AlCl3 catalyzed oxa-Diels-Alder reaction of aromatic aldehydes with simple dienes

Article abstract of DOI:10.1016/j.tet.2016.10.049

A highly regioselective and diastereoselective oxa-Diels-Alder reaction catalyzed by AlCl₃ has been developed. This reaction is efficient and characterized by good functional group compatibility, F, Cl, CN, NO₂, OMe and thiophenyl groups are tolerated. A Lewis acid catalyzed concerted cycloaddition mechanism is proposed based on the results.

Full text of DOI:10.1016/j.tet.2016.10.049

Accepted Manuscript
AlCl catalyzed oxa-Diels-Alder reaction of aromatic aldehydes with simple dienes
3
Wujun Jian, Bo Qian, Hongli Bao, Daliang Li
PII:
S0040-4020(16)31093-6
10.1016/j.tet.2016.10.049
TET 28190
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 20 May 2016
Revised Date: 18 September 2016
Accepted Date: 20 October 2016
Please cite this article as: Jian W, Qian B, Bao H, Li D, AlCl catalyzed oxa-Diels-Alder reaction of
3
aromatic aldehydes with simple dienes, Tetrahedron (2016), doi: 10.1016/j.tet.2016.10.049.
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AlCl3 Catalyzed Oxa-Diels-Alder Reaction of
Aromatic Aldehydes with Simple Dienes
Wujun Jiana,b , Bo Qiana and Hongli Baoa , Daliang Lib
Leave this area blank for abstract info.
a Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of Research on the Structure of Matter, Chinese Academy of
Sciences, 155 Yangqiao Road West, Fuzhou, 350002, P.R. China
bBiomedical Research Center of South China & College of Life Science, Fujian Normal University

1
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Tetrahedron
journal homepage: www.elsevier.com
AlCl3 catalyzed oxa-diels-alder reaction of aromatic aldehydes with simple dienes
Wujun Jiana,b, Bo Qiana and Hongli Baoa , Daliang Lib
a Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences,
155 Yangqiao Road West, Fuzhou, 350002, P.R. China
bBiomedical Research Center of South China & College of Life Science, Fujian Normal University
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Highly regioselective and diastereoselective oxa-Diels-Alder reaction catalyzed by AlCl3 has
been developed. This reaction is efficient and characterized by good functional group
compatibility, F, Cl, CN, NO2, OMe and thiophenyl group are tolerated. A Lewis acid catalyzed
concerted cycloaddition mechanism is proposed based on the results.
Available online
Keywords:
Oxa-Diels-Alder Reaction
Aluminum Chloride
Aldehyde
Simple Diene
1. Introduction
time, Pd2+ catalysts,6 Sc(OPf)3,7 TiCl4,8 HOTf9 or a mixture of
AlCl3 and nitroalkane or SnCl4 with nitroalkane were applied in
The oxa-Diels-Alder reaction between aldehydes and 1,3-
dienes is a powerful synthetic method to construct dihydropyran
scaffold and is widely applied in the synthesis of natural
products.1 However, previous reported oxa-Diels-Alder reaction
has been limited either to the reaction of electron rich dienes such
as Danishefsky’s,2 Brassard’s3 or Rawal’s diene4 with a broad
range of aldehydes or the reaction of activated aldehydes
containing electron-withdrawing groups (e.g., glyoxylates) with a
broad range of dienes. The reaction between aldehydes and
simple dienes mostly is guided by the interaction between the
HOMO of diene and the LUMO of the dienophile (aldehydes).5
As compare to the activated aldehydes, unactivated aldehydes
have higher LUMO level of the πC–O bond. On the other hand, in
comparison to the electron rich dienes, the simple dienes have
lower level of HOMO. The energy gaps between HOMO of
simple dienes and LUMO of aldehydes are relatively higher than
the energy gaps in other two types of Diels-Alder reactions
mentioned above. This is the reason why the oxa-Diels-Alder
reaction of aldehydes and simple dienes is much more
challenging as compared to other Diels-Alder reactions and only
a limited number of oxa-Diels-Alder reactions of unactivated
the oxa-Diels-Alder reactions.10 Later on, Matsubara and co-
workers reported a big breakthrough of oxa-Diels–Alder reaction
between unactivated dienes with unactivated aldehydes under
mild reaction conditions catalyzed by iron(III) porphyrin1b or
iron(IV) corrole complexes.11 Lu and co-workers recently
reported AgBF4 catalyzed oxa-Diels-Alder reaction of
electrically neutral 1,3-dienes and various aldehydes.12
Heteroatoms at the β-position of the aryl aldehydes can greatly
promote the reactivity of the substrates. Franzén and co-workers
reported carbocation catalyzed oxa-Diels-Alder reaction.13
Despite all developments in this field, there are still many issues
that need to be solved in this reaction, for example, the efficiency
of this reaction, the substrate scope and the readily availability of
the catalysts. Due to the innate low reactivity of the substrates,
much more equivalents of dienes or aldehydes were applied in
most catalytic systems. Furthermore, some substrates like 4-
methoxy-bezaldehyde tend to afford no product or product with
low yield. Thus, the development of more efficient catalytic
systems with readily available catalysts is necessary. Herein, we
report the AlCl3 catalyzed oxa-Diels-Alder reaction of
unactivated aldehydes with simple dienes under mild conditions.
