 (t, J=7.2 Hz, 1H), 7.14 (t, J=7.3 Hz, 1H), 7.09 (d,
J=8.2 Hz, 2H), 6.94 (d, J=8.1 Hz, 1H), 6.79 (t, J=7.5 Hz, 1H), 6.72
(d, J=7.7 Hz, 1H), 5.18 (d, J=10.8 Hz, 1H), 4.32 (dd, J=12.1,
5.8 Hz, 1H), 2.40–2.36 (m, 1H), 2.23–2.17 ppm (m, 1H); 13C NMR
(150 MHz, CDCl3): d=155.5, 143.6, 141.0, 131.8, 130.3, 129.6, 128.6,
128.1, 128.0, 126.0, 125.0, 120.7, 120.5, 117.1, 77.9, 42.9, 40.5 ppm;
HRMS calcd for C21H17BrO: 364.0463; found: 364.0455.
2-Phenyl-4-[(E)-styryl]chroman (6i): White solid (108 mg, 87%),
m.p. 118–1208C; IR (neat): n=3027 (m), 1578 (s), 1452 (s), 1239
~
(m), 1047 (s), 737 cmÀ1 (s); 1H NMR (600 MHz, CDCl3): d=7.47 (d,
J=7.2 Hz, 2H), 7.40 (t, J=8.4 Hz, 4H), 7.34–7.31 (m, 3H), 7.23 (dd,
J=8.3, 0.4 Hz, 2H), 7.17 (t, J=0.8 Hz, 1H), 6.94 (dd, J=7.1, 1.0 Hz,
1H), 6.90 (t, J=8.5 Hz, 1H), 6.64 (d, J=15.8 Hz, 1H), 6.13 (dd, J=
15.7, 9.0 Hz, 1H), 5.15 (d, J=11.5 Hz, 1H), 3.95–3.90 (m, 1H), 2.32–
2.28 (m, 1H), 2.12–2.06 ppm (m, 1H); 13C NMR (150 MHz, CDCl3):
d=154.9, 141.2, 137.0, 132.2, 132.0, 129.2, 128.6, 128.5, 128.0 (CHꢁ
2), 127.4, 126.2, 126.0, 124.0, 120.6, 117.0, 77.6, 40.8, 37.9 ppm;
HRMS calcd for C23H20O: 312.1514; found: 312.1522.
4-(4-Bromophenyl)-2-phenylchroman (6d’): Light yellow semisolid
~
(16 mg, 11%); IR (neat): n=3031 (m), 1590 (s), 1441 (s), 1253 (m),
1
1065 (s), 772 cmÀ1 (s); H NMR (600 MHz, CDCl3): d=7.41 (dd, J=
6.8,1.6 Hz, 1H), 7.34–7.26 (m, 6H), 7.20 (t, J=8.5 Hz, 1H), 7.00 (dd,
J=7.2,4.5 Hz, 3H), 6.93 (d, J=6.1 Hz, 1H), 6.87 (t, J=7.0 Hz, 1H),
4.97 (dd, J=10.5,2.2 Hz, 1H), 4.17 (dd, J=5.3,3.4 Hz, 1H), 2.45–2.41
(m, 1H), 2.19–2.16 ppm (m, 1H); 13C NMR (150 MHz, CDCl3): d=
155.3, 145.0, 141.1, 131.5, 130.6, 130.4, 128.5, 128.3, 127.8, 125.9,
122.4, 120.6, 120.4, 117.2, 77.2, 39.7, 38.1 ppm; HRMS calcd for
C21H17BrO: 364.0463; found: 364.0462.
6-Phenyl-6,6a,7,11b-tetrahydroindeno[2,1-c]chromene
(6j):
~
White solid (72 mg, 61%), m.p. 148–1518C; IR (neat): n=2998 (m),
1
1603 (s), 1479 (s), 1231 (m), 751 cmÀ1 (s); H NMR (600 MHz, CDCl3):
2-Phenyl-4-(phenylthio)chroman (6e): White solid (96 mg, 76%),
~
m.p. 125–1288C; IR (neat): n=3300 (br), 1578 (s), 1482 (s), 1265
d=7.53–7.51 (m, 3H), 7.41 (t, J=7.6 Hz, 3H), 7.33 (t, J=7.3 Hz,
1H), 7.15 (t, J=7.3 Hz, 1H), 7.11–7.04 (m, 3H), 6.94–6.88 (m, 2H),
5.33 (d, J=2.1 Hz, 1H), 4.59 (d, J=8.2 Hz, 1H), 3.29–3.24 (m, 1H),
3.13 (dd, J=15.6, 4.6 Hz, 1H), 2.50 ppm (dd, J=15.6, 7.8 Hz, 1H);
13C NMR (150 MHz, CDCl3): d=154.7, 145.6, 142.4, 140.4, 129.2,
128.4, 127.4, 127.3, 127.2, 126.6, 125.6, 124.9, 124.8, 124.5,
121.6,117.7, 77.2, 46.5, 44.9, 30.4 ppm; HRMS calcd for C22H18O:
298.1358; found: 298.1353.
