Oxidative oxo Diels-Alder reactions of Baylis-Hillman adducts with electron-rich alkenes in the presence of IBX

Article abstract of DOI:10.1080/00397911.2010.541967

Baylis-Hillman adducts were oxidized by iodoxybenzoic acid (IBX) to 2-methylene-1,3-dicarbonyl compounds, which can act as oxodiene to react with electron-rich alkenes to generate a variety of oxo Diels-Alder adducts in good yields. Copyright Taylor & Fra

Full text of DOI:10.1080/00397911.2010.541967

This article was downloaded by: [University of Nebraska, Lincoln]
On: 09 October 2014, At: 09:33
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Oxidative oxo Diels–Alder Reactions of
Baylis–Hillman Adducts with Electron-
Rich Alkenes in the Presence of IBX
Jing Yang a , Heping Li a , Bo Shi a , Shengzhi Tian a & Juan Zhang a
a Henan University of Traditional Chinese Medicine , Zhengzhou ,
China
Accepted author version posted online: 17 Nov 2011.Published
online: 03 Feb 2012.
To cite this article: Jing Yang , Heping Li , Bo Shi , Shengzhi Tian & Juan Zhang (2012) Oxidative oxo
Diels–Alder Reactions of Baylis–Hillman Adducts with Electron-Rich Alkenes in the Presence of IBX,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 42:11, 1567-1576, DOI: 10.1080/00397911.2010.541967
To link to this article: http://dx.doi.org/10.1080/00397911.2010.541967
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Synthetic Communications1, 42: 1567–1576, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.541967
OXIDATIVE oxo DIELS–ALDER REACTIONS OF
BAYLIS–HILLMAN ADDUCTS WITH ELECTRON-RICH
ALKENES IN THE PRESENCE OF IBX
Jing Yang, Heping Li, Bo Shi, Shengzhi Tian, and Juan Zhang
Henan University of Traditional Chinese Medicine, Zhengzhou, China
GRAPHICAL ABSTRACT
Abstract Baylis–Hillman adducts were oxidized by iodoxybenzoic acid (IBX) to
2-methylene-1,3-dicarbonyl compounds, which can act as oxodiene to react with
electron-rich alkenes to generate a variety of oxo Diels–Alder adducts in good yields.
Keywords Baylis–Hillman adduct; IBX oxidant; 2-methylene-1,3-dicarbonyl compound;
oxo Diels–Alder reaction
INTRODUCTION
Sequential reactions are a promising field of chemistry, because they allow
complicated molecules to be created using one-pot reactions in a fast, efficient,
and time-saving manner.[1] To facilitate an easy development of a new reaction
cascade, substrate design is quite important, and some molecules, which are easily
available and characterized by organic functional groups that possess different
reactivities, are preferred. Baylis–Hillman adducts, which are among the most inves-
tigated organic compounds in the past decade, possess multiply functionalized
groups, are easy to prepare, and are associated with designable structure, which is
highly desired for synthetic applications and tailoring of molecules.[2] Chemical
transformations of Baylis–Hillman adducts have received much attention during
the past two decades.[3] Various cyclic and acyclic compounds have been prepared
from Baylis–Hillman adducts and their derivatives. Owing to presence of both a dou-
ble bond and a hydroxyl group, Baylis–Hillman adducts were often applied in
designing of sequential reactions.[4] For example, the hydroxyl group can undergo
oxidation to generate a 2-methylene-1,3-dicarbonyl compound that is very reactive
Received October 4, 2010.
Address correspondence to Juan Zhang, Henan University of Traditional Chinese Medicine,
Zhengzhou 450008, China. E-mail: zj19820305@163.com
1567

1568
J. YANG ET AL.
toward nucleophile. Yadav and his coworkers have developed many sequential reac-
tions on the basis of this reaction cascade.[5] Although oxidation of Baylis–Hillman
adducts has been widely used in developing new sequential reactions, the most of
successful examples are dealing with Michael-type reactions by taking advantage
of the highly reactive acrylate moiety. To further extend the utility of Baylis–Hillman
adducts in developing sequential reactions, other basic reactions have to be
considered.
Oxidation of Baylis-Hillman adduct could be performed in the presence of
iodoxybenzoic acide (IBX)[6] or Swern or Dess–Martin oxidants.[7] This offers an
effective method for the synthesis of 2-methylene-1,3-dicarbonyl compounds that
have been previously prepared by either Knoevenagel reaction[8] or pyrolysis of
2-methylthiomethylation products of 1,3-dicarbonyl compounds.[9] To develop a
new reaction cascade on the basis of oxidation of Baylis–Hillman adducts, we have
to know what kind of reactions 2-methylene-1,3-dicarbonyl compounds can partici-
pate in. Gu and his coworkers[10] have observed a high reactivity of such compounds
in oxo Diels–Alder reactions, in which these compounds serve as oxodienes to react
with electron-rich alkenes. However, in the reports of Gu, 2-methylene-1,3-
dicarbonyl compounds were prepared by a known method, Knoevenagel reaction
between 1,3-dicarbonyl compound and formaldehyde. Because reactivity of 1,3-
dicarbonyl compound in the Knoevenagel reaction of formaldehyde is not always
satisfactory, it is necessary to develop an alternative method to the reported one.