aldehydes and simple dienes have been achieved. In the early
———
Hongli Bao. e-mail: hlbao@fjirsm.ac.cn
Daliang Li. e-mail: daliangli@fjnu.edu.cn

2
Tetrahedron
ACCEPTED MANUSCRIPT
2. Results and discussion
CH3
CH3
CH3
CH3
CH3
We initiated our study with benzaldehyde (1) and 2,3-
CH3
O
O
O
H3C
dimethyl-1,3-butadiene (2, DMB) as the model substrates. A
range of potential catalysts were screened and AlCl3 was found
promote the reaction most (Table 1). Dihydropyran product 3
was obtained in benzene at 80 oC with 70% 1H NMR yield when
10 mol % AlCl3 was applied (Table 1, entry 5). Further reaction
conditions screening showed CCl4 is the best solvent and this
reaction takes place at room temperature. To our delight,
reducing the usage of diene’s slightly increased the yield of the
CH3
H3C
CH3
H3C
5cb,c
5a (50%)
5b (70%)
(76%)
CH3
CH3
CH3
CH3
CH3
CH3
O
O
O
O
O
O
5db (65%)
5e (66%)
5f (81%)
1
product. Product with 90% H NMR yield (84% isolated yield)
CH3
CH3
CH3
CH3
CH3
CH3
O
O
O
was obtained when 1:1 aldehyde to dienes was applied (Table 1,
entry 12).
O2N
Cl
NC
Table 1
5id
5gd (67%)
5hd (68%)
(51%)
Reaction conditions optimization.a
CH3
CH3
O
O
O
5jd
6
(64%)
a Reactions were carried out using the catalyst (10 mol %), aldehyde 4 (1
mmol), and diene 2 (1 mmol) in 2 mL of solvent at room temperature for 15 h.
Isolated yields based on aldehyde 4.
Entry
Catalyst
Solvent
benzene
Temp
(oC)
80
80
80
80
80
rt
rt
rt
rt
rt
rt
rt
40
60
80
Ratio of
Yield
(%)b
0
0
0
49
70
8
19
b At 80 oC, the ratio of 4:2 is 1:4.
2:1
4
4
4
4
4
4
4
4
4
3
2
1
1
1
1
c Benzene as solvent.
1
2
3
4
5
6
7
8
Y(OAc)3·4H2O
Sc(OAc)3·6H2O benzene
NiCl2·6H2O
RuCl3·3H2O
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
d At 70 oC.
benzene
benzene
benzene
toluene
xylene
n-hexane
CCl4
CCl4
CCl4
CCl4
CCl4
Table 3
AlCl3 catalyzed oxa-Diels-Alder reaction of benzaldehyde
and substituted dienes 7.a
57
71
72
85
9
10
11
12
13
14
90 (84)c
86
CCl4
CCl4
86
88
15
a
Reactions were carried out using the catalyst (10 mol %), aldehyde 1 (1
mmol), and diene 2 (X mmol) in 2 mL of solvent for 15 h.
b Yields are determined by 1H NMR.
c Yield of isolated product.
