Hetero-Diels-Alder reaction of propenenitriles with enol ethers: A convenient approach to functionalized 3,4-dihydro-2H-pyrans

Article abstract of DOI:10.1007/s00706-007-0824-x

The hetero-Diels-Alder reaction of 3-(N-acetyl-N-benzylamino)-2-formylprop- 2-enenitrile with enol ethers yielded cis/trans diastereoisomers of 2-alkoxy-4-amino-3,4-dihydro-2H-pyran-5-carbonitriles in moderate yields. Acidic hydrolysis of cis-diastereoisomer in concentrated sulfuric acid gave 2-oxo-1,2-dihydropyrydine-3-carbaldehyde. The reaction of 2-benzoyl-3- heteroaromaticprop-2-enenitriles with enol ethers afforded diastereoisomeric cis/trans cycloadducts in good yields. The structure of the products is discussed in terms of configuration and preferred conformation.

Full text of DOI:10.1007/s00706-007-0824-x

Monatsh Chem 139, 647–655 (2008)
DOI 10.1007/s00706-007-0824-x
Printed in The Netherlands
Hetero-Diels-Alder reaction of propenenitriles with enol ethers: a convenient
approach to functionalized 3,4-dihydro-2H-pyrans
Aleksandra Pałasz, Krystyna Bogdanowicz-Szwed
´
Department of Organic Chemistry, Jagiellonian University, Krakow, Poland
Received 1 October 2007; Accepted 9 October 2007; Published online 19 May 2008
# Springer-Verlag 2008
Abstract The hetero-Diels-Alder reaction of 3-(N-
acetyl-N-benzylamino)-2-formylprop-2-enenitrile
with enol ethers yielded cis=trans diastereoisomers
of 2-alkoxy-4-amino-3,4-dihydro-2H-pyran-5-carbo-
nitriles in moderate yields. Acidic hydrolysis of cis-
diastereoisomer in concentrated sulfuric acid gave
2-oxo-1,2-dihydropyrydine-3-carbaldehyde. The re-
action of 2-benzoyl-3-heteroaromaticprop-2-eneni-
triles with enol ethers afforded diastereoisomeric
cis=trans cycloadducts in good yields. The structure
of the products is discussed in terms of configuration
and preferred conformation.
Diels-Alder (HDA) reactions of ꢀ,ꢁ-unsaturated
carbonyl compounds representing an 1-oxa-1,3-buta-
diene system with enol ethers [1–6]. It was stated
that introducing an electron withdrawing group in
the 1-oxa-1,3-diene system can enhance their reac-
tivity [7–12]. Among the electron withdrawing sub-
stituents, the cyano group was found to have the
most pronounced influence on facilitating the reac-
tion of 1-oxadienes with enol ethers. Wyler et al.
have reported that ꢀ,ꢁ-unsaturated acyl cyanides ex-
hibit an extraordinary reactivity towards enol ethers,
yielding 3,4-dihydro-2H-pyran-6-carbonitriles at
room temperature [7, 8]. Recently, we have reported
that HDA reactions of 3-cyano-1-oxa-1,3-butadienes
with enol ethers [13, 14], styrenes [15], or N-vinyl-
2-oxazolidinone [16] lead efficiently to 3,4-dihydro-
2H-pyran-5-carbonitriles. Also, the influence of
cyano, carbonyl, ethoxycarbonyl groups, or sulfur
containing substituents at C-3 in 1-oxa-1,3-buta-
dienes on the intramolecular HDA reaction was ex-
amined [17, 18].
Keywords Diels-Alder reaction; Pyrans; ꢀ,ꢁ-Unsaturated
carbonyl compounds; Enol ethers.
Introduction
Pyran derivatives are common structural subunits in
a variety of important natural products, including
carbohydrates, alkaloids, polyether antibiotics, pher-
omones, and iridoids. Especially 3-amino sugars are
of great interest as parts of biological active com-
pounds or because of their own potential biological
activity. They are present in various antibiotics such
as gentamycin C or adriamycin [1, 2]. Amino deriv-
atives of 3,4-dihydro-2H-pyrans can be efficiently
synthesized by an inverse-electron-demand hetero-
Results and discussion
In this paper, the hetero-Diels-Alder reactions (HDA)
of different 1-oxa-1,3-butadienes with cyano func-
tion at C-3 are described. The first aim of this work
was to investigate reactions of enaminocarbaldehyde
-3-(N-acetyl-N-benzylamino)-2-formylprop-2-eneni-
trile 3, that acted as heterodiene in HDA reaction,
with different enol ethers 4. The object was to show
Correspondence: Aleksandra Pałasz, Department of Organic
´
Chemistry, Jagiellonian University, Krakow, Poland. E-mail:
palasz@chemia.uj.edu.pl