In light of this description, we reasoned that oxidation of Baylis–Hillman adduct
might be an appropriate method. Thus, we report in this communication our pre-
liminary results on oxidative oxo Diels–Alder reaction of Baylis–Hillman reaction
with electron-rich alkenes using IBX as oxidant (Scheme 1).
Initially, 1a was treated in the presence of 1.2 equiv amount of IBX with 4-tert-
butylstyrene, 2a, in acetonitrile. At 80 ꢀC, the expected product, 3a, was obtained in
81% of yield after 5 h of reaction (Table 1, entry 1). IBX is used as oxidant because (i)
IBX is a highly selective and mild oxidant for transformation of the hydroxyl group
to a carbonyl compound[11] and (ii) 2a and 3a are chemically stable toward IBX. The
model reaction was also performed in dichloroethane, toluene, nitromethane, and
1,4-dioxane, and only a small amount of product was obtained under the identical
condition (entries 2 to 5). It should be noted that although two products could be
formed theoretically in the second step of the reaction, oxo Diels–Alder reaction
of the formed 2-methylene-1,3-dicarbonyl intermediate and 2a, only one product
was observed in our system, indicating a specific regioselectivity of the cycloaddition
reaction. Temperature also plays a crucial role in determining the yield of the model
reaction, and it is of interest to note that raising the reaction temperature from 50 ꢀC
to 80 ꢀC resulted in a three-fold increase on the reaction yield (entries 6 and 7). At
low temperature, although the starting material 1a was consumed, in view of the fact
Scheme 1. Oxidative oxo Diels–Alder reaction of Baylis–Hillman reaction with electron-rich alkenes.

DIELS–ALDER REACTIONS OF BAYLIS–HILLMAN ADDUCTS
1569
Table 1. Oxidative oxo Diels–Alder reaction of Baylis–Hillman adduct 1a with 2a in the presence of IBXa
Entry
Solvent
Temperature (ꢀC)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9b
CH3CN
ClCH2CH2Cl
Toluene
80
80
80
80
80
50
65
80
80
5
5
5
5
5
5
5
3
5
81
11
Trace
Trace
Trace
27
CH3NO2
1,4-dioxane
CH3CN
CH3CN
CH3CN
CH3CN
62
74
59
a1a 1 mmol, 2a: 1.5 mmol, solvent: 1 ml.
b1.0 equiv amount of 2a was used.
that a lot of 2-methylene-1,3-dicarbonyl intermediate was observed by means of
thin-layer chromatography (TLC) detection, poor reaction yield might mainly result
from the difficulty of the following oxo Diels–Alder reaction at this temperature.
Further investigation revealed that the reaction was also affected by reaction time
and amount of 2a, and the optimal yield was obtained after 5 h of reaction in the
presence of 1.5 equiv amount of 2a (entries 8 and 9).
Because the product 3a could also be prepared from a known method
(three-component reaction of ethyl benzoylacetate, 2a, and formaldehyde),10 to get
a direct comparison we then investigated the synthesis of 3a by Gu’s method. As
shown in Scheme 2, only 15% yield was obtained by means of the latter method, indi-
cating the efficiency and necessity of the present method for organic synthesis.
Having these results in hand, we then examined substrate scope of the
IBX-induced oxidative oxo Diels–Alder reactions of Baylis–Hillman adducts with
electron-rich alkenes in acetonitrile. As shown in Table 2, a variety of Baylis–Hillman
Scheme 2. Three-component reaction of 4a, 2a, and formaldehyde in water.

1570
J. YANG ET AL.
Table 2. Substrate scope for the model reaction
Entry Baylis–Hillman adduct
Alkene
Time (h)
Product
Yield (%)
1
2
3
1a
1a
1a
5
82
8
5
77
84
4
5
1a
1a
6
6
81
51
6
5
77
7
5
79
(Continued )

DIELS–ALDER REACTIONS OF BAYLIS–HILLMAN ADDUCTS
1571
Table 2. Continued
Entry Baylis–Hillman adduct
Alkene
Time (h)
Product
Yield (%)
8
6
80
9
6
78
10
11
6
5
76
85
12
13
6
8
73
60
adducts were successfully used in this reaction, and the corresponding products were
obtained in good to excellent yields. Styrenes substituted by an electron-donating
group give better yield than the one with electron-withdrawing group (entries 1
and 2). The presence of a methyl group in the a-position of the double bond seems
favorable for the formation of the desired product (entries 3 and 4). An alkyl vinyl

1572
J. YANG ET AL.
ether can also be used as a valid substrate in this reaction, but the yield obtained is
inferior to that of 2a (entry 5). A substituent in the aromatic ring of Baylis–Hillman
adduct is not important for the model reaction, and good yields could be obtained in
the presence of both electron-donating and electron-withdrawing groups (entries 6 to
9). Not only the Baylis–Hillman adduct from aromatic aldehydes but also the
aliphatic aldehyde-generated adduct can also be used in this reaction (entry 10).