1
(m), 737 cmÀ1 (s); H NMR (600 MHz, CDCl3): d=7.77 (d, J=7.8 Hz,
1H), 7.41–7.39 (m, 2H), 7.36 (dd, J=6.5, 1.7 Hz, 4H), 7.31–7.23 (m,
4H), 7.16 (t, J=7.2 Hz, 1H), 6.96 (t, J=7.6 Hz, 1H), 6.88 (dd, J=
8.2,1.2 Hz, 1H), 4.99 (dd, J=11.6, 1.7 Hz, 1H), 4.66 (dd, J=11.5,
6.3 Hz, 1H), 2.45–2.42 (m, 1H), 2.29–2.23 ppm (m, 1H); 13C NMR
(150 MHz, CDCl3): d=155.4, 140.6, 134.0, 132.6, 129.3, 129.0, 128.7,
128.6, 128.2, 127.6, 126.1, 122.1, 120.9, 117.3, 78.0, 43.9, 38.9 ppm;
HRMS calcd for C21H18OS: 350.0799; found: 350.0794.
6-Phenyl-6,6a,7,11b-tetrahydroindeno[2,1-c]chromene
(6j’):
2-Phenyl-4-(phenylthio)chroman (6e’): White semisolid (10 mÀg1,
~
White semisolid (12 mg, 10%); IR (neat): n=2997 (m), 1598 (s),
1
1473 (s), 1237 (m), 758 cmÀ1 (s); H NMR (600 MHz, CDCl3): d=7.52
~
8%); IR (neat): n=3310 (br), 1572 (s), 1489 (s), 1267 (m), 756 cm
1
(s); H NMR (600 MHz, CDCl3): d=7.50 (dd, J=8.4, 1.3 Hz, 2H), 7.41
(d, J=7.3 Hz, 1H), 7.41–7.36 (m, 6H), 7.23 (dd, J=6.6,1.5 Hz, 1H),
7.20–7.16 (m, 3H), 7.04 (t, J=7.6 Hz, 1H), 6.92 (d, J=8.1 Hz, 1H),
4.40 (d, J=6.1 Hz, 1H), 4.39 (d, J=10.6 Hz, 1H), 3.09 (dd, J=16.2,
6.9 Hz, 1H), 2.98–2.95 (m, 1H), 2.58 ppm (d, J=16.3 Hz, 1H);
13C NMR (150 MHz, CDCl3): d=154.9, 145.2, 140.6, 139.9, 130.4,
128.6, 128.4, 127.9, 127.7, 126.9, 126.6, 125.2, 124.2, 122.6, 120.7,
117.3, 78.1, 44.8, 42.7, 34.2 ppm; HRMS calcd for C22H18O: 298.1358;
found: 298.1355.
(dd, J=7.5, 0.6 Hz, 2H), 7.38–7.27 (m, 7H), 7.19–7.17 (m, 1H), 6.93
(t, J=8.6 Hz, 2H), 5.51 (dd, J=10.7, 2.7 Hz, 1H), 4.57 (dd, J=4.0,
2.0 Hz, 1H), 2.25–2.20 (m, 2H), 13C NMR (150 MHz, CDCl3): d=155.3,
141.0, 134.7, 132.5, 130.9, 129.2, 129.1, 128.6, 128.0, 127.7, 126.2,
120.5, 120.3, 117.4, 73.4, 43.9, 35.3 ppm; HRMS calcd for C21H18OS:
350.0799; found: 350.0796.
4-Methyl-2,4-diphenylchroman (6 f): White solid (105 mg, 88%),
~
m.p. 107–1098C; IR (neat): n=3019 (m), 1585 (s), 1488 (s), 1237
6-Phenyl-6a,7,8,12b-tetrahydro-6H-naphtho[2,1-c]chromene
(m), 1072 (s), 759 cmÀ1 (s); 1H NMR (600 MHz, CDCl3): d=7.47 (d,
J=7.4 Hz, 2H), 7.38 (t, J=7.5 Hz, 2H), 7.32–7.27 (m, 5H), 7.18–7.13
(m, 2H), 6.99 (t, J=8.6 Hz, 1H), 6.81 (dd, J=5.7, 1.1 Hz, 2H), 5.25
(dd, J=12.0, 1.6 Hz, 1H), 2.41 (dd, J=12.6, 1.3 Hz, 1H), 2.12 ppm
(dd, J=14.1, 1.9 Hz, 1H), 1.91 (s, 3H); 13C NMR (150 MHz, CDCl3):
d=155.0, 149.6, 141.2, 131.2, 129.9, 128.5, 128.1, 127.9, 127.4,
127.1, 126.1, 126.0, 120.8, 117.3, 75.0, 48.8, 41.0, 29.3 ppm; HRMS
calcd for C22H20O: 300.1514; found: 300.1518.