648
A. Pałasz, K. Bogdanowicz-Szwed
Scheme 1
Table 1 Synthesis of dihydropyrans 5a–5e and 8a–8e
that this enaminecarbaldehyde is a valuable precur-
sor in the synthesis of 4-amino-3,4-dihydro-2H-py-
rans with the skeleton of branched amino sugars of
the garosamine-type [19]. The second aim was to
study the HDA reactions 2-benzoyl-3-heteroaroma-
ticprop-2-enenitrile 7 with enol ethers 4.
Diene Dienophile Products Reaction Yield= Ratio
time=h
a
%
of cis:
transb
3
3
3
3
4a
4b
4c
4d
4e
4a
4b
4d
4a
4a
5a
5b
5c
5d
5e
8a
8b
8c
8d
8e
36
30
44
60
96
48
48
48
48
24
70
48
74
77
48
79
81
76
77
88
2.6:1
1.7:1
1.5:1
3.2:1
–
10:1
9:1
4.5:1
10:1
12:1
The synthesis of enaminecarbaldehyde 3 was
accomplished in a three-step reaction. Starting
3-N,N-dimethylamino-2-formylprop-2-enenitrile 1
(Scheme 1) was obtained in a Vilsmayer-Haack
formylation reaction described by Reichardt and
Kermer [20]. Compound 1 did not give any cycload-
ducts with enol ethers. This is due to the electron
donating amino-function at C-3, which raises the
LUMO energy of the heterodiene. Only N-acyl de-
rivatives of enaminecarbaldehydes are capable to
undergo HDA reactions [21]. In the next steps the
appropriate modification of 1 was made. Reaction of
1 with benzylamine in methylene chloride afforded 2
in 52% yield. Compound 2 was transformed into the
N-acetyl derivative 3 (65%) in reaction with acetyl
chloride in dichloromethane:diethyl ether (2:1) in
the presence of pyridine. The reactions of hetero-
diene 3 with enol ethers 4a–4e were performed in
toluene solution at 110ꢀC for 30–96 h (Table 1). The
progress of the reactions was monitored by TLC.
They afforded two diastereoisomers of 4-(N-acetyl-
N-benzylamino)-2-alkoxy-3,4-dihydro-2H-pyran-5-
3
7a
7a
7a
7b
7c
a
Isolated yields after column chromatography
1
Ratio based on H NMR spectra of crude products
b
carbonitriles 5a–5e in 48–77% yield (Scheme 1).
The cis diastereoisomers were always the main
products. The ratios of diastereoisomers cis=trans
were determined on the basis of 1H NMR spectra of
crude products. The highest ratio of cis=trans dia-
stereoselectivity was observed in the reaction of 3
with 4d, leading to a product ratio of cis-5d:trans-
5d ¼ 3.2:1. In the case of the reaction of 3 with cis-
ethyl-propenyl ether 4e only one diastereoisomer 5e
was isolated. Compounds 5a–5e were separated by
column chromatography and purified further by crys-