Another part of the Baylis–Hillman adduct, the ester group, affects the reaction
significantly, and the tendency we observed here is that the bigger the size of ester
group, the lower the reaction yield (entries 11 to 13).
In conclusion, oxidative oxo Diels–Alder reaction of Baylis–Hillman adduct
with electron-rich alkenes was developed using IBX as oxidant. The reaction can
be divided into the following two steps: (i) selective oxidation of Baylis–Hillman
adducts that generated 2-methylene-1,3-dicarbonyl compound exclusively and (ii)
an oxo Diels–Alder reaction between 2-methylene-1,3-dicarbonyl intermediate and
electron-rich alkene to generate the desired dihydropyrane. This reaction not only
offers an effective alternative route to the substituted dihydropyrane derivatives
but also opens a new way for synthetic utilization of Baylis–Hillman adduct.
EXPERIMENTAL
1
All chemicals are used as received without any purification. H and 13C NMR
spectra were recorded on a Bruker AV-400. Chemical shifts are expressed in parts
per million (ppm) relative to Me4Si in CDCl3. Infrared (IR) spectra were recorded
on a Fourier transform (FT)–IR Bruker (Vertex 70) using KBr technology. High-
resolution mass spectra (HRMS) analysis was measured on a VG ZAB HS Instru-
ment. Melting points were measured by means of an X-4 microscopic melting-point
meter produced by Gongyi City Yuhua Instrument Co.
Typical Procedure for Prins Cyclization of Styrenes
All the reactions were conducted in a 10-mL U-type flask equipped with
magnetic stirring. In a typical reaction, a Baylis–Hillman adduct 1a (206.0 mg,
1.0 mmol) was mixed with 4-tert-butylstyrene (2a, 240.0 mg, 1.5 mmol), acetonitrile
(1 ml) and IBX (364.0 mg) under air. The mixture was then heated at 80 ꢀC for
5 h. After reaction, the mixture was cooled to room temperature and then extracted
with a mixture of ethyl acetate and heptane (v=v ¼ 1=1, 2 ml ꢁ 3). The obtained
organic solutions were concentrated and then isolated with preparative thin-layer
chromatography (TLC) using a mixed solution of ethyl acetate and petroleum ether
as eluting solvent (normally, the ratio of ethyl acetate=petroleum ether is 1=6).
Spectroscopic Data of Products
3-Ethoxycarbonyl-2-phenyl-6-(4-tert-butylphenyl)-5,6-dihydropyran (3a).
1
White solid, mp ¼ 104–105 ꢀC. H NMR (CDCl3): 0.93 (t, J ¼ 7.2 Hz, 3H), 1.31 (s,
9H), 1.94–2.08 (m, 1H), 2.18–2.29 (m, 1H), 2.44–2.58 (m, 1H), 2.70–2.79 (m, 1H),
3.97 (q, J ¼ 7.2 Hz, 2H), 5.03 (dd, Ja ¼ 2.4 Hz, Jb ¼ 10.4 Hz, 1H), 7.30–7.38 (m,
5H), 7.36–7.47 (m, 4H); 13C NMR: 13.9, 23.2, 29.4, 31.6, 34.7, 60.1, 79.1, 104.1,

DIELS–ALDER REACTIONS OF BAYLIS–HILLMAN ADDUCTS
1573
125.8, 125.9, 127.8, 128.9, 129.1, 136.9, 137.9, 151.1, 163.4, 169.1. IR (cmꢂ1): 2985,
2960, 2908, 1689, 1623, 1595, 1288, 1151, 1099, 1033, 1001, 979, 920, 831, 755, 699.
HR-MS: m=z ¼ 387.1936; calcd. for C24H28NaO3 [M þ Na]þ: 387.1928.
3-Ethoxycarbonyl-2-phenyl-6-(4-methoxyphenyl)-5,6-dihydropyran (3b).
