5-Hydroxypent-2-enenitriles as precursors toward dihydropyranones, dienenitriles and functionalized naphthalenes

Article abstract of DOI:10.1016/j.tet.2013.04.118

5-Hydroxypent-2-enenitriles were found to be precursors toward several classes of compounds with synthetic and biological interests. To be specific, upon treatment with sulfuric acid in dichloromethane and depending on the configuration of the C-C double

Full text of DOI:10.1016/j.tet.2013.04.118

Tetrahedron 69 (2013) 5374e5382
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
5-Hydroxypent-2-enenitriles as precursors toward
dihydropyranones, dienenitriles and functionalized naphthalenes
*
*
Xinying Zhang , Xuefei Jia, Nan Liu, Xiaojie Guo, Yunping Song, Xuesen Fan
School of Chemistry and Chemical Engineering, Henan Key Laboratory of Environmental Pollution Control, Key Laboratory of Green Chemical Media and
Reactions, Ministry of Education, Henan Normal University, Xinxiang, Henan 453007, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
5-Hydroxypent-2-enenitriles were found to be precursors toward several classes of compounds with
synthetic and biological interests. To be specific, upon treatment with sulfuric acid in dichloromethane
and depending on the configuration of the CeC double bond and the nature of substituents attached on
the CeC double bond, 5-hydroxypent-2-enenitriles could afford 5,6-dihydropyran-2-ones, 2,4-
Received 11 January 2013
Received in revised form 16 April 2013
Accepted 26 April 2013
Available online 9 May 2013
dienenitriles, or functionalized naphthalenes through intramolecular Pinner reaction,
intramolecular FriedeleCrafts reaction, respectively.
b-elimination or
Keywords:
Ó 2013 Elsevier Ltd. All rights reserved.
5-Hydroxypent-2-enenitriles
Dihydropyranones
Dienenitriles
Functionalized naphthalenes
1. Introduction
As part of our recent studies on functionalized allenes,1 we have
developed a synthetic pathway toward
trile (3) via the tandem reaction of 1,2-allenic ketone (1) with
-substituted cyanoacetate (2) (Scheme 1).1b
d-oxo-a,b-unsaturated ni-
Scheme 2. Proposed synthesis of 2,4-dienenitrile (5) from 3.
a
2. Results and discussion
To check the feasibility of the envisioned pathway to
2,4-dienenitrile (5), (E)-5-hydroxy-2,3-dimethyl-5-phenylpent-2-
enenitrile ((E)-4a), prepared through reduction of (E)-2,3-dimethyl-
5-oxo-5-phenylpent-2-enenitrile ((E)-3a),1b was treated with H2SO4
inTHF under refluxfor 8 h. To ourdelight, it gave theexpected (2E,4E)-
2,3-dimethyl-5-phenylpenta-2,4-dienenitrile ((E,E)-5a) in a yield
of 84% (Scheme 3). However, when (Z)-5-hydroxy-2,3-dimethyl-
5-phenylpent-2-enenitrile ((Z)-4a) was subjected to similar
Scheme 1. Synthesis of d-oxo-a,b-unsaturated nitrile (3a).
As both carbonyl and cyano groups are exceptionally versatile in
organic transformations, we expected -oxo- -unsaturated ni-
d
a,b
triles (3) to serve as valuable precursors toward compounds with
synthetic and biological interests. In this regard, 2,4-dienenitriles
emerged as attractive targets since they are not only essential
building blocks of biologically active natural products, but also in-
termediates to high-electron affinity polymers used to produce
light emitting diodes (LEDs).2e4 Hence, we hypothesized a syn-
thetic method toward 2,4-dienenitrile (5) starting from d-oxo-a,b-
unsaturated nitrile (3) and intermediating with 5-hydroxypent-2-
enenitrile (4) as shown in Scheme 2.
Scheme 3. Formation of (E,E)-5a from (E)-3a and 6a from (Z)-3a.
* Corresponding authors. E-mail address: xinyingzhang@htu.cn (X. Zhang).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.04.118

X. Zhang et al. / Tetrahedron 69 (2013) 5374e5382
5375
Table 2
conditions, the corresponding (2Z,4E)-2,3-dimethyl-5-phenylpenta-
Scope of the reaction leading to 6 from (Z)-4a
2,4-dienenitrile ((Z,E)-5a) was formed only in trace amount. Instead,
5,6-dihydro-3,4-dimethyl-6-phenylpyran-2-one (6a) was isolated in
a yield of 66% (Scheme 3).
Plausible pathways accounting for the formation of (E,E)-5a and
6a were described in Scheme 4. While an acid-promoted de-
hydration of (E)-4a affords (E,E)-5a, an alternative reaction pathway
featured with an intramolecular Pinner reaction5 occurs with (Z)-4a
resulting in the formation of 6a.
Entry
R1
R2
R3
R4
Products
Yieldb (%)
1
2
3
4
5
6
7
8
C6H5
H
H
H
H
H
H
H
H
H
H
H
H
H
H
CH3
CH3
H
H
H
H
H
H
H
CH3
H
H
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
Bn
CH3
CH3
CH3
CH3
CH3
CH3
CH3
Bn
Bn
Bn
Bn
Allyl
Allyl
Allyl
CH3
CH3
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
CH3
Bn
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
6q
6r
75
81
85
78
86
72
88
68
80
79
51
72
79
86
80
82
68
73
78
85
51
48
90
86
81
76
72
m-ClC6H4
p-ClC6H4
m-BrC6H4
p-BrC6H4
m-CH3C6H4
p-CF3C6H4
C6H5
m-ClC6H4
p-BrC6H4
p-CH3C6H4
C6H5
p-FC6H4
p-CF3C6H4
C6H5
4-BrC6H4
C6H5
3-ClC6H4
4-ClC6H4
4-BrC6H4
3-CH3C6H4
4-CH3C6H4
4-CF3C6H4
4-BrC6H4
CH3
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
Scheme 4. Plausible pathways toward (E,E)-5a and 6a.
Literature searching revealed that 5,6-dihydropyran-2(1H)-one
is a privileged structural scaffold frequently found in both natural
products and pharmaceutical agents.6 This promoted us to carry
out thorough studies on the transformation of (Z)-4a with the aim
6s
6t
6u
6v
6w
6x
6y
6z
6aa
to develop it into
a novel synthetic method toward 5,6-
dihydropyran-2(1H)-ones.
Thus, the reaction of (Z)-4a toward 6a was optimized with
regard to solvents and acidic promoters and the results were in-
cluded in Table 1. With H2SO4 as the catalyst, the choice of solvent
turned out to be essential to the proceeding of the reaction. Among
commonly used solvents, such as THF, DMF, CH3CN, EtOH, toluene,
CH2Cl2, and H2O, CH2Cl2 appeared to be the most efficient in me-
diating this tandem process. Of the acidic catalysts screened, H2SO4
exhibited the highest catalytic activity. Finally, the optimal condi-
tions were identified as follows: treating (Z)-4a with 1 equiv of
H2SO4 in CH2Cl2 under reflux for 3 h. Under such conditions, 6a was
obtained in a yield of 75%.
CH3
Ph
Bn
Bn
H
CH3
a
Reaction conditions: 4 (0.5 mmol), H2SO4 (0.5 mmol), CH2Cl2 (5 mL), reflux, 3 h.
Isolated yield.
b
different positions of the substrates, diversely substituted 5,6-
dihydropyran-2(1H)-ones could be obtained.
It is also noted, however, for substrate with strong electron-
donating group on the phenyl ring of R1, namely (Z)-5-hydroxy-5-
(4-methoxyphenyl)-2,3-dimethylpent-2-enenitrile ((Z)-4-A), the
reaction mainly give the corresponding dehydration product,
(2Z,4E)-5-(4-methoxyphenyl)-2,3-dimethylpenta-2,4-dienenitrile
((2Z,4E)-5-A, Scheme 5). The expected 5,6-dihydropyran-2(1H)-
one was formed only in trace amount. It might be explained by the
stabilizing effect of the electron-donating methoxy group on the
proposed cationic intermediate toward 2,4-dienenitrile. The in-
creased stability of the cation intermediate makes the dehydration
more favored than the competing intramolecular Pinner reaction.
Table 1
Optimization for the formation of 6a from (Z)-4aa
Entry
Catalyst
Solvent
T (ꢀC)
t (h)
Yieldb (%)
1
2
3
4
5
6
7
8
9
H2SO4
H2SO4
H2SO4
H2SO4
H2SO4
H2SO4
H2SO4
BF3$Et2O
CF3CO2H
THF
DMF
Reflux
80
Reflux
Reflux
80
Reflux
80
Reflux
Reflux
10
10
5
10
10
3
10
10
15
66
Trace
66
58
22
75
NR
70
CH3CN
EtOH
Toluene
CH2Cl2
H2O
CH2Cl2
CH2Cl2
63
a
Reaction conditions: 4a (0.5 mmol), acid (0.5 mmol), solvent (5 mL).
Isolated yield.
b
Scheme 5. Dehydration favored with electron-donating effect.
With the optimized conditions in hand, we then examined the
scope and generality of the synthetic procedure toward 6. The re-
sults included in Table 2 show that most of the substrates studied
undergo the intramolecular Pinner reaction smoothly to afford the
corresponding 5,6-dihydropyran-2(1H)-ones (6) with moderate to
good yields. Notably, the reactions are compatible with a variety of
functional groups such as chloro, bromo, fluoro, trifluoromethyl,
allyl, and benzyl groups. By varying the substituents attached on
Having established a new protocol for the preparation of 5,6-
dihydropyran-2(1H)-ones (6) from (Z)-5-hydroxypent-2-enenitrile
((Z)-4), we moved our focus back to the synthesis of (2E,4E)-2,4-
dienenitriles ((E,E)-5) from (E)-5-hydroxypent-2-enenitrile ((E)-4).
Optimization study with (E)-4a as a model substrate turned out that
treatment of (E)-4a with 1 equiv of H2SO4 in CH2Cl2 under reflux for
2 h afforded (E,E)-5a in 86% yield.

5376
X. Zhang et al. / Tetrahedron 69 (2013) 5374e5382
The scope and generality of the synthetic strategy toward 2,4-
It is well known that naphthalene skeleton occurs in many bi-
ologically important natural products and building blocks for the
synthesis of pharmaceuticals and polycyclic aromatic electronic
materials.7,8 To date, several efficient methods for the synthesis of
substituted naphthalenes have been reported.9 In spite of their
success, some of these synthetic methods still suffer from expensive
catalysts, harsh reaction conditions or low efficiency. Based on the
above facts, we proceeded to study the feasibility of a one-pot
preparation of 8a directly from (E)-4p. For this purpose, (E)-4p was
firstly treated with H2SO4 in refluxing CH2Cl2 for 2 h. Then DDQ was
added and the mixture was stirred under reflux for another 4 h.
Separation of the resulting mixture gave 8a in a totalyield of 63%. The
dienenitriles (5) were then studied and the results were listed in
Table 3. Generally, good to excellent yields of (2E,4E)-2,4-
dienenitriles were observed and the reaction was found to be
compatible with various functional groups including the electron-
deficient trifluoromethyl and the electron-rich methoxy groups,
thus resulting a general and efficient approach toward 2,4-
dienenitrile derivatives.