With the best conditions in hands, other aryl aldehydes were
examined. In general, para-electron donating group substituted
benzaldehydes afforded the products in relative lower yields (5a
and 5d). Four equivalents of p-methoxy-benzaldehyde were
necessary to deliver the corresponding product in moderate yield
(5d, 65%). Aldehydes with para-electron withdrawing groups,
like 4-chloro, 4-nitrile and 4-nitro benzaldehyde failed to deliver
corresponding products at room temperature. Increasing the
o
reaction temperature to 70 C lead to better reactivities (5g, 5h
and 5i). Meta-substituted benzaldehydes had showed better
reactivity (5e). Ortho-substituents, especially coordinating
substituent benefit this reaction (5f, 81%). The effect of ortho-
substituent was investigated comprehensively in Lu's work.12 2-
o
Naphthaldehyde reacted with DMB (2) at 70 C and afforded
product in 64% yield. Furfural (6) was proved not reactive at all.
a
Table 2
Reactions were carried out using the catalyst (10 mol %), aldehyde 1 (1
mmol), and diene 7 (1 mmol) in 2 mL of solvent at 80 oC for 15 h. Isolated
yields based on aldehyde 1.
AlCl3 catalyzed oxa-Diels-Alder reaction of 2 and aldehydes
4.a
b At room temperature.
c 7a (1.5 mmol, 1.5 equiv).
d 7g (3 mmol, 3 equiv).
e 7i (2 mmol, 2 equiv).

3
Next, substituted 1,3-dienes have been examined. The results
diastereoselective reaction has expanded the substrate scope to
more dienes and arylaldehydes with readily available catalyst.
ACCEPTED MANUSCRIPT
are summarized in Table 3. The reaction of 2-phenyl-1,3-
butadiene with benzaldehyde proceeded smoothly and delivered
corresponding product in 84% yield (8a). Substituents on the
phenyl ring of the dienes affect the reaction slightly and afforded
products from good to excellent yields (8b, 8c, 8d and 8e). 2-
Thiophenyl-1,3-diene has the similar reactivity as 2-phenyl-1,3-
diene does (8f). 2-Methyl-1,3-diene is less reactive (8g). Higher
reaction temperature (70 oC) and more usage of dienes are
necessary to afford the corresponding product for 2-methyl-1,3-
butadiene (8g). Reaction of myrcene with benzaldehyde needed 2
equivalents of myrcene and still yielded product in poor yield (8i,
45%). Trisubstituted 1,3-diene, 2,4-dimethyl-1,3-pentadiene
reacted with benzaldehyde smoothly at room temperature at 1:1
ratio of the two reactants (8h). Cyclobutadiene, 2-methyl-1,3-
pentadiene and 2,4-hexadiene failed to give any product. These
experimental results indicate that the diene must possess a
substituent at the C-2 position and no substituent at the C-1
position for the smooth reaction.
4. Experimental section
4.1. General
All reactions were carried out under an atmosphere of nitrogen
in flame-dried glassware with magnetic stirring unless otherwise
indicated. Commercially obtained reagents were used as received.
Solvents were dried by distillation from sodium or CaH2. Liquids
and solutions were transferred via syringe. All reactions were
monitored by thin-layer chromatography. 1H and 13C NMR
spectra were recorded on Bruker-BioSpin AVANCE III HD.
Data for 1H NMR spectra are reported relative to chloroform as
an internal standard (7.26 ppm) and are reported as follows:
chemical shift (ppm), multiplicity, coupling constant (Hz), and
integration. Data for 13C NMR spectra are reported relative to
chloroform as an internal standard (77.23 ppm) and are reported
in terms of chemical shift (ppm). IR data were obtained from
Bruker VERTEX 70. HRMS data were recorded on Agilent
Technologies 6224 TOF LC/MS.
We next examined the diastereoselectivity of this reaction.
2,4-Disubstituted diene 9 was applied and dihydropyran 10 was
obtained in 48% yield with a diastereomeric ratio more than 10:1
(Scheme 1).
4.2. General Procedure the AlCl3 Catalyzed Oxa-Diels-Alder
Reaction
Aldehyde (1 mmol), diene (1 mmol), AlCl3 (13.4 mg, 10
mol%) and dry CCl4 (2 mL) were added to a flame dried schlenk
tube with a rubber septum under the argon atmosphere. The
reaction mixture was stirred at room temperature for 15 hours.
Then, the mixture was purified by column chromatography on
silica gel(petroleum ether/ethyl acetate = 100/0~50/1) to yield
product.
4.3. Characterization data of compounds
Scheme 1. AlCl3 catalyzed oxa-Diels-Alder reaction.