1
White solid, mp ¼ 91–92 ꢀC. H NMR (CDCl3): 0.94 (t, J ¼ 7.2 Hz, 3H), 1.91–2.05
(m, 1H), 2.13–2.24 (m, 1H), 2.43–2.59 (m, 1H), 2.67–2.79 (m, 1H), 3.81 (s, 3H),
3.96 (q, J ¼ 6.8 Hz, 2H), 4.99 (dd, Ja ¼ 2.0 Hz, Jb ¼ 10.4 Hz, 1H), 6.89 (td,
Ja ¼ 2.0 Hz, Jb ¼ 9.6 Hz, 2H), 7.25–7.35 (m, 5H), 7.37–7.42 (m, 2H); 13C NMR:
13.8, 23.2, 29.4, 55.5, 60.1, 78.9, 104.1, 114.0, 127.5, 127.7, 128.8, 129.1, 132.9,
137.1, 159.5, 163.3, 169.0. IR (cmꢂ1): 2982, 2957, 2933, 1689, 1619, 1598, 1517,
1372, 1255, 1203, 1179, 1155, 1099, 1001, 978, 763, 700. HR-MS: m=z ¼ 338.1550;
calcd. for C21H22O4 [M]: 338.1543.
3-Ethoxycarbonyl-2-phenyl-6-(4-chlorophenyl)-5,6-dihydropyran (3c).
1
Colorless liquid. H NMR (CDCl3): 0.95 (t, J ¼ 7.6 Hz, 3H), 1.87–2.05 (m, 1H),
2.47–2.62 (m, 1H), 2.69–2.79 (m, 1H), 3.96 (q, J ¼ 7.2 Hz, 2H), 7.29–7.39 (m, 7H),
7.38–7.44 (m, 2H); 13C NMR: 13.9, 23.1, 29.6, 60.1, 78.2, 104.3, 127.5, 127.9,
128.8, 129.0, 129.3, 133.9, 136.6, 139.1, 162.9, 168.8. IR (cmꢂ1): 2983, 2932, 2901,
1690, 1627, 1599, 1446, 1288, 1253, 1201, 1157, 1088, 1036, 979, 760, 699. HR-MS:
m=z ¼ 342.1049; calcd. for C20H19ClO3 [M]: 342.1053.
3-Ethoxycarbonyl-6-(4-fluorophenyl)-6-methyl-2-phenyl-5,6-dihydropyran
1
(3d). Colorless liquid. H NMR (CDCl3): 0.88 (t, J ¼ 7.2 Hz, 3H), 1.61 (s, 3H),
1.98–2.09 (m, 1H), 2.17–2.34 (m, 2H), 2.49–2.61 (m, 1H), 3.89 (q, J ¼ 7.2 Hz, 2H),
7.02 (t, J ¼ 8.0 Hz, 2H), 7.33–7.40 (m, 5H), 7.41–7.46 (m, 2H); 13C NMR: 13.7,
20.3, 28.9, 32.4, 59.7, 79.7, 103.2, 115.1, 115.4, 126.3, 126.2, 127.7, 128.4, 128.9,
128.9, 137.4, 140.7, 140.7, 160.6, 161.6, 163.0, 168.3. IR (cmꢂ1): 2981, 2932, 2901,
1690, 1629, 1601, 1444, 1373, 1297, 1233, 1201, 1152, 1094, 1032, 1013, 971, 836,
761, 699. HR-MS: m=z ¼ 340.1511; calcd. for C21H21FO3 [M]: 340.1495.
3-Ethoxycarbonyl-6-methyl-2-phenyl-6-(4-chlorophenyl)-5,6-dihydropyran
1
(3e). Colorless liquid. H NMR (CDCl3): 0.89 (t, J ¼ 6.8 Hz, 3H), 1.60 (s, 3H),
1.96–2.04 (m, 1H), 2.17–2.32 (m, 2H), 2.48–2.59 (m, 1H), 3.89 (q, J ¼ 7.2 Hz, 2H),
7.29–7.36 (m, 3H), 7.37–7.42 (m, 3H), 7.42–7.46 (m, 2H); 13C NMR: 13.7, 20.3,
28.8, 32.3, 59.9, 79.6, 103.6, 126.2, 127.9, 128.7, 128.8, 128.9, 130.1, 133.1, 137.4,
143.7, 161.6, 168.4. IR (cmꢂ1): 2983, 2936, 1689, 1631, 1597, 1494, 1445, 1370,
1296, 1260, 1149, 1093, 1031, 970, 829, 762, 698. HR-MS: m=z ¼ 379.1077; calcd.
for C21H21ClNaO3 [M þ Na]þ: 379.1071.