Table 3
Scope of the reaction leading to (E,E)-5 from (E)-4a
generality and limitation of the one-pot process leading to
naphthalene (8) was then studied. We found that a variety of (E)-5-
hydroxypent-2-enenitriles with a phenyl group on the -position
of the cyano participated in this reaction to give the corresponding
aryl naphthalenes in moderate yields (Table 4). It is notable that this
sequence of reactions provides an attractive alternative to cross-
coupling protocols in some cases for the preparation of biaryls, in-
cluding the 1,10-binaphthyl-4-carbonitrile (8h, entry 8).
a-aryl
a
a-
Entry
R1
R2
R3
R4
Products
Yieldb (%)
1
2
3
4
5
6
7
8
C6H5
H
H
H
H
H
H
H
H
H
H
H
H
H
H
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
Bn
Bn
Bn
Allyl
Allyl
Allyl
CH3
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
86
88
92
91
93
82
86
85
83
86
85
82
88
85
81
m-ClC6H4
p-ClC6H4
m-BrC6H4
p-BrC6H4
m-CH3C6H4
p-CH3OC6H4
p-CF3C6H4
C6H5
m-ClC6H4
p-BrC6H4
C6H5
p-FC6H4
p-CF3C6H4
C6H5
Table 4
Scope of the one-pot synthesis of a
-aryl naphthalenes (8)a
9
10
11
12
13
14
15
Entry
R1
R2
R3
Products
Yieldb (%)
a
Reaction conditions: 4 (0.5 mmol), H2SO4 (0.5 mmol), CH2Cl2 (5 mL), reflux.
Isolated yield.
1
2
3
4
5
6
7
8
9
4-CF3C6H4
3-ClC6H4
4-ClC6H4
4-BrC6H4
3-CH3C6H4
4-CH3C6H4
C6H5
H
H
H
H
H
H
H
H
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
8a
8b
8c
8d
8e
8f
8g
8h
8i
63
52
53
56
42
40
61
35
62
b
To further extend the scope of the above reaction, (E)-5-
hydroxy-3-methyl-2-phenyl-5-(4-(trifluoromethyl)phenyl)pent-2-
enenitrile ((E)-4p), with a phenyl group on the -position of the
cyano, was treated with H2SO4 in CH2Cl2. Interestingly, it gave 2-
methyl-4-(4-(trifluoromethyl)phenyl)-3,4-dihydronaphthalene-1-
carbonitrile (7) as a major product rather than the expected
(2E,4E)-3-methyl-2-phenyl-5-(4-(trifluoromethyl)phenyl)-penta-
2,4-dienenitrile ((E,E)-5p). A mechanism rationalizing the forma-
tion of 7 featured with an intramolecular FriedeleCrafts reaction is
depicted in Scheme 6.
a
1-Naphthyl
4-BrC6H4
CH3
a
Reaction conditions: 4 (0.5 mmol), H2SO4 (0.5 mmol), CH2Cl2 (5 mL), reflux, 2 h;
then DDQ (0.5 mmol), reflux, 4 h.
b
Isolated yield.
In
a
further aspect, inspired by the reaction of (E)-5-
-position
hydroxypent-2-enenitriles with a phenyl group on the
a
of cyano affording a-substituted 3,4-dihydronaphthalenes (7), we
envisioned that tetrahydronaphthalene (9)10e13 might be obtained
from (E)-5-hydroxypent-2-enenitriles having a benzyl group on the
b-position of cyano via an intramolecular FriedeleCrafts reaction as
shown in Scheme 8.
Scheme 6. A plausible pathway for the formation of 7.
Scheme 8. Proposed synthesis of tetrahydronaphthalene (9).
In following studies, we found that upon treatment with 2,3-
dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), compound 7 un-
derwent an oxidative aromatization to give 2-methyl-4-(4-(tri-
fluoromethyl) phenyl)-1-naphthonitrile (8a) in 87% yield (Scheme 7).
In deed, when (E)-3-benzyl-5-hydroxy-2-methylhex-2-ene ni-
trile was treated with H2SO4 in CH2Cl2, the expected 2-(4-methyl-
3,4-dihydronaphthalen-2(1H)-ylidene)propanenitrile (9a) was ob-
tained in a yield of 56%. The success of this strategy was further
demonstrated by the reactions with other substrates and the re-
sults were shown in Table 5.
Finally, sinceeffective separationof(E)-3 and (Z)-3 or (E)-4and(Z)-
4 usually requires considerable efforts due to their structural simi-
larity, the feasibility of one-pot preparation of (2E,4E)-5a and 6a by
Scheme 7. Oxidative aromatization of 7 with DDQ.

X. Zhang et al. / Tetrahedron 69 (2013) 5374e5382
5377
Table 5
(27
mL, 0.5 mmol). The solution was stirred under reflux. Upon
Synthesis of 2-methylene-1,2,3,4-tetrahydronaphthalene (9)a
completion, the reaction was quenched with aqueous Na2CO3. The
resulting mixture was extracted with ethyl acetate (5 mLꢁ3). The
combined organic phases were washed with brine, dried, filtered,
and concentrated under vacuum. The residue was purified by col-
umn chromatography on silica gel eluting with ethyl acetate/hexane
(1:10) to give (2E,4E)-2,3-dimethyl-5-phenylpenta-2,4-dienenitrile
((2E,4E)-5a) in a yield of 86% (79 mg, 0.43 mmol). Other (2E,4E)-
2,4-dienenitrile derivatives were obtained in a similar manner.
Entry
R1
R2
R4
Products
Yieldb (%)
1
2
3
4
CH3
CH3
CH3
Ph
H
H
H
H
CH3
Bn
Ph
9a
9b
9c
9d
56
53
43
48
4.2.1. (2E,4E)-2,3-Dimethyl-5-phenylpenta-2,4-dienenitrile (5a). Yield:
79 mg, 86%. White solid, mp: 104e105 ꢀC; 1H NMR (400 MHz,
CH3
CDCl3)
d
: 2.09 (s, 3H), 2.28 (s, 3H), 6.88 (d, J¼16.0 Hz, 1H), 7.11
a
Reaction conditions: 4 (0.5 mmol), H2SO4 (0.5 mmol), CH2Cl2 (5 mL), reflux, 3 h.
Isolated yield.
(d, J¼16.0 Hz, 1H), 7.32e7.40 (m, 3H), 7.49 (d, J¼7.2 Hz, 2H). 13C NMR
b
(100 MHz, CDCl3) d: 15.9, 18.5, 105.9, 120.8, 123.8, 127.2, 128.9, 129.0,
¼2919, 2211, 1531, 772 cmꢂ1; MS: m/z
using a mixture of (E)-4a and (Z)-4a as substrates was investigated. To
our delight, treating a mixture of (E)-4a and (Z)-4a, obtained through
the reduction of a mixture of (E)-3a and (Z)-3a, with H2SO4 in CH2Cl2
resulted in efficient formation of (2E,4E)-5a and 6a (Scheme 9). In
addition, these two products were separated conveniently as they are
remarkably different in their structural characteristics.
135.2, 136.2, 147.9. IR (KBr)
n
184 (MH)þ. HRMS calcd for C13H14N: 184.1126 [MþH], found:
184.1134.
4.2.2. (2E,4E)-5-(3-Chlorophenyl)-2,3-dimethylpenta-2,4-dienenitrile
(5b). Yield: 95 mg, 88%. White solid, mp: 91e93 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
: 2.10 (s, 3H), 2.26 (s, 3H), 6.80 (d, J¼16.0 Hz, 1H),
7.09 (d, J¼16.0 Hz, 1H), 7.26e7.35 (m, 3H), 7.46 (s, 1H). 13C NMR
(100 MHz, CDCl3) d: 16.0, 18.5, 107.0, 120.5, 125.0, 125.5, 126.8, 128.8,
130.1, 133.6, 134.8, 138.0, 147.4. IR (KBr)
n
¼2924, 2201, 1510, 957,
780 cmꢂ1; MS: m/z 218 (MH)þ. HRMS calcd for C13H13ClN: 218.0737
[MþH], found: 218.0745.
Scheme 9. One-pot preparation of (2E,4E)-5a and 6a from 4a.
3. Conclusion
4.2.3. (2E,4E)-5-(4-Chlorophenyl)-2,3-dimethylpenta-2,4-dienenitrile
(5c). Yield: 100 mg, 92%. White solid, mp: 122e124 ꢀC; 1H NMR
In conclusion, novel synthetic methods for the preparation of 5,6-
dihydropyran-2(1H)-ones, 2,4-dienenitriles, and functionalized
naphthalenes via acid-promoted reactions of 5-hydroxypent-2-
enenitriles with various substitution patterns have been developed.
Notable features of the results reported herein include: (1) various
kinds of target compounds could be obtained from substrates origi-
nated from the same reaction; (2) different transformations could be
performed under almost equally mild conditions without using any
(400 MHz, CDCl3)
7.08 (d, J¼16.0 Hz, 1H), 7.33 (d, J¼7.2 Hz, 2H), 7.41 (d, J¼7.2 Hz, 2H).
13C NMR (100 MHz, CDCl3)
: 15.9, 18.4, 106.5, 120.6, 124.3, 128.3,
d
: 2.10 (s, 3H), 2.27 (s, 3H), 6.83 (d, J¼16.0 Hz, 1H),
d
129.1, 133.8, 134.68, 134.71, 147.5. IR (KBr)
n
¼2923, 2202, 1487,
814 cmꢂ1; MS: m/z 218 (MH)þ. HRMS calcd for C13H13ClN: 218.0737
[MþH], found: 218.0729.
4.2.4. (2E,4E)-5-(3-Bromophenyl)-2,3-dimethylpenta-2,4-dienenitrile
(5d). Yield: 119 mg, 91%. White solid, mp: 112e114 ꢀC; 1H NMR
noble catalysts. In addition,
a mixture of E/Z isomers of 5-
hydroxypent-2-enenitrile could be used directly and two different
kinds of products can be obtained conveniently from the corre-
sponding E or Z isomer via a one-pot procedure. With the above-de-
scribed advantages, these synthetic methods are expected to find
wideapplications insynthetic, medicinal chemistry, and related areas.
(400 MHz, CDCl3)
d
: 2.10 (s, 3H), 2.26 (s, 3H), 6.78 (d, J¼16.0 Hz, 1H),
7.08 (d, J¼16.0 Hz, 1H), 7.23 (t, J¼8.0 Hz,1H), 7.38 (d, J¼7.6 Hz,1H), 7.43
(d, J¼7.6 Hz, 1H), 7.62 (s, 1H). 13C NMR (100 MHz, CDCl3)
d: 16.0, 18.4,
107.1,120.4,123.0,125.1,125.9,129.8,130.3,131.7,133.5,138.3,147.3. IR
(KBr)
n
¼2924, 2204, 779 cmꢂ1; MS: m/z 262 (MH)þ. HRMS calcd for
C13H13BrN: 262.0231 [MþH], found: 262.0235.
4. Experimental section
4.1. General
4.2.5. (2E,4E)-5-(4-Bromophenyl)-2,3-dimethylpenta-2,4-dienenitrile
(5e). Yield: 122 mg, 93%. White solid, mp: 156e157 ꢀC; 1H NMR
(400 MHz, CDCl3)
7.08 (d, J¼16.0 Hz, 1H), 7.34 (d, J¼8.4 Hz, 2H), 7.48 (d, J¼8.0 Hz, 2H).