3,4-Dimethyl-6-phenyl-5,6-dihydro-2H-pyran (3). Clear oil,
157.2 mg, 84%. 1H NMR (400 MHz, CDCl3) δ7.37-7.31 (m, 4H),
7.25-7.23 (m, 1H), 4.53 (dd, J1 = 4.0 Hz, J2 = 8.0 Hz, 1H), 4.21-
4.07 (m, 2H), 2.32 (t, J = 12.0 Hz, 1H), 2.08 (d, J = 16.0 Hz, 1H),
1.67 (s, 3H), 1.57 (s, 3H).13C NMR (100 MHz, CDCl3) δ 141.61,
127.29, 126.32, 124.77, 123.49, 122.79, 75.28, 69.27, 37.54,
17.31, 12.81. IR (thin film): 2959, 2929, 2871, 1509, 1454, 1374,
1233, 1096 cm-1.
Considering the regioselectivities and diastereoselectivities of
this reaction, a Lewis acid catalyzed concerted mechanism is
proposed (Scheme 2). We cannot rule out the stepwise addition
mechanism since it is possible that the ring closing step is much
faster than the isomerization of the allylic cation.
TBSO
O
O
3,4-Dimethyl-6-(4-methylphenyl)-5,6-dihydro-2H-pyran
(5a). Clear oil, 101.8 mg, 50%. H NMR (400 MHz, CDCl3) δ
AlCl3
1
TBSO
7.27 (d, J = 8.0 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 4.52 (dd, J1 =
4.0 Hz, J2 = 8.0 Hz, 1H), 4.21-4.07 (m, 2H), 2.33 (s, 3H), 2.31-
2.26 (m, 1H), 2.06 (d, J = 16.0 Hz, 1H), 1.68 (s, 3H), 1.58 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 138.63, 135.95, 127.97,
124.76, 123.49, 122.86, 75.17, 69.29, 37.50, 20.10, 17.33, 12.83.
HRMS (ESI) calcd for [C14H22NO]+([M+NH4]+): 220.1696,
found: 220.1701.
Cl3Al
Cl3Al
O
O
I
II
OTBS
OTBS
3,4-Dimethyl-6-(3-methylphenyl)-5,6-dihydro-2H-pyran
(5b). Clear oil, 140.4 mg, 70%. H NMR (400 MHz, CDCl3) δ
H
1
AlCl3
O
7.25-7.20 (m, 2H), 7.16 (d, J = 8.0 Hz, 1H), 7.09 (d, J = 8.0 Hz,
1H), 4.52 (dd, J1 = 4.00 Hz, J2 = 8.0 Hz, 1H), 4.22-4.09 (m, 2H),
2.35 (s, 3H), 2.32-2.27 (m, 1H), 2.09 (d, J = 16.0 Hz, 1H), 1.69
(s, 3H), 1.59 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 142.56,
138.00, 128.23, 128.13, 126.49, 124.50, 123.90, 122.91, 76.42,
70.36, 38.58, 21.47, 18.36, 13.86. IR (thin film): 3025, 2918,
2859, 1611, 1448, 1374, 1233, 1096 cm-1. HRMS (ESI) calcd for
[C14H22NO]+([M+NH4]+): 220.1696, found: 220.1700.
Ph
H
cis
Scheme 2. Proposed catalytic cycle for oxa-Diels-Alder
reaction.
3. Conclusion
In summary, we have developed AlCl3 catalyzed oxa-Diels-
Alder reaction between unactivated 1,3-dienes and aryl-
aldehydes. This reaction is characterized by good functional
group compatibility, for instance, F, Cl, CN, NO2, OMe and
thiophenyl groups are tolerated. This reaction is efficient, one
equivalent of dienes is enough to deliver product in good yield
for most of the substrates. This regioselective and
3,4-Dimethyl-6-mesityl-5,6-dihydro-2H-pyran (5c). Clear
1
oil, 176.9 mg, 77%. H NMR (400 MHz, CDCl3) δ 6.78 (s, 2H),
4.90 (dd, J1= 4.0 Hz, J2= 8.0 Hz, 1H), 4.13-4.03 (m, 2H), 2.53 (t,
J = 12.0 Hz,1H), 2.37 (s, 6H), 2.21 (s, 3H), 1.85 (d, J = 16.0 Hz,
1H), 1.66 (s, 3H), 1.57 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
136.44, 136.07, 135.05, 130.07, 125.09, 124.08, 74.36, 70.41,

4
Tetrahedron
ACCEPTED MANUSCRIPT
35.18, 31.82, 22.87, 20.90, 18.47, 14.31, 14.11. IR (thin film):
(s, 3H), 1.61 (s, 3H).13C NMR (100 MHz, CDCl3) δ 140.15,
2953, 2924, 2856, 1458, 1376, 1099 cm-1. HRMS (ESI) calcd for
[C16H26NO]+([M+NH4]+): 248.2009, found: 248.2016.