Ethyl 2-butoxy-3,4-dihydro-6-phenyl-2H-pyran-5-carboxylate (3f). Col-
1
orless liquid. H NMR (CDCl3): 0.88–0.96 (m, 6H), 1.40 (sext, J ¼ 7.6 Hz, 2H),
1.55–1.66 (m, 2H), 1.85–1.93 (m, 1H), 1.96–2.05 (m, 1H), 2.53 (dd, Ja ¼ 6.0 Hz,
Jb ¼ 8.4 Hz, 2H), 3.62 (dd, Ja ¼ 6.8 Hz, Jb ¼ 15.2 Hz, 1H), 3.88–3.99 (m, 3H), 5.22
(bs, 1H), 7.31–7.39 (m, 5H); 13C NMR: 13.8, 14.0, 18.6, 19.4, 26.2, 31.8, 59.9,
68.7, 98.5, 104.5, 127.8, 128.5, 128.9, 137.1, 159.9, 168.5. IR (cmꢂ1): 2961, 2937,
2871, 1693, 1636, 1444, 1371, 1340, 1244, 1155, 1126, 1056, 955, 901, 833, 760,
698. HR-MS: m=z ¼ 304.1712; calcd. for C18H24O4 [M]: 304.1725.

1574
J. YANG ET AL.
3-Ethoxycarbonyl-2,6-di(4-methoxyphenyl)-5,6-dihydropyran
(3g).
1
White solid, mp ¼ 77–78 ꢀC. H NMR (CDCl3): 1.00 (t, J ¼ 6.8 Hz, 3H), 1.91–2.02
(m, 1H), 2.12–2.22 (m, 1H), 2.43–2.53 (m, 1H), 2.67–2.77 (m, 1H), 3.76 (s, 3H),
3.78 (s, 3H), 4.01 (q, J ¼ 6.8 Hz, 2H), 4.95 (dd, Ja ¼ 1.6 Hz, Jb ¼ 10.4 Hz, 1H), 6.83
(d, J ¼ 8.4 Hz, 2H), 6.89 (d, J ¼ 8.4 Hz, 2H), 7.31 (d, J ¼ 8.8 Hz, 2H), 7.37 (d,
J ¼ 8.8 Hz, 2H); 13C NMR: 14.1, 23.5, 29.4, 55.3, 55.3, 60.0, 78.7, 103.2, 113.1,
113.9, 127.6, 129.2, 130.5, 132.9, 159.5, 160.6, 163.2, 169.3. IR (cmꢂ1): 2956, 2931,
2903, 2839, 1681, 1612, 1510, 1467, 1441, 1372, 1359, 1286, 1201, 1173, 1090, 1031,
977, 907, 831, 760. HR-MS: m=z ¼ 368.1657; calcd. for C22H24O5 [M]: 368.1666.
3-Ethoxycarbonyl-2-(4-methylphenyl)-6-(4-methoxyphenyl)-5,6-dihydro-
1
pyran (3h). Colorless liquid. H NMR (CDCl3): 0.98 (t, J ¼ 6.8 Hz, 3H), 1.91–2.02
(m, 1H), 2.14–2.24 (m, 1H), 2.37 (s, 3H), 2.46–2.57 (m, 1H), 2.69–2.79 (m, 1H), 3.81
(s, 3H), 3.99 (q, 7.6 Hz, 2H), 4.97 (dd, Ja ¼ 1.6 Hz, Jb ¼ 10.4 Hz, 1H), 6.89 (d,
J ¼ 8.4 Hz, 2H), 7.15 (d, J ¼ 8.0 Hz, 2H), 7.29 (dd, Ja ¼ 2.4 Hz, Jb ¼ 8.0 Hz, 4H);
13C NMR: 13.9, 21.3, 23.1, 29.4, 55.2, 59.9, 78.5, 103.4, 113.8, 127.2, 128.4, 128.7,
132.8, 133.8, 139.0, 159.3, 163.4, 169.0. IR (cmꢂ1): 2955, 2937, 1688, 1614, 1514,
1460, 1444, 1371, 1352, 1289, 1203, 1174, 1155, 1091, 1034, 1000, 974, 909, 823,
761. HR-MS: m=z ¼ 375.1572; calcd. for C22H24NaO4 [M þ Na]þ: 375.1566.
3-Ethoxycarbonyl-2-(4-chlorophenyl)-6-(4-methoxyphenyl)-5,6-dihydro-
pyran (3i). Colorless liquid. 1H NMR (CDCl3): 0.98 (t, J ¼ 6.8 Hz, 3H), 1.90–2.01 (m,
1H), 2.13–2.24 (m, 1H), 2.44–2.55 (m, 1H), 2.67-2.76 (m, 1H), 3.77 (s, 3H), 3.99 (q,
J¼ 6.8 Hz, 2H), 4.97 (dd, Ja ¼ 2.0 Hz, Jb ¼ 10.4 Hz, 1H), 6.89 (d, J ¼ 8.8 Hz, 2H),
7.25–7.33 (m, 4H), 7.32–7.37 (m, 2H); 13C NMR: 13.9, 23.3, 29.3, 55.3, 60.1, 78.9,
104.4, 114.1, 127.6, 127.9, 130.3, 132.7, 135.2, 135.4, 159.7, 162.3, 168.6. IR (cmꢂ1):
2981, 2957, 2935, 2905, 1691, 1618, 1372, 1289, 1252, 1202, 1179, 1161, 1094, 1136, 976,
910, 830, 760. HR-MS: m=z¼ 395.1026; calcd. for C21H21ClNaO4 [M þ Na]þ: 395.1024.