(6k): White solid (74 mg, 60%), m.p. 153–1558C; IR (neat): n=2939
~
(m), 1605 (s), 1483 (s), 1235 (m), 753 cmÀ1 (s); 1H NMR (600 MHz,
CDCl3): d=7.51–7.50 (m, 2H), 7.44–7.39 (m, 3H), 7.34 (t, J=7.4 Hz,
1H), 7.27 (t, J=7.2 Hz, 1H), 7.21 (t, J=7.5 Hz, 1H), 7.12–7.08 (m,
3H), 6.96 (dd, J=8.1, 1.1 Hz,1H), 6.80 (t, J=7.6 Hz, 1H), 5.50 (d, J=
1.1 Hz, 1H), 4.44 (d, J=4.6 Hz, 1H), 2.68–2.63 (m, 2H), 2.47–2.44
(m, 1H), 1.73–1.67 (m, 1H), 1.56–1.54 ppm (m, 1H); 13C NMR
(150 MHz, CDCl3): d=153.7, 140.0, 137.0, 136.8, 131.5, 129.4, 129.0,
Chem. Eur. J. 2014, 20, 10519 – 10526
www.chemeurj.org
10523
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
1
128.2, 127.6, 127.3, 126.9, 125.7, 125.2, 123.8, 120.7, 116.7, 79.5,
41.5, 37.7, 28.3, 17.1 ppm; HRMS calcd for C23H20O: 312.1514;
found: 312.1517.
1563 (s), 1485 (s), 1241 (m), 733 cmÀ1 (s); H NMR (400 MHz, CDCl3):
d=7.73 (dd, J=11.2, 8.0 Hz, 2H), 7.46–7.44 (m, 2H), 7.42–7.39 (m,
2H), 7.37–7.31 (m, 2H), 7.29–7.25 (m, 2H), 7.13 (t, J=7.6 Hz, 1H),
6.94–6.89 (m, 2H), 6.81–6.78 (m, 1H), 4.77 (d, J=10.4 Hz, 1H), 4.24
(d, J=11.2 Hz, 1H), 2.44–2.37 (m, 1H), 0.73 ppm (d, J=6.8 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=154.6, 147.7, 139.8, 139.5, 139.4,
129.7, 128.6, 128.5, 128.2, 127.5, 124.6, 124.2, 124.0, 123.9, 123.0,
122.5, 120.8, 116.7, 84.2, 47.0, 41.2, 16.0 ppm; HRMS calcd for
C24H20OS: 356.1235, found: 356.1227.
6-Phenyl-6a,7,8,12b-tetrahydro-6H-naphtho[2,1-c]chromene
~
(6k’): White semisolid (10 mg, 8%); IR (neat): n=3030 (m), 1582 (s),
1484 (s), 1235 (m), 738 cmÀ1 (s); 1H NMR (600 MHz, CDCl3): d=
7.34–7.32 (m, 4H), 7.31–7.29 (m, 1H), 7.19–7.13 (m, 6H), 6.95 (dd,
J=8.1, 1.1 Hz, 1H), 6.89 (t, J=7.2 Hz, 1H), 4.90 (d, J=7.0 Hz, 1H),
3.90 (d, J=5.1 Hz, 1H), 2.82–2.79 (m, 2H), 2.68–2.65 (m, 1H), 1.96
(dd, J=13.7, 5.8 Hz, 1H), 1.53–1.50 ppm (m, 1H); 13C NMR
(150 MHz, CDCl3): d=153.8, 140.7, 137.8, 137.0, 130.7, 129.6, 128.5,
128.5, 128.0, 127.9, 126.7, 126.5, 125.7, 123.0, 120.0, 116.8, 79.5,
37.1, 36.6, 27.5, 24.3 ppm; HRMS calcd for C23H20O: 312.1514;
found: 312.1511.