3,4-Dimethyl-6-(4-methoxyphenyl)-5,6-dihydro-2H-pyran
133.39, 132.91, 128.08, 128.03, 127.67, 125.99, 125.68, 124.61,
124.36, 124.20, 123.87, 138.9, 76.37, 70.37, 38.61, 18.42,13.94.
IR (thin film): 3055, 2916, 2884, 2856, 1508, 1447, 1383, 1102
cm-1. HRMS (ESI) calcd for [C17H22NO]+([M+NH4]+): 256.1696,
found: 256.1694.
1
(5d). Clear oil, 142.6 mg, 65%. H NMR (400 MHz, CDCl3) δ
7.23 (d, J = 8.0 Hz, 2H), 6.82 (d, J = 8.0 Hz, 2H), 4.43 (dd, J1=
4.0 Hz, J2= 8.0 Hz, 1H), 4.14-3.99 (m, 2H), 3.72 (s, 3H), 2.27 (t,
J = 16.0 Hz, 1H), 2.00 (d, J = 20.0 Hz, 1H), 1.61 (s, 3H), 1.51 (s,
3H). 13C NMR (100 MHz, CDCl3) δ157.91, 133.81, 126.14,
123.48, 122.85, 112.71, 74.93, 69.31, 54.25, 37.41, 17.33, 12.82.
IR (thin film): 2916, 2857, 1613, 1515, 1248, 1097, 1035, 828
cm-1. HRMS (ESI) calcd for [C14H18Na]+([M+Na]+): 241.1204,
found: 241.1193.
3,4-Dimethyl-6-(3-methoxyphenyl)-5,6-dihydro-2H-pyran
(5e). Clear oil,144.7 mg, 66%. as a clear oil. 1H NMR (400 MHz,
CDCl3) δ 7.27 (t, J = 8.0 Hz, 1H), 6.95 (d, J = 8.0 Hz, 2H), 6.83
(d, J = 8.0, 1H), 4.54 (dd, J1 = 4.0 Hz, J2 = 12.0 Hz, 1H), 4.22-
4.09 (m, 2H), 3.81 (s, 3H), 2.33 (t, J = 16.0 Hz, 1H), 2.10 (d, J =
16.0 Hz, 1H), 1.69 (s, 3H),1.59 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 159.72, 144.33, 129.33, 124.53, 123.84, 118.16,
113.17, 111.05, 76.26, 70.31, 55.23, 38.60, 18.35, 13.86. IR (thin
film): 2918, 2857, 1604, 1454, 1261, 1105, 1048 cm-1. HRMS
(ESI) calcd for [C14H22NO2]+([M+NH4]+): 236.1645, found:
236.1653.
2-Phenyl-4-phenyl-3,6-dihydro-2H-pyrane (8a). White solid,
198.3 mg, 84%. H NMR (400 MHz, CDCl3) δ 7.38-7.28 (m,
1
7H), 7.24-7.15 (m, 3H), 6.13 (s, 1H), 4.61 (dd, J1 = 4.0 Hz, J2 =
12.0 Hz, 1H), 4.53-4.41 (m, 2H), 2.69-2.55 (m, 2H).13C NMR
(100 MHz, CDCl3) δ 142.42, 140.06, 134.43, 128.51, 128.49,
127.67, 127.40, 125.99, 124.80, 122.26, 76.00, 66.86, 34.96. IR
(thin film): 3060, 3031, 2926, 17174, 1448, 1266, 1131, 1027 cm-
1
.
2-Phenyl-4-(4-fluorophenyl)-3,6-dihydro-2H-pyrane (8b).
White solid, 241.4 mg, 95%. 1H NMR (400 MHz, CDCl3) δ 7.44-
7.31 (m, 7H), 7.03 (t, J = 8.0 Hz, 2H), 6.14 (s, 1H), 4.66 (d, J =
8.0 Hz, 1H), 4.58-4.48 (m, 2H), 2.71-2.59 (m, 2H).13C NMR
(100 MHz, CDCl3) δ 163.45, 161.00, 142.29, 136.20, 136.17,
133.50, 128.53, 127.72, 126.40, 126.32, 125.95, 122.13, 122.11,
115.40, 115.19, 75.95, 66.79, 35.09. 19F (376 MHz, CDCl3)
δ115.12. IR (thin film): 3061, 3032, 2926, 2819, 1602, 1509,
1372, 1229, 1160, 1126, 805 cm-1. HRMS (ESI) calcd for
[C17H15FNa]+([M+Na]+): 277.1005, found: 277.1017.