3-Ethoxycarbonyl-2-(4-trifluorophenyl)-6-(4-methoxyphenyl)-5,6-dihydro-
pyran (3j). White solid, mp ¼ 86–87 ꢀC. 1H NMR (CDCl3): 0.93 (t, J ¼ 6.8 Hz, 3H),
1.92–2.05 (m, 1H), 2.17–2.25 (m, 1H), 2.44–2.55 (m, 1H), 2.67–2.75 (m, 1H), 3.76 (s,
3H), 3.96 (q, J ¼ 7.2 Hz, 2H), 4.99 (dd, Ja ¼ 2.0 Hz, Jb ¼ 10.4 Hz, 1H), 6.88 (d,
J ¼ 8.8 Hz, 2H), 7.27 (d, J ¼ 8.8 Hz, 2H), 7.50 (d, J ¼ 8.0 Hz, 2H), 7.57 (d, J ¼ 8.0 Hz,
2H); 13C NMR: 13.6, 23.1, 29.2, 55.4, 60.1, 79.1, 104.9, 114.0, 122.6, 124.6, 124.6,
124.8, 124.8, 125.6, 127.4, 129.3, 129.3, 130.7, 131.0, 132.4, 140.4, 159.6, 161.9,
168.3. IR (cmꢂ1): 2981, 2937, 2909, 2842, 1697, 1636, 1617, 1519, 1325, 1288,
1250, 1169, 1129, 1091, 1066, 1033, 834, 760. HR-MS: m=z ¼ 429.1290, calcd. for
C22H21F3NaO4 [M þ Na]þ: 429.1279.
3-Ethoxycarbonyl-6-(4-methoxyphenyl)-2-(2-phenylethyl)-5,6-dihydro-
1
pyran (3k). Colorless liquid, H NMR (CDCl3): 1.28 (t, J ¼ 6.8 Hz, 3H), 1.72–1.82
(m, 1H), 2.00–2.10 (m, 1H), 2.31–2.43 (m, 1H), 2.43–2.54 (m, 1H), 2.85–2.97 (m,
2H), 2.98–3.09 (m, 2H), 3.80 (s, 3H), 4.18 (q, J ¼ 6.8 Hz, 2H), 4.75 (dd, Ja ¼ 2.0 Hz,
Jb ¼ 10.4 Hz, 1H), 6.89 (d, J ¼ 8.0 Hz, 2H), 7.11–7.19 (m, 3H), 7.21–7.30 (m, 4H); 13
C
NMR: 14.4, 22.3, 29.2, 34.1, 35.3, 55.1, 59.9, 77.9, 101.4, 113.7, 125.8, 127.1, 128.2,
128.5, 133.2, 141.7, 159.3, 167.3, 168.1. IR (cmꢂ1): 3059, 3028, 2953, 2937, 2833,
1701, 1617, 1514, 1458, 1362, 1244, 1200, 1173, 1157, 1116, 1068, 1034, 822, 760,
699. HR-MS: m=z ¼ 366.1858; calcd. for C23H26O4 [M]: 366.1847.

DIELS–ALDER REACTIONS OF BAYLIS–HILLMAN ADDUCTS
1575
3-Methoxycarbonyl-2-phenyl-6-(4-methoxyphenyl)-5,6-dihydropyran (3l).
1
White solid. mp ¼ 68–70 ꢀC. H NMR (CDCl3): 1.91–2.01 (m, 1H), 2.14–2.25 (m,
1H), 2.44–2.55 (m, 1H), 2.66–2.75 (m, 1H), 3.50 (s, 3H), 3.75 (s, 3H), 4.99 (dd,
Ja ¼ 2.0 Hz, Jb ¼ 10.4 Hz, 1H), 6.87 (dt, Ja ¼ 2.0 Hz, Jb ¼ 8.8 Hz, 2H), 7.26 (dt,
Ja ¼ 2.4 Hz, Jb ¼ 8.4 Hz, 2H), 7.30-7.35 (m, 3H), 7.37-7.43 (m, 2H); 13C NMR:
23.1, 29.3, 51.2, 55.2, 78.6, 103.4, 114.0, 127.3, 127.6, 128.7, 129.1, 132.6, 136.6,
159.4, 163.2, 169.0. IR (cmꢂ1): 2942, 1690, 1619, 1599, 1512, 1430, 1354, 1286,
1177, 1160, 1087, 1030, 951, 899, 830, 760, 699. HR-MS: m=z ¼ 347.1259; calcd.
for C20H20NaO4 [M þ Na]þ: 347.1252.