Hetero-Diels-Alder reaction
Table 2 Signals of proton 2-H and 4-H in H NMR spectra of dihydropyrans 5a–5e and 8a–8e
649
1
Compound
dd 2-H ꢂ=ppm,
J3ax,2=J3eq,2=Hz
dd 4-H ꢂ=ppm,
J3ax,4=J3eq,4=Hz
Compound
dd 2-H ꢂ=ppm,
J3ax,2=J3eq,2=Hz
dd 4-H ꢂ=ppm,
J3ax,4=J3eq,4=Hz
cis-5a
5.09, 8.3=2.1
5.72, 9.0=6.3
trans-5a
t 5.04, 2.7
4.87, 10.4=5.6
5.52, 10.2=6.3
cis-5b
cis-5c
cis-5d
5e
cis-8a
cis-8b
cis-8c
cis-8d
cis-8e
5.09, 9.0=2.0
5.08, 8.5=2.5
–
d 4.95, 3.5
5.31, 8.1=2.1
5.29, 7.8=2.1
–
5.78, 8.8=6.5
5.76, 9.0=6.5
ddd 5.59, 8.1=6.6=J6,41.5
d 5.68, 6.0
4.21, 9.6=6.9
4.20, 9.3=6.9
t 4.13, 7.2
trans-5b
trans-5c
trans-5d
–
trans-8a
trans-8b
trans-8c
trans-8d
trans-8e
t 5.05, 3.0
t 5.04, 2.5
–
4.89 br, 5.51, 9.9=6.9
4.82 br, 5.49, 9.9=6.6
4.90, 11.5=6.5, 5.95 br
–
4.24, 9.3=6.0
4.24, 9.6=6.0
4.27, 12.3=6.0
4.03, 8.9=6.7
4.02, 11.1=6.3
–
5.35, 4.5=2.4
5.34, 4.2=2.4
–
5.35, 4.8=2.7
5.39, br t 2.7
t 5.31, 5.0
5.35, 6.9=2.4
t 3.99, 7.3
t 3.94, 7.5
tallization. Compounds 5a–5e were characterized by
1H, 13C NMR, IR, mass spectra, and elemental anal-
the pseudo-axial position and N-acetyl-N-ben-
zylamino moiety occupies the pseudo-equatorial
position (Fig. 1). For trans diastereoisomers trans-
5a–5c, the protons attached to C-2 give rise to
triplets with small coupling constants (3J ¼ 2.5–
3.0 Hz) at ꢂ ¼ 5.04–5.05 ppm. This suggests that
for trans-5a–5c the conformation with an axial alk-
oxy group is preferred due to stabilization by the
anomeric effect. The proton 4-H of trans-5a–5d
resonates at ꢂ ¼ 4.82–5.95 ppm as broad signals
and at ꢂ ¼ 5.49–5.52 ppm as dd with two large cou-
pling constants (3J ¼ 6.3–6.9 and 9.9–11.5 Hz).
Thus, 4-H is pseudo-axial and large N-acetyl-N-ben-
zylamino moiety occupies the pseudo-equatorial po-
1
ysis. H and 13C signal assignments were confirmed
by two-dimensional NMR COSY and HETCOR
spectra. The relative cis and trans configurations at
C-2, C-4 of substituents were assigned on the basis
1
of H NMR spectra. They were deducted from the
chemical shift values and coupling constants of pro-
tons attached to C-2 and C-4 of the dihydropyran
ring that exists in a half-chair conformation [22]
1
(Table 2). In the H NMR spectra of cis-5a–5c the
signal of 2-H appeared as a doublet of doublets at
ꢂ ¼ 5.08–5.09 ppm with small and large coupling
constants (3J ¼ 2.0–2.5, 8.3–9.0 Hz) due to coupling
with two protons at C-3 (Table 2). Thus, 2-H occu-
pies an axial position, and the alkoxy group adopts
an equatorial orientation (Fig. 1).
1
sition (Fig. 1). The H NMR spectrum of trans-5a
was also recorded at 333 K. It is worth to note that in
the spectrum measured at higher temperature two
signals of proton 4-H (ꢂ ¼ 4.87, 5.52 ppm) are ob-
served as one broad signal ꢂ ¼ 5.31 ppm. In the spec-
trum of 5e the signal of 2-H is a doublet at ꢂ ¼
4.97 ppm due to the coupling with one proton 3-H
(3J ¼ 3.5 Hz) and proton 4-H is also observed as dou-
blet at ꢂ ¼ 5.70 ppm with the coupling constants
3J ¼ 6.0 Hz. This suggests that the substituents at-
tached to C-2, C-3 and C-4 are in cis configuration,
the same as in cis-ethyl-propenyl ether 4e.
1
The H NMR spectra of cis-5a–5d reveal the
signals of proton 4-H as a doublet of doublets at
ꢂ ¼ 5.59–5.78 ppm with two large coupling con-
stants (3J ¼ 6.3–6.6, 8.1–9.0 Hz). In the spectrum
of cis-5d the signal of 4-H is a doublet of doublets
due to the coupling of 4-H with two protons 3-H
and with proton 6-H (4J ¼ 1.5 Hz). Thus, 4-H is in
The preferred formation of cis-diastereoisomers
(Table 1) results from the endo transition state inter-
action which is energetically more favorable than
exo transition state one. Thus, cis-products arise
from a kinetically controlled process [23].
It was found that cis diastereoisomers of 3,4-dihy-
dro-2H-pyran derivatives undergo transformation to
trans isomers in the presence of Lewis acid [3, 4,
Fig. 1 Preferred cis:trans configurations and conformations
of cycloadducts 5a–5e and 8a–8e based on 1H NMR analysis