13C NMR (100 MHz, CDCl3)
: 15.9, 18.5, 106.5, 120.6, 122.9, 124.4,
d
: 2.09 (s, 3H), 2.27 (s, 3H), 6.80 (d, J¼16.0 Hz, 1H),
1H and 13C NMR spectra were recorded at 400 and 100 MHz,
respectively. High-resolution mass spectra (HRMS) were performed
on a time-of-flight (ESI-TOF) mass spectrometer. Melting points
were measured with a micro melting point apparatus. All reactions
were monitored by thin-layer chromatography (TLC) using silica gel
plates (silica gel 60 F254 0.25 mm) and components were visualized
d
128.6, 132.0, 133.9, 135.1, 147.6. IR (KBr)
n¼2918, 2203, 1502,
819 cmꢂ1; MS: m/z 262 (MH)þ. HRMS calcd for C13H13BrN: 262.0231
[MþH], found: 262.0238.
by observation under UV light (254 and 365 nm). d-Oxo-a,b-un-
4.2.6. (2E,4E)-5-(3-Methylphenyl)-2,3-dimethylpenta-2,4-dienenitrile
(5f). Yield: 81 mg, 82%. Syrup; 1H NMR (400 MHz, CDCl3)
d
: 2.10
(s, 3H), 2.28 (s, 3H), 2.39 (s, 3H), 6.86 (d, J¼15.6 Hz, 1H), 7.09e7.16
(m, 2H), 7.27e7.31 (m, 3H). 13C NMR (100 MHz, CDCl3)
: 15.9, 18.5,
saturated nitriles (3) were prepared based on our previously pub-
lished procedure.1b 5-Hydroxypent-2-enenitriles (4) were obtained
by reduction of the corresponding d-oxo-a,b-unsaturated nitriles
d
(3) with KBH4 in methanol at ambient temperature.
21.4, 105.7, 120.8, 123.6, 124.4, 127.9, 128.8, 129.9, 135.4, 136.1, 138.5,
148.0. IR (KBr)
n
¼2919, 1328, 785 cmꢂ1; MS: m/z 198 (MH)þ. HRMS
4.2. Typical procedure for the preparation of (2E,4E)-2,3-
dimethyl-5-phenylpenta-2,4-dienenitrile ((2E,4E)-5a) (Table 3)
calcd for C14H16N: 198.1283 [MþH], found: 198.1276.
4.2.7. (2E,4E)-5-(4-Methoxyphenyl)-2,3-dimethylpenta-2,4-dienenitrile
To a flask containing (E)-5-hydroxy-2,3-dimethyl-5-phenylpent-
(5g). Yield: 92 mg, 86%. White solid, mp: 86e88 ꢀC; 1H NMR
2-enenitrile (101 mg, 0.5 mmol) in CH2Cl2 (5 mL) was added H2SO4
(400 MHz, CDCl3) d: 2.07 (s, 3H), 2.26 (s, 3H), 3.83 (s, 3H), 6.82 (d,

5378
X. Zhang et al. / Tetrahedron 69 (2013) 5374e5382
J¼15.6 Hz, 1H), 6.89 (d, J¼8.0 Hz, 2H), 6.97 (d, J¼16.0 Hz, 1H), 7.42 (d,
131.2, 132.9, 134.0, 139.5, 147.9. IR (KBr)
n
¼2929, 2201, 915,
J¼8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d
: 15.8, 18.4, 55.3, 104.6,
822 cmꢂ1; MS: m/z 278 (MH)þ. HRMS calcd for C16H15F3N: 278.1157
[MþH], found: 278.1152.
114.3, 120.1, 121.8, 128.6, 129.0, 134.8, 148.1, 160.4. IR (KBr)
n¼2929,
2197, 1252, 805 cmꢂ1; MS: m/z 214 (MH)þ. HRMS calcd for C14H16NO:
214.1232 [MþH], found: 214.1238.
4.2.15. (2E,4E)-2,3,4-Trimethyl-5-phenylpenta-2,4-dienenitrile
(5o). Yield: 80 mg, 81%. White solid, mp: 114e115 ꢀC; 1H NMR
4.2.8. (2E,4E)-2,3-Dimethyl-5-(4-(trifluoromethyl)phenyl)penta-2,4-
dienenitrile (5h). Yield: 107 mg, 85%. White solid, mp: 116e118 ꢀC;
(400 MHz, DMSO-d6)
d: 1.57 (s, 3H), 1.92 (s, 3H), 2.11 (s, 3H), 6.40 (s,
1H), 7.16e7.22 (m, 3H), 7.29e7.33 (m, 2H). 13C NMR (100 MHz,
1H NMR (400 MHz, CDCl3)
d: 2.12 (s, 3H), 2.29 (s, 3H), 6.90 (d,
DMSO-d6) d: 16.7, 21.2, 23.1, 104.7, 119.6, 127.5, 127.6, 127.7, 129.0,
J¼16.0 Hz, 1H), 7.18 (d, J¼16.0 Hz, 1H), 7.57 (d, J¼8.4 Hz, 2H), 7.62 (d,
136.0, 136.7, 155.7. IR (KBr)
n
¼2921, 2210, 772 cmꢂ1; MS: m/z 198
J¼8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d
: 16.0, 18.4, 107.6, 120.3,
(MH)þ. HRMS calcd for C14H16N: 198.1283 [MþH], found: 198.1288.
125.75, 125.78, 126.1, 127.3, 130.3, 133.5, 139.6, 147.2. IR (KBr)
n
¼2928, 2201, 1324, 827 cmꢂ1; MS: m/z 252 (MH)þ. HRMS calcd for
4.2.16. (2E,4E)-3-Methyl-2-phenyl-5-(4-(trifluoromethyl)phenyl)
penta-2,4-dienenitrile (5p). Yield: 35 mg, 22%. White solid, mp:
C14H13F3N: 252.1000 [MþH], found: 252.0995.
161e163 ꢀC; 1H NMR (400 MHz, CDCl3)
d: 2.50 (s, 3H), 6.98 (d,
4.2.9. (2E,4E)-2-Benzyl-3-methyl-5-phenylpenta-2,4-dienenitrile
J¼16.0 Hz, 1H), 7.14 (d, J¼16.0 Hz, 1H), 7.38e7.47 (m, 7H), 7.56 (d,
(5i). Yield: 108 mg, 83%. White solid, mp: 99e101 ꢀC; 1H NMR
J¼8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d: 19.0, 114.3, 119.2, 125.7,
(400 MHz, CDCl3)
d
: 2.39 (s, 3H), 3.83 (s, 2H), 7.00 (d, J¼16.0 Hz, 1H),
125.8, 127.3, 127.5, 127.8, 128.7, 128.8, 129.0, 129.4, 129.9, 130.3,
7.29e7.42 (m, 9H), 7.50 (d, J¼7.2 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d:
133.4, 134.2, 139.4, 148.6. IR (KBr)
n
¼2929, 2195, 822, 766 cmꢂ1
;
18.8, 35.5, 110.6, 120.1, 123.7, 127.0, 127.3, 128.4, 128.87, 128.94, 129.2,
MS: m/z 314 (MH)þ. HRMS calcd for C19H15F3N: 314.1157 [MþH],
136.1,136.2,137.5,148.4. IR (KBr)
n
¼2928, 2206, 760 cmꢂ1;MS:m/z260
found: 314.1166.
(MH)þ. HRMS calcd for C19H18N: 260.1439 [MþH], found: 260.1448.
4.3. Typical procedure for the preparation of 5,6-dihydro-3,4-
dimethyl-6-phenylpyran-2-one (6a) (Table 2)
4.2.10. (2E,4E)-2-Benzyl-5-(3-chlorophenyl)-3-methylpenta-2,4-
dienenitrile (5j). Yield: 126 mg, 86%. White solid, mp: 122e123 ꢀC;
1H NMR (400 MHz, CDCl3)
d
: 2.36 (s, 3H), 3.82 (s, 2H), 6.90 (d,
To a flask containing (Z)-5-hydroxy-2,3-dimethyl-5-phenylpent-
2-enenitrile (101 mg, 0.5 mmol) in CH2Cl2 (5 mL) was added H2SO4
(27 mL, 0.5 mmol). The solution was stirred under reflux. Upon
J¼16.0 Hz, 1H), 7.25e7.38 (m, 9H), 7.45 (s, 1H). 13C NMR (100 MHz,
CDCl3)
d: 18.9, 35.5, 111.6, 119.9, 124.9, 125.5, 127.0, 127.1, 128.4,
128.9, 129.0, 130.2, 134.7, 134.9, 137.2, 137.9, 147.9. IR (KBr)
n
¼2931,
completion, the reaction was quenched with aqueous Na2CO3. The
resulting mixture was extracted with ethyl acetate (5 mLꢁ3).
The combined organic phases were washed with brine, dried,
filtered, and concentrated under vacuum. The residue was
purified by column chromatography on silica gel eluting with ethyl
acetate/hexane (1:10) to give 5,6-dihydro-3,4-dimethyl-6-
phenylpyran-2-one (6a) in a yield of 75% (76 mg, 0.38 mmol).
Other 5,6-dihydropyran-2-one derivatives were obtained in a simi-
lar manner.
2203, 705 cmꢂ1; MS: m/z 294 (MH)þ. HRMS calcd for C19H17ClN:
294.1050 [MþH], found: 294.1058.
4.2.11. (2E,4E)-2-Benzyl-5-(4-bromophenyl)-3-methylpenta-2,4-
dienenitrile (5k). Yield: 144 mg, 85%. White solid, mp: 130e131 ꢀC;
1H NMR (400 MHz, CDCl3)
d: 2.36 (s, 3H), 3.80 (s, 2H), 6.89 (d,
J¼16.0 Hz, 1H), 7.23e7.36 (m, 8H), 7.49 (d, J¼8.4 Hz, 2H). 13C NMR
(100 MHz, CDCl3) d: 18.8, 35.5, 111.1, 120.0, 123.2, 124.3, 127.1, 128.3,
128.6, 128.9, 132.1, 134.8, 135.0, 137.2, 148.1. IR (KBr)
n
¼3023, 2206,
1486, 723 cmꢂ1; MS: m/z 338 (MH)þ. HRMS calcd for C19H17BrN:
338.0544 [MþH], found: 338.0547.
4.3.1. 3,4-Dimethyl-6-phenyl-5,6-dihydro-2H-pyran-2-one (6a). Yield:
76 mg, 75%. White solid, mp: 98e99 ꢀC (lit.6i 97e97.5 ꢀC); 1H NMR
(400 MHz, CDCl3)
d: 1.94 (s, 3H), 1.97 (s, 3H), 2.40e2.45 (m, 1H),
4.2.12. (2E,4E)-2-Allyl-3-methyl-5-phenylpenta-2,4-dienenitrile
2.66e2.74 (m, 1H), 5.32e5.36 (m, 1H), 7.31e7.40 (m, 5H). 13C NMR
(5l). Yield: 86 mg, 82%. Syrup; 1H NMR (400 MHz, CDCl3)
d
: 2.33 (s,
(100 MHz, CDCl3) d: 12.5, 20.2, 38.2, 122.4, 126.0, 128.4, 128.5, 138.9,
3H), 3.20e3.22 (m, 2H), 5.18e5.22 (m, 2H), 5.84e5.92 (m 1H), 6.93
(d, J¼16.0 Hz, 1H), 7.12 (d, J¼15.6 Hz, 1H), 7.31e7.40 (m, 3H), 7.47 (d,
148.6, 166.2. IR (KBr)
n
¼2919, 1692, 1293, 772 cmꢂ1; MS: m/z 203
(MH)þ. HRMS calcd for C13H15O2: 203.1072 [MþH], found: 203.1077.