tert-Butyl-2-(4-methoxyphenyl)-3,4-dihydro-6-phenyl-2H-pyran-5-carbo-
1
xylate (3m). Colorless liquid. H NMR (CDCl3): 1.17 (s, 9H), 1.92–2.04 (m, 1H),
2.14–2.25 (m, 1H), 2.42–2.55 (m, 1H), 2.67–2.78 (m, 1H), 3.78 (s, 3H), 4.97 (d,
J ¼ 10.4 Hz, 1H), 6.88 (d, J ¼ 8.4 Hz, 2H), 7.24–7.36 (m, 5H), 7.36–7.41 (m, 2H);
13C NMR: 23.4, 27.9, 29.5, 55.5, 78.7, 80.1, 105.6, 113.9, 127.6, 127.8, 128.9,
129.0, 133.1, 137.7, 159.6, 162.6, 168.5. IR (cmꢂ1): 2978, 2936, 2852, 1688, 1636,
1619, 1518, 1449, 1368, 1299, 1252, 1171, 1096, 1034, 975, 833, 760, 698. HR-MS:
m=z ¼ 389.1729, calcd. for C23H26NaO4 [M þ Na]þ: 389.1717.
Cyclohexyl
2-(4-methoxyphenyl)-3,4-dihydro-6-phenyl-2H-pyran-5-
1
carboxylate (3n). White solid, mp ¼ 92–93 ꢀC, H NMR (CDCl3): 0.89–1.28 (m,
5H), 1.33–1.59 (m, 4H), 1.60–1.71 (m, 1H), 1.90–2.02 (m, 1H), 2.12–2.24 (m, 1H),
2.45–2.57 (m, 1H), 2.66–2.79 (m, 1H), 3.77 (s, 3H), 4.63 (sept, J ¼ 4.0 Hz, 1H),
4.97 (d, J ¼ 8.8 Hz, 1H), 6.87 (d, J ¼ 8.4 Hz, 2H), 7.23–7.33 (m, 5H), 7.36–7.46 (m,
2H); 13C NMR: 23.2, 23.7, 23.6, 25.5, 29.3, 31.0, 31.4, 55.2, 72.1, 78.5, 104.2,
113.7, 127.3, 127.5, 128.7, 128.5, 132.7, 136.9, 159.2, 162.7, 168.1. IR (cmꢂ1):
2933, 2851, 1680, 1624, 1613, 1594, 1511, 1442, 1360, 1280, 1231, 1179, 1099,
1032, 970, 822, 760, 698. HR-MS: m=z ¼ 315.1885, calcd. for C25H28NaO4
[M þ Na]þ: 415.1878.
ACKNOWLEDGMENTS
We gratefully acknowledge the financial support from the Doctoral Research
Fund of Henan University of Traditional Chinese Medicine.
REFERENCES
1. (a) Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. G. Cascade reactions in total synthesis.
Angew. Chem. Int. Ed. 2006, 45, 7134–7186; (b) Aubert, C.; Fensterbank, L.; Gandon,
V.; Malacria, M. Complex polycyclic molecules from acyclic precursors via transition
metal–catalyzed cascade reactions. Topics Organometal. Chem. 2006, 19, 259–294; (c)
Bruneau, C.; Derien, S.; Dixneuf, P. H. Cascade and sequential catalytic transformations
initiated by ruthenium catalysts. Topics Organometal. Chem. 2006, 19, 295–326.
2. (a) Basavaiah, D.; Rao, K. V.; Reddy, R. J. The Baylis–Hillman reaction: A novel source
of attraction, opportunities, and challenges in synthetic chemistry. Chem. Soc. Rev. 2007,
36, 1581–1588; (b) Singh, V.; Batra, S. Advances in the Baylis–Hillman reaction-assisted
synthesis of cyclic frameworks. Tetrahedron 2008, 64, 4511–4574; (c) Ma, G.-N.; Jiang,
J.-J.; Shi, M.; Wei, Y. Recent extensions of the Morita–Baylis–Hillman reaction. Chem.

1576
J. YANG ET AL.
Commun. 2009, 37, 5496–5514; (d) Krishna, P. R.; Sachwani, R.; Reddy, P. S. Asymmetric
Baylis–Hillman reaction: An enchanting expedition. Synlett 2008, 2897–2912; (e) Declerck,
V.; Martinez, J.; Lamaty, F. Aza–Baylis–Hillman reaction. Chem. Rev. 2009, 109, 1–48.
3. (a) Gowrisankar, S.; Lee, H. S.; Kim, S. H.; Lee, K. Y.; Kim, J. N. Recent advances in the
Pd-catalyzed chemical transformations of Baylis–Hillman adducts. Tetrahedron 2009, 65,
8769–8780; (b) Wei, Y.; Shi, M. Multifunctional chiral phosphine organocatalysts in cata-
lytic asymmetric Morita–Baylis–Hillman and related reactions. Acc. Chem. Res. 2010, 43,
1005–1018; (c) Bruckmann, A.; Krebs, A.; Bolm, C. Organocatalytic reactions, effects of
ball milling, microwave and ultrasound irradiation. Green Chem. 2008, 10, 1131–1141.