4-(Benzo[b]thiophen-2-yl)-3-ethyl-2-phenylchroman (6q): White
~
solid (80 mg, 55%), m.p. 219–2218C; IR (neat): n=3014 (m), 1561
(s), 1482 (s), 1259 (m), 736 cmÀ1 (s); H NMR (400 MHz, CDCl3): d=
1
7.73 (dd, J=12.4, 8.0 Hz, 2H), 7.48–7.46 (m, 2H), 7.42–7.27 (m, 6H),
7.11 (t, J=7.2 Hz, 1H), 6.95 (d, J=8.0 Hz, 1H), 6.88 (d, J=8.0 Hz,
1H), 6.78 (t, J=7.6 Hz, 1H), 4.93 (d, J=10.0 Hz, 1H), 4.52 (d, J=
11.2 Hz, 1H), 2.46–2.38 (m, 1H), 1.37–1.26 (m, 2H), 0.62 ppm (t, J=
7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=154.4, 148.0, 139.8,
139.4, 139.4, 129.9, 128.6, 128.6, 128.1, 127.6, 124.9, 124.2, 124.0,
123.7, 123.0, 122.5, 120.7, 116.7, 82.2, 45.7, 42.9, 21.4, 8.8 ppm;
HRMS calcd for C25H22OS: 370.1391, found: 370.1392.
4-(Benzo[b]thiophen-2-yl)-2-phenylchroman (6l): White solid
~
(102 mg, 75%), m.p. 216–2188C; IR (neat): n=2921 (m), 1511 (s),
1
1453 (s), 1234 (m), 736 cmÀ1 (s); H NMR (400 MHz, CDCl3): d=7.73
(dd, J=19.6, 7.6 Hz, 2H), 7.51–7.49 (m, 2H), 7.43–7.39 (m, 2H),
7.36–7.32 (m, 2H), 7.28 (td, J=8.0, 1.2 Hz, 1H), 7.25 (s, 1H), 7.20–
7.16 (m, 1H), 7.06 (d, J=7.6 Hz, 1H), 6.97 (dd, J=8.4, 1.2 Hz, 1H),
6.84 (td, J=7.6, 1.2 Hz, 1H), 5.22 (dd, J=11.6, 2.0 Hz, 1H), 4.78 (dd,
J=12.0, 6.0 Hz, 1H), 2.60–2.55 (m, 1H), 2.48–2.39 ppm (m, 1H);
13C NMR (100 MHz, CDCl3): 154.8, 148.3, 140.8, 139.5, 139.5, 129.4,
128.6, 128.4, 128.2, 126.1, 124.2, 124.2, 124.0, 123.1, 122.5, 122.4,
120.7, 117.1, 78.0, 40.6, 39.3 ppm; HRMS calcd for C23H18OS:
342.1078, found: 342.1076.
6-Methoxy-2,4-diphenylchroman (7b): Light yellow solid (77 mg,
75%), m.p. 126–1288C; IR (neat): n=2950 (m), 1600 (s), 1490 (s),
~
1209 (m), 700 cmÀ1 (s); 1H NMR (600 MHz, CDCl3): d=7.46 (d, J=
7.5 Hz, 2H), 7.37 (t, J=7.4 Hz, 2H), 7.30 (t, J=7.4 Hz, 3H), 7.21 (t,
J=7.2 Hz, 3H), 6.88 (d, J=8.8 Hz, 1H), 6.71 (dd, J=8.8, 2.6 Hz, 1H),
6.30 (d, J=2.3 Hz, 1H), 5.13 (d, J=11.2 Hz, 1H), 4.32 (dd, J=12.1,
5.9 Hz, 1H), 3.60 (s, 3H), 2.39–2.36 (m, 1H), 2.23 ppm (m, 1H);
13C NMR (150 MHz, CDCl3): d=153.4, 149.7, 144.3, 141.3, 128.6,
128.5, 128.4, 128.0, 126.8, 126.2, 126.1, 117.5, 114.6, 113.6, 78.0,
55.6, 43.7, 40.7 ppm; HRMS calcd for C22H20O2: 316.1463; found:
316.1459.
4-(Benzofuran-2-yl)-2-phenylchroman (6m): White solid (75 mg,
~
58%), m.p. 177–1798C; IR (neat): n=2945 (m), 2851 (s), 1491 (s),
1269 (m), 1048 (s), 732 cmÀ1 (s); 1H NMR (400 MHz, CDCl3): d=
7.52–7.48 (m, 3H), 7.41–7.37 (m, 3H), 7.34–7.30 (m, 1H), 7.22–7.14
(m, 3H), 7.05 (d, J=7.6 Hz, 1H), 6.96 (d, J=8.4 Hz, 1H), 6.83 (t, J=
7.6 Hz, 1H), 6.59 (s, 1H), 5.20 (dd, J=10.8, 2.8 Hz, 1H), 4.63 (dd, J=
11.6, 6.4 Hz, 1H), 2.60–2.54 (m, 1H), 2.52–2.46 ppm (m, 1H);
13C NMR (100 MHz, CDCl3): d=159.0, 155.1, 154.9, 140.9, 128.8,
128.6, 128.4, 128.4, 128.2, 126.1, 123.7, 122.7, 121.9, 120.8, 120.6,
117.4, 111.1, 103.9, 77.8, 36.9, 36.4 ppm; HRMS calcd for
C23H18O2:326.1307, found: 326.1303.