J¼7.6 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d: 18.7, 33.8, 109.1, 117.5,
119.9, 123.7, 127.2, 128.9, 129.1, 133.2, 135.8, 136.1, 148.6. IR (KBr)
4.3.2. 3,4-Dimethyl-6-(3-chloro)phenyl-5,6-dihydro-2H-pyran-2-
n
¼2933, 2210, 910, 768 cmꢂ1; MS: m/z 210 (MH)þ. HRMS calcd for
one (6b). Yield: 96 mg, 81%. White solid, mp: 90e91 ꢀC; 1H NMR
C15H16N: 210.1283 [MþH], found: 210.1286.
(400 MHz, CDCl3)
2.56e2.64 (m, 1H), 5.24e5.28 (m, 1H), 7.23e7.26 (m, 3H), 7.37 (s,
1H). 13C NMR (100 MHz, CDCl3)
: 12.5, 20.2, 38.0,122.3, 124.1,126.1,
d: 1.89 (s, 3H), 1.94 (s, 3H), 2.37e2.42 (m, 1H),
4.2.13. (2E,4E)-2-Allyl-5-(4-fluorophenyl)-3-methylpenta-2,4-
dienenitrile (5m). Yield: 100 mg, 88%. Yellow solid, mp: 84e86 ꢀC;
d
128.4, 129.9, 134.4, 140.9, 148.7, 165.9. IR (KBr)
n
¼2917, 1700,
1H NMR (400 MHz, CDCl3)
d
: 2.31 (s, 3H), 3.18e3.20 (m, 2H),
5.17e5.21 (m, 2H), 5.83e5.89 (m 1H), 6.88 (d, J¼16.0 Hz, 1H),
7.00e7.08 (m, 3H), 7.43e7.46 (m, 2H). 13C NMR (100 MHz, CDCl3)
18.7, 33.7, 109.1, 115.9, 116.1, 117.6, 119.9, 123.4, 128.86, 128.94,
786 cmꢂ1; MS: m/z 237 (MH)þ. HRMS calcd for C13H14ClO2:
237.0682 [MþH], found: 237.0678.
d:
4.3.3. 3,4-Dimethyl-6-(4-chloro)phenyl-5,6-dihydro-2H-pyran-2-
132.30, 132.33, 133.1, 134.5, 148.4, 161.8, 164.4. IR (KBr)
n
¼2931,
one (6c). Yield: 100 mg, 85%. White solid, mp: 110e111 ꢀC; 1H NMR
2198, 912, 823 cmꢂ1; MS: m/z 228 (MH)þ. HRMS calcd for C15H15FN:
228.1189 [MþH], found: 228.1187.
(400 MHz, CDCl3)
d: 1.92 (s, 3H), 1.96 (s, 3H), 2.38e2.43 (m, 1H),
2.60e2.68 (m, 1H), 5.28e5.32 (m, 1H), 7.32e7.35 (m, 4H). 13C NMR
(100 MHz, CDCl3)
148.4, 165.9. IR (KBr)
HRMS calcd for C13H14ClO2: 237.0682 [MþH], found: 237.0676.
d: 12.5, 20.2, 38.1, 122.5, 127.3, 128.7, 134.1, 137.4,
4.2.14. (2E,4E)-2-Allyl-3-methyl-5-(4-(trifluoromethyl)phenyl)
penta-2,4-dienenitrile (5n). Yield: 118 mg, 85%. Syrup; 1H NMR
(400 MHz, CDCl3) d: 2.34 (s, 3H), 3.21e3.23 (m, 2H), 5.18e5.22 (m,
n
¼2925, 1711, 814 cmꢂ1; MS: m/z 237 (MH)þ.
2H), 5.83e5.89 (m, 1H), 6.93 (d, J¼15.6 Hz, 1H), 7.18 (d, J¼16.0 Hz,
4.3.4. 3,4-Dimethyl-6-(3-bromo)phenyl-5,6-dihydro-2H-pyran-2-
1H), 7.56 (d, J¼8.0 Hz, 2H), 7.62 (d, J¼8.4 Hz, 2H). 13C NMR
one (6d). Yield: 110 mg, 78%. White solid, mp: 97e98 ꢀC; 1H NMR
(100 MHz, CDCl3)
d
: 18.7, 33.8, 110.8, 117.8, 119.6, 125.8, 125.9, 127.3,
(400 MHz, CDCl3) d: 1.92 (s, 3H), 1.96 (s, 3H), 2.40e2.44 (m, 1H),

X. Zhang et al. / Tetrahedron 69 (2013) 5374e5382
5379
2.60e2.68 (m, 1H), 5.27e5.31 (m, 1H), 7.21e7.26 (m, 1H), 7.30 (d,
J¼7.6 Hz, 1H), 7.44 (d, J¼7.2 Hz, 1H), 7.55 (s, 1H). 13C NMR (100 MHz,
CDCl3) d: 20.6, 21.2, 32.3, 38.3, 77.5, 126.0, 126.1, 126.3, 128.3, 128.5,
129.2, 135.8, 138.2, 139.6, 150.4, 165.9. IR (KBr)
n
¼2928, 1710, 1118,
CDCl3)
d
: 12.5, 20.2, 38.1,122.5,122.6,124.5,129.0,130.2,131.4,141.1,
815 cmꢂ1; MS: m/z 293 (MH)þ. HRMS calcd for C20H21O2: 293.1542
[MþH], found: 293.1552.
148.5, 165.8. IR (KBr)
HRMS calcd for C13H14BrO2: 281.0177 [MþH], found: 281.0186.
n
¼2920, 1701, 780 cmꢂ1; MS: m/z 281 (MH)þ.
4.3.12. 3-Allyl-4-methyl-6-phenyl-5,6-dihydro-2H-pyran-2-one
4.3.5. 3,4-Dimethyl-6-(4-bromo)phenyl-5,6-dihydro-2H-pyran-2-
(6l). Yield: 82 mg, 72%. Syrup; 1H NMR (400 MHz, CDCl3)
d: 1.97 (s,
one (6e). Yield: 121 mg, 86%. White solid, mp: 119e120 ꢀC; 1H NMR
3H), 2.42e2.47 (m, 1H), 2.67e2.75 (m, 1H), 3.10e3.24 (m, 2H),
5.00e5.06 (m, 2H), 5.32e5.36 (m,1H), 5.81e5.88 (m,1H), 7.26e7.39
(400 MHz, CDCl3) d: 1.86 (s, 3H), 1.91 (s, 3H), 2.33e2.38 (m, 1H),
2.53e2.60 (m, 1H), 5.21e5.25 (m, 1H), 7.20 (d, J¼8.4 Hz, 2H), 7.42 (d,
(m, 5H). 13C NMR (100 MHz, CDCl3)
d: 20.0, 30.9, 38.3, 77.7, 115.2,
J¼8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d
: 12.5, 20.2, 38.0, 122.2,
124.6, 126.0, 128.4, 128.5, 134.9, 138.8, 150.5, 165.5. IR (KBr)
n
¼2930,
122.3, 127.7, 131.6, 138.0, 148.8, 165.9. IR (KBr)
n
¼2919, 1711, 1135,
1699, 773 cmꢂ1; MS: m/z 229 (MH)þ. HRMS calcd for C15H17O2:
229.1229 [MþH], found: 229.1221.
819 cmꢂ1; MS: m/z 281 (MH)þ. HRMS calcd for C13H14BrO2:
281.0177 [MþH], found: 281.0183.
4.3.13. 3-Allyl-6-(4-fluorophenyl)-4-methyl-5,6-dihydro-2H-pyran-
4.3.6. 3,4-Dimethyl-6-(3-methyl)phenyl-5,6-dihydro-2H-pyran-2-
2-one (6m). Yield: 97 mg, 79%. Syrup; 1H NMR (400 MHz, CDCl3)
d:
one (6f). Yield: 78 mg, 72%. Syrup; 1H NMR (400 MHz, CDCl3)
d:
2.00 (s, 3H), 2.41e2.47 (m, 1H), 2.70e2.77 (m, 1H), 3.11e3.25 (m,
2H), 5.02e5.07 (m, 2H), 5.33e5.36 (m, 1H), 5.82e5.88 (m, 1H),
1.92 (s, 3H), 1.95 (s, 3H), 2.33 (s, 3H), 2.37e2.42 (m, 1H), 2.62e2.70
(m,1H), 5.26e5.30 (m,1H), 7.10e7.16 (m, 2H), 7.21e7.25 (m, 2H). 13C
7.05e7.09 (m, 2H), 7.37e7.40 (m, 2H). 13C NMR (100 MHz, CDCl3)
d:
NMR (100 MHz, CDCl3)
d
: 12.5, 20.2, 21.4, 38.2, 122.3, 123.0, 126.6,
20.1, 30.9, 38.4, 77.1, 115.3, 115.4, 115.6, 124.8, 127.8, 127.9, 134.5,
128.4, 129.1, 138.2, 138.8, 148.9, 166.3. IR (KBr)
n
¼2928, 1708,
134.8, 150.3, 165.4. IR (KBr)
n
¼2931, 1711, 825 cmꢂ1; MS: m/z 247
785 cmꢂ1; MS: m/z 217 (MH)þ. HRMS calcd for C14H17O2: 217.1229
[MþH], found: 217.1236.
(MH)þ. HRMS calcd for C15H16FO2: 247.1134 [MþH], found:
247.1122.
4.3.7. 3,4-Dimethyl-6-(4-(trifluoromethyl)phenyl)-5,6-dihydro-2H-
pyran-2-one (6g). Yield: 119 mg, 88%. White solid, mp: 124e125 ꢀC;
4.3.14. 3-Allyl-4-methyl-6-(4-(trifluoromethyl)-phenyl)-5,6-dihydro-
2H-pyran-2-one (6n). Yield: 127 mg, 86%. Syrup; 1H NMR
(400 MHz, CDCl3) d: 2.00 (s, 3H), 2.47e2.52 (m, 1H), 2.66e2.74 (m,
1H NMR (400 MHz, CDCl3)
d
: 1.91 (s, 3H), 1.96 (s, 3H), 2.42e2.47 (m,
1H), 2.59e2.67 (m, 1H), 5.36e5.40 (m, 1H), 7.50 (d, J¼7.6 Hz, 2H),
1H), 3.11e3.24 (m, 2H), 5.01e5.06 (m, 2H), 5.41e5.45 (m, 1H),
7.60 (d, J¼8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d: 12.4, 20.1, 38.0,
5.79e5.89 (m, 1H), 7.53 (d, J¼8.4 Hz, 2H), 7.64 (d, J¼8.4 Hz, 2H). 13C
122.5, 122.6, 125.3, 125.48, 125.51, 126.2, 130.3, 130.6, 142.9, 148.5,
NMR (100 MHz, CDCl3) d: 20.0, 30.8, 38.2, 76.8, 115.4, 124.8, 125.6,
165.7. IR (KBr)
n
¼2918, 1693, 1330, 836 cmꢂ1; MS: m/z 271 (MH)þ.