3,4-Dimethyl-6-(2-methoxyphenyl)-5,6-dihydro-2H-pyran
(5f). Clear oil, 178.6 mg, 82%. H NMR (400 MHz, CDCl3) δ
2-Phenyl-4-(4-chlorophenyl)-3,6-dihydro-2H-pyrane (8c).
White solid, 197.4 mg, 73%. 1H NMR (400 MHz, CDCl3) δ 7.45-
7.28 (m, 9H), 6.21-6.20 (m, 1H), 4.67 (dd, J1 = 4.0 Hz, J2 = 8.0
Hz, 1H), 4.60-4.48 (m, 2H), 2.73-2.57 (m, 2H).13C NMR (100
MHz, CDCl3) δ 142.20, 138.45, 133.42, 133.11, 128.60, 128.53,
127.74, 126.05, 125.94, 122.80, 75.91, 66.78, 34.86. IR (thin
film): 3062, 3032, 2925, 2820, 1492, 1372, 1262, 1126, 1095,
1012, 751 cm-1.
2-Phenyl-4-(p-tolyl)-3,6-dihydro-2H-pyran (8d). White
solid, 224.4 mg, 90%. 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J =
8.0 Hz, 2H), 7.39 (t, J = 4.0 Hz,2H), 7.31 (d, J = 4.0 Hz,3H),
7.15 (d, J = 8.0 Hz, 2H), 6.16 (s, 1H), 4.67-4.64 (m, 1H), 4.58-
4.49 (m, 2H), 2.73-2.62 (m, 2H), 2.34 (s, 3H).13C NMR (100
MHz, CDCl3) δ 142.49, 137.21, 137.14, 134.21, 129.17, 128.50,
127.65, 125.99, 124.65, 121.35, 76.03, 66.88, 34.97, 21.12. IR
(thin film): 3056, 3028, 2923, 2817, 1514, 1452, 1371, 1126,
1022, 699 cm-1. HRMS (ESI) calcd for [C18H18Na]+([M+Na]+):
273.1255, found: 273.1271.
1
7.48 (d, J = 8.0 Hz, 1H), 7.25 (t, J = 8.0 Hz, 1H), 7.00 (t, J = 8.0
Hz, 1H), 6.86 (d, J = 8.0 Hz, 1H), 4.92 (dd, J1 = 4.0 Hz, J2 = 8.0
Hz, 1H), 4.23-4.09 (m, 2H), 3.82 (s, 3H), 2.21-2.10 (m, 2H), 1.67
(s, 3H), 1.59 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 155.80,
131.29, 128.01, 126.05, 124.36, 124.22, 120.88, 110.15, 70.77,
70.43, 55.33, 37.41, 18.35, 13.88. IR (thin film): 2918, 2884,
1589, 1493, 1463, 1243, 1099, 1050, 1032, 753 cm-1. HRMS
(ESI) calcd for [C14H22NO2]+([M+NH4]+): 219.1380, found:
219.1387.
3,4-Dimethyl-6-(4-chlorophenyl)-5,6-dihydro-2H-pyran
1
(5g). Clear oil, 150.5 mg, 67%. H NMR (400 MHz, CDCl3)
δ7.33-7.27 (m, 4H), 4.53 (dd, J1 = 4.0 Hz, J2 = 8.0 Hz, 1H), 4.21-
4.07 (m, 2H), 2.27 (t, J = 12.0 Hz, 1H), 2.08 (d, J = 16.0 Hz, 1H),
1.68 (s, 3H), 1.58 (s, 3H). 13C NMR (100 MHz, CDCl3) δ141.23,
132.98, 128.45, 127.19, 124.58, 123.61, 75.54, 70.23, 38.50,
18.34, 13.85. IR (thin film): 2919, 2886, 2858, 1491, 1090, 1014,
821 cm-1.
2-Phenyl-4-(4-methoxyphenyl)- 3,6-dihydro-2H-pyran (8e).
1
3,4-Dimethyl-6-(4-benzonitrile)-5,6-dihydro-2H-pyran (5h).