6-Methoxy-2,4-diphenylchroman (7b’): Light yellow semisolid
(16 mg, 12%); IR (neat): n=2953 (m), 1600 (s), 1493 (s), 1215 (m),
1043 (s), 700 cmÀ1 (s); H NMR (600 MHz, CDCl3): d=7.32–7.29 (m,
7H), 7.22 (t, J=7.6 Hz, 1H), 7.14 (d, J=8.3 Hz, 2H), 6.94 (d, J=
8.9 Hz, 1H), 6.79 (dd, J=8.6,3.1 Hz, 1H), 6.50 (d, J=2.9 Hz, 1H),
4.99 (dd, J=10.5, 2.3 Hz, 1H), 4.19 (dd, J=5.6, 3.3 Hz, 1H), 3.68 (s,
3H), 2.44–2.41 (m, 1H), 2.23–2.20 ppm (m, 1H); 13C NMR (150 MHz,
CDCl3): d=153.4, 149.5, 145.9, 141.4, 128.6, 128.4, 128.3, 127.7,
126.4, 126.0, 123.4, 117.7, 114.7, 114.6, 73.0, 55.7, 40.5, 38.3 ppm;
HRMS calcd for C22H20O2: 316.1463; found: 316.1462.
~
1
4-(Benzo[b]thiophen-2-yl)-4-methyl-2-phenylchroman
(6n):
~
White solid (95 mg, 67%), m.p. 207–2098C; IR (neat): n=3003 (m),
1
1510 (s), 1463 (s), 1265 (m), 739 cmÀ1 (s); H NMR (400 MHz, CDCl3):
d=7.68 (dd, J=12.0, 7.6 Hz, 2H), 7.49–7.47 (m, 2H), 7.39 (t, J=
7.2 Hz, 2H), 7.34–7.29 (m, 2H), 7.27 (dd, J=8.4, 1.2 Hz, 1H), 7.19 (s,
1H), 7.16–7.14 (m, 1H), 7.11–7.09 (m, 1H), 6.96 (dd, J=8.4, 1.2 Hz,
1H), 6.87–6.83 (m, 1H), 5.24 (dd, J=12.0, 1.6 Hz, 1H), 2.61 (t, J=
13.2 Hz, 1H), 2.28 (dd, J=14.0, 2.0 Hz, 1H), 2.01 ppm (s, 3H);
13C NMR (100 MHz, CDCl3): d=155.8, 154.2, 140.7, 139.5, 139.4,
129.5, 129.4, 128.6, 128.5, 128.2, 128.1, 126.2, 124.1, 123.9, 123.1,
122.1, 120.8, 117.4, 74.9, 48.2, 40.1, 30.8 ppm; HRMS calcd for
C24H20OS: 356.1235, found: 356.1230.
6-Chloro-2,4-diphenylchroman (7c): White solid (67 mg, 66%),
~
m.p. 121–1238C; IR (neat): n=3002 (m), 1581 (s), 1485 (s), 1242
(m), 735 cmÀ1 (s); H NMR (600 MHz, CDCl3): d=7.46 (d, J=7.3 Hz,
1
2H), 7.38 (t, J=7.3 Hz, 2H), 7.34–7.32 (m, 3H), 7.27 (t, J=7.3 Hz,
1H), 7.20 (dd, J=8.4.1.4 Hz, 2H), 7.09–7.07 (m, 1H), 6.88 (d, J=
8.7 Hz, 1H), 6.74 (d, J=2.5 Hz, 1H), 5.18 (dd, J=11.5,1.7 Hz, 1H),
4.30 (dd, J=12.1, 5.8 Hz, 1H), 2.41–2.38 (m, 1H), 2.27–2.21 ppm (m,
1H); 13C NMR (150 MHz, CDCl3): d=154.1, 143.5, 140.7, 129.3,
128.8, 128.6, 128.4, 128.2, 127.8, 127.3, 127.0, 126.0, 125.3, 118.4,
78.3, 43.4, 40.1 ppm; HRMS calcd for C21H17ClO: 320.0968; found:
320.0963.