126.2, 134.7, 142.7, 150.2, 165.0. IR (KBr)
n
¼2931, 1693, 838 cmꢂ1
;
HRMS calcd for C14H14F3O2: 271.0946 [MþH], found: 271.0952.
MS: m/z 297 (MH)þ. HRMS calcd for C16H16F3O2: 297.1102 [MþH],
found: 297.1108.
4.3.8. 3-Benzyl-4-methyl-6-phenyl-5,6-dihydro-2H-pyran-2-one
(6h). Yield: 95 mg, 68%. White solid, mp: 85e86 ꢀC; 1H NMR
4.3.15. 3,4,5-Trimethyl-6-phenyl-5,6-dihydro-2H-pyran-2-one (6o).
Yield: 86 mg, 80%. White solid, mp: 94e95 ꢀC; 1H NMR (400 MHz,
(400 MHz, CDCl3)
1H), 3.74e3.90 (m, 2H), 5.36e5.39 (m, 1H), 7.18e7.30 (m, 5H),
7.32e7.39 (m, 5H). 13C NMR (100 MHz, CDCl3)
: 20.6, 32.3, 38.3,
d: 2.05 (s, 3H), 2.48e2.53 (m, 1H), 2.75e2.83 (m,
CDCl3)
d
: 1.14 (d, J¼7.2 Hz, 3H), 1.88 (s, 6H), 2.68 (t, J¼6.8 Hz, 1H),
d
5.05 (d, J¼6.4 Hz, 1H), 7.27e7.35 (m, 5H). 13C NMR (100 MHz,
77.5, 126.0, 126.1, 126.4, 128.3, 128.4, 128.6, 138.7, 139.6, 150.2, 165.7.
CDCl3) d: 12.8, 15.9, 18.2, 39.5, 83.1, 122.1, 126.6, 128.2, 128.4,
IR (KBr)
n
¼2918, 1698, 770 cmꢂ1; MS: m/z 279 (MH)þ. HRMS calcd
138.8, 152.2, 165.3. IR (KBr)
n
¼2911, 1699, 771 cmꢂ1; MS: m/z 217
for C19H19O2: 279.1385 [MþH], found: 279.1388.
(MH)þ. HRMS calcd for C14H17O2: 217.1229 [MþH], found:
217.1222.
4.3.9. 3-Benzyl-6-(3-chlorophenyl)-4-methyl-5,6-dihydro-2H-pyran-
2-one (6i). Yield: 125 mg, 80%. White solid, mp: 101e102 ꢀC; 1H
4.3.16. 6-(4-Bromophenyl)-3,4,5-trimethyl-5,6-dihydro-2H-pyran-2-
NMR (400 MHz, CDCl3)
(m, 1H), 3.73e3.88 (m, 2H), 5.30e5.34 (m, 1H), 7.18e7.32 (m, 8H),
7.41 (s, 1H). 13C NMR (100 MHz, CDCl3)
: 20.7, 32.3, 38.1, 76.7, 124.1,
d
: 2.04 (s, 3H), 2.46e2.51 (m,1H), 2.68e2.75
one (6p). Yield: 121 mg, 82%. White solid, mp: 152e154 ꢀC; 1H NMR
(400 MHz, CDCl3)
d
: 1.07 (d, J¼7.2 Hz, 3H), 1.83 (s, 6H), 2.60 (t,
d
J¼6.8 Hz, 1H), 4.97 (d, J¼6.8 Hz, 1H), 7.12 (d, J¼8.4 Hz, 2H), 7.41 (d,
126.2, 126.3, 128.3, 128.5, 128.6, 128.8, 130.0, 134.5, 139.4, 140.7,
J¼8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d: 12.7, 15.8, 18.3, 39.4,
150.4, 165.4. IR (KBr)
n
¼3026, 2937, 1703, 724 cmꢂ1; MS: m/z 313
82.3, 122.0, 122.2, 128.4, 131.5, 137.9, 152.3, 165.1. IR (KBr)
n
¼2918,
(MH)þ. HRMS calcd for C19H18ClO2: 313.0995 [MþH], found:
1698, 770 cmꢂ1; MS: m/z 295 (MH)þ. HRMS calcd for C14H16BrO2:
295.0334 [MþH], found: 295.0341.
313.0988.
4.3.10. 3-Benzyl-6-(4-bromophenyl)-4-methyl-5,6-dihydro-2H-py-
4.3.17. 4-Methyl-3,6-diphenyl-5,6-dihydro-2H-pyran-2-one (6q). Yield:
90 mg, 68%. White solid, mp: 106e107 ꢀC; 1H NMR (400 MHz,
ran-2-one (6j). Yield: 141 mg, 79%. White solid, mp: 120e121 ꢀC;
1H NMR (400 MHz, CDCl3)
d: 2.05 (s, 3H), 2.46e2.51 (m, 1H),
CDCl3)
d
: 1.91 (s, 3H), 2.60e2.65 (m, 1H), 2.86e2.93 (m, 1H), 5.53e5.57
2.69e2.76 (m, 1H), 3.73e3.88 (m, 2H), 5.31e5.35 (m, 1H), 7.17e7.27
(m, 1H), 7.32e7.48 (m, 10H). 13C NMR (100 MHz, CDCl3)
d: 21.5, 38.2,
(m, 7H), 7.50 (d, J¼8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d
: 20.6,
77.8, 126.1, 127.7, 128.1, 128.5, 128.6, 128.9, 130.0, 134.6, 138.7, 151.4,
32.3, 38.2, 122.4, 126.1, 126.5, 127.6, 128.3, 128.5, 131.7, 137.8, 139.4,
164.9. IR (KBr)
calcd for C18H17O2: 265.1229 [MþH], found: 265.1232.
n
¼2915, 1701, 773 cmꢂ1; MS: m/z 265 (MH)þ. HRMS
150.0, 165.4. IR (KBr)
n
¼2925, 1712, 1123, 819 cmꢂ1; MS: m/z 357
(MH)þ. HRMS calcd for C19H18BrO2: 357.0490 [MþH], found:
357.0479.
4.3.18. 6-(3-Chlorophenyl)-4-methyl-3-phenyl-5,6-dihydro-2H-py-
ran-2-one (6r). Yield: 109 mg, 73%. White solid, mp: 120e121 ꢀC;
4.3.11. 3-Benzyl-4-methyl-6-p-tolyl-5,6-dihydro-2H-pyran-2-one
1H NMR (400 MHz, CDCl3)
d
: 1.88 (s, 3H), 2.58e2.83 (m, 2H),
5.47e5.50 (m, 1H), 7.24 (d, J¼6.8 Hz, 2H), 7.32e7.40 (m, 6H), 7.48 (s,
1H). 13C NMR (100 MHz, CDCl3)
: 21.5, 38.0, 77.0,124.2,126.2,127.8,
128.2, 128.60, 128.64, 130.01, 130.04, 134.4, 134.5, 140.8, 151.7, 164.6.
(6k). Yield: 75 mg, 51%. Syrup; 1H NMR (400 MHz, CDCl3)
d: 2.05 (s,
3H), 2.37 (s, 3H), 2.45e2.51 (m, 1H), 2.75e2.82 (m, 1H), 3.75e3.90
d
(m, 2H), 5.33e5.37 (m, 1H), 7.18e7.30 (m, 9H). 13C NMR (100 MHz,

5380
X. Zhang et al. / Tetrahedron 69 (2013) 5374e5382
IR (KBr)
n
¼3058, 2909, 1703, 788 cmꢂ1; MS: m/z 299 (MH)þ. HRMS
150.2, 166.8. IR (KBr)
n
¼3020, 2926, 1708, 708 cmꢂ1; MS: m/z 217
calcd for C18H16ClO2: 299.0839 [MþH], found: 299.0838.
(MH)þ. HRMS calcd for C14H17O2: 217.1229 [MþH], found: 217.1226.
4.3.19. 6-(4-Chlorophenyl)-4-methyl-3-phenyl-5,6-dihydro-2H-py-
4.3.26. 3,4-Dibenzyl-6-methyl-5,6-dihydro-2H-pyran-2-one (6z). Yield:
ran-2-one (6s). Yield: 116 mg, 78%. White solid, mp: 128e130 ꢀC;
111 mg, 76%. Syrup; 1H NMR (400 MHz, CDCl3)
d
: 1.33 (d, J¼6.4 Hz,
1H NMR (400 MHz, CDCl3)
d
: 1.90 (s, 3H), 2.58e2.63 (m, 1H),
2.80e2.87 (m, 1H), 5.49e5.53 (m, 1H), 7.23e7.25 (m, 2H), 7.32e7.41
(m, 7H). 13C NMR (100 MHz, CDCl3)
: 21.5, 38.1, 127.4, 127.8, 128.2,
3H), 2.15e2.25 (m, 2H), 3.68 (s, 2H), 3.89e3.99 (m, 2H), 4.41e4.46
(m, 1H), 7.01e7.03 (m, 2H), 7.18e7.31 (m, 8H). 13C NMR (100 MHz,
d
CDCl3) d: 20.6, 32.2, 35.1, 39.6, 72.9, 126.2, 126.7, 127.0, 128.3,
128.8, 129.9, 134.3, 134.4, 137.2, 151.3, 164.6. IR (KBr)
n
¼2922, 1703,
128.5, 128.78, 128.85, 136.6, 139.8, 152.0, 166.4. IR (KBr)
n
¼3024, 2929,
827 cmꢂ1; MS: m/z 299 (MH)þ. HRMS calcd for C18H16ClO2:
299.0839 [MþH], found: 299.0832.
1709, 706 cmꢂ1; MS: m/z 293 (MH)þ. HRMS calcd for C20H21O2:
293.1542 [MþH], found: 293.1546.
4.3.20. 6-(4-Bromophenyl)-4-methyl-3-phenyl-5,6-dihydro-2H-py-
4.3.27. 4-Benzyl-3-methyl-6-phenyl-5,6-dihydro-2H-pyran-2-one
ran-2-one (6t). Yield: 146 mg, 85%. White solid, mp: 149e150 ꢀC;
(6aa). Yield: 100 mg, 72%. White solid, mp: 112e113 ꢀC; 1H NMR
1H NMR (400 MHz, CDCl3)
d
: 1.90 (s, 3H), 2.58e2.63 (m, 1H),
2.78e2.82 (m, 1H), 5.49e5.52 (m, 1H), 7.22e7.24 (m, 2H), 7.34e7.40
(m, 5H), 7.52e7.55 (m, 2H). 13C NMR (100 MHz, CDCl3)
: 21.5, 38.1,
(400 MHz, CDCl3)
1H), 3.62e3.71 (m, 2H), 5.28e5.32 (m, 1H), 7.14 (d, J¼7.6 Hz, 2H),
7.24e7.35 (m, 8H). 13C NMR (100 MHz, CDCl3)
: 12.9, 35.8, 39.6,
d: 2.14 (s, 1H), 2.36e2.42 (m, 1H), 2.52e2.60 (m,
d
d
122.4, 127.7,127.8,128.2, 128.8, 130.0,131.8,134.4, 137.8,151.4,164.6.
