Key words N-heterocyclic carbene - catalysis - 2-(2-aroylvinyl)cinnamaldehyde - α,β-unsaturated
imine - indane
A large number of indane derivatives are known to have a wide spectrum of biological
activity. For example, indanes A substituted by 4-aminobutyl and benzyl show strong antibacterial activity (Figure
[1 ]).[1 ] 5-(5,6-Dichloroindan-1-yl)-1H -tetrazole (B ) and 5-[(5,6-dichloroindan-1-yl)methyl]-1H -tetrazole (C ) display significant analgesic and anti-inflammatory activity.[2 ] The indanyl-substituted guanidiniums D have been investigated as small-molecule HIV-1 entry inhibitors,[3 ] and the sulfamides of 1-amino- and 2-aminoindanes E and F are potential carbonic anhydrase isoenzymes inhibitors.[4 ] 3-Amino-1-(indan-5-yloxy)propan-2-ol derivatives G exhibited blocking activity for Na+ channels, useful as potent sodium-channel blockers for the treatment of stroke victims.[5 ] Various indane derivatives H derived from 7-aminoindan-4-ol are potent liver-selective thyroid hormone receptor
β (TRβ) agonists for the treatment of dyslipidemia,[6 ] while the 1-aminoindan-2-ol or 2-aminoindan-1-ol derivatives I and J have highly potent protein kinase C inhibitory activity.[7 ] Due to their biological, pharmaceutical, and synthetic importance, interest in the
synthesis of novel indane derivatives remains undiminished.[2 ]
[8 ]
Figure 1 Some bioactive indane derivatives
Cascade reactions catalyzed by N-heterocyclic carbenes (NHCs) have received attention
due to the resulting rapid generation of complex products.[9 ] A few N-heterocyclic carbene catalyzed reactions have been reported to produce different
indene or indane derivatives. For example, the cascade reactions of 2-formylcinnamates
with imines, phthalaldehydes with imines, and phthalaldehydes with 3-aroylacrylates
in the presence of NHC catalysts gave substituted indan-1-ones,[10a ]
[b ]
[c ] while NHC-catalyzed reaction of 3,3′-(1,2-phenylene)bis(1-phenylpropenones) with
aldehydes produced 1,2,3-trisubstituted indanes.[10d ] Under catalysis by NHCs, the dimerization of o -formylchalcones or o -formylcinnamates, or the reaction of o -formylchalcones with phthalaldehydes, afforded indene-spiro-indanone derivatives.[10e ] On the other hand, the dimerization of phthalaldehydes catalyzed by a imidazole
or triazole carbene produced dihydroisobenzofuran-spiro-indanones or indeno[2,1-a ]indanone derivatives, respectively.[10f ] NHC-catalyzed self-reaction of 2-(2-aroylvinyl)cinnamaldehydes gave indeno[2,1-c ]pyran-1-ones that were converted into indane-2-carboxylates or indane-2-carboxamides
by the addition of alcohols or amines,[11a ]
[b ] and the oxidative NHC-catalyzed cascade reaction between 2-(2-aroylvinyl)cinnamaldehydes
and β-diketones produced 9-(β-diketones)indeno[2,1-c ]pyran-1-ones.[11c ] Our attention has mainly focused on NHC-catalyzed reactions in recent years.[10f ]
[12 ] We are interested in NHC-catalyzed reactions of multifunctional reactants in terms
of various possible reaction pathways and complex structures of products. We envisioned
that the reaction between α,β-unsaturated aldehydes linked with a Michael acceptor
and α,β-unsaturated imines might have several different pathways. Thus, we studied
the NHC-catalyzed reaction of 2-(2-aroylvinyl)cinnamaldehydes with N -sulfonyl ketimines, which provided an efficient and stereoselective method for the
synthesis of highly functionalized indane derivatives.
We started this work by studying the reaction employing 2-(2-benzoylvinyl)cinnamaldehyde
(1a ) and 1,3-diphenyl-N -tosylprop-2-en-1-imine (2a ) as model substrates (Table [1 ]). At ambient temperature and in dichloromethane, the reaction of 1a with 2a (1a /2a 1:1.5) was initially catalyzed using 20 mol% of various triazole carbenes 3a′ –d′ that were generated from triazolium salts 3a –d with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). All these reactions produced product
4a , which was confirmed to be 9-[1,3-diphenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one by spectroscopic and single crystal X-ray diffraction analyses,[13 ] and the highest yield (66%) of 4a was obtained from the reaction catalyzed by N -(pentafluorophenyl)pyrrolo[2,1-c ]triazole carbene 3d′ (entries 1–4). Replacement of triazole carbene catalysts with thiazole carbene 3e′ or imidazole carbenes 3f′ and 3g′ resulted in no product or trace yields of product. Under the catalysis of triazole
carbene 3d′ , the reaction conditions were further optimized by varying temperature, solvent,
and the base used to generate the carbene catalyst. It was found that decreasing reaction
temperature to 0 °C improved the yield of 4a to 78%, however, further decreasing the temperature to –20 °C did not benefit the
reaction, while elevating the temperature to the boiling point of dichloromethane
led to the formation of product in a lower yield (entries 7–9). At 0 °C, the use of
other solvents including benzene, acetone, acetonitrile, and tetrahydrofuran, or other
bases like potassium tert -butoxide, sodium hydride, and cesium carbonate, all diminished the yield of product
(entries 10–16). In addition to the major product 4a , a small amount of a minor product (below 10%) was detected in the crude product
of most reactions by 1 H NMR.
Table 1 Optimization of the Reaction Conditions
Entry
NHC precursor
Base
Solvent
Temp (°C)
Time
Yield (%) of 4a
1
3a
DBU
CH2 Cl2
r.t.
5 h
30a
2
3b
DBU
CH2 Cl2
r.t.
5 h
19a
3
3c
DBU
CH2 Cl2
r.t.
5 h
21a
4
3d
DBU
CH2 Cl2
r.t.
20 min
66
5
3e
DBU
CH2 Cl2
r.t.
24 h
trace
6
3f
DBU
CH2 Cl2
r.t.
8 h
–b
7
3g
DBU
CH2 Cl2
r.t.
8 h
–b
8
3d
DBU
CH2 Cl2
0
20 min
78
9
3d
DBU
CH2 Cl2
–20
30 min
64
10
3d
DBU
CH2 Cl2
reflux
5 min
55
11
3d
Cs2 CO3
CH2 Cl2
0
2 h
59
12
3d
t -BuOK
CH2 Cl2
0
1 h
65
13
3d
NaH
CH2 Cl2
0
2 h
45
14
3d
DBU
benzene
0
4 h
46a
15
3d
DBU
acetone
0
4 h
59
16
3d
DBU
MeCN
0
4 h
45a
17
3d
DBU
THF
0
2 h
65
a The enal 1a was not totally consumed.
b Not found.
