Synthesis of Tetrahydro-1H-indeno[1,2-b]pyridine via Cascade Cyclization and Friedel-Crafts Reaction

Article abstract of DOI:10.1021/acs.joc.6b00988

A convenient protocol has been established for the synthesis of 1-tosyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine via cascade cyclization and Friedel-Crafts reaction of 4-methyl-N-(pent-4-yn-1-yl)benzenesulfonamides and aldehydes in good yields. The methodology has been used for the total synthesis of the antidepressant agent (±)-5-phenyl-2,3,4,4a,5,9b-hexahydro-1H-indeno[1,2-b]pyridine.

Full text of DOI:10.1021/acs.joc.6b00988

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Article
Synthesis of Tetrahydro-1H-indeno[1,2-b]pyridine
via Cascade Cyclization and Friedel-Crafts Reaction
Upasana Borthakur, Madhurjya Borah, Manash Jyoti Deka, and Anil K. Saikia
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00988 • Publication Date (Web): 14 Sep 2016
Downloaded from http://pubs.acs.org on September 16, 2016
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Synthesis of Tetrahydro-1H-indeno[1,2-b]pyridine via Cascade
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Cyclization and Friedel-Crafts Reaction
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Upasana Borthakur, Madhurjya Borah, Manash J. Deka and Anil K. Saikia*
Department of Chemistry
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Indian Institute of Technology Guwahati, Guwahati - 781039, India.
Fax: +91-361-2690762.
e-mail: asaikia@iitg.ernet.in
RECEIVED DATE (will be automatically inserted after manuscript is accepted).
ABSTRACT: A convenient protocol has been established for the synthesis of 1-tosyl-
2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine via cascade cyclization and Friedel-Crafts
reaction of 4-methyl-N-(pent-4-yn-1-yl)benzenesulfonamides and aldehydes in good yields.
The methodology has been used for the total synthesis of antidepressant agent (+)-5-phenyl-
2,3,4,4a,5,9b-hexahydro-1H-indeno[1,2-b]pyridine.
INTRODUCTION
The tetrahydro-1H-indeno[1,2-b]pyridines are class of nitrogen heterocycles containing
piperidine ring fused to 2,3-dihydro-1H-indene. Many molecules of these possess biological
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activity like other nitrogen containing alkaloids. As for example, hexahydroindenopyridine
(HHIP) 1 is a new class of compounds known for their antidepressant,1 and inhibition of 11β-
hydroxysteroid dehydrogenase enzyme 1 (11β-HSD1).2 On the other hand, 2,4a,9,9a-
tetrahydro-1H-indeno[2,1-b]pyridine ring system is found in natural products such as
haouamines A (2) and B (3), two metabolites, isolated from the ascidian Aplidium
haouarianum (Figure 1).3 There are only a few methods for the synthesis of 1H-indeno[1,2-
b]pyridines1b,4. The major drawback of these methods is the requirement of multistep
procedures.1b,4 Therefore, the development of highly efficient methods for the synthesis of
1H-indeno[1,2-b]pyridines are still in demand.
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Figure 1. Biologically important indeno[1,2-b]pyridine
Cascade reactions are gaining importance in organic synthesis due to its ability to form
complex molecular framework.5 Similarly, Friedel-Crafts reaction is one of the important
reaction in organic synthesis for C-C bond formation.4d,6 On the other hand, tandem Prins-
and Friedel-Crafts7 and aza-Prins-Friedel-Crafts8 reactions are considered as an efficient
methodology for the synthesis of variously substituted heterocyclic compounds. Jin and
coworkers have reported the triflic acid catalyzed cascade cyclization of arenyl enynes via
acetylene-cation cyclization and Fridel-Crafts type reaction.9 On the basis of these facts, we
envisioned that the reaction of α-sulfonamido-alkynes 4 with aldehydes 5 under Lewis acidic
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conditions would provide intermediate 6 (Scheme 1). Tandem aza-Prins cyclization and
Friedel-Crafts type reaction may provide product 8. The product 8 may rearrange to give
more stable enamide 9.
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Scheme 1 Possible reaction pathways
RESULTS AND DISCUSSION
In continuation of our interest in the synthesis of nitrogen heterocycles we were in search of a
methodology for the synthesis of these nitrogen heterocycles.10 In this article we now present
a simple method for the synthesis of tetrahydro-1H-indeno[1,2-b]pyridine framework from
the reaction of 4-methyl-N-(pent-4-yn-1-yl)benzenesulfonamides and aldehydes. To start
with,
4-methyl-N-(5-phenylpent-4-yn-1-yl)benzenesulfonamide
was
reacted
with
parachlorobenzaldehyde in dichloromethane with two equivalents of boron trifluoride
etherate and 5-(4-chlorophenyl)-1-tosyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine 9d was
obtained in 45 % yield in 12h, instead of proposed product 7-chloro-5- phenyl-1-tosyl-
2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine 9d'. The structure of the compound 9d was
determined from NMR and X-ray crystallographic analysis (see SI).11 To optimize the
reaction conditions, different reagents and solvents were screened and the results are
.
summerized in Table 1. The reaction with one equivalent of BF3 OEt2 gave 38% yield. The
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same reaction with two equivalents of BF3 OEt2 in 1,2-dichloroethane (DCE) gave 70% yield,
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but in toluene it produced only 30% yield. The reaction was also performed in different
Lewis and Brønsted acidic conditions. Metal triflates such as zinc, copper, indium and silver
triflates were also screened for the reaction. Out of these, only zinc, copper and indium
triflates gave 13%, 9% and 25% yields, respectively. In the case of AgOTf, starting material
was recovered in 98% yield. Similarly, metal salts InCl3 and FeCl3 gave 18 and 20% yields,
respectively. Brønsted acids such as camphor sulfonic acid (CSA) failed to give the desired
product but starting material was recovered in 96% yield. On the other hand, triflic acid
(TfOH) gave 20% yield.