White solid, 196.1 mg, 74%. H NMR (400 MHz, CDCl3) δ 7.45
1
Clear oil, 145.7 mg, 68% as. H NMR (400 MHz, CDCl3) δ7.65
(d, J = 8.0 Hz, 2H), 7.40-7.30 (m, 5H), 6.88 (d, J = 8.00 Hz, 2H),
6.11 (s, 1H), 4.68 (dd, J1 = 8.0 Hz, J2 = 12.0 Hz, 1H), 4.58-4.48
(m, 2H), 3.80 (s, 3H), 2.71-2.65 (m, 2H).13C NMR (100 MHz,
CDCl3) δ 159.03, 142.49, 133.75, 132.67, 128.48, 127.63,
125.98, 125.84, 120.46, 113.82, 76.03, 66.87, 55.31, 35.02. IR
(thin film): 3060, 3033, 2927, 2833, 1607, 1513, 1272, 1250,
1186, 1126, 1035, 700 cm-1.HRMS (ESI) calcd for
[C18H19O2]+([M+H]+): 267.1385, found: 267.1398.
(d, J = 12.0 Hz, 2H), 7.49 (d, J = 8.0 Hz, 2H),4.61 (dd, J1 = 4.0
Hz, J2 = 12.0 Hz, 1H), 4.22-4.10 (m, 2H), 2.24-2.16 (m, 1H),
2.12 (d, J = 16.0 Hz, 1H), 1.69 (s, 3H), 1.60 (s, 3H).13C NMR
(100 MHz, CDCl3) δ 148.10, 132.19, 126.34, 124.67, 123.33,
118.94, 111.02, 75.35, 70.12, 38.35, 18.32, 13.84. IR (thin film):
2919, 2887, 2858, 2227, 1506, 1101 cm-1. HRMS (ESI) calcd for
[C14H19N2O]+([M+NH4]+): 231.1492, found: 231.1484.
3,4-Dimethyl-6-(4-nitrophenyl)-5,6-dihydro-2H-pyran (5i).
Clear oil, 120.5 mg, 52%. 1H NMR (400 MHz, CDCl3) δ 8.21 (d,
J = 8.0 Hz, 2H), 7.55 (d, J = 8.0 Hz, 2H),4.66 (dd, J1 = 4.0 Hz, J2
= 8.0 Hz, 1H), 4.24-4.11 (m, 2H), 2.25-2.11 (m, 2H), 1.70 (s,
3H), 1.61 (s, 3H). 13C NMR (100 MHz, CDCl3) δ150.15, 147.13,
126.37, 124.70, 123.59, 123.28, 75.17, 70.12, 38.41, 18.31,
13.84. IR (thin film): 2919, 2887, 2858, 1605, 1520, 1346, 1104,
852 cm-1. HRMS (ESI) calcd for [C13H19N2O3]+([M+NH4]+):
251.1390, found: 251.1390.
2-Phenyl-4-(thiophen-3-yl)-3,6-dihydro-2H-pyran
(8f).
White solid, 214.5 mg, 89%. 1H NMR (400 MHz, CDCl3) δ 7.45-
7.37 (m, 4H), 7.33-7.25 (m, 3H), 7.12 (s, 1H), 6.19 (s, 1H), 4.67-
4.64 (m, 1H), 4.57-4.48 (m, 1H), 2.72-2.63 (m, 2H).13C NMR
(100 MHz, CDCl3) δ142.32, 141.92, 129.91, 128.52, 127.71,
125.99, 125.83, 124.44, 121.23, 118.97, 75.87, 66.53, 35.03. IR
(thin film): 3061, 3028, 2924, 2852, 2818, 2360, 1453, 1365,
1217, 1123, 1021, 773 cm-1. HRMS (ESI) calcd for
[C15H15OS]+([M+H]+): 243.0844, found: 243.0861.
3,4-Dimethyl-6-(naphthalen-2-yl)-5,6-dihydro-2H-pyran
(5j). White solid, 153.0 mg, 64%. H NMR (400 MHz, CDCl3)
2-Phenyl-4-methyl-3,6-dihydro-2H-pyran (8g). Clear oil,
110.0 mg, 63%. H NMR (400 MHz, CDCl3) δ 7.30-7.22 (m,
1
1
δ7.82 (d, J = 4.0 Hz, 4H), 7.50 (d, J = 8.0 Hz, 1H), 7.45 (t, J =
4.0 Hz, 2H), 4.72 (dd, J1 = 4.0 Hz, J2 = 12.0 Hz, 1H), 4.27-4.14
(m, 2H), 2.41 (t, J = 12.0 Hz, 1H), 2.18 (d, J = 16.0 Hz, 1H), 1.70
4H), 7.18-7.14 (m, 1H), 5.39 (s, 1H), 4.44 (dd, J1 = 4.0 Hz, J2 =
12.0 Hz, 1H), 4.21 (s, 2H), 2.23 (t, J = 12.0 Hz, 1H), 2.02 (d, J =
20.0 Hz, 1H), 1.64 (s, 3H).13C NMR (100 MHz, CDCl3) δ

5
13648. h) Tietze, L. F.; Kettschau, G. Top. Curr. Chem. 1997,
142.71, 132.05, 128.42, 127.48, 125.91, 119.91, 75.84, 66.52,
37.81, 23.01. IR (thin film): 2929, 2910, 2890, 2821, 1450, 1380,
1162, 1119, 1036, 699 cm-1.HRMS (ESI) calcd for
[C12H14Na]+([M+Na]+): 197.0942, found: 197.0926.