4-(Benzofuran-2-yl)-4-methyl-2-phenylchroman (6o): White solid
~
(74 mg, 55%), m.p. 172–1748C; IR (neat): n=2976 (m), 1507 (s),
1472 (s), 1266 (m), 735 cmÀ1 (s); 1H NMR (400 MHz, CDCl3): d=
7.51–7.48 (m, 3H), 7.39 (t, J=7.6 Hz, 2H), 7.35–7.31 (m, 2H), 7.20–
7.12 (m, 3H), 7.03 (dd, J=7.6, 1.6 Hz, 1H), 6.97 (d, J=7.6 Hz, 1H),
6.84–6.80 (m, 1H), 6.63 (s, 1H), 5.26 (dd, J=12.0, 1.6 Hz, 1H), 2.79
(t, J=13.2 Hz, 1H), 2.12 (dd, J=14.0, 2.0 Hz, 1H), 1.90 ppm (s, 3H);
13C NMR (100 MHz, CDCl3): d=163.5, 154.8, 154.4, 140.9, 128.6,
128.5, 128.3, 128.1, 128.1, 127.0, 126.2, 123.7, 122.5, 120.9, 120.5,
117.6, 111.1, 102.9, 74.4, 42.9, 38.4, 28.7 ppm; HRMS calcd for
C24H20O2: 340.1463, found: 340.1468.
6-Chloro-2,4-diphenylchroman (7c’): White semisolid (10 mÀg1,
~
10%); IR (neat): n=3011 (m), 1582 (s), 1485 (s), 1239 (m), 752 cm
(s); 1H NMR (600 MHz, CDCl3): d=7.32–7.28 (m, 7H), 7.25 (t, J=
8.1 Hz, 1H), 7.14 (dd, J=6.8, 3.0 Hz, 1H), 7.11 (d, J=7.6 Hz, 2H),
6.94 (d, J=5.7 Hz, 2H), 5.03 (dd, J=10.3, 2.3 Hz, 1H), 4.16 (t, J=
4.7 Hz, 1H), 2.43–2.39 (m, 1H), 2.25–2.22 ppm (m, 1H); 13C NMR
(150 MHz, CDCl3): d=154.0, 145.2, 140.9, 130.1, 128.6, 128.6, 128.5,
128.2, 127.9, 126.7, 125.9, 125.2, 124.7, 118.4, 73.4, 40.1, 37.8 ppm;
HRMS calcd for C21H17ClO: 320.0968; found: 320.0981.
4-(Benzo[b]thiophen-2-yl)-3-methyl-2-phenylchroman
(6p):
~
White solid (110 mg, 78%), m.p. 212–2148C; IR (neat): n=2927 (m),
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Full Paper
2-(4-Chlorophenyl)-4-phenylchroman (7d): White solid (60 mg,
124.0, 123.9, 123.0, 122.5, 120.7, 116.7, 114.0, 83.8, 55.3, 47.1, 41.1,
16.0 ppm; HRMS calcd for C25H22O2S: 386.1341, found: 386.1339.
~
53%), m.p. 165–1688C; IR (neat): n=3057 (m), 1712 (s), 1484 (s),
1
1265 (m), 736 cmÀ1 (s); H NMR (600 MHz, CDCl3): d=7.44–7.42 (m,
4-(Benzo[b]thiophen-2-yl)-6-methoxy-3-methyl-2-phenylchroman
2H), 7.37 (d, J=8.5 Hz, 2H), 7.33 (t, J=7.3 Hz, 2H), 7.27 (t, J=
7.8 Hz, 1H), 7.22 (d, J=8.4 Hz, 2H), 7.15 (t, J=8.1 Hz, 1H), 6.95 (dd,
J=8.1, 0.9 Hz, 1H), 6.82–6.77 (m, 2H), 5.20 (dd, J=11.5, 1.7 Hz,
1H), 4.35 (dd, J=12.2, 5.8 Hz, 1H), 2.41–2.38 (m, 1H), 2.26–
2.20 ppm (m, 1H); 13C NMR (150 MHz, CDCl3): d=155.2, 144.3,
139.7, 133.7, 129.8, 128.7(CHx2), 128.5, 127.8, 127.4, 126.8, 125.5,
120.7, 116.9, 77.3, 43.3, 40.6 ppm; HRMS calcd for C21H17ClO:
320.0968; found: 320.0969.