4. (a) Cabrera, S.; Aleman, J.; Bolze, P.; Bertelsen, S.; Joergensen, K. A. An unexpected
organocatalytic asymmetric tandem Michael=Morita–Baylis–Hillman reaction. Angew.
Chem. Int. Ed. 2008, 47, 121–125; (b) Wang, W.; Yu, M. One-pot sequential Baylis–
Hillman and Michael reactions. Tetrahedron Lett. 2004, 45, 7141–7143; (c) Chandrasekhar,
S.; Saritha, B.; Jagadeshwar, V.; Narsihmulu, C.; Vijay, D.; Sarma, G. D.; Jagadeesh, B.
Hydroxy-assisted catalyst–free Michael addition–dehydroxylation of Baylis–Hillman
adducts in poly(ethylene glycol). Tetrahedron Lett. 2006, 47, 2981–2984.
5. (a) Yadav, L. D. S.; Srivastava, V. P.; Patel, R. Ionic liquid [Hmim]HSO4–promoted one-
pot oxidative conjugate addition of sulfur-centered nucleophiles to Baylis–Hillman
adducts. Tetrahedron Lett. 2008, 49, 3142–3146; (b) Yadav, J. S.; Reddy, B. V. S.; Singh,
A. P.; Basak, A. K. The first one-pot oxidative Michael reaction of Baylis–Hillman
adducts with indoles promoted by iodoxybenzoic acid. Tetrahedron Lett. 2007, 48,
4169–4172; (c) Yadav, J. S.; Reddy, B. V. S.; Singh, A. P.; Basak, A. K. One-pot oxidative
allylation of Morita–Baylis–Hillman adducts with allyltrimethylsilane promoted by
Dess–Martin periodinane=boron trifluoride–diethyl ether complex. Synthesis 2008, 469–
473; (d) Yadav, J. S.; Reddy, B. V. S.; Singh, A. P.; Basak, A. K. IBX=Sc(OTf)3-
promoted one-pot oxidative conjugate addition of allyltrimethylsilane to Baylis–Hillman
adducts. Tetrahedron Lett. 2007, 48, 7546–7548
6. Yadav, L. D. S.; Awasthi, C.; Rai, A. Ionic liquid–promoted one-pot oxidative Michael
addition of TMSCN to Baylis–Hillman adducts. Tetrahedron Lett. 2008, 49, 6360–6363.
7. Lawrence, N. J.; Crump, J. P.; McGown, A. T.; Hadfield, J. A. Reaction of Baylis–Hillman
products with Swern and Dess–Martin oxidants. Tetrahedron Lett. 2001, 42, 3939–3941.
8. (a) Bugarin, A.; Jones, K. D.; Connell, B. T. Efficient, direct a-methylenation of carbonyls
mediated by diisopropylammonium trifluoroacetate. Chem. Commun. 2010, 46, 1715–
1717; (b) Vale, J. A.; Zanchetta, D. F.; Moran, P. J. S.; Rodrigues, J. A. R. Efficient a-
methylenation of carbonyl compounds in ionic liquids at room temperature. Synlett
2009, 75–78.
9. Yamauchi, M.; Katayama, S.; Watanabe, T. 2-Methylthiomethylation of 1,3-dicarbonyl com-
pounds and synthesis of 2-methylene-1,3-dicarbonyl compounds. Synthesis 1982, 935–937.
10. (a) Li, M.; Chen, C.; He, F.; Gu, Y. Multicomponent reactions of 1,3-cyclohexanediones
and formaldehyde in glycerol: stabilization of paraformaldehyde in glycerol resulted from
using dimedone as substrate. Adv. Synth. Catal. 2010, 352, 519–530; (b) Gu, Y.; De Sousa,
R.; Frapper, G.; Bachmann, C.; Barrault, J.; Jerome, F. Catalyst-free aqueous multicom-
ponent domino reactions from formaldehyde and 1,3-dicarbonyl derivatives. Green Chem.
2009, 11, 1968–1972; (c) Gu, Y.; Barrault, J.; Jerome, F. Trapping of active methylene
intermediates with alkenes, indoles, or thiols: Towards highly selective multicomponent
reactions. Adv. Synth. Catal. 2009, 351, 3269–3278.
11. (a) Tohma, H.; Kita, Y. Hypervalent iodine reagents for the oxidation of alcohols and
their application to complex molecule synthesis. Adv. Synth. Catal. 2004, 346, 111–124;
(b) Wirth, T. IBX–New reactions with an old reagent. Angew. Chem. Int. Ed. 2001, 40,
2812–2814.