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Table 1. Optimization of the reaction condition
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Table 2. Synthesis of tetrahydro-1H-indeno[1,2-b]pyridine
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With this optimized conditions in hand, we further examined the scope of the reaction with
variety of substrates (Table 2). It was observed from the Table 2 that alkynes having aryl
substituents (entries 1-14, 16 and 18) gave the desired product in good yields. Both electron-
withdrawing and electron-donating groups in the aromatic ring of the aldehydes gave
moderate to high yields. However, aldehyde having highly electron donating methoxy group
on the aromatic ring (entry 17) decomposed under these reaction conditions. Similarly,
methyl and bromide substituted aryl groups (entries 12-14) in the alkyne side chain gave
moderate yields. In this case, mixture of unidentified by-products were observed. On the
contrary, substrate (entry 15) having electron withdrawing nitro group on the aromatic ring
failed to give product. This is due to the destabilization of carbocation 10 formed during the
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reaction (Scheme 2). The structure of the products was determined by H, 13C NMR and X-
ray crystallographic analysis of 9d, 9e, 9k and 9n (see SI).11 The sharp down field shift of C-
5H proton of compounds 9b and 9e (δ 5.04 ppm) is due to the electron withdrawing effect of
ortho substituted chloride and bromide groups on the aromatic ring. Ethyl substituted alkyne
(entry 16) gave trans product 9p with respect to ethyl and phenyl at 2 and 5 positions, the
stereochemistry of which was determined by X-ray crystallographic analysis (see SI).11 The
structure of the products in Table 2 is in contrast to the proposed structure in which aromatic
ring of aldehyde is taking part in Friedel-Crafts reaction (Scheme 1). But in reality aromatic
ring of the alkyne side chain is taking part in Friedel-Crafts reaction. Therefore, a mechanism
of the reaction is proposed as shown in Scheme 2. The boron trifluoride etherate activates the
carbonyl group of the aldehyde for the nucleophilic attack by alkyne group which is
subsequently attacked by tosylamide group to form intermediate 11, which after
decomposition generates carbocation 12. The carbocation 12 is attacked by aryl group to
give the Friedel-Crafts product 9a-r.
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Scheme 2. Mechanism for the formation of tetrahydro-1H-indeno[1,2-b]pyridine
There is an unexpected result in the reaction of alkyne 4a with phenylacetaldehyde 5o and 2-
phenylpropanal 5p (entries 19 and 20) where sulphonamide substituted aromatized products
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9s and 9t were obtained in 71 and 74% yields, respectively (Table 3). The structure of
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compounds 9s and 9t was determined from H, C NMR, COSEY and HMQC analysis of
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compound 9s (see SI). Compound 9s shows broad singlet at δ 4.44 ppm in H NMR and
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eighteen signals in the aromatic region of C NMR. Moreover, proton at δ 4.44 ppm do not
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correlate with carbon in HMQC analysis (see SI). This indicates that this peak belong to the
Table 3. Formation of naphthalene derivative
–NH- proton of –NHTs group. It was observed from the Table 3 that alkynes having aryl
substituents (entries 19 and 20) gave the desired product but terminal alkyne 4f (entry 21)
failed to produce the same.
The formation of 9s and 9t is shown in Scheme 3. In this case, aldehyde 5 enolized under
Lewis acidic conditions, which subsequently reacts with alkyne 4 to form Diels-Alder adduct
13, which after aromatization gives naphthalene derivatives 9s-t.12
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Scheme 3. Mechanism for the formation of naphthalene derivatives
The former strategy is successfully applied for the synthesis of (+)-5-phenyl-2,3,4,4a,5,9b-
hexahydro-1H-indeno[1,2-b]pyridine (1). The compound 1 is considered as antidepressant
agent.1a The synthesis started with the reduction of (+)-9a with sodium cyanoborohydride and
trifluoroacetic acid in dichloromethane to give diastereomeric mixtures cis-(+)-14a and
Scheme 4. Total synthesis of (+)-5-phenyl-2,3,4,4a,5,9b-hexahydro-1H-indeno[1,2-
b]pyridine.
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trans-(+)-14b, in 60% and 10% yields, respectively (Scheme 4). The compound (+)-14a after
deprotection of tosyl group with sodium naphthalide gave final product (+)-1.1a The cis and
trans stereochemistry of compounds (+)-14a and (+)-14b were determined by coupling
constants and NOE experiments.1a The vicinal coupling constant of proton C-9bH of (+)-14a,
resonating at 5.47 ppm, was found to be 5.6 Hz. Similarly, the vicinal coupling constant of
proton C-9bH of (+)-14b, resonating at 5.10 ppm, was also found to be 5.6 Hz. This indicates
that in both the compounds the configuration of ring junction is same. As seen from the
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Figure 2. Coupling constants and NOE of compounds (+)-14a and (+)-14b
mechanism of formation of (+)14a and (+)14b from (+)-9a after protonation and subsequent
addition of hydride, the stereochemistry of ring junction should be cis (Scheme 5). Out of the
two possible transition states 15a and 15b, in their chair conformation, transition state 15a is
more favoured than 15b due to the repulsion between the phenyl group and incoming
cyanoborohydride in the latter. On the other hand, the vicinal coupling constants of proton C-
5H of (+)-14a, resonating at 4.41 ppm, and (+)-14b, resonating at 3.82 ppm, were found to be
6.0 and 12.7 Hz, respectively. The compound (+)-14a showed a clear characteristic NOE
correlation between the hydrogens C-9bH and C-5H, which clearly indicates that the two
hydrogens are cis to each other (Figure 2). Whereas, there was no such NOE correlation
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between the hydrogens C-9bH and C-5H in compound (+)-14b. Therefore, the configuration
of C-9bH and C-5H protons of compound (+)-14b is trans.
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Scheme 5. Mechanism of formation of hexahydro-1H-indeno[1,2-b]pyridine
CONCLUSIONS
In conclusion, we have developed a mild and efficient method for the synthesis of tetrahydro-
1H-indeno[1,2-b]pyridine via cascade cyclization of alkyne tosylamides and aryl aldehydes
in good yields. The reaction is compatible with a wide range of functional groups such as
ester, nitro, nitrile and halides. The methodology is used for the synthesis of biologically
active molecule (+)-5-Phenyl-2,3,4,4a,5,9b-hexahydro-1H-indeno[1,2-b]pyridine.
EXPERIMENTAL SECTION
General Information: All the reagents were of reagent grade (AR grade) and were used
as purchased without further purification. Melting points were recorded in an open capillary
tube and are uncorrected. Fourier transform-infra red (FT-IR) spectra were recorded as neat
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liquid or KBr pellets. NMR spectra were recorded in CDCl3 with tetramethylsilane as the
internal standard for 1H (600 MHz, 400 MHz) or 13C (150 MHz, 100 MHz) NMR. Chemical
shifts (δ) are reported in ppm and spin-spin coupling constants (J) are given in Hz. HRMS
spectra were recorded using Q-TOF mass spectrometer.
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Synthesis of sulfonamide: The starting materials 4-methyl-N-(pent-4-yn-1-yl)benzene-
sulfonamide (4a-f) derivatives were prepared from the literature procedure.13 Compounds 4a
and 4f are known and their spectroscopic data agreed well with the reported data.13
General Procedure for Formation of Indenopyridine:
To a solution of N-tosylated alkyne amine (100 mg, 0.3 mmol) in dry 1,2-dichloroethane (2
o
.
mL) was added benzaldehyde (35 mg, 0.33 mmol) at 0 C, followed by BF3 OEt2 (84 mg, 0.6
mmol). The reaction mixture was brought to room temperature and kept for 12 h. After
completion of the reaction, as determined by TLC, dichloroethane was added to the reaction
mixture, washed with saturated sodium bicarbonate and brine solutions, and dried over
anhydrous Na2SO4. Evaporation of the solvent gave the crude product, which was purified
by column chromatography using ethyl acetate and hexane as eluents.
4-Methyl-N-(5-(p-tolyl)pent-4-yn-1-yl)benzenesulfonamide (4b):
o
1
Colorless solid; mp 99-101 C; Rf (hexane/ EtOAc 4:2) 0.58; yield 229 mg, 70% H NMR
(600 MHz, CDCl3) δ 1.72-1.77 (m, 2 H), 2.33 (s, 3 H), 2.39 (s, 3 H), 2.41 (t, J = 7.2 Hz, 2 H),
3.10-3.12 (m, 2 H), 5.01 (brs, 1 H), 7.07 (d, J = 7.8 Hz, 2 H), 7.22 (d, J = 8.4 Hz, 2 H), 7.27
13
(d, J = 7.8 Hz, 2 H), 7.76 (d, J = 8.4 Hz, 2 H); C NMR (150 MHz, CDCl3) δ 16.9, 21.6,
21.7, 28.5, 42.5, 81.9, 87.7, 127.3, 128.3, 129.1, 129.9, 131.5, 137.0, 138.0, 143.5; IR (KBr,
neat) 3276, 3052, 2925, 2851, 1912, 1892, 1599, 1429, 1326, 1159, 1093, 958, 815, 665 cm-1;
HRMS (ESI) calcd. for C19H22NO2S (M + H)+ 328.1366, found 328.1384.
N-(5-(4-Bromophenyl)pent-4-yn-1-yl)-4-methylbenzenesulfonamide (4c):
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Colorless solid; mp 114-116 C; Rf (hexane/ EtOAc 4:2) 0.6; yield 262, mg, 67% H NMR
(400 MHz, CDCl3) δ 1.73-1.80 (m, 2 H), 2.41 (s, 3 H), 2.43 (t, J = 7.2 Hz, 2 H), 3.09-3.14
(m, 2 H), 4.78 (brs, 1 H), 7.19 (d, J = 8.4 Hz, 2 H), 7.28 (d, J = 8.0 Hz, 2 H), 7.40 (d, J = 8.4
8
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Hz, 2 H), 7.75 (d, J = 8.0 Hz, 2 H); C NMR (100 MHz, CDCl3) δ 16.9, 21.8, 28.4, 42.4,
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80.9, 89.8, 122.1, 122.6, 127.3, 129.9, 131.6, 133.2, 137.0, 143.7; IR (KBr, neat) 3275, 3059,
2927, 2855, 1644, 1583, 1487, 1325, 1160, 1071, 1010, 817, 737, 663 cm-1; HRMS (ESI)
calcd. for C18H19BrNO2S (M + H)+ 394.0294, found 394.0313.
4-Methyl-N-(5-(4-nitrophenyl)pent-4-yn-1-yl)benzenesulfonamide (4d):
1
Colorless solid; mp 126-128; Rf (hexane/ EtOAc 2:1) 0.33; yield 250 mg, 70%; H NMR
(400 MHz, CDCl3) δ 1.77-1.85 (m, 2 H), 2.42 (s, 3 H), 2.51 (t, J = 6.8 Hz, 2 H), 3.11-3.16
(m, 2 H), 4.52 (brs, 1 H), 7.30 (d, J = 8.0 Hz, 2 H), 7.48 (d, J = 8.4 Hz, 2 H), 7.76 (d, J = 8.0
13
Hz, 2 H), 8.15 (d, J = 8.4 Hz, 2 H); C NMR (150 MHz, CDCl3) δ 16.9, 21.7, 28.3, 42.3,
80.3, 94.8, 123.6, 127.2, 129.9, 130.8, 132.4, 136.9, 143.7, 146.9; IR (KBr, neat) 3298,
2925, 2228, 1593, 1515, 1342, 1158, 1094, 854, 750, 688 cm-1; HRMS (ESI) calcd. for
C18H19N2O4S (M + H)+ 359.1060, found 359.1086.
4-Methyl-N-(7-phenylhept-6-yn-3-yl)benzenesulfonamide (4e):
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Colorless solid; mp 65-67; Rf (hexane/ EtOAc 9:1) 0.33; yield 249 mg, 73%; H NMR (400
MHz, CDCl3) δ 0.81 (t, J = 7.2 Hz, 3 H), 1.38-1.47 (m, 1 H), 1.49-1.57 (m, 1 H), 1.58-1.66
(m, 1 H), 1.69-1.74 (m, 1 H), 2.30-2.36 (m, 2 H), 2.38 (s, 3 H), 3.30-3.39 (m, 1 H), 4.83 (brs,
1 H), 7.25 (d, J = 8.0 Hz, 2 H), 7.28-7.30 (m, 3 H), 7.35-7.38 (m, 2 H), 7.78 (d, J = 8.0 Hz, 2
H); 13C NMR (100 MHz, CDCl3) δ 9.8, 16.0, 21.6, 27.8, 33.4, 54.8, 81.3, 89.3, 123.8, 127.1,
127.8, 128.3, 129.7, 131.6, 138.2, 143.3; IR (KBr, neat) 3282, 3059, 2966, 2876, 2236,
1953, 1599, 1491, 1307, 1161, 1093, 1008, 912, 758, 664 cm-1; HRMS (ESI) calcd. for
C20H24NO2S (M + H)+ 342.1522, found 342.1530.
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5-Phenyl-1-tosyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine (9a):
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o
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Colorless solid; mp 150-152 C; Rf (hexane/ EtOAc 9:1) 0.49; yield 73 mg, 57%; H NMR
(600 MHz, CDCl3) δ 1.21-1.27 (m, 1 H), 1.37-1.41 (m, 1 H), 1.87 (dt, J = 18.6 and 6.6 Hz, 1
H), 2.08 (dt, J = 18.6 and 7.2 Hz, 1 H), 2.41 (s, 3 H), 3.54 (ddd, J = 12.6, 7.2 and 3.0 Hz, 1
H), 3.81 (ddd, J = 14.4, 6.6 and 3.0 Hz, 1 H), 4.29 (s, 1 H), 6.95 (d, J = 7.2 Hz, 2 H), 7.13-
7.16 (m, 2 H), 7.21-7.28 (m, 5 H), 7.31-7.34 (m, 1 H), 7.66 (d, J = 7.8 Hz, 2 H), 8.01 (d, J =
7.8 Hz, 1 H); 13C NMR (150 MHz, CDCl3) δ 19.1, 21.8, 22.1, 47.9, 55.9, 122.5, 123.7, 125.6,
127.0, 127.2, 128.1, 128.3, 128.9, 129.8, 136.1, 136.7, 138.8, 139.8, 141.1, 144.1, 146.6; IR
(KBr, neat) 3060, 2926, 2856, 1600, 1493, 1454, 1353, 1166, 1092, 985, 811, 662 cm-1;
HRMS (ESI) calcd. for C25H24NO2S (M + H)+ 402.1522, found 402.1521.
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5-(2-Chlorophenyl)-1-tosyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine (9b):
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Colorless solid; mp 162-164 C; Rf (hexane/ EtOAc 9:1) 0.53; yield 86 mg, 62%; H NMR
(400 MHz, CDCl3) δ 1.26-1.29 (m, 1 H), 1.37-1.41 (m, 1 H), 1.85 (ddd, J = 10.8, 6.6 and 4.2
Hz, 1 H), 2.18 (ddd, J = 18.0, 11.4 and 6.6 Hz, 1 H), 2.41 (s, 3 H), 3.55 (ddd, J = 13.8, 9.6
and 4.2 Hz, 1 H), 3.81 (ddd, J = 15.0, 9.6 and 5.4 Hz, 1 H), 5.04 (s, 1 H), 6.47 (d, J = 7.6 Hz,
1 H), 7.04 (t, J = 9.6 Hz, 1 H), 7.16 (t, J = 7.6 Hz, 2 H), 7.24 (d, J = 8.0 Hz, 2 H), 7.21 (s, 1
H), 7.33 (t, J = 8.0 Hz, 1 H), 7.44 (d, J = 8.0 Hz, 1 H), 7.66 (d, J = 8.0 Hz, 2 H), 8.01 (d, J =
8.0 Hz, 1 H); 13C NMR (150 MHz, CDCl3) δ 19.1, 21.8, 22.0, 47.9, 51.4, 122.7, 123.7, 125.7,
127.2, 127.4, 128.1, 128.4, 128.5, 129.9, 135.2, 136.1, 137.1, 137.8, 141.2, 144.1, 146.1; IR
(KBr, neat) 3063, 2928, 2855, 1597, 1490, 1456, 1354, 1164, 1091, 986, 813, 740 cm-1;
HRMS (ESI) calcd. for C25H23ClNO2S (M + H)+ 436.1133, found 436.1118.
5-(3-Chlorophenyl)-1-tosyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine (9c):
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Colorless solid; mp 156-158 C; Rf (hexane/ EtOAc 9:1) 0.48; yield 90 mg, 65%; H NMR
(600MHz, CDCl3) δ 1.17-1.21 (m, 1 H), 1.39-1.43 (m, 1 H), 1.85 (ddd, J = 18.6, 6.6 and 4.2
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Hz, 1 H), 2.01 (ddd, J = 18.6, 9.6 and 7.8 Hz, 1 H), 2.41 (s, 3 H), 3.49 (ddd, J = 13.2, 10.2
and 3.0 Hz, 1 H), 3.90 (ddd, J = 14.4, 5.4 and 3.0 Hz, 1 H), 4.24 (s, 1 H), 6.88 (s, 1 H), 6.94
(d, J = 7.2 Hz, 1 H), 7.12 (d, J = 7.2 Hz, 1 H), 7.17 (t, J = 7.2 Hz, 1 H), 7.20-7.22 (m, 2 H),
7.27 (d, J = 7.8 Hz, 2 H), 7.35 (t, J = 7.2 Hz, 1 H), 7.66 (d, J = 7.8 Hz, 2 H), 8.03 (d, J = 7.8
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Hz, 1 H); C NMR (150 MHz, CDCl3) δ 19.0, 21.9, 22.1, 48.0, 55.4, 122.8, 123.7, 125.8,
126.9, 127.3, 127.5, 127.9, 128.1, 130.0, 130.2, 134.7, 137.3, 141.0, 142.0, 144.2, 145.9; IR
(KBr, neat) 3059, 2926, 2856, 1596, 1457, 1352, 1164, 1093, 987, 811, 688 cm-1; HRMS
(ESI) calcd. for C25H23ClNO2S (M + H)+ 436.1133, found 436.1135.
5-(4-Chlorophenyl)-1-tosyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine (9d):
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Colorless solid; mp 159-161 C; Rf (hexane/ EtOAc 9:1) 0.58; yield 97 mg, 70%; H NMR
(600 MHz, CDCl3) δ 1.23-1.29 (m, 1 H), 1.39-1.42 (m, 1 H), 1.84 (ddd, J = 18.6, 7.2 and 5.4
Hz, 1 H), 2.08 (ddd, J = 15.0, 7.8 and 4.2 Hz, 1 H), 2.42 (s, 3 H), 3.54 (ddd, J = 16.8, 9.6 and
3.0 Hz, 1 H), 3.79 (ddd, J = 14.4, 6.6 and 3.6 Hz, 1 H), 4.26 (s, 1 H), 6.88 (d, J = 7.8 Hz, 2
H), 7.10 (d, J = 7.2 Hz, 1 H), 7.15 (t, J = 7.8 Hz, 1 H), 7.21-7.26 (m, 4 H), 7.34 (t, J = 7.2
Hz, 1 H), 7.66 (d, J = 7.8 Hz, 2 H), 8.00 (d, J = 7.8 Hz, 1 H); 13C NMR (150 MHz, CDCl3) δ
19.1, 21.8, 22.0, 47.8, 55.1, 122.6, 123.6, 125.7, 127.2, 128.0, 129.1, 129.6, 129.8, 132.9,
136.0, 136.9, 138.2, 138.3, 141.0, 144.1, 146.1; IR (KBr, neat) 3063, 2927, 2856, 1618, 1597,
1490, 1354, 1164, 1091, 1017, 986, 813, 766 cm-1; HRMS (ESI) calcd. for C25H23ClNO2S (M
+ H)+ 436.1133, found 436.1135.
5-(2-Bromophenyl)-1-tosyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine (9e):
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Colorless solid; mp 182-184 C; Rf (hexane/ EtOAc 9:1) 0.53; yield 81 mg, 53%; H NMR
(400 MHz, CDCl3) δ 1.22-1.30 (m, 1 H), 1.36-1.42 (m, 1 H), 1.86 (ddd, J = 19.2, 7.2 and 4.8
Hz, 1 H), 2.20 (ddd, J = 19.2, 7.6 and 4.0 Hz, 1 H), 2.42 (s, 3 H), 3.55 (ddd, J = 14.4, 6.4 and
3.2 Hz, 1 H), 3.80 (ddd, J = 14.0, 6.4 and 3.2 Hz, 1 H), 5.04 (s, 1 H), 6.43-6.46 (m, 1 H),
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7.06-7.10 (m, 2 H), 7.16 (t, J = 7.2 Hz, 1 H), 7.21-7.25 (m, 3 H), 7.35 (t, J = 7.2 Hz, 1 H),
7.61-7.63 (m, 1 H), 7.67 (d, J = 8.0 Hz, 2 H), 8.01 (d, J = 8.0 Hz, 1 H); 13C NMR (150 MHz,
CDCl3) δ 19.1, 21.8, 22.0, 47.9, 54.2, 122.7, 123.6, 125.7, 127.2, 128.0, 128.1, 128.6, 128.7,
129.9, 133.1, 137.1, 138.5, 139.6, 141.1, 144.1, 146.2; IR (KBr, neat) 2959, 2927, 2854,
1594, 1466, 1353, 1164, 1093, 1026, 987, 811, 765 cm-1; HRMS (ESI) calcd. for
C25H23BrNO2S (M + H)+ 480.0627, found 480.0608.
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5-(3-Bromophenyl)-1-tosyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine (9f):
Colorless solid; mp 178-180 oC; Rf (hexane/ EtOAc 9:1) 0.54; yield 90 mg, 59%; 1H NMR
(400 MHz, CDCl3) δ 1.10-1.21 (m, 1 H), 1.37-1.44 (m, 1 H), 1.84 (ddd, J = 18.8, 6.8 and 3.6
Hz, 1 H), 2.09 (ddd, J = 19.2, 8.0 and 4.0 Hz, 1 H), 2.41 (s, 3 H), 3.46 (ddd, J = 17.2, 7.2 and
3.2 Hz, 1 H), 3.89 (ddd, J = 14.4, 5.6 and 3.6 Hz, 1 H), 4.23 (s, 1 H), 6.98 (d, J = 7.6 Hz, 1
H), 7.06 (s, 1 H), 7.13 (d, J = 7.8 Hz, 1 H), 7.15-7.18 (m, 2 H), 7.29 (d, J = 7.8 Hz, 2 H),
7.35 (t, J = 7.8 Hz, 2 H), 7.66 (d, J = 7.8 Hz, 2 H), 8.03 (d, J = 7.8 Hz, 1 H); 13C NMR (150
MHz, CDCl3) δ 19.0, 21.9, 22.0, 47.9, 55.3, 122.7, 123.6, 125.7, 127.2, 127.3, 128.0, 129.9,
130.4, 130.5, 130.7, 137.1, 137.9, 140.9, 142.1, 144.2, 145.8; IR (KBr, neat) 2925, 2854,
1594, 1467, 1352, 1297, 1164, 1093, 1025, 988, 812, 765 cm-1; HRMS (ESI) calcd. for
C25H23BrNO2S (M + H)+ 480.0627, found 480.0625.
5-(3-Nitrophenyl)-1-tosyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine (9g):
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Colorless solid; mp 115-117 C; Rf (hexane/ EtOAc 9:1) 0.28; yield 77 mg, 54%; H NMR
(600 MHz, CDCl3) δ 1.18-1.22 (m, 1 H), 1.41-1.45 (m, 1 H), 1.83 (dt, J = 18.6 and 4.8 Hz, 1
H), 2.14(dt, J = 18.6 and 7.8 Hz, 1 H), 2.42 (s, 3 H), 3.49-3.54 (m, 1 H), 3.86 (dt, J = 14.4
and 4.8 Hz, 1 H), 4.39 (s, 1 H), 7.10 (d, J = 7.2 Hz, 1 H), 7.17 (t, J = 7.2 Hz, 1 H), 7.29 (d, J
= 7.8 Hz, 2 H), 7.33 (d, J = 7.8 Hz, 1 H), 7.37 (t, J = 7.2 Hz, 1 H), 7.46 (t, J = 7.8 Hz, 1 H),
7.70 (d, J = 7.8 Hz, 2 H), 7.85 (s, 1 H), 8.04 (d, J = 7.8 Hz, 1 H), 8.10 (d, J = 7.8 Hz, 1 H);
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13C NMR (150 MHz, CDCl3) δ 19.1, 21.8, 22.1, 47.8, 55.2, 122.5, 123.1, 123.6, 126.0, 127.6,
128.0, 130.0, 134.6, 135.8, 136.9, 137.9, 141.0, 142.2, 144.4, 145.4, 148.9; IR (KBr, neat)
3065, 2926, 2854, 1620, 1599, 1500, 1455, 1352, 1163, 1092, 987, 810, 740 cm-1; HRMS
(ESI) calcd. for C25H23N2O4S (M + H)+ 447.1373, found 447.1370.
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1-Tosyl-5-(4-(trifluoromethyl)phenyl)-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine (9h):
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Colorless solid; mp 166-168 C; Rf (hexane/ EtOAc 9:1) 0.45; yield 91 mg, 61%; H NMR
(400 MHz, CDCl3) δ 1.25-1.33 (m, 1 H), 1.39-1.43 (m, 1 H), 1.83 (dt, J = 18.0 and 6.4 Hz, 1
H), 2.10 (dt, J = 19.2 and 7.2 Hz, 1 H), 2.42 (s, 3 H), 3.55 (ddd, J = 14.0, 6.8 and 3.2 Hz, 1
H), 3.80 (ddd, J = 14.0, 6.0 and 2.8 Hz, 1 H), 4.35 (s, 1 H), 7.06-7.11 (m, 3 H), 7.17 (t, J =
7.6 Hz, 1 H), 7.24 (d, J = 8.0 Hz, 2 H), 7.35 (t, J = 7.6 Hz, 1 H), 7.51 (d, J = 8.0 Hz, 2 H),
7.67 (d, J = 8.0 Hz, 2 H), 8.01(d, J = 8.0 Hz, 1 H); 13C NMR (150 MHz, CDCl3) δ 19.1, 21.8,
22.0, 47.8, 55.4, 122.8, 123.7, 124.3 (q, J = 270.5 Hz), 125.8, 125.9 (q, J = 3.6 Hz), 125.9,
127.4, 128.1, 128.7, 129.5 (q, J = 32.3 Hz), 130.0, 136.0, 137.3, 137.8, 141.1, 144.3, 145.8;
19F NMR (376 MHz, CDCl3/C6F6) δ 99.27; IR (KBr, neat) 3065, 2926, 2853, 1617, 1459,
1326, 1164, 1123, 1066, 1018, 817, 733 cm-1; HRMS (ESI) calcd. for C26H23F3NO2S (M +
H)+ 470.1396, found 470.1392.
4-(1-Tosyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridin-5-yl)benzonitrile (9i):
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Colorless solid; mp 154-156 C; Rf (hexane/ EtOAc 4:1) 0.4; yield 106 mg, 78%; H NMR
(600 MHz, CDCl3) δ 1.25-1.31 (m, 1 H), 1.40-1.44 (m, 1 H), 1.81 (dt, J = 15.0 and 6.6 Hz, 1
H), 2.11 (dt, J = 18.6 and 7.2 Hz, 1 H), 2.43 (s, 3 H), 3.55 (ddd, J = 14.4, 9.6 and 3.6 Hz, 1
H), 3.78 (ddd, J = 14.4, 7.2 and 3.0 Hz, 1 H), 4.34 (s, 1 H), 7.06-7.09 (m, 3 H), 7.17 (t, J =
7.8 Hz, 1 H), 7.25 (d, J = 8.4 Hz, 2 H), 7.36 (t, J = 7.8 Hz, 1 H), 7.55 (d, J = 7.8 Hz, 2 H),
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7.67 (d, J = 8.4 Hz, 2 H), 8.01 (d, J = 7.8 Hz, 1 H); C NMR (150 MHz, CDCl3) δ 19.2,
21.9, 22.0, 47.8, 55.6, 111.2, 118.9, 122.9, 123.6, 125.9, 127.6, 128.1, 129.1, 129.9, 132.8,
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136.0, 137.2, 137.7, 141.0, 144.3, 145.4, 145.9; IR (KBr, neat) 3064, 2925, 2855, 2228, 1604,
1499, 1458, 1352, 1298, 1164, 1092, 1022, 987, 816, 737 cm-1; HRMS (ESI) calcd. for
C26H23N2O2S (M + H)+ 427.1475, found 427.1474.
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Methyl 4-(1-tosyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridin-5-yl)benzoate (9j):
Colorless solid; mp 120-122 oC; Rf (hexane/ EtOAc 9:1) 0.37; yield 110 mg, 75%; 1H NMR
(600 MHz, CDCl3) δ 1.20-1.30 (m, 1 H), 1.35-1.45 (m, 1 H), 1.81 (dt, J = 18.6 and 5.4 Hz, 1
H), 2.10 (dt, J = 18.6 and 7.8 Hz, 1 H), 2.42 (s, 3 H), 3.52-3.57 (m, 1 H), 3.78-3.84 (m, 1 H),
3.91 (s, 3 H), 4.34 (s, 1 H), 7.03 (d, J = 7.8 Hz, 2 H), 7.10 (d, J = 7.2 Hz, 1 H), 7.16 (t, J = 7.2
Hz, 1 H), 7.25 (d, J = 7.8 Hz, 2 H), 7.35 (t, J = 7.2 Hz, 1 H), 7.67 (d, J = 7.8 Hz, 2 H), 7.93
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(d, J = 7.8 Hz, 2 H), 8.02 (d, J = 7.8 Hz, 1 H); C NMR (100 MHz, CDCl3) δ 19.0, 21.8,
22.0, 47.8, 52.3, 55.6, 122.7, 123.6, 125.7, 127.3, 128.0, 128.3, 129.2, 129.9, 130.3, 135.9,
137.2, 137.9, 141.0, 144.2, 145.4, 145.9, 167.0; IR (KBr, neat) 3063, 2956, 2852, 1925, 1729,
1606, 1494, 1459, 1352, 1275, 1159, 1106, 1020, 987, 814, 765 cm-1; HRMS (ESI) calcd. for
C27H26NO4S (M + H)+ 460.1577, found 460.1580.
5-(p-Tolyl)-1-tosyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine (9k):
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Colorless solid; mp 125-127 C; Rf (hexane/ EtOAc 9:1) 0.50; yield 114mg, 87%; H NMR
(600 MHz, CDCl3) δ 1.20-1.30 (m, 1 H), 1.32-1.45 (m, 1 H), 1.87 (dt, J = 19.2 and 5.4 Hz, 1
H), 2.07 (dt, J = 19.2 and 7.2 Hz, 1 H), 2.32 (s, 3 H), 2.41 (s, 3 H), 3.52-3.57 (m, 1 H), 3.78-
3.82 (m, 1 H), 4.25 (s, 1 H), 6.85 (d, J = 7.2 Hz, 2 H), 7.06 (d, J = 7.2 Hz, 2 H), 7.11-7.15 (m,
2 H), 7.23 (d, J = 7.2 Hz, 2 H), 7.30-7.34 (m, 1 H), 7.66 (d, J = 7.2 Hz, 2 H), 8.00 (d, J = 7.2
Hz, 1 H); 13C NMR (150 MHz, CDCl3) δ 19.1, 21.3, 21.8, 22.1, 47.9, 55.5, 122.4, 123.6,
125.5, 126.9, 128.1, 128.2, 129.6, 129.8, 136.1, 136.5, 136.6, 136.7, 138.8, 141.0, 144.0,
146.8; IR (KBr, neat) 3061, 2927, 2853, 1606, 1458, 1352, 1298, 1165, 1092, 1022, 986, 765
cm-1; HRMS (ESI) calcd. for C26H26NO2S (M + H)+ 416.1679, found 416.1678.
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7-Methyl-5-phenyl-1-tosyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine (9l):
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Colorless solid; mp 127-129 C; Rf (hexane/ EtOAc 9:1) 0.45; yield 72 mg, 57%; H NMR
(600 MHz, CDCl3) δ 1.20-1.28 (m, 1 H), 1.34-1.40 (m, 1 H), 1.84 (dt, J = 19.2 and 6.0 Hz, 1
H), 2.06 (dt, J = 19.2 and 7.2 Hz, 1 H), 2.31 (s, 3 H), 2.41 (s, 3 H), 3.51-3.56 (m, 1 H), 3.80-
3.84 (m, 1 H), 4.24 (s, 1 H), 6.95-6.96 (m, 3 H), 7.14 (d, J = 7.2 Hz, 1 H), 7.19-7.38 (m, 5 H),
7.66 (t, J = 7.8 Hz, 2 H), 7.89 (d, J = 7.8 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 19.1, 21.5,
21.8, 22.0, 47.9, 55.7, 122.2, 124.5, 127.1, 127.7, 128.1, 128.3, 128.9, 129.8, 135.3, 136.1,
136.6, 137.6, 138.3, 140.0, 144.0, 146.9; IR (KBr, neat) 2924, 2855, 1603, 1493, 1451, 1347,
1164, 1091, 985, 817, 737 cm-1; HRMS (ESI) calcd. for C26H26NO2S (M + H)+ 416.1679,
found 416.1683.
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7-Methyl-5-(4-nitrophenyl)-1-tosyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine (9m):
1
Colorless solid; mp 130-132oC; Rf (hexane/ EtOAc 9:1) 0.35; yield 79 mg, 56%; H NMR
(600 MHz, CDCl3) δ 1.25-1.30 (m, 1 H), 1.40-1.45 (m, 1 H), 1.80 (dt, J = 18.6 and 6.0 Hz, 1
H), 2.11 (dt, J = 18.6 and 7.2 Hz, 1 H), 2.31 (s, 3 H), 2.43 (s, 3 H), 3.53-3.57 (m, 1 H), 3.80
(dt, J = 11.4 and 3.0 Hz, 1 H), 4.36 (s, 1 H), 6.90 (s, 1 H), 7.12 (d, J = 8.4 Hz, 2 H), 7.17 (d, J
= 7.8 Hz, 1 H), 7.26 (d, J = 8.4 Hz, 2 H), 7.67 (d, J = 8.4 Hz, 2 H), 7.90 (d, J = 7.8 Hz, 1 H),
13
8.12 (d, J = 8.4 Hz, 2 H); C NMR (100 MHz, CDCl3) δ 19.1, 21.5, 21.8, 22.0, 47.8, 55.1,
122.6, 124.2, 124.5, 128.0, 128.3, 129.1, 129.9, 130.7, 135.8, 136.0, 137.6, 138.2, 144.3,
145.6, 147.2, 148.3; IR (KBr, neat) 2925, 2855, 1600, 1523, 1347, 1164, 1091, 814, 777 cm-
1; HRMS (ESI) calcd. for C26H25N2O4S (M + H)+ 461.1530, found 461.1529.
7-Bromo-5-phenyl-1-tosyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine (9n):
o
1
Colorless solid; mp 180-182 C; Rf (hexane/ EtOAc 9:1) 0.42; yield 64 mg, 52%; H NMR
(600 MHz, CDCl3) δ 1.18-1.27 (m, 1 H), 1.35-1.39 (m, 1 H), 1.84 (dt, J = 19.2 and 6.0 Hz, 1
H), 2.06 (dt, J = 19.2 and 7.2 Hz, 1 H), 2.42 (s, 3 H), 3.51-3.56 (m, 1 H), 3.81 (ddd, J = 14.4,
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6.0 and 3.0 Hz, 1 H), 4.26 (s, 1 H), 6.93 (d, J = 7.2 Hz, 2 H), 7.24-7.30 (m, 6 H), 7.45 (d, J =
8.4 Hz, 1 H), 7.64 (d, J = 8.4 Hz, 2 H), 7.88 (d, J = 8.4 Hz, 1 H); 13C NMR (150 MHz,
CDCl3) δ 19.0, 21.8, 22.0, 47.9, 55.8, 119.7, 124.0, 126.9, 127.5, 128.1, 128.2, 129.1, 129.9,
130.1, 135.9, 136.3, 138.8, 139.0, 140.0, 144.2, 148.6; IR (KBr, neat) 2924, 2855, 1603,
1451, 1347, 1164, 1091, 985, 816, 737 cm-1; HRMS (ESI) calcd. for C25H23BrNO2S (M + H)+
480.0627, found 480.0626.
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2-Ethyl-5-phenyl-1-tosyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine (9p):
Crystalline solid; mp 169-171 oC; Rf (hexane/ EtOAc 9:1) 0.60; yield 102 mg, 81%; 1H NMR
(600 MHz, CDCl3) δ 1.00 (t, J = 7.2 Hz, 3 H), 1.03-1.07 (m, 1 H), 1.24-1.29 (m, 1 H), 1.34
(dd, J = 13.8 and 7.2 Hz, 1 H), 1.49-1.55 (m, 1 H), 1.78 (dd, J = 19.2 and 6.6 Hz, 1 H), 2.12
(dt, J = 19.2 and 8.4 Hz, 1 H), 2.38 (s, 3 H), 4.06-4.09 (m, 1 H), 4.20 (s, 1 H), 7.01 (d, J =
7.8 Hz, 2 H), 7.15 (s, 2 H), 7.19 (d, J = 7.2 Hz, 2 H), 7.23-7.29 (m, 3 H), 7.33 (t, J = 7.2 Hz, 1
H), 7.64 (d, J = 7.8 Hz, 2 H), 8.04 (d, J = 7.8 Hz, 1 H); 13C NMR (150 MHz, CDCl3) δ 11.2,
19.1, 21.8, 22.2, 24.4, 55.8, 57.8, 122.6, 123.5, 125.4, 127.0, 127.1, 128.1, 128.2, 128.8,
129.7, 134.2, 135.6, 137.7, 139.7, 141.8, 143.9, 146.5; IR (KBr, neat) 3062, 2966, 2870,
1674, 1598, 1493, 1457, 1347, 1169, 1092, 1024, 949, 763 cm-1; HRMS (ESI) calcd. for
C27H28NO2S (M + H)+ 430.1835, found 430.1833.
5-(4-Fluorophenyl)-1-tosyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine (9r):
1
Colorless gum; Rf (hexane/ EtOAc 9:13) 0.58; yield 70 mg, 52%; H NMR (600 MHz,
CDCl3) δ 1.24-1.30 (m, 1 H), 1.38-1.42 (m, 1 H), 1.85 (dt, J = 18.6 and 6.6 Hz, 1 H), 2.08
(dt, J = 18.6 and 7.2 Hz, 1 H), 2.42 (s, 3 H), 3.55 (ddd, J = 12.0, 9.0 and 2.4 Hz, 1 H), 3.79
(ddd, J = 14.4, 6.6 and 3.6 Hz, 1 H), 4.27 (s, 1 H), 6.90-6.96 (m, 4 H), 7.11 (d, J = 7.2 Hz, 1
H), 7.16 (d, J = 7.2 Hz, 1 H), 7.20-7.25 (m, 2 H), 7.34 (t, J = 7.2 Hz, 1 H), 7.66 (d, J = 8.4
13
Hz, 2 H), 8.00 (d, J = 7.8 Hz, 1 H); C NMR (150 MHz, CDCl3) δ 19.2, 21.8, 22.0, 47.9,
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55.1, 115.7 (d, J = 21.0 Hz), 122.6, 123.6, 125.7, 127.2, 128.1, 129.7 (d, J = 7.5 Hz), 129.8,
135.5, 136.1, 136.8, 138.4, 140.9, 144.1, 146.4, 162.1 (d, J = 244.5 Hz); 19F NMR (376 MHz,
CDCl3/C6F6) δ 39.16; IR (KBr, neat) 2924, 2854, 1601, 1507, 1459, 1352, 1161, 1093, 815,
735 cm-1; HRMS (ESI) calcd. for C25H23FNO2S (M + H)+ 420.1428, found 420.1430.
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4-Methyl-N-(3-(1-phenylnaphthalen-2-yl)propyl)benzenesulfonamide (9s):
o
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Colurless solid; mp 183-185 C; Rf (hexane/ EtOAc 4:1) 0.43; yield 94 mg, 71%; H NMR
(600 MHz, CDCl3) δ 1.57-1.60 (m, 2 H), 2.33 (s, 3 H), 2.44 (t, J = 7.2 Hz, 2 H), 2.72-2.76
(m, 2 H), 4.44 (brs, 1 H), 7.12 (d, J = 7.2 Hz, 2 H), 7.18 (d, J = 7.8 Hz, 2 H), 7.24-7.27 (m, 3
H), 7.33-7.36 (m, 1 H), 7.38-7.42 (m, 3 H), 7.60 (d, J = 7.8 Hz, 2 H), 7.71 (d, J = 7.8 Hz, 1
13
H), 7.76 (d, J = 7.8 Hz, 1 H); C NMR (150 MHz, CDCl3) δ 21.6, 30.7, 31.3, 42.8, 125.3,
126.1, 126.6, 127.2, 127.5, 127.9, 128.5, 128.6, 129.8, 130.4, 130.5, 132.2, 133.1, 136.2,
137.9, 138.2, 139.2, 143.4; IR (KBr, neat) 3060, 2960, 2855, 1597, 1490, 1454, 1328, 1160,
1094, 1023, 817, 750 cm-1; HRMS (ESI) calcd. for C26H26NO2S (M + H)+ 416.1679, found
416.1675.
4-Methyl-N-(3-(4-methyl-1-phenylnaphthalen-2-yl)propyl)benzenesulfonamide (9t):
o
1
Colorless solid; mp 108-110 C; Rf (hexane/ EtOAc 4:1) 0.41; yield 101mg, 74%; H NMR
(600 MHz, CDCl3) δ 1.60-1.66 (m, 2 H), 2.41 (s, 3 H), 2.45 (t, J = 7.2 Hz, 2 H), 2.70 (s, 3 H),
2.77-2.81 (m, 2 H), 4.37 (brs, 1 H), 7.17-7.19 (m, 3 H), 7.24 (d, J = 8.4 Hz, 2 H), 7.33-7.35
13
(m, 2 H), 7.41-7.47 (m, 4 H), 7.64 (d, J = 8.4 Hz, 2 H), 7.98 (d, J = 8.4 Hz, 1 H); C NMR
(150 MHz, CDCl3) δ 19.6, 21.7, 30.7, 31.3, 42.9, 124.0, 125.1, 125.8, 127.2, 127.3, 128.2,
128.5, 129.8, 130.6, 130.7, 131.3, 133.2, 134.0, 135.8, 136.6, 137.1, 139.5, 143.4; IR (KBr,
neat) 3063, 2925, 2854, 1598, 1494, 1442, 1326, 1160, 1095, 1032, 760 cm-1; HRMS (ESI)
calcd. for C27H28NO2S (M + H)+ 430.1835, found 430.1834.
5-Phenyl-1-tosyl-2,3,4,4a,5,9b-hexahydro-1H-indeno[1,2-b]pyridine (14a):
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Colorless solid; mp 74-76 oC; Rf (hexane/ EtOAc 9:1) 0.5; yield 60 mg, 60%; H NMR (400
MHz, CDCl3) δ 0.91-1.00 (m, 2 H), 125-1.28 (m, 2 H), 2.44 (s, 3 H), 2.46-2.50 (m, 1 H), 2.86
(t, J = 12.8 Hz, 1 H), 3.86 (d, J = 14.0 Hz, 1 H), 4.41 (d, J = 6.0 Hz, 1 H), 5.47 (d, J = 5.6
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Hz, 1 H), 7.19-7.25 (m, 6 H), 7.27-7.34 (m, 5 H), 7.84 (d, J = 8.0 Hz, 2 H); C NMR (150
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MHz, CDCl3) δ 21.8, 22.4, 23.2, 42.0, 44.9, 52.7, 60.5, 124.1, 125.8, 127.1, 127.2, 127.4,
127.7, 128.4, 129.6, 130.0, 138.1, 138.7, 141.1, 142.2, 143.4; IR (KBr, neat) 3028, 2926,
2856, 1598, 1495, 1452, 1332, 1162, 1022, 719 cm-1; HRMS (ESI) calcd. for C25H26NO2S
(M + H)+ 404.1679, found 404.1678.
5-Phenyl-1-tosyl-2,3,4,4a,5,9b-hexahydro-1H-indeno[1,2-b]pyridine (14b):
Colorless solid; mp 69-71 oC; Rf (hexane/ EtOAc 9:1) 0.21; yield 10 mg, 10%; 1H NMR (600
MHz, CDCl3) δ 1.57-1.61 (m, 2 H), 182-1.85 (m, 1 H), 1.97 (dd, J = 13.2 and 9.2 Hz, 1 H),
2.21-2.28 (m, 1 H), 2.31 (s, 3 H), 2.42-2.47 (m, 1 H), 3.12 (dt, J = 12.8 and 3.6 Hz, 1 H), 3.82
(d, J = 12.7 Hz, 1 H), 5.10 (d, J = 5.6 Hz, 1 H), 6.98 (d, J = 7.2 Hz, 3 H), 7.16-7.26 (m, 10
H); 13C NMR (150 MHz, CDCl3) δ 21.6, 24.0, 25.3, 40.1, 41.8, 42.0, 60.6, 126.3, 127.2,
127.7, 128.3, 128.4, 128.5, 129.2, 129.3, 129.6, 130.1, 136.9, 138.1, 139.7, 142.5; IR (KBr,
neat) 3027, 2924, 1600, 1492, 1449, 1336, 1159, 1099, 701 cm-1; HRMS (ESI) calcd. for
C25H26NO2S (M + H)+ 404.1679, found 404.1681.
5-Phenyl-2,3,4,4a,5,9b-hexahydro-1H-indeno[1,2-b]pyridine (1):
1
Colorless solid; mp 85-87oC; Rf (DCM/ MeOH 9:1) 0.33; yield 43mg, 70%; H NMR (400
MHz, CDCl3) δ 0.98-1.12 (m, 2 H), 122-1.43 (m, 2 H), 2.57-2.66 (m, 2 H), 2.87 (d, J = 12.4
Hz, 1 H), 4.39 (d, J = 6.0 Hz, 1 H), 4.55 (d, J = 5. Hz, 1 H), 7.22-7.28 (m, 5 H), 7.29-7.36 (m,
13
3 H), 7.49 (d, J = 7.2 Hz, 1 H); C NMR (150 MHz, CDCl3) δ 22.9, 25.2, 41.5, 46.0, 53.2,
61.0, 123.7, 126.1, 126.8, 127.1, 127.3, 128.4, 129.7, 139.2, 143.5, 143.9; IR (KBr, neat)
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3440, 2926, 2853, 1641, 1453, 1154, 1076, 1031, 775, 703 cm-1; HRMS (ESI) calcd. for
C18H20N (M + H)+ 250.1590, found 250.1589.
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ACKNOWLEDGMENTS
Authors are grateful to Council of Scientific and Industrial Research (CSIR), New Delhi,
(Grant No. 02/0159/13/EMR-II) and CoE, MHRD, New Delhi for financial support. Authors
are also thankful to Central Instrument Facility (CIF) of IIT Guwahati for NMR and XRD
facilities.
Supporting Information Available: 1H and 13C NMR spectra of all new compounds and X-
ray crystallographic data of compounds 9d, 9e, 9k, 9n and 9p are included. This material is
available free of charge via the Internet at http://pubs.acs.org.
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