78.0, 123.3, 126.0, 127.0, 128.4, 128.5, 128.6, 128.9, 136.8, 138.7,
IR (KBr)
n
¼2916, 1699, 826 cmꢂ1; MS: m/z 343 (MH)þ. HRMS calcd
150.2, 166.4. IR (KBr)
n
¼3025, 2932, 1700, 708 cmꢂ1; MS: m/z 279
for C18H16BrO2: 343.0334 [MþH], found: 343.0349.
(MH)þ. HRMS calcd for C19H19O2: 279.1385 [MþH], found:
279.1375.
4.3.21. 4-Methyl-3-phenyl-6-m-tolyl-5,6-dihydro-2H-pyran-2-one
(6u). Yield: 71 mg, 51%. White solid, mp: 116e118 ꢀC; 1H NMR
(400 MHz, CDCl3)
2.85e2.93 (m, 1H), 5.50e5.54 (m, 1H), 7.18 (d, J¼7.2 Hz, 1H),
7.25e7.42 (m, 8H). 13C NMR (100 MHz, CDCl3)
: 21.4, 21.5, 38.3,
d
: 1.91 (s, 3H), 2.39 (s, 3H), 2.59e2.64 (m, 1H),
4.4. Typical procedure for the preparation of 7
d
To a flask containing (E)-5-hydroxy-3-methyl-2-phenyl-5-(4-
(trifluoromethyl)phenyl)pent-2-enenitrile (166 mg, 0.5 mmol) in
CH2Cl2 (5 mL) was added H2SO4 (27 mL, 0.5 mmol). The solution
77.9, 123.1, 126.7, 127.7, 128.1, 128.5, 128.8, 129.2, 130.0, 134.6, 138.4,
138.6, 151.4, 164.9. IR (KBr)
n
¼2930, 1708, 771 cmꢂ1; MS: m/z 279
(MH)þ. HRMS calcd for C19H19O2: 279.1385 [MþH], found:
was stirred under reflux. Upon completion, the mixture was neu-
tralized with aqueous Na2CO3, and then extracted with ethyl ace-
tate (5 mLꢁ3). The combined organic phases were washed with
brine, dried, filtered, and concentrated under vacuum. The residue
was purified by column chromatography on silica gel eluting with
ethyl acetate/hexane (1:20) to give 2-methyl-4-(4-(tri-
fluoromethyl)phenyl)-3,4-dihydronaphthalene-1-carbonitrile (7)
in a yield of 68% (107 mg, 0.34 mmol).
279.1381.
4.3.22. 4-Methyl-3-phenyl-6-p-tolyl-5,6-dihydro-2H-pyran-2-one
(6v). Yield: 67 mg, 48%. White solid, mp: 129e130 ꢀC; 1H NMR
(400 MHz, CDCl3)
2.85e2.92 (m, 1H), 5.50e5.53 (m, 1H), 7.21e7.26 (m, 4H), 7.32e7.42
(m, 5H). 13C NMR (100 MHz, CDCl3)
: 21.2, 21.5, 38.2, 77.8, 126.0,
d: 1.90 (s, 3H), 2.38 (s, 3H), 2.58e2.63 (m, 1H),
d
127.7, 128.1, 128.8, 129.3, 130.0, 134.6, 135.7, 138.3, 151.4, 165.0. IR
(KBr)
n
¼2922, 1698, 718 cmꢂ1; MS: m/z 279 (MH)þ. HRMS calcd for
4.4.1. 2-Methyl-4-(4-(trifluoromethyl)phenyl)-3,4-dihydrona-phthalene-
1-carbonitrile (7). Yield: 107 mg, 68%. Syrup; 1H NMR (400 MHz,
C19H19O2: 279.1385 [MþH], found: 279.1376.
CDCl3)
(d, J¼7.2 Hz, 1H), 7.19e7.24 (m, 3H), 7.34 (t, J¼7.6 Hz, 1H), 7.56e7.59
(m, 3H). 13C NMR (100 MHz, CDCl3)
: 23.4, 38.2, 42.7, 109.6, 116.2,
d: 2.24 (s, 3H), 2.69e2.86 (m, 2H), 4.24 (t, J¼7.6 Hz, 1H), 6.86
4.3.23. 4-Methyl-3-phenyl-6-(4-(trifluoromethyl)- phenyl)-5,6-
dihydro-2H-pyran-2-one (6w). Yield: 150 mg, 90%. White solid,
d
mp: 123e124 ꢀC; 1H NMR (400 MHz, CDCl3)
d
: 1.92 (s, 3H),
124.9, 125.7, 127.9, 128.4, 128.6, 129.2, 129.6, 134.6, 146.9, 152.9. MS: m/z
314 (MH)þ. HRMS calcd for C19H15F3N: 314.1157 [MþH], found:
314.1158.
2.63e2.68 (m, 1H), 2.82e2.89 (m, 1H), 5.60e5.63 (m, 1H), 7.24 (d,
J¼6.8 Hz, 1H), 7.35e7.43 (m, 3H), 7.60 (d, J¼8.0 Hz, 2H), 7.68 (d,
J¼8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d: 21.6, 38.2, 76.9, 125.6,
125.7, 126.2, 127.9, 128.2, 128.9, 129.9, 134.2, 142.6, 151.2, 164.4. IR
(KBr)
n
¼2947, 2867, 1710, 1130, 836, 701 cmꢂ1; MS: m/z 333
4.5. Typical procedure for the one-pot preparation of 8a
(Table 4)
(MH)þ. HRMS calcd for C19H16F3O2: 333.1102 [MþH], found:
333.1089.
To a flask containing (E)-5-hydroxy-3-methyl-2-phenyl-5-(4-
(trifluoromethyl)phenyl)pent-2-enenitrile (166 mg, 0.5 mmol) in
4.3.24. 6-(4-Bromophenyl)-4,5-dimethyl-3-phenyl-5,6-dihydro-2H-
pyran-2-one (6x). Yield: 153 mg, 86%. White solid, mp:
CH2Cl2 (5 mL) was added H2SO4 (27 mL, 0.5 mmol). The solution was
138e140 ꢀC; 1H NMR (400 MHz, CDCl3)
d
: 1.26 (d, J¼6.8 Hz, 3H),
stirred under reflux. Upon complete consumption of the starting
material as indicated by TLC analysis, DDQ (114 mg, 0.5 mmol) was
added. The mixture was stirred under reflux. Upon completion, the
mixture was filtered through Celite and the filter cake was washed
twice with CH2Cl2 (5 mL). The combined filtrate was neutralized
with aqueous Na2CO3, and then extracted with ethyl acetate
(5 mLꢁ3). The combined organic phases were washed with brine,
dried, filtered, and concentrated under vacuum. The residue was
purified by column chromatography on silica gel eluting with ethyl
acetate/hexane (1:20) to give 2-methyl-4-(4-(trifluoromethyl)-
phenyl)-1-naphthonitrile (8a) in a yield of 63% (98 mg, 0.32 mmol).
Other naphthalene-1-carbonitriles were obtained in a similar
manner.
1.79 (s, 3H), 2.80e2.84 (m, 1H), 5.21 (d, J¼6.8 Hz, 1H), 7.15 (d,
J¼7.2 Hz, 2H), 7.26e7.39 (m, 5H), 7.53 (d, J¼8.4 Hz, 2H). 13C NMR
(100 MHz, CDCl3) d: 15.9, 19.7, 39.7, 82.5, 122.4, 127.8, 128.2, 128.4,
128.6, 129.9, 131.7, 134.7, 137.7, 155.0, 163.8. IR (KBr)
n
¼2921, 1711,
1010, 697 cmꢂ1; MS: m/z 357 (MH)þ. HRMS calcd for C19H18BrO2:
357.0490 [MþH], found: 357.0498.
4.3.25. 4-Benzyl-3,6-dimethyl-5,6-dihydro-2H-pyran-2-one (6y). Yield:
88 mg, 81%. Syrup; 1H NMR (400 MHz, CDCl3)
d
: 1.32 (d, J¼6.0 Hz,
3H), 2.06 (s, 3H), 2.15e2.20 (m, 2H), 3.54e3.67 (m, 2H), 4.38e4.42 (m,
2H), 7.14 (d, J¼7.2 Hz, 1H), 7.26e7.34 (m, 3H). 13C NMR (100 MHz,
CDCl3) d: 12.8, 20.6, 35.1, 39.5, 73.0, 122.9, 126.9, 128.6, 128.9, 137.0,

X. Zhang et al. / Tetrahedron 69 (2013) 5374e5382
5381
4.5.1. 2-Methyl-4-(4-(trifluoromethyl)phenyl)-1-naphthonitrile
(8a). Yield: 98 mg, 63%. White solid, mp: 156e157 ꢀC; 1H NMR
2.83 (s, 3H), 7.33e7.36 (m, 3H), 7.45e7.54 (m, 4H), 7.60e7.67 (m,
2H), 7.99 (d, J¼8.0 Hz, 1H), 8.02 (d, J¼8.0 Hz, 1H), 8.36 (d, J¼8.4 Hz,
(400 MHz, CDCl3)
d
: 2.80(s, 3H), 7.35 (s,1H), 7.52(t, J¼7.6 Hz,1H), 7.59
1H). 13C NMR (100 MHz, CDCl3)
d: 21.4, 109.1, 117.3, 125.1, 125.4,
(d, J¼7.6 Hz, 2H), 7.70 (t, J¼7.6 Hz, 1H), 7.78e7.80 (m, 3H), 8.30 (d,
126.0, 126.2, 126.5, 126.7, 127.3, 127.6, 128.4, 128.5, 128.7, 129.7,
J¼8.0 Hz,1H). 13C NMR (100 MHz, CDCl3)
d: 21.3, 109.5, 116.9, 125.38,
131.0, 132.2, 133.0, 133.5, 136.8, 142.4, 143.7. IR (KBr)
n
¼3055, 2918,
125.45, 125.49, 126.2, 127.0, 128.6, 128.7, 129.4, 130.1, 130.6, 133.2,
2219, 804 cmꢂ1; MS: m/z 294 (MH)þ. HRMS calcd for C22H16N:
294.1283 [MþH], found: 294.1285.
142.3, 142.8, 143.4. IR (KBr)
n
¼2921, 2216, 818 cmꢂ1; MS: m/z 312
(MH)þ. HRMS calcd for C19H13F3N: 312.1000 [MþH], found: 312.1011.