The scope of the reaction was then studied under the optimized conditions using α,β-unsaturated
aldehydes 1 and α,β-unsaturated imines 2 that bear different substituents. It was found that the substituents of both reactants
have a small influence on the reaction. As illustrated in Table [2 ], the reaction between 2-(2-aroylvinyl)cinnamaldehyde 1 and α,β-unsaturated imine 2 substituted by either electron-donating or electron-withdrawing groups on any of
the four phenyl rings in 1 and 2 , proceeded rapidly and efficiently to furnish products 4 in 69–84% yields in 20 minutes (entries 1–10, 13–15). Since the two phenyl groups
of 2-(2-aroylvinyl)cinnamaldehydes 1 and the phenyl on the imine group of ketimines 2 are remote from the site of the reaction between 1 and 2 , we considered that the steric effects of the substituents attached to these three
phenyl rings could be ignored. Thus, we only examined the influence of the position
of substituent attached to the phenyl group at C3 of ketimine 2 . 3-(4-Methoxyphenyl)prop-2-en-1-imine 2c and 3-(3-methoxyphenyl)prop-2-en-1-imine 2e gave higher yields of products (71–79%) than that of 3-(2-methoxyphenyl)prop-2-en-1-imine
2f (63%) when they reacted with enal 1a (entries 9, 11, and 12). In addition to the product 4 , the minor product 5 was detected in the crude products by 1 H NMR in 3–19% yields (ratio 4 /5 ~4:1–21:1). Initially, we thought that compounds 5 were diastereomers of products 4 . However, after the isolation of compound 5j , the spectroscopic characterization and single crystal X-ray diffraction analysis[13 ] confirmed that 5j was 8-(benzoylmethyl)-3-(4-bromophenyl)-2-[phenyl(4-tolylsulfonamido)methylene]-3,3a,8,8a-tetrahydrocyclopenta[a ]inden-1(2H )-one, which is derived from the intramolecular transformation of one diastereomer
of the major product 4j . The minor products 5 were difficult to separate from the corresponding major products 4 by chromatography due to the fact that each pair of 4 and 5 has a similar polarity. Thus, with the exception of 5j which has the highest yield (19%) and the largest difference of polarity to 4j , other minor products 5 were not isolated. The byproducts 5 can be removed from the major products 4 by recrystallization.
Table 2 The Reaction of 2-(2-Aroylvinyl)cinnamaldehydes 1 with 1,3-Diaryl-N -tosylprop-2-en-1-imines 2 under Optimized Conditions
Entry
1
R1
R2
2
R3
R4
Yielda (%)
Ratiod 4 /5
Total
4
b
5
b,c
1
1a
H
H
2a
H
H
81
4a : 78
5a : 3
24:1
2
1b
Me
H
2a
H
H
84
4b : 76
5b : 8
10:1
3
1c
OMe
H
2a
H
H
92
4c : 84
5c : 8
10:1
4
1d
F
H
2a
H
H
80
4d : 69
5d : 11
6:1
5
1e
H
Me
2a
H
H
82
4e : 78
5e : 4
20:1
6
1f
H
OMe
2a
H
H
76
4f : 72
5f : 4
20:1
7
1g
H
Br
2a
H
H
77
4g : 70
5g : 7
10:1
8
1a
H
H
2b
4-Me
H
79
4h : 71
5h : 8
9:1
9
1a
H
H
2c
4-OMe
H
78
4i : 71
5i : 7
10:1
10
1a
H
H
2d
4-Br
H
89
4j : 70
5j : 19
4:1
11
1a
H
H
2e
3-OMe
H
86
4k : 79
5k : 7
12:1
12
1a
H
H
2f
2-OMe
H
76
4l : 63
5l : 13
5:1
13
1a
H
H
2g
H
Me
82
4m : 74
5m : 8
9:1
14
1a
H
H
2h
H
OMe
80
4n : 70
5n : 10
7:1
15
1a
H
H
2i
H
Br
83
4o : 74
5o : 9
8:1
a The isolated yields.
b The yields of 4 and 5 were calculated based on the ratios of 4 /5 and the total yields of products.
c Except 5j , other minor products 5 were not isolated and characterized.
d The ratios of 4 /5 were detected by 1 H NMR on the crude products.
To account for the formation of 3-aryl-9-[1,3-diaryl-3-(4-tolylsulfonamido)allyl]indeno[2,1-c ]pyran-1-ones 4 and 8-(aroylmethyl)-3-aryl-2-[aryl(4-tolylsulfonamido)methylene]-3,3a,8,8a-tetrahydrocyclopenta[a ]inden-1(2H )-ones 5 from 2-(2-aroylvinyl)cinnamaldehydes 1 and N -tosyl ketimines 2 , a cascade reaction mechanism comprising two Michael additions is proposed (Scheme
[1 ]). Firstly, the homoenolate 6 derived from enal 1 and carbene 3′ undergoes intermolecular Michael addition to α,β-unsaturated imine 2 to form enamine anion 7 , which isomerizes to enolate 8 by proton transfer. The intramolecular Michael addition of 8 yields diastereomeric indane intermediates 9 and 10 . Intramolecular lactonization of 9 and 10 forms 9-[1,3-diaryl-3-(4-tolylsulfonamido)allyl]indeno[2,1-c ]pyran-1-ones 4 and 11 , respectively. This reaction occurs by a cascade process to form four stereocenters,
however, only the racemates of (4aS ,9S ,9aS ,1′R )- and (4aR ,9R ,9aR ,1′S )-9-[1,3-diaryl-3-(4-tolylsulfonamido)allyl]indeno[2,1-c ]pyran-1-ones 4 are found in the reaction. The stereoselective formation of products 4 can be explained by the steric effects of substituents. In the formation of the indane
ring of 4 , the substituents attached to the stereocenters at C9 and C9a are arranged in a trans configuration to reduce the repulsion of substituents, while the two fused C4a and
C9a stereocenters are in a cis configuration to avoid fused-ring strain. The minor cyclopenta[a ]inden-1-one products 5 are derived from the isomerization of minor diastereomers 11 by the intramolecular addition of the enamine to the δ-lactone species of 11 under the catalysis of a base, such as triazole carbene or DBU. However, the major
diastereomers 4 could not undergo such a transformation as the enamine and δ-lactone species of 4 are trans substituted on the indane ring.
The lactone moiety of indeno[2,1-c ]pyran-1-ones are known to be easily cleaved by the addition of nucleophiles, such
as alcohols or amines.[11a ]
[b ] Therefore, it would be possible to convert 9-[3-(sulfonamido)allyl]indeno[2,1-c ]pyran-1-ones 4 into various highly functionalized indane derivatives. To extend the applications
of the current reaction in the synthesis of indane derivatives, the different transformations
of 3-aryl-9-[1,3-diaryl-3-(tolylsulfonamido)allyl]indeno[2,1-c ]pyran-1-ones 4 were examined. For example, 4a was converted into methyl 1-(benzoylmethyl)-3-[1,3-diphenyl-3-(4-tolylsulfonamido)allyl]indane-2-carboxylate
(14 ) in 82% yield on heating in refluxing methanol. At ambient temperature, the hydrolysis
of 4a with aqueous 30% sodium hydroxide solution followed by saturated aqueous solution
of ammonium chloride in tetrahydrofuran afforded 1-(benzoylmethyl)-3-(2-benzoyl-1-phenylethyl)indane-2-carboxylic
acid (15 ) in 80% yield. Reduction of 4a with lithium aluminum hydride in tetrahydrofuran produced 9-[1,3-diphenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-1,4a,9,9a-tetrahydroindeno[2,1-c ]pyran (16 ) in 70% yield (Scheme [2 ]).