~
(7h): White solid (111 mg, 81%), m.p. 226–2288C; IR (neat): n=
2943 (m), 1599 (s), 1493(s), 1219 (m), 700 cmÀ1 (s); 1H NMR
(400 MHz, CDCl3): d=7.73 (dd, J=13.6, 8.0 Hz, 2H), 7.45–7.25 (m,
8H), 6.84 (d, J=8.8 Hz, 1H), 6.73–6.70 (m, 1H), 6.49 (d, J=0.8 Hz,
1H), 4.70 (d, J=10.0 Hz, 1H), 4.20 (d, J=10.8 Hz, 1H), 3.60 (s, 3H),
2.44–2.33 (m, 1H), 0.71 ppm (d, J=6.8 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=153.6, 148.8, 147.6, 139.9, 139.6, 139.4, 128.6, 128.5,
127.5, 125.2,124.2, 124.0, 123.9, 123.0, 122.5, 117.3, 114.6, 114.0,
84.2, 55.7, 47.3, 41.3, 16.0 ppm; HRMS calcd for C25H22O2S:
386.1341, found: 386.1345.
2-(4-Chlorophenyl)-4-phenylchroman (7d’): White semisolid
~
(11 mg, 10%); IR (neat): n=3051 (m), 1711 (s), 1489 (s), 1270 (m),
1
735 (s); H NMR (600 MHz, CDCl3): d=7.30–7.27 (m, 4H), 7.24–7.21
4-(Benzo[b]thiophen-2-yl)-6-chloro-3-methyl-2-phenylchroman
(m, 3H), 7.20 (t, J=6.9 Hz, 1H), 7.09 (dd, J=7.4 Hz, 2H), 6.98 (dd,
J=8.2, 0.9 Hz, 1H), 6.95 (dd, J=7.6, 1.5 Hz, 1H), 6.86 (t, J=7.5 Hz,
1H), 4.99 (dd, J=10.5, 2.4 Hz, 1H), 4.19 (dd, J=5.4, 3.5 Hz, 1H),
2.40–2.35 (m, 1H), 2.22–2.18 ppm (m, 1H); 13C NMR (150 MHz,
CDCl3): d=155.1, 145.8, 140.0, 133.5, 130.8, 128.6, 128.6, 128.5,
128.2, 127.4, 126.5, 122.9, 120.7, 117.0, 72.5, 40.1, 38.3 ppm; HRMS
calcd for C21H17ClO: 320.0968; found: 320.0967.
~
(7i): White solid (106 mg, 85%), m.p. 241–2438C; IR (neat): n=
2928 (m), 1712 (s), 1582 (s), 1261 (m), 737 cmÀ1 (s); 1H NMR
(400 MHz, CDCl3): d=7.75 (dd, J=12.4, 6.0 Hz, 2H), 7.43–7.28 (m,
8H), 7.08–7.06 (m, 1H), 6.89 (d, J=1.2 Hz, 1H), 6.82 (d, J=7.2 Hz,
1H), 4.74 (d, J=8.0 Hz, 1H), 4.19 (d, J=8.8 Hz, 1H), 2.41–2.33 (m,
1H), 0.71 ppm (d, J=5.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=
153.2, 146.6, 139.9, 139.4, 139.1, 129.2, 128.7, 128.7, 128.2, 127.5,
126.1, 125.6, 124.3, 124.2, 124.2, 123.1, 122.5, 118.2, 84.4, 46.8, 40.8,
15.9 ppm; HRMS calcd for C24H19OSCl: 390.0845, found: 390.0838.
2-(4-Bromophenyl)-4-phenylchroman (7e): Light brown solid
~
(58 mg, 51%), m.p. 174–1768C; IR (neat): n=3053 (m), 1712 (s),
1
1265 (m), 736 cmÀ1 (s); H NMR (600 MHz, CDCl3): d=7.53–7.51 (m,
4-(Benzo[b]thiophen-2-yl)-2-(4-chlorophenyl)-3-methylchroman
2H), 7.38–7.36 (m, 2H), 7.33 (t, J=7.3 Hz, 2H), 7.26 (t, J=6.4 Hz,
1H), 7.22 (dd, J=7.0,1.3 Hz, 2H), 7.15 (t, J=8.1 Hz, 1H), 6.95 (dd,
J=8.1, 0.9 Hz, 1H), 6.82–6.77 (m, 2H), 5.18 (dd, J=11.5, 1.6 Hz,
1H), 4.35 (dd, J=12.1, 5.8 Hz, 1H), 2.41–2.38 (m, 1H), 2.25–
2.19 ppm (m, 1H); 13C NMR (150 MHz, CDCl3): d=155.2, 143.3,
140.2, 131.7, 129.8, 128.7, 128.5, 127.8, 127.7, 126.8, 125.5, 121.8,
120.7, 116.9, 77.3, 43.3, 40.5 ppm; HRMS calcd for C21H17BrO:
364.0463; found: 364.0466.