4.5.9. 4-(4-Bromophenyl)-2,3-dimethyl-1-naphthonitrile (8i). Yield:
104 mg, 62%. White solid, mp: 162e163 ꢀC; 1H NMR (400 MHz,
4.5.2. 4-(3-Chlorophenyl)-2-methyl-1-naphthonitrile (8b). Yield: 72
mg, 52%. White solid, mp: 114e115 ꢀC; 1H NMR (400 MHz, CDCl3)
d:
CDCl3)
d
: 2.17 (s, 3H), 2.74 (s, 3H), 7.10 (d, J¼8.4 Hz, 2H), 7.33 (d,
2.78 (s, 3H), 7.34 (s, 2H), 7.45e7.46 (m, 3H), 7.51 (t, J¼8.0 Hz, 1H),
J¼8.4 Hz, 1H), 7.39 (t, J¼8.0 Hz, 1H), 7.57 (t, J¼7.6 Hz, 1H), 7.66 (d,
7.67 (t, J¼7.6 Hz, 1H), 7.84 (d, J¼8.8 Hz, 1H), 8.27 (d, J¼8.4 Hz, 1H).
J¼8.0 Hz, 2H), 8.20 (d, J¼8.0 Hz, 1H). 13C NMR (100 MHz, CDCl3)
d:
13C NMR (100 MHz, CDCl3)
d: 21.3, 109.2, 117.1, 125.3, 126.4, 126.9,
18.0, 20.1, 109.7, 117.6, 121.9, 124.9, 126.6, 126.8, 127.5, 131.0, 131.2,
127.9, 128.3, 128.6, 128.7, 129.4, 129.7, 129.8, 133.2, 134.5, 140.9,
131.3, 131.9, 133.1, 137.8, 142.0, 142.6. IR (KBr)
n
¼2952, 2211, 817,
142.3, 143.4. IR (KBr)
n
¼3059, 2921, 2218, 799, 765 cmꢂ1; MS: m/z
770 cmꢂ1; MS: m/z 336 (MH)þ. HRMS calcd for C19H15BrN:
336.0388 [MþH], found: 336.0382.
278 (MH)þ. HRMS calcd for C18H13ClN: 278.0737 [MþH], found:
278.0745.
4.6. Typical procedure for the preparation of 2-(4-methyl-3,4-
4.5.3. 4-(4-Chlorophenyl)-2-methyl-1-naphthonitrile (8c). Yield: 74
mg, 53%. White solid, mp: 148e149 ꢀC; 1H NMR (400 MHz, CDCl3)
dihydronaphthalene-2(1H)-ylidene)propanenitrile (9a) (Table 5)
d
: 2.78 (s, 3H), 7.33 (s, 1H), 7.39 (d, J¼8.4 Hz, 2H), 7.48e7.52 (m, 3H),
7.68 (t, J¼7.6 Hz, 1H), 7.84 (d, J¼8.4 Hz, 1H), 8.27 (d, J¼8.4 Hz, 1H).
13C NMR (100 MHz, CDCl3)
: 21.3, 109.0, 117.1, 125.3, 126.4, 126.8,
To a flask containing (E)-3-benzyl-5-hydroxy-2-methylhex-2-
enenitrile (108 mg, 0.5 mmol) in CH2Cl2 (5 mL) was added H2SO4
(27 mL, 0.5 mmol). The solution was stirred under reflux. Upon
d
128.5, 128.68, 128.74, 129.5, 131.0, 133.3, 134.3, 137.5, 142.3, 143.7. IR
completion, the reaction was quenched with aqueous Na2CO3 and
the mixture was extracted with ethyl acetate (5 mLꢁ3). The com-
bined organic phases were washed with brine, dried, filtered, and
concentrated under vacuum. The residue was purified by column
chromatography on silica gel eluting with ethyl acetate/hexane
(1:10) to give 2-(4-methyl-3,4-dihydronaphthalene-2(1H)-ylidene)
propanenitrile (9a) in a yield of 56% (55 mg, 0.28 mmol). Other 2-
methylene-1,2,3,4-tetrahydronaphthalenes were obtained in
a similar manner.
(KBr)
n
¼2923, 2218, 813 cmꢂ1; MS: m/z 278 (MH)þ. HRMS calcd for
C18H13ClN: 278.0737 [MþH], found: 278.0743.
4.5.4. 4-(4-Bromophenyl)-2-methyl-1-naphthonitrile (8d). Yield: 90
mg, 56%. White solid, mp: 164e165 ꢀC; 1H NMR (400 MHz, CDCl3)
d
: 2.78 (s, 3H), 7.32e7.34 (m, 3H), 7.51 (t, J¼7.6 Hz, 1H), 7.64e7.70
(m, 3H), 7.83 (d, J¼8.4 Hz, 1H), 8.28 (d, J¼8.4 Hz, 1H). 13C NMR
(100 MHz, CDCl3) d: 21.3, 109.1, 117.1, 122.5, 125.3, 126.4, 126.8,
128.5, 128.6, 129.5, 131.3, 131.7, 133.3, 138.0, 142.3, 143.7. IR (KBr)
n
¼2946, 2210, 819 cmꢂ1; MS: m/z 322 (MH)þ. HRMS calcd for
4.6.1. (Z)-2-(4-Methyl-3,4-dihydronaphthalen-2(1H)-ylidene)pro-
C18H13BrN: 322.0231 [MþH], found: 322.0241.
panenitrile (9a). Yield: 55 mg, 56%. Syrup; 1H NMR (400 MHz,
CDCl3)
2.62e2.67 (m, 1H), 3.02e3.07 (m, 1H), 3.71e4.01 (m, 2H), 7.18e7.26
(m, 4H). 13C NMR (100 MHz, CDCl3)
: 15.7, 20.2, 33.2, 35.9, 37.2,
d
: 1.31 (d, J¼6.8 Hz, 3H), 1.93 (s, 3H), 2.29e2.35 (m, 1H),
4.5.5. 2-Methyl-4-m-tolyl-1-naphthonitrile (8e). Yield: 54 mg, 42%.
White solid, mp: 126e128 ꢀC; 1H NMR (400 MHz, CDCl3)
d
: 2.46 (s,
d
3H), 2.78 (s, 3H), 7.25e7.51 (m, 6H), 7.66 (t, J¼7.6 Hz, 1H), 7.92 (d,
102.5, 119.4, 125.8, 126.56, 126.63, 128.0, 134.0, 141.4, 154.8. IR (KBr)
n
J¼8.4 Hz, 1H), 8.28 (d, J¼8.4 Hz, 1H). 13C NMR (100 MHz, CDCl3)
d:
¼2962, 2209, 1309, 758 cmꢂ1; MS: m/z 198 (MH)þ. HRMS calcd for
21.3, 21.5, 108.5, 117.3, 125.2, 126.5, 126.8, 126.9, 128.3, 128.6, 128.9,
C14H16N: 198.1283 [MþH], found: 198.1276.
129.8, 130.3, 133.3, 138.2, 139.1, 142.3, 145.2. IR (KBr)
n
¼2931, 2218,
810 cmꢂ1; MS: m/z 258 (MH)þ. HRMS calcd for C19H16N: 258.1283
[MþH], found: 258.1282.
4.6.2. (Z)-2-(4-Methyl-3,4-dihydronaphthalen-2(1H)-ylidene)-3-
phenylpropanenitrile (9b). Yield: 73 mg, 53%. Syrup; 1H NMR
(400 MHz, CDCl3)
2.78e2.84 (m, 1H), 3.05e3.10 (m, 1H), 3.61e3.71 (m, 2H), 3.83e4.10
(m, 2H), 7.22e7.39 (m, 9H). 13C NMR (100 MHz, CDCl3)
: 20.4, 33.3,
35.5, 36.1, 37.4, 107.6, 118.8, 126.0, 126.7, 126.8, 127.0, 128.2, 128.4,
d
: 1.35 (d, J¼7.2 Hz, 3H), 2.48e2.54 (m, 1H),
4.5.6. 2-Methyl-4-p-tolyl-1-naphthonitrile (8f). Yield: 52 mg, 40%.
White solid, mp: 134e135 ꢀC; 1H NMR (400 MHz, CDCl3)
d: 2.47 (s,
d
3H), 2.78 (s, 3H), 7.32e7.37 (m, 5H), 7.48 (t, J¼7.6 Hz, 1H), 7.66 (t,
J¼7.6 Hz, 1H), 7.93 (d, J¼7.6 Hz, 1H), 8.27 (d, J¼8.4 Hz, 1H). 13C NMR
128.8, 133.7, 137.3, 141.3, 155.6. IR (KBr)
n
¼3062, 2963, 2209,
(100 MHz, CDCl3)
d: 21.26, 21.29, 108.4, 117.3, 125.2, 126.5, 126.8,
758 cmꢂ1; MS: m/z 274 (MH)þ. HRMS calcd for C20H20N: 274.1596
[MþH], found: 274.1605.
128.3, 128.7, 129.2, 129.6, 129.8, 133.3, 136.2, 138.0, 142.3, 145.1. IR
(KBr)
n
¼2959, 2918, 2214, 1286, 834 cmꢂ1; MS: m/z 258 (MH)þ.
HRMS calcd for C19H16N: 258.1283 [MþH], found: 258.1273.
4.6.3. (Z)-2-(4-Methyl-3,4-dihydronaphthalen-2(1H)-ylidene)-2-
phenylacetonitrile (9c). Yield: 56 mg, 43%. Syrup; 1H NMR
4.5.7. 2-Methyl-4-phenyl-1-naphthonitrile (8g). Yield: 74 mg, 61%.
(400 MHz, CDCl3)
2.70e2.75 (m, 1H), 2.96e3.01 (m, 1H), 3.96e4.19 (m, 2H), 7.22e7.26
(m, 4H), 7.31e7.44 (m, 5H). 13C NMR (100 MHz, CDCl3)
: 20.7, 33.7,
36.6, 37.1, 110.0, 118.5, 126.2, 126.6, 126.7, 128.3, 128.3, 128.4, 128.7,
d
: 1.21 (d, J¼6.8 Hz, 3H), 2.45e2.50 (m, 1H),
White solid, mp: 114e115 ꢀC; 1H NMR (400 MHz, CDCl3)
d: 2.79 (s,
3H), 7.36 (s, 1H), 7.45e7.54 (m, 6H), 7.67 (t, J¼7.6 Hz, 1H), 7.91 (d,
d
J¼8.4 Hz, 1H), 8.28 (d, J¼8.4 Hz, 1H). 13C NMR (100 MHz, CDCl3)
d:
21.3, 108.6, 117.2, 125.2, 126.6, 126.8, 128.1, 128.4, 128.5, 128.7,
128.8, 129.0, 129.1, 133.3, 141.3, 157.2. IR (KBr)
n
¼3061, 2960, 2213,
129.67, 129.74, 133.3, 139.1, 142.3, 145.1. IR (KBr)
n
¼3053, 2921, 2217,
759, 699 cmꢂ1; MS: m/z 260 (MH)þ. HRMS calcd for C19H18N:
260.1439 [MþH], found: 260.1442.
766, 704 cmꢂ1; MS: m/z 244 (MH)þ. HRMS calcd for C18H14N:
244.1126 [MþH], found: 244.1136.
4.6.4. (Z)-2-(4-phenyl-3,4-dihydronaphthalen-2(1H)-ylidene)pro-
4.5.8. 3-Methyl-1,10-binaphthyl-4-carbonitrile (8h). Yield: 52 mg,
panenitrile (9d). Yield: 62 mg, 48%. Syrup; 1H NMR (400 MHz,
35%. White solid, mp: 120e122 ꢀC; 1H NMR (400 MHz, CDCl3)
d:
CDCl3) d: 1.68 (s, 3H), 2.83e2.86 (m, 2H), 3.84e4.29 (m, 3H), 6.91 (d,

5382
X. Zhang et al. / Tetrahedron 69 (2013) 5374e5382
J¼7.6 Hz, 1H), 7.08 (d, J¼7.6 Hz, 2H), 7.12e7.34 (m, 6H). 13C NMR
Fabbroni, S.; Gentilucci, L.; Perciaccante, R.; Piccinelli, F.; Tolomelli, A. Tetrahe-
dron 2004, 60, 5031 and references therein; (h) Hanessian, S.; Seid, M.; Nilsson,
I. Tetrahedron Lett. 2002, 43, 1991; (i) Carlson, R. M.; Oyler, A. R.; Peterson, J. R. J.
Org. Chem. 1975, 40, 1610.
(100 MHz, CDCl3) d: 15.4, 36.2, 37.3, 45.5, 103.1, 119.4, 126.6, 126.8,
127.1, 128.2, 128.3, 128.4, 128.6, 134.6, 138.8, 143.2, 153.5. IR (KBr)
¼3055, 2953, 2212, 760 cmꢂ1; MS: m/z 260 (MH)þ. HRMS calcd for
7. (a) Seong, B. L.; Han, M. L. Chem. Lett. 1982, 627; (b) Trujillo, J. M.; Jorge, R. E.;
Boada, J. Phytochemistry 1990, 29, 2991; (c) Ward, R. S. Nat. Prod. Rep. 1995, 12,
183; (d) Ukita, T.; Nakamura, Y.; Kubo, A.; Yamamoto, Y.; Takahashi, M.; Kotera,
J.; Ikeo, T. J. Med. Chem. 1999, 42, 1293; (e) Xie, X.; Kozlowski, M. C. Org. Lett.
2001, 3, 2661; (f) Silva, O.; Gomes, E. T. J. Nat. Prod. 2003, 66, 447; (g) Dai, J.; Liu,
n
C19H18N: 260.1439 [MþH], found: 260.1441.
Acknowledgements
€
Y.; Zhou, Y.-D.; Nagle, D. G. J. Nat. Prod. 2007, 70, 1824; (h) Brasholz, M.; Sorgel,
S.; Azap, C.; Reissig, H.-U. Eur. J. Org. Chem. 2007, 3801; (i) Krohn, K.; Kounam, S.
F.; Cludius-Brandt, S.; Draeger, S.; Schulz, B. Eur. J. Org. Chem. 2008, 3615; (j)
Lowell, A. N.; Fennie, M. W.; Kozlowski, M. C. J. Org. Chem. 2008, 73, 1911.
8. Watson, M. D.; Fechtenkotter, A.; Mullen, K. Chem. Rev. 2001, 101, 1267.
9. (a) Kim, S. H.; Kim, Y. M.; Lee, H. S.; Kim, J. N. Tetrahedron Lett. 2010, 51, 1592;
(b) Balamurugan, R.; Gudla, V. Org. Lett. 2009, 11, 3116; (c) Duan, S.; Sinha-
Mahapatra, D. K.; Herndon, J. W. Org. Lett. 2008, 10, 1541; (d) Zhang, X.;
Sarkar, S.; Larock, R. C. J. Org. Chem. 2006, 71, 236; (e) Wang, Y.; Xu, J.;
Burton, D. J. J. Org. Chem. 2006, 71, 7780; (f) Lewis, K. D.; Matzger, A. J. J. Am.
Chem. Soc. 2005, 127, 9968; (g) Nishii, Y.; Yoshida, T.; Asano, H.; Wakasugi, K.;
Morita, J.; Aso, Y.; Yoshida, E.; Motoyoshiya, J.; Aoyama, H.; Tanabe, Y. J. Org.
Chem. 2005, 70, 2667; (h) de Koning, C. B.; Rousseau, A. L.; van Otterlo, W. A.
L. Tetrahedron 2003, 59, 7; (i) Kabalka, G. W.; Ju, Y.; Wu, Z. J. Org. Chem. 2003,
We are grateful to the National Natural Science Foundation of
China (21172057, 21272058), RFDP (20114104110005), and PCSIRT
(IRT 1061) for financial support.
Supplementary data
The X-ray crystal structures of 5e, 6b, 8i and the copies of 1H and
13C NMR spectra of 5ae5p, 6ae6aa, 7, 8ae8i, and 9ae9d. Supple-
mentary data associated with this article can be found in the online
version, at http://dx.doi.org/10.1016/j.tet.2013.04.118.
ꢀ
ꢀ
68, 7915; (j) Barluenga, J.; Vazquez-Villa, H.; Ballesteros, A.; Gonzalez, J. M.
Org. Lett. 2003, 5, 4121; (k) Viswanathan, G. S.; Wang, M.; Li, C.-J. Angew.
Chem., Int. Ed. 2002, 41, 2138.
References and notes
10. For examples in which tetrahydronaphthalene derivatives act as scaffolds of
biological agents or parts of naturally occurring products, please see: (a) Pinto,
O.; Sardinha, J.; Vaz, P. D.; Piedade, F.; Calhorda, J. J.; Abramovitch, R.; Zazareth,
N.; Pinto, M.; Nascimento, M. S. J.; Rauter, A. P. J. Med. Chem. 2010, 54, 3175; (b)
Barker, M.; Clackers, M.; Copley, R.; Demaine, D. A.; Humphreys, D.; Inglis, G. G.
A.; Johnston, M. J.; Jones, H. T.; Haase, M. V.; House, D.; Loiseau, R.; Nisbet, L.;
Pacquet, F.; Skone, P. A.; Shanahan, S. E.; Tape, D.; Vinader, V. M.; Washingtone,
M.; Uings, I.; Upton, R.; McLay, I. M.; Macdonald, S. J. F. J. Med. Chem. 2006, 49,
4216; (c) Kim, I.-H.; Par, Y.-K.; Hammock, B. D.; Nishi, K. J. Med. Chem. 2011, 54,
1752; (d) Pu, J.; Deng, K. W.; Butera, J.; Chlenov, M.; Gilbert, A.; Kagan, M.;
Mattes, J.; Resnick, L. Tetrahedron 2010, 66, 1963; (e) Ahmad, S.; Doweyko, L.;
Ashfaq, A.; Ferrara, F. N.; Bisaha, F. S.; Schmidt, J. B.; DiMarco, J.; Conder, M.
L.; Jenkins-West, T.; Normandin, D. E.; Russell, A. D.; Smith, M. A.; Levesque,
P. C.; Lodge, N. J.; Lloyd, J.; Stein, P. D.; Atwal, K. S. Bioorg. Med. Chem. Lett.
2004, 14, 99.
1. (a) Fan, X. S.; Wang, Y. Y.; Qu, Y. Y.; Xu, H. Y.; He, Y.; Zhang, X. Y.; Wang, J. J. J. Org.
Chem. 2011, 76, 982; (b) Zhang, X. Y.; Jia, X. F.; Fang, L. L.; Liu, N.; Wang, J. J.; Fan,
X. S. Org. Lett. 2011, 13, 5024; (c) Xu, H. Y.; Zhang, X. Y.; He, Y.; Guo, S. H.; Fan, X.
S. Chem. Commun. 2012, 3121.
2. (a) Mandai, T.; Gotoh, J.; Otera, J.; Kawada, M. Chem. Lett. 1980, 313; (b)
Chikhalikar, S.; Bhawe, V.; Ghotekar, B.; Jachak, M.; Ghagare, M. J. Org. Chem.
2011, 76, 3829; (c) Nakao, Y.; Yada, A.; Ebata, S.; Hiyama, T. J. Am. Chem. Soc.
2007, 129, 2428; (d) Chow, T. J.; Lin, R.; Ko, C. W.; Tao, Y. T. J. Mater. Chem. 2002,
12, 42.
3. Manimekalai, A.; Balamurugan, A. J. Mol. Struct. 2011, 995, 78.
4. Recent examples on the preparation of 2,4-dienenitriles: (a) Tomioka, T.;
Sankranti, R.; Vaughan, T. G.; Maejima, T.; Yanase, T. J. Org. Chem. 2011, 76, 8053;
(b) Qin, C.; Jiao, N. J. Am. Chem. Soc. 2010, 132, 15893; (c) Krishna, C. V.; Bhonde,
V. R.; Devendar, A.; Maitra, S.; Mukkanti, K.; Iqbal, J. Tetrahedron Lett. 2008, 49,
2013; (d) Huang, H. Y.; Wang, H. M.; Kang, I. J.; Chen, L. C. J. Chin. Chem. Soc.
2003, 50, 1053; (e) Clary, K. N.; Back, T. G. Synlett 2007, 2995.
5. Recent examples on intramolecular Pinner reaction, see: (a) Grossman, R. B.;
Rasne, R. M. Org. Lett. 2001, 3, 4027; (b) Silvina, V. J.; Pellegrinet, S. C.; Colombo,
M. I. J. Org. Chem. 2007, 72, 3702.
11. For a recent FriedeleCrafts reaction of tetrahydronaphthols, see: Penick, M. A.;
Mahindaratne, P. D.; Guiterrez, R. D.; Smith, T. D.; Tiekink, R. T.; Negrete, G. R. J.
Org. Chem. 2008, 73, 6378.
ꢀ
12. For recent examples for the preparation tetrahydronaphthalenes, see: (a) Grise,
C. M.; Barriault, L. Org. Lett. 2006, 8, 5905; (b) Riou, M.; Barriault, L. J. Org. Chem.
2008, 73, 7436; (c) Huang, W.; Zheng, P. Z.; Zhang, Z. X.; Liu, R. T.; Chen, Z. X.;
Zhou, X. G. J. Org. Chem. 2008, 73, 6845; (d) Kuwano, R.; Shige, T. J. Am. Chem.
Soc. 2007, 129, 3802; (e) Faul, M. M.; Ratz, A. M.; Sullivan, K. A.; Trankle, W. G.;
Winneroske, L. L. J. Org. Chem. 2011, 66, 5772.
6. (a) Fisyuk, A. S.; Bundel, Y. G. Chem. Heterocycl. Compd. 1999, 35, 125; (b) Fisyuk,
A. S.; Poendaev, N. V. Molecules 2002, 7, 124; (c) Fisyuk, A. S.; Bogza, Y. P.;
Poendaev, N. V.; Goncharov, D. S. Chem. Heterocycl. Compd. 2010, 46, 844; (d)
Tolmachova, N. A.; Dolovanyuk, V. G.; Gerus, I. I.; Kondratov, I. S.; Polovinko, V.
V.; Bergander, K.; Haufe, G. Synthesis 2011, 1149; (e) Golovach, N. M.; Sukach, V.
13. For 2-methylene-1,2,3,4-tetrahydronaphthalene used as starting material for
the synthesis of non-racemic Fixolide, see: Ciappa, A.; Scrivant, A.; Matteoli, U. J.
Mol. Catal. A: Chem. 2004, 219, 217.
ꢀ
A.; Vovk, M. V. Russ. J. Org. Chem. 2010, 46, 1070; (f) Fernandez-García, J. M.;
ꢀ
Fernandez-Rodríguez, M. A.; Aguilar, E. Org. Lett. 2011, 13, 5172; (g) Cardillo, G.;