Scheme 1 The proposed mechanism for the formations of 3-aryl-9-[1,3-diaryl-3-(4-tolylsulfonamido)allyl]indeno[2,1-c ]pyran-1-ones 4 and 8-(aroylmethyl)-3-aryl-2-[aryl(4-tolylsulfonamido)methylene]-3,3a,8,8a-tetrahydrocyclopenta[a ]inden-1(2H )-ones 5 from the reaction 2-(2-aroylvinyl)cinnamaldehydes 1 with 1,3-diaryl-N -tosylprop-2-en-1-imines 2
Scheme 2 The transformations of 9-[1,3-diphenyl-3-(4-tolylsulfonamido)allyl]-3-phenylindeno[2,1-c ]pyran-1-one 4a
Scheme 3 Asymmetric reaction of 2-(2-benzoylvinyl)cinnamaldehyde 1a with N -tosyl ketimine 2a catalyzed by chiral triazole carbenes
Enantioselective synthesis of 9-[3-(sulfonamido)allyl]indeno[2,1-c ]pyran-1-ones 4 was also attempted using chiral triazole carbenes. As shown in Scheme [3 ], while chiral pyrrolo[2,1-c ]triazole carbene 3h did not promoted the reaction of enal 1a with N -tosyl ketimine 2a , a small amount of product 4a (15%) was obtained from the reaction catalyzed by N -(pentafluorophenyl)hexahydroindeno[2,1-b ]triazolo[3,4-c ][1,4]oxazine carbene 3i . However, to our delight, under catalysis by N -phenylhexahydroindeno[2,1-b ]triazolo[3,4-c ][1,4]oxazine carbene 3j , the reaction of enal 1a with ketimine 2a provided 4a in 45% yield with high enantioselectivity (90% ee, absolute configuration of 4a was not determined.) (Scheme [3 ]). This initial study on the asymmetric reaction of 2-(2-benzoylvinyl)cinnamaldehyde
(1a ) with N -tosyl ketimine 2a indicates that the enantioselective synthesis of 9-[3-(sulfonamido)allyl]indeno[2,1-c ]pyran-1-ones 4 can be achieved using chiral triazole carbene 3j as the catalyst.
In summary, we have developed an efficient NHC-catalyzed reaction of 2-(2-aroylvinyl)cinnamaldehydes
with α,β-unsaturated imines, which produced good yields of novel 3-aryl-9-[1,3-diaryl-3-(4-tolylsulfonamido)allyl]indeno[2,1-c ]pyran-1-ones with high diastereoselectivity. Indane is a framework that is found
in a large number of bioactive and pharmaceutically important molecules. This work
provided unique indane derivatives that are amenable to further transformations.
Commercially available chemical reagents were used without further purification. Anhyd
CH2 Cl2 was prepared by distillation over P2 O5 . Melting points are uncorrected. Petroleum ether = PE. 1 H (400 or 500 MHz) and 13 C NMR (100 or 125 MHz) were recorded in the indicated solvents using a Bruker instrument.
IR spectra were recorded using an AVATAR 360 FT-IR spectrophotometer. Mass spectra
were recorded on a Surveyor MSQ Plus (ESI) instrument. Column chromatography was performed
using 200–300 mesh silica gel. The 2-(2-aroylvinyl)cinnamaldehydes 1 ,[14 ] 1,3-diaryl-N -tosylprop-2-en-1-imines 2 ,[15 ] and NHC precursor 3d
[16 ] were prepared according to literature methods.
NHC-Catalyzed Reaction of 2-(2-Aroylvinyl)cinnamaldehydes 1 with 1,3-Diaryl-N -tosylprop-2-en-1-imines 2; General Procedure
NHC-Catalyzed Reaction of 2-(2-Aroylvinyl)cinnamaldehydes 1 with 1,3-Diaryl-N -tosylprop-2-en-1-imines 2; General Procedure
Under N2 atmosphere and at 0 °C, 2-(2-aroylvinyl)cinnamaldehyde 1 (0.5 mmol), 1,3-diaryl-N -tosylprop-2–en-1-imines 2 (0.75 mmol), N -(pentafluorophenyl)pyrrolo[2,1-c ]triazolium salt 3d (0.1 mmol), and 4-Å molecular sieves (250 mg) were mixed in anhyd CH2 Cl2 (10 mL). The mixture was stirred for 10 min at 0 °C, and then DBU (0.1 mmol) was
added using a microsyringe. The mixture was stirred at 0 °C for ca. 20–30 min until
the enal 1 had been consumed. After removal of molecular sieves and the solvent, the residue
was purified by flash column chromatography (silica gel, PE–CH2 Cl2 –EtOAc, 16:4:1) to give 4 , which contained a trace amount of byproduct 5 . The major product 4 was further purified by recrystallization (n -hexane–CH2 Cl2 ).
(4aS *,9S *,9aS *,1′R *,Z )-9-[1,3-Diphenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4a)
(4aS *,9S *,9aS *,1′R *,Z )-9-[1,3-Diphenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4a)
White crystals; yield: 243 mg (0.39 mmol, 78%); mp 180–182 °C.
IR: 3250, 1748, 1628, 1595 cm–1 .
1 H NMR (400 MHz, acetone-d
6 ): δ = 8.08 (s, 1 H), 7.68 (d, J = 7.0 Hz, 2 H), 7.52–7.54 (m, 2 H), 7.51 (d, J = 8.3 Hz, 2 H), 7.42 (t, J = 7.7 Hz, 2 H), 7.39 (d, J = 6.8 Hz, 1 H), 7.21–7.35 (m, 8 H), 7.16 (d, J = 7.7 Hz, 2 H), 7.11 (d, J = 7.8 Hz, 2 H), 7.09 (d, J = 5.6 Hz, 1 H), 6.85 (d, J = 7.5 Hz, 1 H), 6.22 (d, J = 5.1 Hz, 1 H), 6.01 (d, J = 10.9 Hz, 1 H), 4.22 (t, J = 5.0 Hz, 1 H), 4.02–4.06 (m, 2 H), 3.15 (dd, J = 8.8, 4.6 Hz, 1 H), 2.23 (s, 3 H).
13 C NMR (100 MHz, acetone-d
6 ): δ = 171.1, 148.9, 144.9, 144.1, 142.1, 142.0, 140.0, 138.6, 137.4, 133.5, 130.4,
129.9, 129.4, 129.2, 128.92, 128.90, 128.8, 128.7, 128.1, 127.9, 127.7, 127.4, 126.2,
125.9, 125.4, 124.9, 101.6, 54.6, 46.5, 45.8, 41.4, 21.5.
HRMS (ESI): m /z [M + H]+ calcd for C40 H34 NO4 S: 624.2209; found: 624.2218.
(4aS *,9S *,9aS *,1′R *,Z )-9-[1,3-Diphenyl-3-(4-tolylsulfonamido)allyl]-6-methyl-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4b)
(4aS *,9S *,9aS *,1′R *,Z )-9-[1,3-Diphenyl-3-(4-tolylsulfonamido)allyl]-6-methyl-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4b)
White crystals; yield: 242 mg (0.38 mmol, 76%); mp 126–128 °C.
IR: 3335, 1751, 1598 cm–1 .
1 H NMR (500 MHz, acetone-d
6 ): δ = 8.09 (s, 1 H), 7.69 (d, J = 7.2 Hz, 2 H), 7.52–7.55 (m, 2 H), 7.52 (d, J = 8.2 Hz, 2 H), 7.44 (t, J = 7.6 Hz, 2 H), 7.40 (t, J = 6.9 Hz, 1 H), 7.25–7.32 (m, 6 H), 7.16 (br s, 3 H), 7.12 (d, J = 8.0 Hz, 2 H), 6.93 (d, J = 7.7 Hz, 1 H), 6.71 (d, J = 7.8 Hz, 1 H), 6.22 (d, J = 5.0 Hz, 1 H), 5.97 (d, J = 10.8, 1 H), 4.17 (t, J = 5.2 Hz, 1 H), 3.98–4.03 (m, 2 H), 3.12 (dd, J = 8.6, 4.6 Hz, 1 H), 2.28 (s, 3 H), 2.25 (s, 3 H).
13 C NMR (100 MHz, acetone-d
6 ): δ = 171.1, 148.8, 145.0, 144.1, 142.2, 140.0, 139.0, 138.6, 138.5, 137.4, 133.6,
130.4, 129.9, 129.4, 129.1, 128.9, 128.87, 128.73, 128.65, 128.2, 127.7, 127.4, 125.9,
125.8, 125.4, 125.3, 101.7, 54.3, 46.8, 45.8, 41.3, 21.5, 21.3.
HRMS (ESI): m /z [M + H]+ calcd for C41 H36 NO4 S: 638.2365; found: 638.2368.
(4aS *,9S *,9aS *,1′R *,Z )-9-[1,3-Diphenyl-3-(4-tolylsulfonamido)allyl]-6-methoxy-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4c)
(4aS *,9S *,9aS *,1′R *,Z )-9-[1,3-Diphenyl-3-(4-tolylsulfonamido)allyl]-6-methoxy-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4c)
White crystals; yield: 284 mg (0.42 mmol, 84%); mp 166–167 °C.
IR: 3298, 1751, 1614, 1593 cm–1 .
1 H NMR (500 MHz, acetone-d
6 ): δ = 8.08 (s, 1 H), 7.69 (d, J = 7.2 Hz, 2 H), 7.54–7.56 (m, 2 H), 7.52 (d, J = 8.3 Hz, 2 H), 7.44 (t, J = 7.7 Hz, 2 H), 7.40 (t, J = 7.3 Hz, 1 H), 7.23–7.32 (m, 6 H), 7.16 (d, J = 6.8 Hz, 2 H), 7.13 (d, J = 8.0 Hz, 2 H), 6.94 (s, 1 H), 6.71 (d, J = 8.4 Hz, 1 H), 6.67 (dd, J = 8.4, 2.0 Hz, 1 H), 6.22 (d, J = 5.0 Hz, 1 H), 5.99 (d, J = 10.9 Hz, 1 H), 4.15 (t, J = 5.1 Hz, 1 H), 4.02 (dd, J = 8.6, 5.1 Hz, 1 H), 3.99 (dd, J = 10.9, 5.7 Hz, 1 H), 3.76 (s, 3 H), 3.15 (dd, J = 8.7, 4.7 Hz, 1 H), 2.25 (s, 3 H).
13 C NMR (100 MHz, acetone-d
6 ): δ = 171.1, 161.0, 148.9, 146.4, 144.1, 142.2, 140.0, 138.6, 137.4, 133.64, 133.58,
130.4, 129.9, 129.4, 129.1, 128.9, 128.7, 128.2, 127.7, 127.4, 126.8, 125.9, 125.4,
114.0, 110.0, 101.6, 55.7, 54.0, 47.0, 46.0, 41.6, 21.5.
HRMS (ESI): m /z [M + Na]+ calcd for C41 H35 NO5 SNa: 676.2128; found: 676.2145.
(4aS *,9S *,9aS *,1′R *,Z )-9-[1,3-Diphenyl-3-(4-tolylsulfonamido)allyl]-6-fluoro-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4d)
(4aS *,9S *,9aS *,1′R *,Z )-9-[1,3-Diphenyl-3-(4-tolylsulfonamido)allyl]-6-fluoro-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4d)
White crystals; yield: 225 mg (0.35 mmol, 69%); mp 136–138 °C.
IR: 3189, 1732, 1595 cm–1 .
1 H NMR (400 MHz, acetone-d
6 ): δ = 8.17 (s, 1 H), 7.69 (d, J = 7.2 Hz, 2 H), 7.51–7.52 (m, 4 H), 7.39–7.45 (m, 3 H), 7.27–7.30 (m, 6 H), 7.18
(d, J = 6.6 Hz, 2 H), 7.13 (d, J = 7.9 Hz, 3 H), 6.89 (br s, 2 H), 6.25 (d, J = 5.0 Hz, 1 H), 6.07 (d, J = 10.7 Hz, 1 H), 4.20 (t, J = 4.3 Hz, 1 H), 4.08 (dd, J = 10.3, 5.6 Hz, 1 H), 4.02 (dd, J = 7.4, 5.6 Hz, 1 H), 3.24 (dd, J = 8.3, 3.3 Hz, 1 H), 2.26 (s, 3 H).
13 C NMR (100 MHz, acetone-d
6 ): δ = 170.6, 164.9, 162.5, 149.3, 147.5, 147.4, 144.1, 142.0, 139.9, 138.7, 137.9,
137.3, 133.5, 130.3, 130.0, 129.4, 129.2, 128.9, 128.8, 128.7, 128.1, 127.7, 127.6,
127.5, 126.1, 125.5, 114.9, 114.6, 111.9, 111.6, 100.8, 54.1, 46.8, 46.1, 41.4, 21.5.
HRMS (ESI): m /z [M + H]+ calcd for C40 H33 FNO4 S: 642.2114; found: 642.2102.
(4aS *,9S *,9aS *,1′R *,Z )-9-[1,3-Diphenyl-3-(4-tolylsulfonamido)allyl]-3-(4-methylphenyl)-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4e)
(4aS *,9S *,9aS *,1′R *,Z )-9-[1,3-Diphenyl-3-(4-tolylsulfonamido)allyl]-3-(4-methylphenyl)-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4e)
White crystals; yield: 249 mg (0.39 mmol, 78%); mp 185–187 °C.
IR: 3162, 1727, 1601 cm–1 .
1 H NMR (500 MHz, acetone-d
6 ): δ = 8.11 (s, 1 H), 7.58 (d, J = 8.1 Hz, 2 H), 7.51–7.54 (m, 4 H), 7.31–7.35 (m, 4 H), 7.22–7.28 (m, 6 H), 7.17
(d, J = 6.9 Hz, 2 H), 7.12 (d, J = 8.1 Hz, 2 H), 7.10 (d, J = 8.2 Hz, 1 H), 6.84 (d, J = 7.5 Hz, 1 H), 6.17 (d, J = 4.9 Hz, 1 H), 6.01 (d, J = 10.9 Hz, 1 H), 4.22 (t, J = 5.0 Hz, 1 H), 4.02–4.05 (m, 2 H), 3.14 (dd, J = 8.7, 4.6 Hz, 1 H), 2.35 (s, 3 H), 2.24 (s, 3 H).
13 C NMR (100 MHz, acetone-d
6 ): δ = 171.1, 149.0, 145.0, 144.1, 142.1, 142.0, 140.0, 139.9, 138.7, 137.4, 130.8,
130.4, 130.0, 129.2, 128.9, 128.8, 128.7, 128.2, 127.8, 127.7, 127.4, 126.2, 125.9,
125.4, 124.8, 100.6, 54.7, 46.5, 45.9, 41.4, 21.5, 21.2.
HRMS (ESI): m /z [M + H]+ calcd for C41 H36 NO4 S: 638.2365; found: 638.2371.
(4aS *,9S *,9aS *,1′R *,Z )-9-[1,3-Diphenyl-3-(4-tolylsulfonamido)allyl]-3-(4-methoxyphenyl)-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4f)
(4aS *,9S *,9aS *,1′R *,Z )-9-[1,3-Diphenyl-3-(4-tolylsulfonamido)allyl]-3-(4-methoxyphenyl)-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4f)
White crystals; yield: 235 mg (0.36 mmol, 72%); mp 180–181 °C.
IR: 3238, 1746, 1604 cm–1 .
1 H NMR (500 MHz, acetone-d
6 ): δ = 8.11 (s, 1 H), 7.63 (d, J = 8.8 Hz, 2 H), 7.53–7.54 (m, 2 H), 7.52 (d, J = 8.3 Hz, 2 H), 7.22–7.34 (m, 8 H), 7.16 (d, J = 6.8 Hz, 2 H), 7.12 (d, J = 8.1 Hz, 2 H), 7.10 (d, J = 10.2 Hz, 1 H), 6.99 (d, J = 8.8 Hz, 2 H), 6.84 (d, J = 7.5 Hz, 1 H), 6.07 (d, J = 5.0 Hz, 1 H), 6.00 (d, J = 10.9 Hz, 1 H), 4.20 (t, J = 4.9 Hz, 1 H), 4.00–4.05 (m, 2 H), 3.84 (s, 3 H), 3.12 (dd, J = 8.7, 4.7 Hz, 1 H), 2.24 (s, 3 H).
13 C NMR (100 MHz, acetone-d
6 ): δ = 171.2, 161.4, 148.9, 145.1, 144.1, 142.1, 142.0, 140.0, 138.7, 137.4, 130.4,
129.1, 128.92, 128.86, 128.79, 128.72, 128.1, 127.8, 127.7, 127.4, 126.9, 126.2, 126.0,
125.9, 124.8, 114.8, 99.5, 55.7, 54.6, 46.6, 45.9, 41.4, 21.5.
HRMS (ESI): m /z [M + H]+ calcd for C41 H36 NO5 S: 654.2314; found: 654.2312.
(4aS *,9S *,9aS *,1′R *,Z )-3-(4-Bromophenyl)-9-[1,3-diphenyl-3-(4-tolylsulfonamido)allyl]-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4g)
(4aS *,9S *,9aS *,1′R *,Z )-3-(4-Bromophenyl)-9-[1,3-diphenyl-3-(4-tolylsulfonamido)allyl]-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4g)
White crystals; yield: 246 mg (0.35 mmol, 70%); mp 206–208 °C.
IR: 3162, 1735, 1598 cm–1 .
1 H NMR (500 MHz, acetone-d
6 ): δ = 8.09 (s, 1 H), 7.65 (d, J = 8.6 Hz, 2 H), 7.62 (d, J = 8.7 Hz, 2 H), 7.50–7.52 (m, 4 H), 7.23–7.35 (m, 8 H), 7.16 (d, J = 6.6 Hz, 2 H), 7.13 (d, J = 7.5 Hz, 3 H), 6.86 (d, J = 7.4 Hz, 1 H), 6.32 (d, J = 4.6 Hz, 1 H), 6.02 (d, J = 10.7 Hz, 1 H), 4.23 (t, J = 4.7 Hz, 1 H), 4.03–4.06 (m, 2 H), 3.18 (dd, J = 8.1, 3.9 Hz, 1 H), 2.25 (s, 3 H).
13 C NMR (100 MHz, acetone-d
6 ): δ = 170.8, 148.0, 144.6, 144.1, 142.1, 142.0, 139.9, 138.7, 137.4, 132.8, 132.5,
130.4, 129.2, 128.92, 128.86, 128.7, 128.1, 127.9, 127.7, 127.4, 127.3, 126.3, 126.0,
124.8, 123.4, 102.4, 54.7, 46.4, 45.9, 41.5, 21.5.
HRMS (ESI): m /z [M + H]+ calcd for C40 H33 BrNO4 S:702.1314; found: 702.1309.
(4aS *,9S *,9aS *,1′R *,Z )-9-[1-(4-Methylphenyl)-3-phenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4h)
(4aS *,9S *,9aS *,1′R *,Z )-9-[1-(4-Methylphenyl)-3-phenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4h)
White crystals; yield: 229 mg (0.36 mmol, 71%); mp 146–147 °C.
IR: 3347, 3282, 1749, 1598 cm–1 .
1 H NMR (500 MHz, acetone-d
6 ): δ = 8.05 (s, 1 H), 7.70 (d, J = 7.3 Hz, 2 H), 7.53–7.54 (m, 2 H), 7.52 (d, J = 8.1 Hz, 2 H), 7.44 (t, J = 7.5 Hz, 2 H), 7.40 (t, J = 7.0 Hz, 1 H), 7.35 (d, J = 7.6 Hz, 1 H), 7.31–7.32 (m, 3 H), 7.24 (t, J = 7.3 Hz, 1 H), 7.11–7.13 (m, 3 H), 7.09 (d, J = 8.5 Hz, 2 H), 7.04 (d, J = 7.8 Hz, 2 H), 6.88 (d, J = 7.5 Hz, 1 H), 6.22 (d, J = 4.9 Hz, 1 H), 5.99 (d, J = 11.0 Hz, 1 H), 4.18 (t, J = 5.0 Hz, 1 H), 4.05 (dd, J = 8.3, 5.1 Hz, 1 H), 3.97 (dd, J = 10.5, 5.4 Hz, 1 H), 3.15 (dd, J = 8.7, 4.9 Hz, 1 H), 2.33 (s, 3 H), 2.24 (s, 3 H).
13 C NMR (100 MHz, acetone-d
6 ): δ = 171.1, 148.9, 144.8, 144.1, 142.1, 140.0, 139.1, 138.6, 137.3, 136.8, 133.6,
130.3, 129.9, 129.8, 129.4, 128.9, 128.8, 128.7, 128.1, 127.8, 127.7, 126.2, 126.1,
125.4, 124.9, 101.7, 54.6, 46.5, 45.4, 41.4, 21.5, 21.1.
HRMS (ESI): m /z [M + H]+ calcd for C41 H36 NO4 S:638.2365; found: 638.2371.
(4aS *,9S *,9aS *,1′R *,Z )-9-[1-(4-Methoxyphenyl)-3-phenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4i)
(4aS *,9S *,9aS *,1′R *,Z )-9-[1-(4-Methoxyphenyl)-3-phenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4i)
White crystals; yield: 235 mg (0.36 mmol, 71%); mp 149–151 °C.
IR: 3281, 1745, 1609 cm–1 .
1 H NMR (500 MHz, acetone-d
6 ): δ = 8.05 (s, 1 H), 7.69 (d, J = 7.3 Hz, 2 H), 7.54 (d, J = 7.1 Hz, 2 H), 7.52 (d, J = 8.3 Hz, 2 H), 7.44 (t, J = 7.0 Hz, 2 H), 7.41 (t, J = 7.0 Hz, 1 H), 7.31–7.35 (m, 4 H), 7.24 (t, J = 7.2 Hz, 1 H), 7.13 (d, J = 8.1 Hz, 2 H), 7.12 (d, J = 8.3 Hz, 1 H), 7.06 (d, J = 8.5 Hz, 2 H), 6.89 (d, J = 7.4 Hz, 1 H), 6.83 (d, J = 8.5 Hz, 2 H), 6.23 (d, J = 4.9 Hz, 1 H), 5.98 (d, J = 10.8 Hz, 1 H), 4.16 (t, J = 4.9 Hz, 1 H), 4.02 (dd, J = 8.4, 5.3 Hz, 1 H), 3.96 (dd, J = 10.5, 5.6 Hz, 1 H), 3.81 (s, 3 H), 3.16 (dd, J = 8.6, 4.7 Hz, 1 H), 2.25 (s, 3 H).
13 C NMR (100 MHz, acetone-d
6 ): δ = 171.1, 159.4, 148.9, 144.8, 144.1, 142.2, 140.0, 138.7, 137.2, 133.9, 133.6,
130.4, 129.9, 129.4, 128.8, 128.78, 128.72, 128.1, 127.9, 127.7, 126.3, 126.2, 125.4,
124.8, 114.5, 101.7, 55.5, 54.7, 46.4, 45.1, 41.4, 21.5.
HRMS (ESI): m /z [M + H]+ calcd for C41 H36 NO5 S: 654.2314; found: 654.2310.
(4aS *,9S *,9aS *,1′R *,Z )-9-[1-(4-Bromophenyl)-3-phenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4j)
(4aS *,9S *,9aS *,1′R *,Z )-9-[1-(4-Bromophenyl)-3-phenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4j)
White crystals; yield: 245 mg (0.35 mmol, 70%); mp 164–165 °C.
IR: 3278, 1744, 1598 cm–1 .
1 H NMR (500 MHz, acetone-d
6 ): δ = 8.24 (s, 1 H), 7.69 (d, J = 7.4 Hz, 2 H), 7.55 (d, J = 3.7 Hz, 2 H), 7.50 (d, J = 7.9 Hz, 2 H), 7.40–7.45 (m, 5 H), 7.31–7.38 (m, 4 H), 7.24 (t, J = 7.5 Hz, 1 H), 7.11–7.14 (m, 5 H), 6.86 (d, J = 7.5 Hz, 1 H), 6.22 (d, J = 4.7 Hz, 1 H), 5.99 (d, J = 10.9 Hz, 1 H), 4.22 (t, J = 5.2 Hz, 1 H), 4.05–4.08 (m, 2 H), 3.21 (dd, J = 8.2, 4.7 Hz, 1 H), 2.26 (s, 3 H).
13 C NMR (100 MHz, acetone-d
6 ): δ = 171.1, 148.9, 144.9, 144.2, 141.7, 141.6, 139.8, 138.6, 137.9, 133.5, 132.1,
131.0, 130.3, 129.9, 129.4, 129.0, 128.9, 128.7, 128.2, 128.0, 127.7, 126.1, 125.4,
125.2, 124.9, 120.9, 101.6, 54.5, 46.5, 45.3, 41.5, 21.5.
HRMS (ESI): m /z [M + H]+ calcd for C40 H33 BrNO4 S 702.1314; found: 702.1309.
(3S *,3aS *,8R *,8aS *,Z )-8-(Benzoylmethyl)-3-(4-bromophenyl)-2-[phenyl(4-tolylsulfonamido)methylene]-3,3a,8,8a-tetrahydrocyclopenta[a ]inden-1(2H )-one (5j)
(3S *,3aS *,8R *,8aS *,Z )-8-(Benzoylmethyl)-3-(4-bromophenyl)-2-[phenyl(4-tolylsulfonamido)methylene]-3,3a,8,8a-tetrahydrocyclopenta[a ]inden-1(2H )-one (5j)
White crystals; yield: 70 mg (0.1 mmol, 19%); mp 125–126 °C.
IR: 3436, 1687, 1650, 1570 cm–1 .
1 H NMR (500 MHz, CDCl3 ): δ = 12.44 (s, 1 H), 8.21 (d, J = 7.4 Hz, 2 H), 7.71 (t, J = 7.4 Hz, 1 H), 7.63 (t, J = 7.7 Hz, 2 H), 7.23–7.25 (m, 3 H), 7.17 (d, J = 8.4 Hz, 2 H), 7.14 (t, J = 7.4 Hz, 1 H), 7.05 (t, J = 7.4 Hz, 1 H), 7.01 (d, J = 8.3 Hz, 2 H), 6.97 (t, J = 7.7 Hz, 2 H), 6.71–6.74 (m, 3 H), 6.54 (d, J = 8.0 Hz, 2 H), 5.72 (d, J = 7.8 Hz, 1 H), 4.78 (d, J = 9.8 Hz, 1 H), 4.28 (t, J = 9.6 Hz, 1 H), 4.05–4.14 (m, 2 H), 3.85 (t, J = 9.2 Hz, 1 H), 3.68 (d, J = 13.8 Hz, 1 H), 2.41 (s, 3 H).
13 C NMR (100 MHz, acetone-d
6 ): δ = 210.2, 199.4, 147.0, 145.1, 141.8, 141.2, 138.8, 138.1, 133.6, 133.1, 132.6,
132.1, 130.8, 130.3, 130.26, 130.0, 129.5, 128.9, 128.2, 128.1, 128.0, 127.7, 126.6,
123.7, 120.5, 119.9, 54.6, 49.2, 48.5, 42.1, 39.9, 21.5.
HRMS (ESI): m /z [M + H]+ calcd for C40 H33 BrNO4 S: 702.1314; found: 702.1304.
(4aS *,9S *,9aS *,1′R *,Z )-9-[1-(3-Methoxyphenyl)-3-phenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4k)
(4aS *,9S *,9aS *,1′R *,Z )-9-[1-(3-Methoxyphenyl)-3-phenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4k)
White crystals; yield: 261 mg (0.4 mmol, 79%); mp 191–192 °C.
IR: 3255, 1747, 1606 cm–1 .
1 H NMR (500 MHz, acetone-d
6 ): δ = 8.06 (s, 1 H), 7.69 (d, J = 7.3 Hz, 2 H), 7.55 (d, J = 5.1 Hz, 2 H), 7.50 (d, J = 7.8 Hz, 2 H), 7.39–7.45 (m, 3 H), 7.31–7.35 (m, 4 H), 7.25 (t, J = 7.2 Hz, 1 H), 7.20 (t, J = 7.9 Hz, 1 H), 7.15 (d, J = 7.5 Hz, 1 H), 7.12 (d, J = 7.9 Hz, 2 H), 6.95 (d, J = 7.2 Hz, 1 H), 6.78–6.82 (m, 2 H), 6.66 (s, 1 H), 6.24 (d, J = 4.8 Hz, 1 H), 6.06 (d, J = 10.8 Hz, 1 H), 4.23 (t, J = 4.8 Hz, 1 H), 3.98–4.02 (m, 2 H), 3.74 (s, 3 H), 3.23 (dd, J = 8.5, 4.9 Hz, 1 H), 2.25 (s, 3 H).
13 C NMR (100 MHz, acetone-d
6 ): δ = 170.1, 159.6, 148.0, 144.0, 143.2, 142.7, 141.3, 139.0, 137.8, 136.4, 132.7,
129.4, 129.2, 128.9, 128.5, 128.0, 127.8, 127.2, 127.0, 126.8, 125.4, 124.5, 123.9,
120.1, 113.8, 112.1, 100.7, 54.5, 53.7, 45.5, 45.1, 40.5, 20.5.
HRMS (ESI): m /z [M + H]+ calcd for C41 H36 NO5 S: 654.2314; found: 654.2313.
(4aS *,9S *,9aS *,1′R *,Z )-9-[1-(2-Methoxyphenyl)-3-phenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4l)
(4aS *,9S *,9aS *,1′R *,Z )-9-[1-(2-Methoxyphenyl)-3-phenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4l)
White crystals; yield: 209 mg (0.32 mmol, 63%); mp 204–206 °C.
IR: 3203, 1735, 1600 cm–1 .
1 H NMR (500 MHz, acetone-d
6 ): δ = 7.97 (s, 1 H), 7.68 (d, J = 7.2 Hz, 2 H), 7.54–7.57 (m, 2 H), 7.39–7.45 (m, 5 H), 7.37 (d, J = 7.4 Hz, 1 H), 7.30–7.33 (m, 4 H), 7.27 (d, J = 7.6 Hz, 1 H), 7.23 (t, J = 7.4 Hz, 1 H), 7.12 (t, J = 7.2 Hz, 1 H), 7.00–7.05 (m, 4 H), 6.96 (t, J = 7.5 Hz, 1 H), 6.20 (d, J = 5.0 Hz, 1 H), 6.00 (d, J = 10.6 Hz, 1 H), 4.35 (t, J = 5.8 Hz, 1 H), 4.19 (dd, J = 8.2, 5.1 Hz, 1 H), 4.11 (dd, J = 10.4, 6.4 Hz, 1 H), 3.91 (s, 3 H), 2.97 (dd, J = 8.4, 5.2 Hz, 1 H), 2.28 (s, 3 H).
13 C NMR (100 MHz, DMSO-d
6 ): δ = 169.8, 156.2, 147.2, 143.7, 142.3, 141.3, 138.9, 137.4, 134.8, 132.1, 129.7,
129.0, 128.6, 128.2, 127.8, 127.7, 127.4, 126.6, 126.5, 126.0, 125.96, 125.5, 124.2,
123.5, 120.0, 110.9, 100.8, 55.3, 51.7, 45.9, 40.0, 39.0, 21.0.
HRMS (ESI): m /z [M + H]+ calcd for C41 H36 NO5 S: 654.2314; found: 654.2327.
(4aS *,9S *,9aS *,1′R *,Z )-9-[3-(4-Methylphenyl)-1-phenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4m)
(4aS *,9S *,9aS *,1′R *,Z )-9-[3-(4-Methylphenyl)-1-phenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4m)
White crystals; yield: 236 mg (0.37 mmol, 74%); mp 168–169 °C.
IR: 3268, 1734, 1600 cm–1 .
1 H NMR (500 MHz, acetone-d
6 ): δ = 8.05 (s, 1 H), 7.69 (d, J = 8.1 Hz, 2 H), 7.51 (d, J = 8.1 Hz, 2 H), 7.38–7.45 (m, 5 H), 7.35 (d, J = 7.3 Hz, 1 H), 7.22–7.28 (m, 4 H), 7.15 (d, J = 6.8 Hz, 2 H), 7.09–7.13 (m, 5 H), 6.83 (d, J = 7.6 Hz, 1 H), 6.23 (d, J = 5.0 Hz, 1 H), 5.94 (d, J = 10.9 Hz, 1 H), 4.22 (t, J = 4.9 Hz, 1 H), 4.05 (dd, J = 8.7, 4.8 Hz, 1 H), 4.02 (dd, J = 11.1, 5.6 Hz, 1 H), 3.14 (dd, J = 8.7, 4.7 Hz, 1 H), 2.24 (s, 3 H), 2.07 (s, 3 H).
13 C NMR (100 MHz, acetone-d
6 ): δ = 171.1, 148.9, 144.9, 144.1, 142.2, 138.7, 137.41, 137.38, 137.1, 133.6, 130.4,
129.9, 129.4, 129.1, 128.9, 128.8, 128.1, 127.8, 127.7, 127.4, 126.2, 125.4, 124.8,
124.7, 101.6, 54.7, 46.6, 45.8, 41.4, 21.5, 21.1.
HRMS (ESI): m /z [M + H]+ calcd for C41 H36 NO4 S: 638.2565; found: 638.2371.
(4aS *,9S *,9aS *,1′R *,Z )-9-[3-(4-Methoxyphenyl)-1-phenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4n)
(4aS *,9S *,9aS *,1′R *,Z )-9-[3-(4-Methoxyphenyl)-1-phenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4n)
White crystals; yield: 229 mg (0.35 mmol, 70%); mp 176–177 °C.
IR: 3173, 1737, 1605 cm–1 .
1 H NMR (500 MHz, acetone-d
6 ): δ = 8.02 (s, 1 H), 7.69 (d, J = 7.4 Hz, 2 H), 7.50 (d, J = 8.1 Hz, 2 H), 7.38–7.47 (m, 5 H), 7.35 (d, J = 7.6 Hz, 1 H), 7.22–7.29 (m, 4 H), 7.16 (d, J = 6.8 Hz, 2 H), 7.11 (d, J = 7.9 Hz, 2 H), 7.10 (d, J = 7.5 Hz, 1 H), 6.86 (d, J = 8.6 Hz, 2 H), 6.83 (d, J = 7.7 Hz, 1 H), 6.22 (d, J = 4.9 Hz, 1 H), 5.87 (d, J = 10.8 Hz, 1 H), 4.22 (t, J = 5.0 Hz, 1 H), 4.05 (dd, J = 8.4, 5.1 Hz, 1 H), 4.02 (dd, J = 10.9, 5.7 Hz, 1 H), 3.82 (s, 3 H), 3.15 (dd, J = 8.6, 4.7 Hz, 1 H), 2.24 (s, 3 H).
13 C NMR (100 MHz, acetone-d
6 ): δ = 171.1, 160.8, 148.9, 144.9, 144.1, 142.3, 142.0, 138.7, 137.2, 133.6, 132.2,
130.3, 129.9, 129.43, 129.41, 129.1, 128.9, 128.8, 127.8, 127.7, 127.3, 126.2, 125.4,
124.8, 123.7, 114.1, 101.7, 55.6, 54.7, 46.6, 45.8, 41.5, 21.5.
HRMS (ESI): m /z [M + H]+ calcd for C41 H36 NO5 S: 654.2314; found: 654.2311.
(4aS *,9S *,9aS *,1′R *,Z )-9-[-(4-Bromophenyl)-1-phenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4o)
(4aS *,9S *,9aS *,1′R *,Z )-9-[-(4-Bromophenyl)-1-phenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-9,9a-dihydroindeno[2,1-c ]pyran-1(4aH )-one (4o)
White crystals; yield: 259 mg (0.37 mmol, 74%); mp 183–185 °C.
IR: 3441, 1728, 1633, 1595 cm–1 .
1 H NMR (500 MHz, acetone-d
6 ): δ = 8.19 (s, 1 H), 7.69 (d, J = 7.2 Hz, 2 H), 7.51 (d, J = 9.7 Hz, 2 H), 7.45 (br s, 4 H), 7.44 (t, J = 7.6 Hz, 2 H), 7.40 (t, J = 7.3 Hz, 1 H), 7.34 (d, J = 7.4 Hz, 1 H), 7.23–7.27 (m, 4 H), 7.12–7.15 (m, 5 H), 6.86 (d, J = 7.6 Hz, 1 H), 6.23 (d, J = 5.1 Hz, 1 H), 6.09 (d, J = 11.0 Hz, 1 H), 4.20 (t, J = 5.2 Hz, 1 H), 4.01–4.04 (m, 2 H), 3.17 (dd, J = 8.7, 4.5 Hz, 1 H), 2.24 (s, 3 H).
13 C NMR (100 MHz, acetone-d
6 ): δ = 171.0, 148.9, 144.8, 144.3, 141.9, 141.8, 139.3, 138.4, 136.3, 133.5, 131.8,
130.5, 130.1, 129.9, 129.4, 129.2, 128.9, 128.86, 127.9, 127.7, 127.5, 126.7, 126.2,
125.4, 124.9, 122.4, 101.6, 54.6, 46.4, 45.9, 41.4, 21.5.
HRMS (ESI): m /z [M + H]+ calcd for C40 H33 BrNO4 S: 702.1314; found: 702.1310.
Methyl (1S *,2R *,3S *,1′R *,Z )-1-(Benzoylmethyl)-3-[1,3-diphenyl-3-(4-tolylsulfonamido)allyl]indane-2-carboxylate
(14)
Methyl (1S *,2R *,3S *,1′R *,Z )-1-(Benzoylmethyl)-3-[1,3-diphenyl-3-(4-tolylsulfonamido)allyl]indane-2-carboxylate
(14)
Indeno[2,1-c ]pyran-1-one 4a (100 mg, 0.16 mmol) was dissolved in MeOH (5 mL) at r.t. The mixture was heated under
reflux for about 30 min until 4a had been consumed. After removal of the solvent under vacuum, the residue was rapidly
purified by column chromatography (silica gel, petroleum ether–EtOAc, 5:1) to give
14 as white crystals; yield: 85 mg (0.13 mmol, 82%); mp 90–91 °C.
IR: 3339, 3271, 1723, 1682 cm–1 .
1 H NMR (500 MHz, acetone-d
6 ): δ = 7.99 (d, J = 7.2 Hz, 2 H), 7.62 (t, J = 7.3 Hz, 1 H), 7.54 (d, J = 8.5 Hz, 1 H), 7.50 (d, J = 8.1 Hz, 2 H), 7.44–7.48 (m, 4 H), 7.12–7.28 (m, 11 H), 7.09 (d, J = 6.9 Hz, 2 H), 7.05 (d, J = 7.4 Hz, 1 H), 6.03 (d, J = 10.4 Hz, 1 H), 4.01 (dd, J = 14.1, 8.4 Hz, 1 H), 3.95 (dd, J = 14.4, 7.0 Hz, 1 H), 3.83 (t, J = 6.6 Hz, 1 H), 3.35 (d, J = 8.4 Hz, 1 H), 3.34 (d, J = 5.7 Hz, 1 H), 3.29 (s, 3 H), 3.23 (dd, J = 8.2, 4.8 Hz, 1 H), 2.31 (s, 3 H).
13 C NMR (100 MHz, acetone-d
6 ): δ = 198.8, 174.8, 145.9, 144.1, 144.0, 143.8, 142.4, 140.0, 139.1, 138.2, 136.4,
133.7, 130.4, 129.4, 129.3, 129.1, 128.71, 128.68, 128.13, 128.05, 128.0, 127.7, 127.5,
127.3, 126.1, 124.4, 54.1, 51.8, 51.6, 47.1, 42.0, 41.2, 21.5.
HRMS: m /z [M + Na]+ calcd for C41 H37 NO5 SNa: 678.2285; found: 678.2271.
(1S *,2R *,3S *,1′S *)-1-(Benzoylmethyl)-3-(2-benzoyl-1-phenylethyl)indane-2-carboxylic Acid (15)
(1S *,2R *,3S *,1′S *)-1-(Benzoylmethyl)-3-(2-benzoyl-1-phenylethyl)indane-2-carboxylic Acid (15)
At r.t., 30% aq NaOH soln (80 mg, 0.6 mmol) was added dropwise to a solution of 4a (186 mg, 0.3 mmol) in THF (10 mL). The mixture was stirred at r.t. for about 1 h
until 4a had been consumed. The mixture was neutralized with sat. aq NH4 Cl to pH ~ 6–7 and it was then stirred for further 5–6 h at r.t. The mixture was extracted
with CH2 Cl2 (15 × 3 mL), and the combined extracts were dried (anhyd MgSO4 ) and concentrated under vacuum. The residue was purified by column chromatography
(silica gel, PE–EtOH–EtOAc, 40:2:1) to give 15 as white crystals; yield: 117 mg (0.24 mmol, 80%); mp 179–180 °C.
IR: 3438, 1698, 1686, 1679 cm–1 .
1 H NMR (500 MHz, CDCl3 ): δ = 7.78 (d, J = 7.7 Hz, 4 H), 7.45 (d, J = 7.3 Hz, 1 H), 7.42 (d, J = 7.3 Hz, 1 H), 7.34 (t, J = 8.1 Hz, 2 H), 7.29 (t, J = 7.6 Hz, 2 H), 7.11–7.18 (m, 4 H), 7.05–7.09 (m, 4 H), 6.95 (d, J = 7.4 Hz, 1 H), 3.76–3.82 (m, 2 H), 3.72 (dd, J = 14.6, 7.7 Hz, 1 H), 3.46 (d, J = 6.0 Hz, 2 H), 3.28 (d, J = 8.1 Hz, 1 H), 3.26 (dd, J = 15.5, 8.2 Hz, 1 H), 3.17 (dd, J = 18.0, 6.1 Hz, 1 H).
13 C NMR (100 MHz, CDCl3 ): δ = 198.8, 198.5, 179.0, 144.3, 143.4, 141.2, 137.2, 136.9, 133.1, 133.0, 128.5,
128.33, 128.3, 128.0, 127.5, 127.1, 126.8, 125.1, 123.4, 52.7, 50.4, 43.6, 41.9, 40.7,
39.8.
HRMS (ESI): m /z [M + Na]+ calcd for C33 H28 O4 Na: 511.1880; found: 511.1867.
(4aR *,9S *,9aS *,1′R *,Z )-9-[1,3-Diphenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-1,4a,9,9a-tetrahydroindeno[2,1-c ]pyran (16)
(4aR *,9S *,9aS *,1′R *,Z )-9-[1,3-Diphenyl-3-(4-tolylsulfonamido)allyl]-3-phenyl-1,4a,9,9a-tetrahydroindeno[2,1-c ]pyran (16)
Under N2 atmosphere and at r.t., LiAlH4 (55 mg, 1.44 mmol) was added to a solution of 4a (300 mg, 0.48 mmol) in anhyd THF (10 mL). The mixture was stirred at r.t. for ca.
1 h until 4a had been consumed. The reaction was quenched by the addition of 2 M aq HCl (5 mL)
under 0 °C. After extraction with CH2 Cl2 (10 × 3 mL), the product 16 was isolated by rapid column chromatography (silica gel, PE–EtOAc, 5:1).
White crystals; yield: 207 mg (0.34 mmol, 70%); mp 108–110 °C.
IR: 3341, 3276, 1647, 1598 cm–1 .
1 H NMR (500 MHz, acetone-d
6 ): δ = 7.47 (d, J = 7.9 Hz, 2 H), 7.46 (s, 1 H), 7.39 (d, J = 8.2 Hz, 2 H), 7.34 (dd, J = 7.4, 3.6 Hz, 1 H), 7.15–7.23 (m, 7 H), 7.09–7.13 (m, 6 H), 7.00 (t, J = 7.4 Hz, 1 H), 6.95 (dd, J = 7.8, 1.9 Hz, 2 H), 6.79 (d, J = 7.5 Hz, 1 H), 5.92 (d, J = 10.5 Hz, 1 H), 5.82 (d, J = 4.9 Hz, 1 H), 3.97 (dd, J = 10.6, 5.0 Hz, 1 H), 3.85 (dd, J = 10.5, 6.7 Hz, 1 H), 3.39 (t, J = 5.9 Hz, 1 H), 3.15 (t, J = 11.0 Hz, 1 H), 3.02 (d, J = 6.6 Hz, 1 H), 2.32–2.40 (m, 1 H), 2.24 (s, 3 H).
13 C NMR (100 MHz, acetone-d
6 ): δ = 153.0, 147.9, 144.1, 143.0, 142.5, 140.0, 139.0, 136.6, 136.2, 130.4, 129.1,
128.9, 128.8, 128.72, 128.67, 128.4, 128.0, 127.9, 127.7, 127.2, 127.1, 125.32, 125.27,
99.7, 68.1, 53.7, 47.9, 40.84, 40.8, 21.5.
HRMS (ESI): m /z [M + H]+ calcd for C40 H36 NO3 S: 610.2410; found: 610.2394.