~
(7j): White solid (103 mg, 83%), m.p. 251–2538C; IR (neat): n=
2920 (m), 1702 (s), 1484 (s), 1265 (m), 736 cmÀ1 (s); 1H NMR
(400 MHz, CDCl3): d=7.73 (dd, J=11.6, 7.6 Hz, 2H), 7.38–7.31 (m,
5H), 7.29–7.25 (m, 2H), 7.13 (t, J=7.6 Hz, 1H), 6.93–6.87 (m, 2H),
6.80 (t, J=7.6 Hz, 1H), 4.74 (d, J=10.0 Hz, 1H), 4.22 (d, J=10.8 Hz,
1H), 2.37–2.30 (m, 1H), 0.72 ppm (s, 3H); 13C NMR (100 MHz,
CDCl3): d=154.5, 147.5, 139.8, 139.4, 138.0, 129.8, 129.6, 128.9,
128.8, 128.3, 124.3, 124.1, 124.0, 123.0, 122.5, 120.9, 117.5, 116.7,
83.4, 46.9, 41.2, 15.9 ppm; HRMS calcd for C24H19ClOS: 390.0845,
found: 390.0844.
2-(4-Bromophenyl)-4-phenylchroman (7e’): Light brown semisolid
~
(11 mg, 10%); IR (neat): n=3049 (m), 1705 (s), 1266 (m), 1059 (s),
1
736 cmÀ1 (s); H NMR (600 MHz, CDCl3): d=7.44–7.42 (m, 2H), 7.29
(t, J=7.5 Hz, 2H), 7.23–7.21 (m, 1H), 7.20–7.17 (m, 3H), 7.09 (d, J=
7.4 Hz, 2H), 6.99–6.94 (m, 2H), 6.86 (t, J=7.3 Hz, 1H), 4.97 (dd, J= Acknowledgements
10.5, 2.4 Hz, 1H), 4.19 (dd, J=5.3, 3.4 Hz, 1H), 2.38–2.35 (m, 1H),
2.21–2.19 ppm (m, 1H); 13C NMR (150 MHz, CDCl3): d=155.0, 145.8,
The authors wish to thank the National Science Council,
140.5, 131.6, 130.8, 128.6, 128.5, 128.2, 127.7, 126.5, 122.9, 121.6,
120.7, 117.0, 72.6, 40.0, 38.3 ppm; HRMS calcd for C21H17BrO:
364.0463; found: 364.0459.
Taiwan and the Ministry of Education for supporting this work.
Keywords: cycloaddition · diastereoselectivity · gold · oxygen
heterocycles · synthetic methods
4-(Benzo[b]thiophen-2-yl)-2-(2-methoxyphenyl)-3-methylchro-
man (7 f): White solid (101 mg, 73%), m.p. 223–22À518C; IR (neat):
n=2921 (m), 1565 (s), 1483 (s), 1265 (m), 736 cm (s); 1H NMR
~
(400 MHz, CDCl3): d=7.73 (dd, J=11.6, 7.6 Hz, 2H), 7.54 (dd, J=
7.6, 1.6 Hz, 1H), 7.35–7.25 (m, 4H), 7.12 (t, J=7.6 Hz, 1H), 7.05 (t,
J=7.6 Hz, 1H), 6.95–6.88 (m, 3H), 6.79 (t, J=7.6 Hz, 1H), 5.43 (d,
J=10.0 Hz, 1H), 4.29 (d, J=10.8 Hz, 1H), 3.83 (s, 3H), 2.47–2.37 (m,
1H), 0.76 ppm (d, J=6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=
157.1, 155.1, 148.1, 139.8, 139.5, 129.7, 129.2, 128.1, 128.0, 127.7,
124.8, 124.2, 123.9, 123.8, 123.0, 122.5, 121.1, 120.5, 116.8, 115.7,
110.7, 55.5, 47.2, 41.5, 15.0 ppm; HRMS calcd for C25H22O2S:
386.1341, found: 386.1345.
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4-(Benzo[b]thiophen-2-yl)-2-(4-methoxyphenyl)-3-methylchro-
~
man (7g): White solid (56 mg, 41%), m.p. 231–2338C; IR (neat): n=
2920 (m), 1578 (s), 1473 (s), 1261 (m), 737 cmÀ1 (s); 1H NMR
(400 MHz, CDCl3): d=7.73 (dd, J=11.6, 7.6 Hz, 2H), 7.38–7.35 (m,
2H), 7.33–7.31 (m, 1H), 7.29–7.27 (m, 2H), 7.11 (t, J=7.6 Hz, 1H),
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1H), 0.72 (d, J=6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=159.7,
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Published online on July 15, 2014
Chem. Eur. J. 2014, 20, 10519 – 10526
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ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim