Synthesis of cis-3,4-diarylpiperidines and cis-3,4-diaryltetrahydropyrans

Article abstract of DOI:10.1016/j.tet.2007.02.055

Substituted cis-3,4-diarylpiperidines and cis-3,4-diaryltetrahydropyrans are synthesized in modest overall yields starting from 4-aryl-1,2,5,6-tetrahydropyridines and 4-aryl-1,2,5,6-tetrahydropyrans via the following sequence: (1) pinacol-type ring contraction having the?combination of m-chloroperoxybenzoic acid and boron trifluoride etherate, (2) Grignard addition with arylmagnesium bromide reagents and followed by boron trifluoride etherate-mediated intramolecular ring-expanded rearrangement, and (3) hydrogenation with hydrogen on 10% palladium-activated carbon. A facile synthesis of 3,4-diarylpyridines was also described by base-induced aromatization.

Full text of DOI:10.1016/j.tet.2007.02.055

Tetrahedron 63 (2007) 3312–3320
Synthesis of cis-3,4-diarylpiperidines and cis-3,4-
diaryltetrahydropyrans
b
a
Meng-Yang Chang,a, Chun-Yu Lin and Ching-Yi Hung
*
aDepartment of Applied Chemistry, National University of Kaohsiung, No. 700, Kaohsiung University Rd., Kaohsiung 811, Taiwan
bDepartment of Chemistry, National Sun Yat-Sen University, Kaohsiung 804, Taiwan
Received 18 January 2007; revised 13 February 2007; accepted 14 February 2007
Available online 20 February 2007
Abstract—Substituted cis-3,4-diarylpiperidines and cis-3,4-diaryltetrahydropyrans are synthesized in modest overall yields starting from 4-
aryl-1,2,5,6-tetrahydropyridines and 4-aryl-1,2,5,6-tetrahydropyrans via the following sequence: (1) pinacol-type ring contraction having
the combination of m-chloroperoxybenzoic acid and boron trifluoride etherate, (2) Grignard addition with arylmagnesium bromide reagents
and followed by boron trifluoride etherate-mediated intramolecular ring-expanded rearrangement, and (3) hydrogenation with hydrogen on
10% palladium-activated carbon. A facile synthesis of 3,4-diarylpyridines was also described by base-induced aromatization.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
hydrogenation with hydrogen in the presence of a catalytic
amount of 10% palladium on activated carbon.
Depending on the substitution pattern and functionalization,
different derived substitutents in the structural skeleton of
piperidines1 and tetrahydropyrans2 with six-membered het-
erocyclic ring have been shown to be effective biologically
active compounds. While a great number of piperidines, tet-
rahydropyrans, and their derivatives with this specific substi-
tution pattern are of particular interest, more significant
effortstoward thedevelopmentof newmethodsforsynthesiz-
ing different substituted piperidines3 and tetrahydropyrans4
are needed. In orderto address thisissue and continueour pre-
liminary investigation,5 we want to utilize this useful combi-
nation of m-chloroperoxybenzoic acid (MCPBA) and boron
trifluoride etherate (BF3-OEt2) toward the frameworks of
cis-3,4-diarylpiperidines and cis-3,4-diaryltetrahydropyrans.
Ar1
Ar1
Ar2
Ar2
X
4
X
3
Ar1
Ar1
CHO
X=NTs or O
X
X
2
1
Scheme 1. Synthetic approach toward cis-3,4-diarylpiperidines and cis-3,4-
diaryltetrahydropyrans.
As shown in Scheme 1, an easy synthetic approach of
cis-3,4-diarylpiperidines and cis-3,4-diaryltetrahydropyrans
starting from 4-aryl-1,2,5,6-tetrahydropyridine and 4-aryl-
1,2,5,6-tetrahydropyran was described as the following
sequence: (1) regioselective pinacol-type ring contraction
with the combination of m-chloroperoxybenzoic acid and
boron trifluoride etherate, (2) Grignard addition with differ-
ent arylmagnesium bromide reagents, (3) boron trifluoride
etherate-mediated regioselective rearrangement, and (4)
2. Results and discussion
2.1. Synthesis of cis-3,4-diarylpiperidines and
cis-3,4-diaryltetrahydropyrans
For the preparation of cis-3,4-diarylpiperidines 4Aa–
4Ae and 4Ba–4Be and cis-3,4-diaryltetrahydropyrans
4Ca–4Ce, three starting materials 4-aryl-1,2,5,6-tetrahydro-
pyridines 1A (Ar1¼C6H5) and 1B (Ar1¼4-FC6H4) and 4-
phenyl-1,2,5,6-tetrahydropyran 1C were easily prepared
from 1-tosylpiperidin-4-one and tetrahydro-4H-pyran-4-
one via Grignard addition followed by dehydration. By our
preliminary synthetic experiences,5a–c aldehydes 2A–2C
were first prepared by epoxidation of olefin 1A–1C with
Keywords: m-Chloroperoxybenzoic acid; Boron trifluoride etherate; cis-3,4-
Diarylpiperidines; cis-3,4-Diaryltetrahydropyrans; 3,4-Diarylpyridines.
* Corresponding author. Tel.: +886 7 5919464; fax: +886 7 5919348;
e-mail: mychang@nuk.edu.tw
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.02.055

M.-Y. Chang et al. / Tetrahedron 63 (2007) 3312–3320
3313
m-chloroperoxybenzoic acid at rt for 3 h followed by regio-
selective ring contraction of the resulting epoxides with
boron trifluoride etherate at 0 ꢀC for 15 min.
olefins 3Aa–3Ae, 3Ba–3Be, and 3Ca–3Cf were immedi-
ately formed as the sole products by the intramolecular
rearrangement of intermediates II and IV. During two regio-
selective approaches, other rearranged frameworks were
not observed under the boron trifluoride etherate-mediated
condition.
Next, Grignard addition of aldehydes 2A–2C with different
arylmagnesium bromide reagents (a, C6H5; b, 2-MeC6H4;
c, 2-MeOC6H4; d, 3-MeOC6H4; e, 4-MeOC6H4; f, 2,6-
Me2C6H3) in tetrahydrofuran at ꢁ78 ꢀC for 2 h yielded
a pair of secondary alcohols in nearly 1:1 ratios (monitored
by TLC plate) as shown in Scheme 2. Without purification,
boron trifluoride etherate-mediated rearrangement of the
resulting secondary alcohols afforded 4,5-diaryl-1,2,5,6-
tetrahydropyridines 3Aa–3Ae and 3Ba–3Be, and 4,5-di-
aryl-1,2,5,6-tetrahydropyrans 3Ca–3Cf at 0 ꢀC for 2 h.
Compounds 4Aa–4Ae, 4Ba–4Be, and 4Ca–4Ce were easily
obtained by the hydrogenation with hydrogen on 10% palla-
dium-activated carbon at rt for 10 h (Scheme 2). The relative
configuration of the structure of compound 4Cb with two
contiguous stereocenters is based on a single-crystal X-ray
analysis as shown in Figure 1.7 With the result in hand,
the assignment of two diaryl functional groups on the other
framework of 3,4-diarylpiperidines 4Aa–4Ae and 4Ba–4Be,
and 3,4-diaryltetrahydropyrans 4Ca–4Ce could be also
arranged as the cis configuration.
Ar1
X
Ar1
X
Ar1
O
BF3
O
1) MCPBA
2) BF3-OEt2
BF3
To deserve to be mentioned, compounds 4Ad and 4Bd were
the 4-arylpreclamol analogs. Preclamol was reported to be
the first selective D2-like dopamine autoreceptor agonist.8
If the –CH2O– motif was introduced into compounds
4Ba–Be between 3-aryl group and piperidine skeleton dur-
ing the structural modification, it would exhibit the structural
characteristics of paroxetine. Paroxetine (Paxil/Seroxat) is
a selective serotonin reuptake inhibitor used as an anti-
depressant and anti-Parkinson agent.9
X
1A X=NTs, Ar1=C6H5
I
II
1B X=NTs, Ar =
4-FC6H4
1
1C X=O, Ar1=C6H5
Ar1
X
Ar1
Ar1
HO
1) Ar2MgBr
2) BF3-OEt2
H
Ar2
Ar2
BF3
CHO
X
X
With compounds 3Aa–3Ae in hand, a facile synthesis of
3,4-diarylpyridines 5Aa–5Ae via potassium tert-butoxide-
mediated aromatization was also examined. Treatment of
compounds 3Aa–3Ae with potassium tert-butoxide in tetra-
hydrofuran at rt for 10 min afforded 3,4-diarylpyridines
5Aa–5Ae in 45–55% yields.10 In view of the experimental
simplicity, the preparation of 3,4-diarylpiperidine 5Aa was
also conducted in a multigram scale (20 mmol) with 31%
overall yield in three steps from aldehyde 2A.
2A X=NTs, Ar1=C6H5 (85%)
III
IV
2B X=NTs, Ar = -FC H4 (80%)
4
1
6
For 2A and 2B
Ar2 = (a) C6H5;
(b) 2-MeC6H4;
(c) 2-MeOC6H4;
(d) 3-MeOC H ;
(e) 4-MeOC66H44
For 2C
2C X=O, Ar1=C6H5 (85%)
Ar2 = (a) C6H5;
(b) 2-MeC6H4;
(c) 2-MeOC6H4;
(d) 3-MeOC6H4;
(e) 4-MeOC6H4;
(f) 2,6-Me2C6H3
Ph
5Aa (51%)
Ar2
5Ab (48%)
5Ac (50%)
5Ad (45%)
5Ae (55%)
t-BuOK
N
(for 3Aa~Ae)
Ar1
Ar2
Ar1
X
Ar2
H2, Pd/C
X=NTs
X=NTs
X=O
3Aa (75%) 3Ba (75%) 3Ca (76%)
3Ab (76%) 3Bb (65%) 3Cb (70%)
3Ac (75%) 3Bc (70%) 3Cc (72%)
3Ad (70%) 3Bd (60%) 3Cd (73%)
3Ae (73%) 3Be (70%) 3Ce (70%)
3Cf (61%)
X
X=NTs
X=NTs
X=O
4Aa (80%) 4Ba (85%) 4Ca (90%)
4Ab (78%) 4Bb (82%) 4Cb (92%)
4Ac (80%) 4Bc (80%) 4Cc (88%)
4Ad (82%) 4Bd (75%) 4Cd (89%)
4Ae (80%) 4Be (80%) 4Ce (85%)
Scheme 2. Synthesis of cis-3,4-diarylpiperidines 4Aa–4Ae and 4Ba–4Be,
cis-3,4-diaryltetrahydropyrans 4Ca–4Ce, and 3,4-diarylpyridines 5Aa–
5Ae.
How is the regioselective rearrangement of ring contraction
and ring expansion initiated by boron trifluoride etherate?
During the ring-reconstructed structural migration of inter-
mediate I with six-membered piperidine or tetrahydropyran
ring and intermediate III with five-membered pyrrolidine or
tetrahydrofuran ring, the most likely explanation would be
that it is controlled by involvement of the heteroatom (nitro-
gen or oxygen) lone pair. We believed that heteroatom lone
pair plays the important role to promote the occurrence of re-
arrangement reaction.6 The resulting aldehydes 2A–2C and
Figure 1. X-ray crystallography of compound 4Cb.

3314
M.-Y. Chang et al. / Tetrahedron 63 (2007) 3312–3320
2.2. Synthetic application toward compound 2A
4. Experimental section
When compound 2A was treated by Grignard addition with
vinylmagnesium bromide, ring-expanded rearrangement
with boron trifluoride etherate, and aromatization of com-
pound 3Af with potassium tert-butoxide, the sole 3-ethyl-
4-phenylpyridine 5Af was obtained in 56% yield. The
most likely explanation of reaction mechanism from com-
pound 3Af to compound 5Af would be that terminal olefin
isomerizes to internal olefin followed by desulfonation and
aromatization under the basic condition. The aliphatic sub-
stitutent was also introduced on the skeleton of pyridine
ring by our methods as shown in Scheme 3.
4.1. General
Tetrahydrofuran (THF) was distilled prior to use. All other
reagents and solvents were obtained from commercial sour-
ces and used without further purification. Reactions were
routinely carried out under an atmosphere of dry nitrogen
with magnetic stirring. Products in organic solvents were
dried with anhydrous magnesium sulfate before concentra-
tion in vacuo.
4.2. A representative procedure for compounds
3Aa–3Ah, 3Ba–3Be, and 3Ca–3Cf
Ph
Ph
A solution of aryl- or vinyl- or methylmagnesium bromide
(0.5 M in tetrahydrofuran, 1 mL) was added to a solution
of compounds 2A–2C (0.3 mmol) in tetrahydrofuran (5 mL)
at ꢁ78 ꢀC. The reaction mixture was stirred at rt for 2 h. The
total procedure was monitored by TLC until the reaction was
completed. Without further purification, boron trifluoride
etherate (0.5 mL) was added to a stirred solution of the
resulting reaction mixture at 0 ꢀC. The reaction mixture
was stirred at rt for 15 min. Saturated sodium bicarbonate
solution (1 mL) was added to the reaction mixture and the
solvent was concentrated. Water (2 mL) and ethyl acetate
(10 mL) were added to the residue and the mixture was
filtered through a short plug of Celite. The filtrate was
concentrated. The residue was extracted with ethyl acetate
(3ꢂ20 mL). The combined organic layers were washed with
brine, dried, filtered, and evaporated to afford crude product.
Purification on silica gel (hexane/ethyl acetate¼10/1–6/1)
afforded compounds 3Aa–3Ah, 3Ba–3Be, and 3Ca–3Cf.
1) vinylMgBr
2) BF3-OEt2
t-BuOK
2A
N
N
Ts
3Af (74%)
5Af (56%)
1) PhMgBr
2) PCC
Ph
Ph
Me
1) MeMgBr
2) BF3-OEt2
Ph
Ph
N
Ts
3Ag (59%)
Ph
O
N
1) PhMgBr
Ts
2) BF3-OEt2
Ph
HN
Ts
2Aa (70%)
Ph
3Ah (69%)
Scheme 3. Synthetic application of aldehyde 2A.
In the other way, compound 2Aa was afforded by treatment
of ketone 2A with Grignard addition of phenylmagnesium
bromide and oxidation of pyridinium chlorochromate and
Celite in 70% overall yields. With ketone 2Aa in hand,
the ring-expanded 3-methyl-3,4-diphenylpiperidine 3Ag
was still yielded by Grignard addition of ketone 2Aa with
methylmagnesium bromide followed by boron trifluoride
etherate. Further, the ring-opening 3,4,4-triphenyl-3-buten-
1-amine 3Ah was isolated in 69% yield by Grignard addition
of ketone 2Aa with phenylmagnesium bromide followed
by boron trifluoride etherate. Based on these results, we envi-
sioned that geminal diaryl groups are the important substitu-
tents, which easily provides a more stable benzylic cation in
the overall process. It is worthy of note that compound 3Ah
is a Tamoxifen analog with interesting biological activities.11
4.2.1. 1-(4-Methylphenylsulfonyl)-4,5-diphenyl-1,2,5,6-
tetrahydropyridine (3Aa). Oil; IR (CHCl3) 3027, 2923,
1
1598, 1346, 1161, 1106, 757 cmꢁ1; H NMR (500 MHz,
CDCl3) d 7.58 (d, J¼8.0 Hz, 2H), 7.25–7.13 (m, 12H),
6.20 (t, J¼3.5 Hz, 1H), 4.07 (br s, 1H), 4.03 (dd, J¼3.5,
17.5 Hz, 1H), 3.75 (dt, J¼2.5, 17.5 Hz, 1H), 3.49 (dd,
J¼4.5, 11.5 Hz, 1H), 3.34 (dd, J¼4.5, 11.5 Hz, 1H), 2.42
(s, 3H); 13C NMR (125 MHz, CDCl3) d 143.47, 140.82,
139.46, 137.74, 133.33, 129.53 (2ꢂ), 128.42 (2ꢂ), 128.40
(2ꢂ), 128.24 (2ꢂ), 127.69 (2ꢂ), 127.25, 126.77, 125.83
(2ꢂ), 121.40, 50.63, 45.29, 43.81, 21.49; HRMS (ESI) m/z
calcd for C24H24NO2S (M++1) 390.1528, found 390.1530;
Anal. Calcd for C24H23NO2S: C, 74.00; H, 5.95; N, 3.60.
Found: C, 73.68; H, 6.15; N, 3.96.
4.2.2. 5-(2-Methylphenyl)-1-(4-methylphenylsulfonyl)-4-
phenyl-1,2,5,6-tetrahydropyridine (3Ab). Oil; IR
3. Conclusion
(CHCl3) 3024, 2923, 1598, 1345, 1164, 1094, 753 cmꢁ1
;
In summary, we present a straightforward synthesis of cis-
3,4-diarylpiperidines, cis-3,4-diaryltetrahydropyrans, and
3,4-diarylpyridines by the treatment of 4-aryl-1,2,5,6-tetra-
hydropyridines via the regioselective ring contraction,
Grignard addition, regioselective ring expansion, and hydro-
genation or aromatization sequence. The exhibited method-
ology provided a new approach for the preparation of
substituted piperidines, tetrahydropyrans, and pyridines with
potential biological activities. We are currently studying the
scope of this process as well as additional applications of the
method for the synthesis of 2-azatriphenylene.
1H NMR (500 MHz, CDCl3) d 7.58 (d, J¼8.0 Hz, 2H),
7.26 (d, J¼8.0 Hz, 2H), 7.18–7.12 (m, 6H), 7.08–7.05 (m,
1H), 7.01–6.97 (m, 2H), 6.24 (t, J¼3.5 Hz, 1H), 4.28 (br s,
1H), 3.98 (d, J¼17.0 Hz, 1H), 3.84 (dt, J¼2.5, 17.0 Hz,
1H), 3.40 (dd, J¼4.5, 12.0 Hz, 1H), 3.30 (dd, J¼4.5,
12.0 Hz, 1H), 2.43 (s, 3H), 2.42 (s, 3H); 13C NMR
(125 MHz, CDCl3) d 143.44, 139.58, 138.34, 138.23,
134.95, 133.52, 130.42, 129.53 (2ꢂ), 128.43, 128.25 (2ꢂ),
127.65 (2ꢂ), 127.20, 126.67, 126.01, 125.54 (2ꢂ), 121.61,
48.88, 45.22, 39.65, 21.48, 19.51; HRMS (ESI) m/z calcd
for C25H26NO2S (M++1) 404.1684, found 404.1683; Anal.

M.-Y. Chang et al. / Tetrahedron 63 (2007) 3312–3320
3315
Calcd for C25H25NO2S: C, 74.41; H, 6.24; N, 3.47. Found:
C, 74.59; H, 6.56; N, 3.13.
(m, 1H), 2.99 (dd, J¼4.0, 11.5 Hz, 1H), 2.44 (s, 3H); 13C
NMR (125 MHz, CDCl3) d 143.61, 139.56, 137.90,
137.35, 133.14, 129.65 (2ꢂ), 128.31 (2ꢂ), 127.75 (2ꢂ),
127.44, 126.01 (2ꢂ), 120.30, 117.54, 48.20, 45.35, 41.41,
21.52; HRMS (ESI) m/z calcd for C20H22NO2S (M++1)
340.1371, found 340.1376.
4.2.3. 5-(2-Methoxyphenyl)-1-(4-methylphenylsulfonyl)-
4-phenyl-1,2,5,6-tetrahydropyridine (3Ac). Mp¼169–
170 ꢀC (recrystallized from hexane and ethyl acetate); IR
(CHCl3) 3020, 2918, 1598, 1490, 1343, 1163, 1096,
756 cmꢁ1
;
1H NMR (500 MHz, CDCl3) d 7.54 (d,
4.2.7. 5-Methyl-1-(4-methylphenylsulfonyl)-4,5-di-
phenyl-1,2,5,6-tetrahydropyridine (3Ag). Oil; H NMR
1
J¼8.0 Hz, 2H), 7.23–7.13 (m, 7H), 7.00 (dd, J¼1.5,
7.5 Hz, 1H), 6.81 (t, J¼8.0 Hz, 2H), 6.76 (d, J¼7.5 Hz,
1H), 6.27 (t, J¼3.5 Hz, 1H), 4.52 (br s, 1H), 4.09 (dd,
J¼3.5, 17.0 Hz, 1H), 3.86 (s, 3H), 3.69 (dt, J¼2.5,
17.0 Hz, 1H), 3.61 (dd, J¼3.5, 12.0 Hz, 1H), 3.18 (dd,
J¼3.5, 12.0 Hz, 1H), 2.40 (s, 3H); 13C NMR (125 MHz,
CDCl3) d 156.45, 143.23, 139.30, 137.59, 133.64, 129.56,
129.42 (2ꢂ), 128.49, 128.24 (2ꢂ), 127.80, 127.71 (2ꢂ),
127.24, 125.51 (2ꢂ), 121.33, 120.36, 110.07, 55.35, 48.60,
45.18, 36.25, 21.49; HRMS (ESI) m/z calcd for
C25H26NO3S (M++1) 420.1633, found 420.1635; Anal.
Calcd for C25H25NO3S: C, 71.57; H, 6.01; N, 3.34. Found:
C, 71.40; H, 5.86; N, 3.66.
(500 MHz, CDCl3) d 7.53 (d, J¼8.0 Hz, 2H), 7.40–7.38
(m, 2H), 7.33–7.25 (m, 5H), 7.16–7.10 (m, 3H), 6.93–6.91
(m, 2H), 5.97 (t, J¼3.5 Hz, 1H), 4.03 (dd, J¼4.0, 17.0 Hz,
1H), 3.69 (dd, J¼3.0, 17.0 Hz, 1H), 3.41 (d, J¼11.5 Hz,
1H), 2.92 (d, J¼11.5 Hz, 1H), 2.42 (s, 3H), 1.46 (s, 3H); 13C
NMR (125 MHz, CDCl3) d 144.05, 143.66, 143.39, 139.94,
133.48, 129.55 (2ꢂ), 128.21 (2ꢂ), 127.82 (2ꢂ), 127.68
(2ꢂ), 127.67 (2ꢂ), 127.25 (2ꢂ), 127.00, 126.65, 122.13,
57.76, 45.38, 43.57, 23.73, 21.51; HRMS (ESI) m/z calcd
for C25H26NO2S (M++1) 404.1684, found 404.1688.
4.2.8. 3,4,5-Triphenyl-3-butenyl-1-benzasulfonamide
(3Ah). Oil; 1H NMR (500 MHz, CDCl3) d 7.55 (d,
J¼8.5 Hz, 2H), 7.37–7.28 (m, 3H), 7.23–7.20 (m, 4H),
7.15–7.11 (m, 3H), 7.03–6.98 (m, 5H), 6.86–6.84 (m, 2H),
4.18 (t, J¼6.0 Hz, 1H), 2.93 (q, J¼7.0 Hz, 2H), 6.62 (t,
J¼7.0 Hz, 2H), 2.42 (s, 3H); 13C NMR (125 MHz, CDCl3)
d 143.20, 142.49, 142.38, 142.09, 140.77, 136.73, 135.89,
130.40 (2ꢂ), 129.58 (2ꢂ), 129.33 (2ꢂ), 129.20 (2ꢂ),
128.45 (2ꢂ), 128.20 (2ꢂ), 127.48 (2ꢂ), 127.02, 127.00
(2ꢂ), 126.71, 126.17, 41.90, 35.52, 21.50; HRMS (ESI) m/z
calcd for C29H28NO2S (M++1) 454.1841, found 454.1840.
4.2.4. 5-(3-Methoxyphenyl)-1-(4-methylphenylsulfonyl)-
4-phenyl-1,2,5,6-tetrahydropyridine (3Ad). Oil; IR
(CHCl3) 3027, 2916, 1598, 1488, 1344, 1164, 755 cmꢁ1
;
1H NMR (500 MHz, CDCl3) d 7.57 (d, J¼8.5 Hz, 2H),
7.25 (d, J¼8.5 Hz, 2H), 7.20–7.12 (m, 6H), 6.78 (d,
J¼8.0 Hz, 1H), 6.70 (dd, J¼2.0, 8.0 Hz, 1H), 6.69 (s, 1H),
6.19 (t, J¼4.0 Hz, 1H), 4.03 (br s, 1H), 4.01 (dd, J¼3.5,
17.5 Hz, 1H), 3.76 (dt, J¼2.5, 17.5 Hz, 1H), 3.72 (s, 3H),
3.49 (dd, J¼4.0, 12.0 Hz, 1H), 3.35 (dd, J¼4.0, 12.0 Hz,
1H), 2.42 (s, 3H); 13C NMR (125 MHz, CDCl3) d 159.52,
143.46, 142.46, 139.50, 137.70, 133.45, 129.55 (2ꢂ),
129.34, 128.27 (2ꢂ), 127.69 (2ꢂ), 127.28, 125.81 (2ꢂ),
121.48, 120.92, 114.27, 112.03, 55.04, 50.52, 45.22,
43.79, 21.49; HRMS (ESI) m/z calcd for C25H26NO3S
(M++1) 420.1633, found 420.1634.
4.2.9. 4-(4-Fluorophenyl)-1-(4-methylphenylsulfonyl)-5-
phenyl-1,2,5,6-tetrahydropyridine (3Ba). Oil; IR
(CHCl3) 3028, 2920, 1600, 1510, 1344, 1224, 1163, 1106,
1
970, 816, 758 cmꢁ1; H NMR (500 MHz, CDCl3) d 7.58
(d, J¼8.0 Hz, 2H), 7.26–7.13 (m, 9H), 6.86 (dd, J¼8.5,
8.5 Hz, 2H), 6.14 (t, J¼3.5 Hz, 1H), 4.01 (br s, 1H), 3.99
(d, J¼3.0, 17.0 Hz, 1H), 3.75 (dt, J¼3.0, 17.0 Hz, 1H),
3.45 (dd, J¼4.5, 11.5 Hz, 1H), 3.36 (dd, J¼4.5, 11.5 Hz,
1H), 2.42 (s, 3H); 13C NMR (125 MHz, CDCl3) d 162.94,
160.97, 143.54, 140.56, 136.93, 135.61, 135.58, 133.29,
129.58 (2ꢂ), 128.48, 128.39, 127.69 (2ꢂ), 127.49, 127.43,
126.90, 121.39, 115.20, 115.03, 50.58, 45.24, 44.00,
21.49; HRMS (ESI) m/z calcd for C24H23FNO2S (M++1)
408.1434, found 408.1437; Anal. Calcd for C24H22FNO2S:
C, 70.74; H, 5.44; N, 3.44. Found: C, 70.50; H, 5.63; N, 3.20.
4.2.5. 5-(4-Methoxyphenyl)-1-(4-methylphenylsulfonyl)-
4-phenyl-1,2,5,6-tetrahydropyridine (3Ae). Oil; IR
(CHCl3) 3014, 2915, 1510, 1345, 1246, 1164, 755 cmꢁ1
;
1H NMR (500 MHz, CDCl3) d 7.58 (d, J¼8.5 Hz, 2H),
7.26 (d, J¼8.5 Hz, 2H), 7.19–7.14 (m, 5H), 7.09 (d,
J¼8.5 Hz, 2H), 6.74 (d, J¼8.5 Hz, 2H), 6.17 (t, J¼3.5 Hz,
1H), 4.03 (dd, J¼3.5, 17.5 Hz, 1H), 4.01 (br s, 1H), 3.75
(s, 3H), 3.72 (dt, J¼2.0, 17.5 Hz, 1H), 3.46 (dd, J¼4.5,
11.5 Hz, 1H), 3.29 (dd, J¼4.5, 11.5 Hz, 1H), 2.42 (s, 3H);
13C NMR (125 MHz, CDCl3) d 158.36, 143.45, 139.56,
138.03, 133.39, 132.91, 129.53 (2ꢂ), 129.35 (2ꢂ), 128.24
(2ꢂ), 127.71 (2ꢂ), 127.24, 125.84 (2ꢂ), 121.13, 113.81
(2ꢂ), 55.10, 50.78, 45.39, 43.01, 21.49; HRMS (ESI) m/z
calcd for C25H26NO3S (M++1) 420.1633, found 420.1634;
Anal. Calcd for C25H25NO3S: C, 71.57; H, 6.01; N, 3.34.
Found: C, 71.71; H, 6.26; N, 3.59.
4.2.10. 4-(4-Fluorophenyl)-5-(2-methylphenyl)-1-(4-
methylphenylsulfonyl)-1,2,5,6-tetrahydropyridine
(3Bb). Mp¼150–151 ꢀC (recrystallized from hexane and
ethyl acetate); IR (CHCl3) 3024, 2923, 1600, 1510, 1344,
1164, 1094, 970, 817, 757, 666 cmꢁ1; 1H NMR (500 MHz,
CDCl3) d 7.56 (d, J¼8.0 Hz, 2H), 7.26 (d, J¼8.0 Hz, 2H),
7.12 (d, J¼7.5 Hz, 1H), 7.08–7.06 (m, 3H), 7.01–6.96 (m,
2H), 6.85 (t, J¼7.5 Hz, 2H), 6.17 (t, J¼3.5 Hz, 1H), 4.23
(br s, 1H), 3.97 (d, J¼17.0 Hz, 1H), 3.83 (dt, J¼2.5,
17.0 Hz, 1H), 3.41 (dd, J¼4.5, 12.0 Hz, 1H), 3.29 (dd,
J¼4.5, 12.0 Hz, 1H), 2.42 (s, 3H), 2.41 (s, 3H); 13C NMR
(125 MHz, CDCl3) d 162.90, 160.94, 143.51, 138.09,
137.43, 135.75, 135.02, 130.52, 129.56 (2ꢂ), 128.39,
127.67 (2ꢂ), 127.21, 127.14, 126.81, 126.09, 121.62,
115.23, 115.06, 48.89, 45.19, 39.81, 21.49, 19.51; HRMS
4.2.6. 1-(4-Methylphenylsulfonyl)-4-phenyl-5-vinyl-
1,2,5,6-tetrahydropyridine (3Af). Oil; IR (CHCl3) 3026,
1
2920, 1598, 1457, 1345, 1164, 1093, 764, 670 cmꢁ1; H
NMR (500 MHz, CDCl3) d 7.71 (d, J¼8.5 Hz, 2H), 7.35–
7.24 (m, 7H), 5.95 (t, J¼3.5 Hz, 1H), 5.82 (ddd, J¼7.5,
9.5, 17.0 Hz, 1H), 5.09 (d, J¼17.0 Hz, 1H), 5.08 (d,
J¼11.0 Hz, 1H), 4.00 (dd, J¼3.5, 17.0 Hz, 1H), 3.61 (dd, J¼
3.5, 11.5 Hz, 1H), 3.50 (dt, J¼2.5, 17.0 Hz, 1H), 3.48–3.46

3316
M.-Y. Chang et al. / Tetrahedron 63 (2007) 3312–3320
1
(ESI) m/z calcd for C25H25FNO2S (M++1) 422.2590, found
422.2593; Anal. Calcd for C25H24FNO2S: C, 71.23; H, 5.74;
N, 3.32. Found: C, 71.09; H, 5.46; N, 3.61.
749, 699 cmꢁ1; H NMR (500 MHz, CDCl3) d 7.31–7.14
(m, 10H), 6.36 (t, J¼2.5 Hz, 1H), 4.51 (dt, J¼2.5,
17.5 Hz, 1H), 4.43 (dt, J¼2.5, 17.5 Hz, 1H), 4.05 (dd,
J¼4.0, 11.0 Hz, 1H), 3.92 (dd, J¼4.0, 11.0 Hz, 1H), 3.87
(br s, 1H); 13C NMR (125 MHz, CDCl3) d 142.03, 139.53,
136.32, 128.40 (2ꢂ), 128.38 (2ꢂ), 128.26 (2ꢂ), 127.09,
126.48, 125.55 (2ꢂ), 124.44, 71.47, 66.21, 43.21; HRMS
(ESI) m/z calcd for C17H17O (M++1) 237.1280, found
237.1282; Anal. Calcd for C17H16O: C, 86.40; H, 6.82.
Found: C, 86.65; H, 6.68.
4.2.11. 4-(4-Fluorophenyl)-5-(2-methoxyphenyl)-1-(4-
methylphenylsulfonyl)-1,2,5,6-tetrahydropyridine
(3Bc). Mp¼155–156 ꢀC (recrystallized from hexane and
ethyl acetate); IR (CHCl3) 1917, 1599, 1509, 1490, 1342,
1242, 1158, 1096, 816, 754, 666 cmꢁ1
;
1H NMR
(500 MHz, CDCl3) d 7.55 (d, J¼8.0 Hz, 2H), 7.23 (d,
J¼8.0 Hz, 2H), 7.19–7.14 (m, 3H), 6.98 (dd, J¼1.5,
8.0 Hz, 1H), 6.86 (t, J¼8.5 Hz, 2H), 6.82 (d, J¼8.0 Hz,
1H), 6.76 (t, J¼8.0 Hz, 1H), 6.19 (t, J¼3.5 Hz, 1H), 4.47
(br s, 1H), 4.06 (dd, J¼3.0, 16.5 Hz, 1H), 3.86 (s, 3H),
3.68 (dt, J¼3.0, 16.5 Hz, 1H), 3.57 (dd, J¼3.5, 12.0 Hz,
1H), 3.19 (dd, J¼3.5, 12.0 Hz, 1H), 2.41 (s, 3H); 13C
NMR (125 MHz, CDCl3) d 162.99, 161.04, 156.44,
143.30, 136.79, 135.43, 133.57, 129.45 (2ꢂ), 128.22,
127.94, 127.71 (2ꢂ), 127.14, 127.08, 121.20, 120.39,
115.17, 115.00, 110.12, 55.35, 48.60, 45.14, 36.34, 21.50;
HRMS (ESI) m/z calcd for C25H25FNO3S (M++1)
438.1539, found 438.1537; Anal. Calcd for C25H24FNO3S:
C, 68.63; H, 5.53; N, 3.20. Found: C, 68.78; H, 5.36; N, 3.59.
4.2.15. 3-(2-Methylphenyl)-4-phenyl-3,6-dihydro-2H-py-
ran (3Cb). Oil; IR (CHCl3) 3022, 2923, 1601, 1492, 1459,
1127, 1077, 760, 696 cmꢁ1; H NMR (500 MHz, CDCl3)
1
d 7.25–7.13 (m, 7H), 7.09–7.04 (m, 2H), 6.40 (t,
J¼2.5 Hz, 1H), 4.52 (dt, J¼2.5, 17.0 Hz, 1H), 4.43 (dt,
J¼2.5, 17.0 Hz, 1H), 4.12 (br s, 1H), 4.04 (dd, J¼4.0,
11.0 Hz, 1H), 3.83 (dd, J¼4.0, 11.0 Hz, 1H), 2.44 (s, 3H);
13C NMR (125 MHz, CDCl3) d 139.63, 139.40, 136.72,
134.96, 130.36, 128.43, 128.30 (2ꢂ), 127.06, 126.41,
126.03, 125.30 (2ꢂ), 124.67, 69.85, 66.24, 39.02, 19.64;
HRMS (ESI) m/z calcd for C18H19O (M++1) 251.1436,
found 251.1434; Anal. Calcd for C18H18O: C, 86.36; H,
7.25. Found: C, 86.58; H, 7.06.
4.2.12. 4-(4-Fluorophenyl)-5-(3-methoxyphenyl)-1-(4-
methylphenylsulfonyl)-1,2,5,6-tetrahydropyridine
(3Bd). Oil; IR (CHCl3) 3019, 2917, 1599, 1509, 1217, 1163,
755 cmꢁ1; 1H NMR (500 MHz, CDCl3) d 7.57 (d, J¼8.0 Hz,
2H), 7.26 (d, J¼8.0 Hz, 2H), 7.16–7.12 (m, 3H), 6.86 (t,
J¼8.5 Hz, 2H), 6.75 (d, J¼8.0 Hz, 1H), 6.71 (dd, J¼2.5,
8.5 Hz, 1H), 6.67 (br s, 1H), 6.13 (t, J¼3.5 Hz, 1H), 3.99–
3.96 (m, 2H), 3.80–3.72 (m, 1H), 3.72 (s, 3H), 3.45 (dd,
J¼4.0, 11.5 Hz, 1H), 3.36 (dd, J¼4.0, 11.5 Hz, 1H), 2.42
(s, 3H); 13C NMR (125 MHz, CDCl3) d 161.01, 159.57,
143.51, 142.20, 136.89, 135.60, 133.40, 129.58 (2ꢂ),
129.44, 127.69 (2ꢂ), 127.47, 127.40, 121.46, 120.88,
115.24, 115.06, 114.35, 112.03, 55.07, 50.49, 45.18,
43.97, 21.51; HRMS (ESI) m/z calcd for C25H25FNO3S
(M++1) 438.1539, found 438.1539; Anal. Calcd for
C25H24FNO3S: C, 68.63; H, 5.53; N, 3.20. Found: C,
68.50; H, 5.90; N, 3.43.
4.2.16. 3-(2-Methoxyphenyl)-4-phenyl-3,6-dihydro-2H-
pyran (3Cc). Oil; IR (CHCl3) 2913, 1489, 1457, 1241,
1130, 1028, 753 cmꢁ1
;
1H NMR (500 MHz, CDCl3)
d 7.32 (d, J¼7.5 Hz, 2H), 7.21 (t, J¼7.5 Hz, 2H), 7.16–
7.13 (m, 3H), 6.86 (d, J¼8.5 Hz, 1H), 6.81 (t, J¼7.5 Hz,
1H), 6.42 (t, J¼2.5 Hz, 1H), 4.49 (dd, J¼2.5, 17.0 Hz,
1H), 4.43 (dt, J¼2.5, 17.0 Hz, 1H), 4.37 (br s, 1H), 3.97
(dd, J¼3.5, 11.0 Hz, 1H), 3.93 (dd, J¼3.5, 11.0 Hz, 1H),
3.89 (s, 3H); 13C NMR (125 MHz, CDCl3) d 156.58,
139.34, 136.22, 129.72, 129.51, 128.24 (2ꢂ), 127.46,
127.04, 125.23 (2ꢂ), 124.51, 120.40, 110.09, 69.89, 66.23,
55.37, 35.38; HRMS (ESI) m/z calcd for C18H19O2 (M++1)
267.1385, found 267.1385; Anal. Calcd for C18H18O2: C,
81.17; H, 6.81. Found: C, 81.29; H, 7.03.
4.2.17. 3-(3-Methoxyphenyl)-4-phenyl-3,6-dihydro-2H-
pyran (3Cd). Oil; IR 2916, 1600, 1488, 1261, 1151, 1045,
4.2.13. 4-(4-Fluorophenyl)-5-(4-methoxyphenyl)-1-(4-
methylphenylsulfonyl)-1,2,5,6-tetrahydropyridine
755, 699 (CHCl3) cmꢁ1 1H NMR (500 MHz, CDCl3)
;
d 7.30 (d, J¼7.0 Hz, 2H), 7.24–7.14 (m, 4H), 6.87 (d,
J¼7.5 Hz, 1H), 6.82 (br s, 1H), 6.71 (dd, J¼3.0, 8.0 Hz,
1H), 6.35 (t, J¼2.5 Hz, 1H), 4.50 (dd, J¼2.5, 17.5 Hz,
1H), 4.41 (dt, J¼2.5, 17.5 Hz, 1H), 4.04 (dd, J¼4.0,
11.0 Hz, 1H), 3.93 (dd, J¼4.0, 11.0 Hz, 1H), 3.80 (br s,
1H), 3.75 (s, 3H); 13C NMR (125 MHz, CDCl3) d 159.56,
143.70, 139.54, 136.25, 129.31, 128.29 (2ꢂ), 127.10,
125.53 (2ꢂ), 124.47, 120.92, 114.54, 111.47, 71.37, 66.18,
55.07, 43.19; HRMS (ESI) m/z calcd for C18H19O2 (M++1)
267.1385, found 267.1388; Anal. Calcd for C18H18O2: C,
81.17; H, 6.81. Found: C, 80.95; H, 6.98.
(3Be). Oil; IR (CHCl3) 2907, 1509, 1339, 1162, 755 cmꢁ1
;
1H NMR (500 MHz, CDCl3) d 7.58 (d, J¼8.5 Hz, 2H),
7.26 (d, J¼5.0 Hz, 2H), 7.14 (dd, J¼5.0, 8.5 Hz, 2H), 7.06
(d, J¼8.5 Hz, 2H), 6.86 (t, J¼8.5 Hz, 2H), 6.75 (d,
J¼8.5 Hz, 2H), 6.11 (t, J¼3.5 Hz, 1H), 4.00 (d, J¼
17.0 Hz, 1H), 3.95 (br s, 1H), 3.76 (s, 3H), 3.72 (dt, J¼
2.5, 17.0 Hz, 1H), 3.42 (dd, J¼4.0, 11.5 Hz, 1H), 3.30 (dd,
J¼4.0, 11.5 Hz, 1H), 2.42 (s, 3H); 13C NMR (125 MHz,
CDCl3) d 158.45, 143.51, 137.23, 133.34, 132.62, 135.70,
135.68, 129.56 (2ꢂ), 129.34 (2ꢂ), 127.71 (2ꢂ), 127.50,
127.43, 121.11, 115.21, 115.03, 113.87 (2ꢂ), 55.12, 50.73,
45.25, 43.20, 21.51; HRMS (ESI) m/z calcd for
C25H25FNO3S (M++1) 438.1539, found 438.1540; Anal.
Calcd for C25H24FNO3S: C, 68.63; H, 5.53; N, 3.20. Found:
C, 68.88; H, 5.72; N, 3.44.
4.2.18. 3-(4-Methoxyphenyl)-4-phenyl-3,6-dihydro-2H-
pyran (3Ce). Oil; IR (CHCl3) 2914, 1610, 1510, 1302,
1
1247, 1032, 828, 748 cmꢁ1; H NMR (500 MHz, CDCl3)
d 7.30 (d, J¼8.0 Hz, 2H), 7.24–7.14 (m, 5H), 6.79 (d,
J¼8.5 Hz, 2H), 6.33 (t, J¼2.5 Hz, 1H), 4.49 (dd, J¼2.5,
17.0 Hz, 1H), 4.41 (dt, J¼2.5, 17.0 Hz, 1H), 4.02 (dd,
J¼4.0, 11.0 Hz, 1H), 3.89 (dd, J¼2.5, 11.0 Hz, 1H), 3.82
(br s, 1H), 3.75 (s, 3H); 13C NMR (125 MHz, CDCl3)
4.2.14. 3,4-Diphenyl-3,6-dihydro-2H-pyran (3Ca).
Mp¼75–76 ꢀC (recrystallized from hexane and ethyl ace-
tate); IR (CHCl3) 3025, 2916, 1600, 1493, 1445, 1127,

M.-Y. Chang et al. / Tetrahedron 63 (2007) 3312–3320
3317
d 158.19, 139.61, 136.61, 134.13, 129.31 (2ꢂ), 128.26 (2ꢂ),
127.06, 125.56 (2ꢂ), 124.24, 113.81 (2ꢂ), 71.63, 66.19,
55.15, 42.35; HRMS (ESI) m/z calcd for C18H19O2 (M++1)
267.1385, found 267.1388; Anal. Calcd for C18H18O2: C,
81.17; H, 6.81. Found: C, 81.29; H, 6.70.
132.42, 129.73, 129.62 (2ꢂ), 129.30, 128.15 (2ꢂ), 127.94
(2ꢂ), 127.70 (2ꢂ), 126.56, 126.46, 125.80, 50.93, 47.02,
46.06, 38.46, 26.19, 21.55, 19.38; HRMS (ESI) m/z calcd
for C25H28NO2S (M++1) 406.1841, found 406.1843; Anal.
Calcd for C25H27NO2S: C, 74.04; H, 6.71; N, 3.45. Found:
C, 74.23; H, 6.91; N, 3.26.
4.2.19. 3-(2,6-Dimethylphenyl)-4-phenyl-3,6-dihydro-
2H-pyran (3Cf). Oil; IR (CHCl3) 2907, 1238, 1457, 1216,
4.3.3. cis-3-(2-Methoxyphenyl)-1-(4-methylphenylsul-
fonyl)-4-phenylpiperidine (4Ac). Mp¼170–171 ꢀC (re-
crystallized from hexane and ethyl acetate); IR (CHCl3)
1
754, 696 cmꢁ1; H NMR (500 MHz, CDCl3) d 7.20–7.05
(m, 5H), 6.99 (d, J¼7.5 Hz, 1H), 6.93 (d, J¼7.5 Hz, 1H),
6.74 (d, J¼7.5 Hz, 1H), 6.14 (dd, J¼3.0, 5.5 Hz, 1H),
4.64–4.61 (m, 1H), 4.47 (t, J¼3.0 Hz, 2H), 4.09 (dd,
J¼6.0, 12.0 Hz, 1H), 3.84 (dd, J¼9.5, 12.0 Hz, 1H), 2.53
(s, 3H), 2.23 (s, 3H); 13C NMR (125 MHz, CDCl3)
d 139.77, 139.42, 137.11, 136.85, 136.01, 130.18, 128.35,
127.98 (2ꢂ), 126.92, 126.43, 125.33 (2ꢂ), 123.09, 67.65,
66.04, 38.92, 21.41, 20.29; HRMS (ESI) m/z calcd for
C19H21O (M++1) 265.1592, found 265.1597.
1
2918, 1491, 1352, 1245, 1164, 1094, 758, 715 cmꢁ1; H
NMR (500 MHz, CDCl3) d 8.10 (dd, J¼1.5, 8.0 Hz, 1H),
7.69 (d, J¼8.0 Hz, 2H), 7.37 (d, J¼8.0 Hz, 2H), 7.14 (dt,
J¼1.5, 8.0 Hz, 1H), 7.04–7.03 (m, 3H), 6.95 (dt, J¼1.0,
7.5 Hz, 1H), 6.67–6.65 (m, 2H), 6.48 (d, J¼1.0, 7.5 Hz,
1H), 4.10–4.06 (m, 1H), 3.99 (dt, J¼2.0, 11.5 Hz, 1H),
3.82–3.80 (m, 1H), 3.01 (s, 3H), 2.91 (ddd, J¼3.5, 4.5,
12.5 Hz, 1H), 2.82 (dd, J¼4.0, 11.5 Hz, 1H), 2.51 (dt,
J¼2.5, 11.5 Hz, 1H), 2.47 (s, 3H), 2.35 (dt, J¼4.5,
13.0 Hz, 1H), 1.67 (dd, J¼3.5, 13.0 Hz, 1H); 13C NMR
(125 MHz, CDCl3) d 156.88, 143.54, 142.93, 132.39,
130.01, 129.61 (2ꢂ), 128.70, 127.96 (2ꢂ), 127.83 (2ꢂ),
127.47, 127.22 (2ꢂ), 126.01, 120.19, 109.55, 54.49, 50.86,
47.11, 45.45, 34.85, 25.70, 21.56; HRMS (ESI) m/z calcd
for C25H28NO3S (M++1) 422.1790, found 422.1787; Anal.
Calcd for C25H27NO3S: C, 71.23; H, 6.46; N, 3.32. Found:
C, 71.46; H, 6.32; N, 3.58.
4.3. A representative procedure for compounds
4Aa–4Ae, 4Ba–4Be, and 4Ca–4Ce
Palladium (10%) on activated carbon (5 mg) was added to
a stirring solution of compounds 3Aa–3Ae or 3Ba–3Be or
3Ca–3Ce (0.2 mmol) in methanol (10 mL). Then hydrogen
was bubbled into the mixture for 10 min and the reaction
mixture was continued to stir at rt for 10 h. The catalyst
was filtered through a short plug of Celite and washed
with methanol (2ꢂ10 mL). The combined organic layers
were evaporated to afford crude product. Purification on
silica gel (hexane/ethyl acetate¼10/1) afforded compounds
4Aa–4Ae, 4Ba–4Be, and 4Ca–4Ce.
4.3.4. cis-3-(3-Methoxyphenyl)-1-(4-methylphenylsul-
fonyl)-4-phenylpiperidine (4Ad). Mp¼199–200 ꢀC (re-
crystallized from hexane and ethyl acetate); IR (CHCl3)
2913, 1597, 1337, 1165, 754, 720 cmꢁ1
;
1H NMR
(500 MHz, CDCl3) d 7.71 (d, J¼8.5 Hz, 2H), 7.38 (d,
J¼8.5 Hz, 2H), 7.15–7.12 (m, 3H), 7.00 (d, J¼8.0 Hz,
2H), 6.76–6.72 (m, 2H), 6.69 (dd, J¼2.5, 8.5 Hz, 1H),
6.63 (br s, 1H), 4.18 (d, J¼11.0 Hz, 1H), 4.15–4.11 (m,
1H), 3.60 (s, 3H), 3.11 (br s, 1H), 2.93 (dt, J¼4.0,
12.5 Hz, 1H), 2.81 (dd, J¼4.0, 12.0 Hz, 1H), 2.50 (d,
J¼2.5, 11.0 Hz, 1H), 2.47 (s, 3H), 2.30 (dt, J¼4.0,
12.5 Hz, 1H), 1.73 (dq, J¼2.5, 12.5 Hz, 1H); 13C NMR
(125 MHz, CDCl3) d 158.56, 143.62, 142.54, 140.64,
132.43, 129.66 (2ꢂ), 128.28, 127.93 (4ꢂ), 127.83 (2ꢂ),
126.45, 122.46, 114.94, 112.88, 55.03, 50.81, 47.11,
45.87, 44.80, 24.96, 21.56; HRMS (ESI) m/z calcd for
C25H28NO3S (M++1) 422.1790, found 422.1792; Anal.
Calcd for C25H27NO3S: C, 71.23; H, 6.46; N, 3.32. Found:
C, 71.50; H, 6.68; N, 3.44.
4.3.1. cis-1-(4-Methylphenylsulfonyl)-3,4-diphenylpiper-
idine (4Aa). Mp¼142–143 ꢀC (recrystallized from hexane
and ethyl acetate); IR (CHCl3) 3027, 2918, 1493, 1452,
1352, 1339, 1165, 1095, 755, 717 cmꢁ1
;
1H NMR
(500 MHz, CDCl3) d 7.71 (d, J¼8.0 Hz, 2H), 7.38 (d,
J¼8.0 Hz, 2H), 7.14–7.07 (m, 8H), 6.71–6.69 (m, 2H),
4.18–4.12 (m, 2H), 3.12 (br s, 1H), 2.91 (ddd, J¼3.5, 4.5,
13.0 Hz, 1H), 2.82 (dd, J¼4.0, 11.5 Hz, 1H), 2.50 (dt,
J¼2.5, 11.5 Hz, 1H), 2.48 (s, 3H), 2.30 (dq, J¼4.0,
13.0 Hz, 1H), 1.71 (dd, J¼3.0, 13.0 Hz, 1H); 13C NMR
(125 MHz, CDCl3) d 143.64, 142.48, 139.26, 132.32,
130.01 (2ꢂ), 129.66 (2ꢂ), 127.96 (2ꢂ), 127.88 (2ꢂ),
127.79 (2ꢂ), 127.40 (2ꢂ), 126.42, 126.40, 50.88, 47.15,
45.88, 44.90, 24.88, 21.57; HRMS (ESI) m/z calcd for
C24H26NO2S (M++1) 392.1684, found 392.1687; Anal.
Calcd for C24H25NO2S: C, 73.62; H, 6.44; N, 3.58. Found:
C, 73.82; H, 6.56; N, 3.70.
4.3.5. cis-3-(4-Methoxyphenyl)-1-(4-methylphenylsul-
fonyl)-4-phenylpiperidine (4Ae). Mp¼185–186 ꢀC (re-
crystallized from hexane and ethyl acetate); IR (CHCl3)
3027, 2952, 1610, 1596, 1463, 1338, 1250, 1182, 1163,
4.3.2. cis-3-(2-Methylphenyl)-1-(4-methylphenylsul-
fonyl)-4-phenylpiperidine (4Ab). Oil; IR (CHCl3) 3026,
1
1034, 954, 755, 713 cmꢁ1; H NMR (500 MHz, CDCl3)
2926, 1492, 1351, 1341, 1168, 1094, 920, 760, 715 cmꢁ1
;
d 7.71 (d, J¼8.5 Hz, 2H), 7.38 (d, J¼8.5 Hz, 2H), 7.14–
7.11 (m, 3H), 7.03 (d, J¼8.5 Hz, 2H), 6.73–6.71 (m, 2H),
6.64 (d, J¼8.5 Hz, 2H), 4.14 (d, J¼11.5 Hz, 2H), 3.75 (s,
3H), 3.08 (br s, 1H), 2.89 (dt, J¼4.0, 14.0 Hz, 1H), 2.79
(dd, J¼4.0, 11.5 Hz, 1H), 2.50–2.45 (m, 1H), 2.47 (s, 3H),
2.29 (dt, J¼4.0, 13.0 Hz, 1H), 1.70 (dd, J¼2.5, 13.0 Hz,
1H); 13C NMR (125 MHz, CDCl3) d 158.00, 143.62,
142.61, 131.36, 130.96 (2ꢂ), 129.63 (2ꢂ), 127.90 (2ꢂ),
127.86 (2ꢂ), 127.80 (3ꢂ), 126.34, 112.72 (2ꢂ), 55.05,
51.16, 47.16, 45.92, 44.06, 24.79, 21.53; HRMS (ESI)
1H NMR (500 MHz, CDCl3) d 8.14 (d, J¼8.0 Hz, 1H),
7.70 (d, J¼8.0 Hz, 2H), 7.37 (d, J¼8.0 Hz, 2H), 7.21 (t,
J¼8.0 Hz, 1H), 7.11–7.01 (m, 4H), 6.85 (d, J¼7.5 Hz,
1H), 6.60 (d, J¼7.5 Hz, 2H), 4.12–4.09 (m, 1H), 3.98 (d,
J¼12.0 Hz, 1H), 3.43 (br s, 1H), 2.93 (dt, J¼4.0, 12.5 Hz,
1H), 2.86 (dd, J¼4.0, 11.5 Hz, 1H), 2.58 (dt, J¼2.5,
11.5 Hz, 1H), 2.48 (s, 3H), 2.43 (dt, J¼4.0, 12.5 Hz, 1H),
1.69 (dd, J¼4.0, 11.5 Hz, 1H), 1.44 (s, 3H); 13C NMR
(125 MHz, CDCl3) d 143.58, 142.29, 138.52, 137.32,

3318
M.-Y. Chang et al. / Tetrahedron 63 (2007) 3312–3320
m/z calcd for C25H28NO3S (M++1) 422.1790, found
422.1791.
(CHCl3) 2917, 1659, 1509, 1338, 1195, 923, 717 cmꢁ1; 1H
NMR (500 MHz, CDCl3) d 7.70 (d, J¼8.5 Hz, 2H), 7.38
(d, J¼8.0 Hz, 2H), 7.01 (t, J¼8.5 Hz, 1H), 6.82 (t,
J¼8.5 Hz, 2H), 6.72 (br s, 1H), 6.69–6.66 (m, 4H), 4.16
(d, J¼11.5 Hz, 1H), 4.13 (d, J¼11.5 Hz, 1H), 3.66 (s, 3H),
3.05 (br s, 1H), 2.91 (dt, J¼4.0, 12.0 Hz, 1H), 2.79 (dd,
J¼4.0, 12.0 Hz, 1H), 2.50–2.46 (m, 1H), 2.47 (s, 3H), 2.26
(dq, J¼4.0, 13.0 Hz, 1H), 1.69 (dq, J¼4.0, 13.0 Hz, 1H);
13C NMR (125 MHz, CDCl3) d 162.45, 160.51, 158.72,
143.67, 140.48, 132.42, 129.69 (2ꢂ), 129.21, 129.15,
128.39, 127.91 (2ꢂ), 122.55, 115.10, 114.78, 114.61,
112.79, 55.08, 50.74, 47.07, 45.19, 44.84, 25.31, 21.57;
HRMS (ESI) m/z calcd for C25H27FNO3S (M++1)
440.1696, found 440.1698; Anal. Calcd for C25H26FNO3S:
C, 68.31; H, 5.96; N, 3.19. Found: C, 68.50; H, 6.23; N, 3.45.
4.3.6. cis-4-(4-Fluorophenyl)-1-(4-methylphenylsul-
fonyl)-3-phenylpiperidine (4Ba). Mp¼165–166 ꢀC (re-
crystallized from hexane and ethyl acetate); IR (CHCl3)
3028, 2925, 1600, 1510, 1339, 1224, 1168, 1096, 954,
759 cmꢁ1
;
1H NMR (500 MHz, CDCl3) d 7.70 (d,
J¼8.0 Hz, 2H), 7.37 (d, J¼8.0 Hz, 2H), 7.16–7.10 (m,
5H), 6.80 (dd, J¼8.5, 8.5 Hz, 2H), 6.63 (dd, J¼8.5,
8.5 Hz, 2H), 4.14 (d, J¼12.0 Hz, 2H), 3.07 (br s, 1H), 2.91
(dt, J¼4.0, 13.0 Hz, 1H), 2.80 (dd, J¼4.0, 12.0 Hz, 1H),
2.48 (dt, J¼2.5, 11.5 Hz, 1H), 2.47 (s, 3H), 2.26 (dq,
J¼4.0, 13.0 Hz, 1H) 1.68 (dq, J¼4.0, 13.0 Hz, 1H); 13C
NMR (125 MHz, CDCl3) d 162.40, 160.45, 143.68,
139.05, 138.21, 132.27, 130.01 (2ꢂ), 129.66 (2ꢂ), 129.16,
127.93 (2ꢂ), 127.52 (2ꢂ), 126.53, 114.73, 114.56, 50.77,
47.08, 45.17, 44.90, 25.16, 21.55; HRMS (ESI) m/z calcd
for C24H25FNO2S (M++1) 410.1590, found 410.1593;
Anal. Calcd for C24H24FNO2S: C, 70.39; H, 5.91; N, 3.42.
Found: C, 70.61; H, 5.83; N, 3.60.
4.3.10. cis-4-(4-Fluorophenyl)-3-(4-methoxyphenyl)-1-
(4-methylphenylsulfonyl)piperidine (4Be). Oil; IR
(CHCl3) 2916, 1510, 1334, 1250, 1163, 548 cmꢁ1 1H
;
NMR (500 MHz, CDCl3) d 7.69 (d, J¼8.0 Hz, 2H), 7.37
(d, J¼8.0 Hz, 2H), 7.02 (d, J¼8.5 Hz, 2H), 6.81 (t,
J¼8.5 Hz, 2H), 6.67–6.63 (m, 4H), 4.12 (d, J¼11.0 Hz,
2H), 3.75 (s, 3H), 3.02 (br s, 1H), 2.85 (dd, J¼4.0,
13.0 Hz, 1H), 2.77 (dd, J¼4.0, 12.0 Hz, 1H), 2.47 (s, 3H),
2.43 (dd, J¼3.0, 15.0 Hz, 1H), 2.22 (dq, J¼4.0, 13.0 Hz,
1H), 1.67–1.65 (m, 1H); 13C NMR (125 MHz, CDCl3)
d 162.54, 158.13, 143.66, 138.36, 132.27, 131.12, 131.01
(2ꢂ), 129.66 (2ꢂ), 129.20, 129.15, 127.93 (2ꢂ), 114.76,
114.59, 112.86 (2ꢂ), 55.10, 51.09, 47.15, 44.13, 30.94,
25.11, 21.57; HRMS (ESI) m/z calcd for C25H27FNO3S
(M++1) 440.1696, found 440.1697.
4.3.7. cis-4-(4-Fluorophenyl)-3-(2-methylphenyl)-1-(4-
methylphenylsulfonyl)piperidine (4Bb). Oil; 1H NMR
(500 MHz, CDCl3) d 8.14 (d, J¼7.5 Hz, 1H), 7.69 (d,
J¼8.0 Hz, 2H), 7.37 (d, J¼8.0 Hz, 2H), 7.22 (t, J¼7.5 Hz,
1H), 7.10 (t, J¼7.5 Hz, 1H), 6.87 (d, J¼7.5 Hz, 1H), 6.72
(dd, J¼8.5, 9.0 Hz, 2H), 6.54 (dd, J¼8.5, 9.0 Hz, 2H),
4.10 (d, J¼9.5 Hz, 1H), 3.97 (d, J¼11.5 Hz, 1H), 3.39 (br
s, 1H), 2.92 (dt, J¼4.5, 12.5 Hz, 1H), 2.84 (dd, J¼4.5,
11.5 Hz, 1H), 2.56 (dt, J¼3.0, 11.5 Hz, 1H), 2.47 (s, 3H),
2.38 (dq, J¼3.0, 12.0 Hz, 1H), 1.66 (dq, J¼3.0, 12.0 Hz,
1H), 1.47 (s, 3H); 13C NMR (125 MHz, CDCl3) d 162.56,
160.62, 143.64, 138.29, 137.17, 132.39, 129.87, 129.64
(2ꢂ), 129.45, 129.30, 127.96 (2ꢂ), 126.63, 125.95, 114.57,
114.41, 109.46, 50.86, 47.00, 45.30, 38.36, 26.47, 21.57,
19.50; HRMS (ESI) m/z calcd for C25H27FNO2S (M++1)
424.1747, found 424.1750; Anal. Calcd for C25H26FNO2S:
C, 70.89; H, 6.19; N, 3.31. Found: C, 71.02; H, 6.33; N, 3.52.
4.3.11. cis-3,4-Diphenyltetrahydropyran (4Ca). Oil; IR
(CHCl3) 3085, 3061, 3027, 2951, 1602, 1493, 1452, 1190,
1
1126, 1095, 1013, 765 cmꢁ1; H NMR (500 MHz, CDCl3)
d 7.17–7.07 (m, 8H), 6.81–6.79 (m, 2H), 4.36 (dd,
J¼11.5 Hz, 1H), 4.31 (dd, J¼3.0, 11.5 Hz, 1H), 4.04 (dd,
J¼3.0, 11.5 Hz, 1H), 3.72 (dt, J¼2.5, 11.5 Hz, 1H), 3.32
(dt, J¼4.5, 13.0 Hz, 1H), 2.98 (br s, 1H), 2.28 (dq, J¼4.5,
13.0 Hz, 1H), 1.55 (dd, J¼2.0, 13.0 Hz, 1H); 13C NMR
(125 MHz, CDCl3) d 143.25, 140.67, 130.19 (2ꢂ), 127.82
(4ꢂ), 127.18 (2ꢂ), 126.17, 125.97, 72.53, 68.71, 46.55,
45.56, 26.04; HRMS (ESI) m/z calcd for C17H19O (M++1)
239.1436, found 239.1441; Anal. Calcd for C17H18O: C,
85.67; H, 7.61. Found: C, 85.86; H, 7.76.
4.3.8. cis-4-(4-Fluorophenyl)-3-(2-methoxyphenyl)-1-(4-
methylphenylsulfonyl)piperidine (4Bc). Oil; IR (CHCl3)
1
2917, 1597, 1509, 1338, 1244, 1162, 752 cmꢁ1; H NMR
(500 MHz, CDCl3) d 8.21 (dd, J¼1.5, 7.5 Hz, 1H), 7.79
(d, J¼8.0 Hz, 2H), 7.47 (d, J¼8.0 Hz, 2H), 7.25 (dt,
J¼1.5, 7.5 Hz, 1H), 7.06 (t, J¼7.5 Hz, 1H), 6.83 (dd, J¼
8.5, 9.0 Hz, 2H), 6.71 (dd, J¼5.5, 8.5 Hz, 2H), 6.60 (d, J¼
8.5 Hz, 1H), 4.21–4.17 (m, 1H), 4.09 (d, J¼11.5 Hz, 1H),
3.88–3.85 (m, 1H), 3.20 (s, 3H), 2.99 (dt, J¼4.0, 12.5 Hz,
1H), 2.89 (dd, J¼4.0, 11.5 Hz, 1H), 2.60 (dd, J¼3.5,
12.0 Hz, 1H), 2.57 (s, 3H), 2.40 (dq, J¼3.5, 13.0 Hz, 1H),
1.74 (dq, J¼3.5, 13.0 Hz, 1H); 13C NMR (125 MHz,
CDCl3) d 160.30, 156.72, 143.60, 138.63, 132.33, 130.03,
129.63 (2ꢂ), 129.18, 129.12, 128.37, 127.96 (2ꢂ), 127.64,
120.27, 113.95, 113.79, 109.46, 54.45, 50.80, 47.08,
44.71, 34.72, 25.87, 21.57; HRMS (ESI) m/z calcd for
C25H27FNO3S (M++1) 440.1696, found 440.1701; Anal.
Calcd for C25H26FNO3S: C, 68.31; H, 5.96; N, 3.19. Found:
C, 68.65; H, 6.11; N, 3.42.
4.3.12. cis-3-(2-Methylphenyl)-4-phenyltetrahydropyran
(4Cb). Mp¼126–127 ꢀC (recrystallized from hexane and
1
ethyl acetate); H NMR (500 MHz, CDCl3) d 8.19 (dd,
J¼1.0, 7.5 Hz, 1H), 7.22 (t, J¼7.5 Hz, 1H), 7.15–7.06 (m,
4H), 6.87 (d, J¼7.5 Hz, 1H), 6.71 (d, J¼8.5 Hz, 2H), 4.33
(ddd, J¼2.0, 4.0, 11.0 Hz, 1H), 4.26 (d, J¼11.5 Hz, 1H),
4.04 (dd, J¼2.5, 12.5 Hz, 1H), 3.75 (dt, J¼2.5, 11.5 Hz,
1H), 3.32 (dt, J¼4.5, 12.5 Hz, 1H), 3.25 (br s, 1H), 2.42
(dq, J¼4.5, 13.5 Hz, 1H), 1.52 (dd, J¼2.5, 13.5 Hz, 1H),
1.42 (s, 3H); 13C NMR (125 MHz, CDCl3) d 143.10,
139.90, 137.67, 129.80, 129.59, 128.19 (2ꢂ), 127.67 (2ꢂ),
126.35, 126.17, 125.44, 72.80, 68.72, 46.05, 40.18, 27.31,
19.39; HRMS (ESI) m/z calcd for C18H21O (M++1)
253.1592, found 253.1596; Anal. Calcd for C18H20O: C,
85.67; H, 7.99. Found: C, 85.93; H, 8.22. Single-crystal
X-ray diagram: crystal of compound 4Cb was grown by
slow diffusion of ethyl acetate into a solution of compound
4.3.9. cis-4-(4-Fluorophenyl)-3-(3-methoxyphenyl)-1-
(4-methylphenylsulfonyl)piperidine (4Bd). Mp¼152–
153 ꢀC (recrystallized from hexane and ethyl acetate); IR

M.-Y. Chang et al. / Tetrahedron 63 (2007) 3312–3320
3319
4Cb in dichloromethane to yield colorless prism. The com-
pound crystallizes in the monoclinic crystal system. Space
20 min. Water (1 mL) was added to the residue and the reac-
tion mixture was concentrated. The residue was extracted
with ethyl acetate (3ꢂ20 mL). The combined organic layers
were washed with brine, dried, filtered, and evaporated to af-
ford crude product. Purification on silica gel (hexane/ethyl
acetate¼20/1) afforded compounds 5Aa–5Af.
˚
˚
group P2(1)/c, a¼9.8430(19) A, b¼5.8261(11) A, c¼
3
24.461(5) A, V¼1401.3(5) A , Z¼4, dcalcd¼1.196 mg/m3,
absorption coefficient¼0.072 mmꢁ1, R indices (all data)
R1¼0.0706, wR2¼0.1333, F(000)¼544, 2q range (1.67–
28.35ꢀ).
˚
˚
4.4.1. 3,4-Diphenylpyridine (5Aa).12a Mp¼116–117 ꢀC
(recrystallized from hexane and ethyl acetate) (lit.12a
mp¼113–114 ꢀC); IR (CHCl3) 3058, 3025, 1585, 1473,
4.3.13. cis-3-(2-Methoxyphenyl)-4-phenyltetrahydro-
pyran (4Cc). Mp¼81–82 ꢀC (recrystallized from hexane
and ethyl acetate); IR (CHCl3) 2913, 1577, 1488, 1261,
1445, 1399, 1074, 761, 577 cmꢁ1 1H NMR (500 MHz,
;
1
1093, 774, 698 cmꢁ1; H NMR (500 MHz, CDCl3) d 8.08
CDCl3) d 8.65 (s, 1H), 8.64 (d, J¼5.0 Hz, 1H), 7.39 (d,
J¼5.0 Hz, 1H), 7.31–7.26 (m, 6H), 7.18–7.15 (m, 4H); 13C
NMR (125 MHz, CDCl3) d 150.33, 148.37, 147.97,
138.37, 137.39, 136.05, 129.77 (2ꢂ), 129.29 (2ꢂ), 128.31
(4ꢂ), 128.00, 127.45, 124.79; HRMS (ESI) m/z calcd for
C17H14N (M++1) 232.1126, found 232.1130; Anal. Calcd
for C17H13N: C, 88.28; H, 5.67; N, 6.06. Found: C, 88.43;
H, 5.82; N, 6.35.
(dd, J¼1.5, 8.0 Hz, 1H), 7.14 (dt, J¼1.5, 7.5 Hz, 1H),
7.10–7.05 (m, 3H), 6.94 (dt, J¼1.0, 7.5 Hz, 1H), 6.77–
6.75 (m, 2H), 6.49 (dd, J¼1.0, 8.5 Hz, 1H), 4.29 (ddd,
J¼2.0, 4.5, 11.0 Hz, 1H), 4.24 (d, J¼11.5 Hz, 1H), 4.01
(dd, J¼3.5, 12.0 Hz, 1H), 3.70 (dt, J¼2.5, 11.5 Hz, 1H),
3.60 (t, J¼4.0 Hz, 1H), 3.28 (dt, J¼3.5, 13.0 Hz, 1H), 3.00
(s, 3H), 2.32 (dq, J¼4.5, 13.0 Hz, 1H), 1.49 (dd, J¼2.0,
13.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) d 157.13,
143.75, 130.49, 130.05, 127.87 (2ꢂ), 127.16 (3ꢂ), 125.78,
119.81, 109.50, 72.74, 68.76, 54.41, 45.35, 36.83, 26.78;
HRMS (ESI) m/z calcd for C18H21O2 (M++1) 269.1542,
found 269.1545; Anal. Calcd for C18H20O2: C, 80.56; H,
7.51. Found: C, 80.72; H, 7.35.
4.4.2. 3-(2-Methylphenyl)-4-phenylpyridine (5Ab). Oil;
IR (CHCl3) 3059, 3024, 1584, 1472, 1443, 1398, 1076,
1
1003, 840, 728, 699 cmꢁ1; H NMR (500 MHz, CDCl3)
d 8.66 (d, J¼5.0 Hz, 1H), 8.54 (s, 1H), 7.40 (d, J¼5.0 Hz,
1H), 7.25–7.10 (m, 9H), 1.88 (s, 3H); 13C NMR
(125 MHz, CDCl3) d 151.06, 148.61, 148.30, 138.52,
137.23, 136.15, 135.64, 130.60, 130.06, 128.84 (2ꢂ),
128.14 (2ꢂ), 127.94, 127.88, 125.68, 124.01, 19.91;
HRMS (ESI) m/z calcd for C18H16N (M++1) 246.1283,
found 246.1288; Anal. Calcd for C18H15N: C, 88.13; H,
6.16; N, 5.71. Found: C, 88.40; H, 6.35; N, 5.42.
4.3.14. cis-3-(3-Methoxyphenyl)-4-phenyltetrahydro-
pyran (4Cd). Mp¼102–103 ꢀC (recrystallized from hexane
and ethyl acetate); IR (CHCl3) 2960, 1608, 1510, 1455,
1259, 1093, 802 cmꢁ1
;
1H NMR (500 MHz, CDCl3)
d 7.18–7.13 (m, 3H), 7.01 (t, J¼8.0 Hz, 1H), 6.84–6.82
(m, 2H), 6.75 (d, J¼7.5 Hz, 1H), 6.67 (dd, J¼2.0, 8.0 Hz,
1H), 6.56 (t, J¼2.0 Hz, 1H), 4.35 (d, J¼11.5 Hz, 1H), 4.29
(dd, J¼2.5, 11.5 Hz, 1H), 4.01 (dd, J¼3.0, 11.5 Hz, 1H),
3.70 (dt, J¼2.0, 11.5 Hz, 1H), 3.57 (s, 3H), 3.31 (dt,
J¼4.5, 13.0 Hz, 1H), 2.95 (br s, 1H), 2.27 (dq, J¼4.5,
13.0 Hz, 1H), 1.56–1.54 (m, 1H); 13C NMR (125 MHz,
CDCl3) d 158.47, 143.30, 142.13, 128.04, 127.87 (2ꢂ),
127.84 (2ꢂ), 126.19, 122.69, 115.57, 112.01, 72.41, 68.68,
54.96, 46.57, 45.53, 26.03; HRMS (ESI) m/z calcd for
C18H21O2 (M++1) 269.1542, found 269.1544; Anal. Calcd
for C18H20O2: C, 80.56; H, 7.51. Found: C, 80.74; H, 7.80.
4.4.3. 3-(2-Methoxyphenyl)-4-phenylpyridine (5Ac). Oil;
IR (CHCl3) 3027, 2934, 1584, 1493, 1461, 1251, 1026,
700 cmꢁ1
;
1H NMR (500 MHz, CDCl3) d 8.62 (d,
J¼5.0 Hz, 1H), 8.59 (s, 1H), 7.36 (d, J¼5.0 Hz, 1H), 7.29
(dt, J¼1.5, 8.0 Hz, 2H), 7.25–7.22 (m, 2H), 7.19 (dd,
J¼1.5, 7.5 Hz, 1H), 7.16–7.14 (m, 2H), 6.97 (t, J¼7.0 Hz,
1H), 6.74 (d, J¼8.0 Hz, 1H), 3.34 (s, 3H); 13C NMR
(125 MHz, CDCl3) d 156.37, 151.11, 149.08, 148.39,
139.43, 132.83, 131.40, 129.42, 128.27 (2ꢂ), 127.87 (2ꢂ),
127.61, 126.71, 123.89, 120.66, 110.86, 54.83; HRMS
(ESI) m/z calcd for C18H16NO (M++1) 262.1232, found
262.1232; Anal. Calcd for C18H15NO: C, 82.73; H, 5.79;
N, 5.36. Found: C, 82.98; H, 5.61; N, 5.20.
4.3.15. cis-3-(4-Methoxyphenyl)-4-phenyltetrahydro-
pyran (4Ce). Oil; H NMR (500 MHz, CDCl3) d 7.18–
1
7.12 (m, 3H), 7.50 (d, J¼9.0 Hz, 2H), 6.81–6.79 (m, 2H),
6.63 (d, J¼9.0 Hz, 2H), 4.32 (d, J¼11.5 Hz, 1H), 4.30–
4.28 (m, 1H), 4.01 (dd, J¼3.0, 11.5 Hz, 1H), 3.74 (s, 3H),
3.69 (dt, J¼2.0, 11.5 Hz, 1H), 3.27 (dt, J¼4.0, 12.5 Hz,
1H), 2.92 (br s, 1H), 2.25 (dq, J¼4.0, 13.0 Hz, 1H), 1.53
(dd, J¼2.0, 13.0 Hz, 1H); 13C NMR (125 MHz, CDCl3)
d 168.81, 54.42, 143.78, 142.14 (2ꢂ), 138.87 (2ꢂ), 138.83
(2ꢂ), 137.12, 123.54 (2ꢂ), 83.80, 79.73, 66.07, 56.74,
56.64, 37.03; HRMS (ESI) m/z calcd for C18H21O2 (M++1)
269.1542, found 269.1546; Anal. Calcd for C18H20O2: C,
80.56; H, 7.51. Found: C, 80.42; H, 7.67.
4.4.4. 3-(3-Methoxyphenyl)-4-phenylpyridine (5Ad). Oil;
IR (CHCl3) 3028, 2936, 1588, 1471, 1322, 1221, 1045, 779,
750 cmꢁ1; 1H NMR (500 MHz, CDCl3) d 8.66 (s, 1H), 8.63
(d, J¼5.0 Hz, 1H), 7.37 (d, J¼5.0 Hz, 1H), 7.30–7.27 (m,
3H), 7.19–7.17 (m, 3H), 6.82 (dd, J¼2.5, 8.5 Hz, 1H),
6.76 (d, J¼7.5 Hz, 1H), 6.67 (t, J¼2.5 Hz, 1H), 3.64 (s,
3H); 13C NMR (125 MHz, CDCl3) d 159.33, 150.35,
148.20, 138.75, 138.47, 135.83, 129.33, 129.20 (2ꢂ),
128.31 (3ꢂ), 127.96, 124.70, 122.20, 115.15, 113.40,
55.10; HRMS (ESI) m/z calcd for C18H16NO (M++1)
262.1232, found 262.1234.
4.4. A representative procedure for compounds
5Aa–5Af
4.4.5. 3-(4-Methoxyphenyl)-4-phenylpyridine (5Ae).12b
Mp¼133–134 ꢀC (recrystallized from hexane and ethyl ace-
tate); IR (CHCl3) 3030, 2957, 1609, 1514, 1474, 1293, 1223,
Potassium tert-butoxide (50 mg, 0.45 mmol) was added to
a stirring solution of olefins 3Aa–3Af (0.1 mmol) in tetrahy-
drofuran (10 mL). The reaction mixture was stirred at rt for
1178, 1036, 831, 751, 700 cmꢁ1 1H NMR (500 MHz,
;
CDCl3) d 8.62 (s, 1H), 8.59 (d, J¼5.0 Hz, 1H), 7.33 (d,

3320
M.-Y. Chang et al. / Tetrahedron 63 (2007) 3312–3320
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J¼5.0 Hz, 1H), 7.29–7.27 (m, 3H), 7.18–7.16 (m, 2H), 7.07
(d, J¼9.0 Hz, 2H), 6.81 (d, J¼9.0 Hz, 2H), 3.79 (s, 3H); 13C
NMR (125 MHz, CDCl3) d 158.93, 150.76, 148.06, 147.70,
138.73, 135.44, 130.87 (2ꢂ), 129.81, 129.24 (2ꢂ), 128.28
(2ꢂ), 127.77, 124.63, 113.76 (2ꢂ), 55.17; HRMS (ESI)
m/z calcd for C18H16NO (M++1) 262.1232, found
262.1234; Anal. Calcd for C18H15NO: C, 82.73; H, 5.79;
N, 5.36. Found: C, 82.92; H, 5.92; N, 5.53.
1
4.4.6. 3-Ethyl-4-phenylpyridine (5Af).12c Oil; H NMR
(500 MHz, CDCl3) d 8.60 (br s, 1H), 8.51 (d, J¼5.0 Hz,
1H), 7.52–7.46 (m, 3H), 7.36 (d, J¼5.0 Hz, 1H), 7.34–
7.32 (m, 2H), 2.73 (q, J¼7.5 Hz, 2H), 1.16 (t, J¼7.5 Hz, 3H);
HRMS (ESI) m/z calcd for C13H14N (M++1) 184.1126,
found 184.1132.
Acknowledgements
The authors would like to thank the National Science Coun-
cil (NSC 95-2113-M-390-003-MY2) of the Republic of
China for financial support.
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