ACCEPTED MANUSCRIPT
189, 1. i) Bednarski, M. D.; Lyssikatos, J. P. Comprehensive
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Academic Press: New York, 1987. k) Schmidt, R. R. Acc. Chem.
Res. 1986, 19, 250.
2-Phenyl-4,6,6-trimethyl-3,6-dihydro-2H-pyran (8h). Clear
1
oil, 133.7 mg, 66%. H NMR (400 MHz, CDCl3) δ 7.64 (d, J =
2. a) Edwards, H. J.; Goggins, S.; Frost, C, G. Molecules 2015, 20,
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P. M. Eur. J. Org. Chem. 2012, 3765. c) De Rosa, M.; Soriente, A.
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8.0 Hz, 2H), 7.56 (t, J = 8.0 Hz, 2H), 7.47 (t, J = 8.0 Hz, 1H),
5.62 (s, 1H), 4.94 (dd, J1 = 4.0 Hz, J2 = 12.0 Hz, 1H), 2.43-2.36
(m, 1H), 2.23-2.18 (m, 1H), 1.94 (s, 3H),1.57 (s, 3H), 1.55 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 143.46, 130.17, 129.13,
128.55, 128.51, 127.42, 126.31, 126.26, 73.59, 71.02, 37.90,
30.21, 26.30, 23.22. IR (thin film): 2971, 2928, 2911, 1705,
1451, 1379, 1201, 1069, 698 cm-1.HRMS (ESI) calcd for
[C14H19O]+([M+H]+): 203.1436, found: 203.1421.
4-(4-Methylpent-3-en-1-yl)-2-phenyl-3,6-dihydro-2H-pyran
1
(8i). Clear oil, 101.8 mg, 45%. H NMR (400 MHz, CDCl3)
δ7.39-7.24 (m, 5H), 5.50 (s, 1H), 5.12 (s, 1H), 4.53 (d, J = 12.0
Hz, 1H), 4.34 (s, 2H), 2.34-2.28 (m, 1H), 2.14-2.05 (m, 5H), 1.69
(s, 3H), 1.61 (s, 3H).13C NMR (100 MHz, CDCl3) δ 142.71,
135.80, 131.83, 128.39, 127.46, 125.89, 123.89,119.44, 75.89,
66.55, 36.99, 36.34, 25.95, 25.73, 17.75. IR (thin film): 2964,
2930, 1717, 1452, 1378, 1267,1120, 1062, 1027, 700 cm-1.
HRMS (ESI) calcd for [C17H22Na]+([M+Na]+): 265.1568, found:
256.1576.
10. Clear oil, 77.4 mg, 48%, dr> 10:1, determined by 1H
NMR. 1H NMR (400 MHz, CDCl3) δ 7.32-7.17 (m, 5H), 5.50
(s, 1H), 4.52 (dd, J1 = 4.0 Hz, J2 = 12.0 Hz, 1H), 4.24 (m,
1H), 3.74 (m, 1H), 3.51 (m, 1H), 2.16 (m, 1H), 2.02 (d, J =
16.0 Hz, 1H), 1.68 (s, 3H),0.84 (s, 9H), 0.01 (d, J = 8.0 Hz,
6H). 13C NMR (100 MHz, CDCl3) δ 141.74, 132.12, 127.23,
126.25, 124.80, 120.37, 75.28, 74.88, 65.36, 37.19, 24.91,
21.93, 17.35, -6.19, -6.27. HRMS (ESI) calcd for
[C19H34NO2Si]+ ([M+NH4]+): 336.2353, found: 336.2355.
Acknowledgments
We thank NSFC (grant no. 21402200), The Young 1000
Talents Program for financial support.
7. Hanamoto, T.; Sugimoto, Y.; Jin, Y. Z.; Inanaga, J. Bull. Chem.
Soc. Jap. 1997, 70, 1421.
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