650
A. Pałasz, K. Bogdanowicz-Szwed
Scheme 2
21]. When cis-5a was submitted to the action of
boron fluoride etherate, a mixture of cis-5a:trans-
5a ¼ 1:3.4 was obtained after 24 h at room tempera-
ture (1H NMR analysis).
In the next series of experiments the reactions of
2-benzoyl-3-heteroaromaticprop-2-enenitriles 7a–7c
with enol ethers 4a, 4b, and 4d were investigated.
The reactions were performed with methylene chlo-
ride as the solvent at room temperature for 1–2 days
and the cycloadducts 8a–8e were obtained with 76–
88% yields (Scheme 3, Table 1). The highest ratio of
cis=trans diastereosletivity was observed in the reac-
tion of 7c with 4a, leading to a product ratio of cis-
8e:trans-8e ¼ 12:1. The reactions of 7a or 7b with
ether 4a gave products also with high diastereoselec-
tivity cis:trans ¼ 10:1.
Acidic hydrolysis of cis-5a in concentrated sulfu-
ric acid (60%) gave 2-oxo-1,2-dihydropyrydine-3-
carbaldehyde 6 with 63% yield. Compound 6 has
been already described [24, 25]. Formation of 6
can be rationalized as depicted in Scheme 2. In
the first step, the acidic medium causes the opening
of the pyran ring and the hydrolysis of the cyano
group to the amide leading to the intermediate A.
Elimination of acetylbenzylamine and ethanol from
A furnishes the intermediate B, which undergoes
intramolecular condensation yielding compound 6.
The structure of dihydropyrans 8a–8e was estab-
lished on the basis of analytical and spectroscopic
data. 1H and 13C signal assignments were confirmed
Scheme 3

Hetero-Diels-Alder reaction
651
3-N-Benzylamino-2-formylprop-2-enenitrile (2, C11H10N2O)
To a stirred solution of 1.9 g 3-N,N-dimethylamino-2-formyl-
prop-2-enenitrile 1 (15 mmol) in 20cm3 anhydrous dichloro-
methane, a solution of 1.6 g benzylamine (15 mmol) in 10cm3
CH2Cl2 was added. The mixture was allowed to stir at room
temperature for 1 h, then the solvent was evaporated. The
crude mixture was triturated with 15cm3 toluene. The result-
ing precipitate was filtered off and purified by column chro-
matography on silica gel using chloroform=methanol (20=1)
as eluent. Crystallization from toluene gave (1.45 g) colorless
crystals; mp 117ꢀC; yield 52%; IR (HCB=nujol): ꢃꢀ¼ 3173
(NH), 2930 (CH), 2200 (CN), 1633 (C¼O), 1570 (C¼C)
by two-dimensional NMR COSY and HETCOR
1
spectra. In the H NMR spectra of cis-8a–8e the
signal of 2-H appeared as a doublet of doublets at
ꢂ ¼ 5.29–5.35 ppm with small and large coupling
constants (3J ¼ 2.1–2.4, 6.9–8.1 Hz) (Table 2).
Thus, 2-H occupies an axial position, and the alkoxy
group adopts an equatorial orientation (Fig. 1). The
1H NMR spectra of cis-8a–8e reveal the signals
proton 4-H at ꢂ ¼ 3.94–4.21 ppm as a doublet of
doublets with two large coupling constants (3J ¼
3
cmꢁ1
;
1H NMR (300.18MHz, CDCl3): ꢂ ¼ 4.52 (s, 0.85
6.9, 9.3–9.6 Hz) or as triplets with J ¼ 7.2–7.5 Hz.
CH2Ph), 4.53 (s, 0.85 CH2Ph), 4.56 (s, 0.15 CH2Ph), 4.57
(s, 0.15 CH2Ph), 7.23–7.43 (m, 6 3-H, PhH), 9.12 (s, 0.15
CHO-E), 9.30 (d, J ¼ 3.4 Hz, 0.85 CHO-Z), 10.77 (br, 1 NH)
ppm; 13C NMR (75.48 MHz, CDCl3): ꢂ ¼ 53.6, 53.8 (NCH2),
83.6 (C-2), 119.3 (CN), 127.7, 127.8, 128.9, 129.0, 129.3,
134.43, 134.8 (PhC), 158.5, 158.8 (C-3), 187.9 (CHO) ppm;
Thus, 4-H is the pseudo-axial and heteroaromatic
moiety occupies the pseudo-equatorial position
(Fig. 1). For trans diastereoisomers trans-8a–8e,
the protons attached to C-2 give rise to doublet of
doublets with two small coupling constants (3J ¼
2.4–2.7 and 4.2–4.8 Hz) at ꢂ ¼ 5.34–5.39ppm. This
suggests that for trans-8a–8e the conformation with
an axial alkoxy group is preferred due to stabiliza-
tion by the anomeric effect. The proton 4-H of trans-
8a–8e resonates at ꢂ ¼ 4.02–4.27 ppm as doublet of
doublets with two large coupling constants (3J ¼
6.0–6.7 and 8.9–12.3 Hz). Thus, 4-H is pseudo-axial
and heteroaromatic ring occupies the pseudo-equa-
torial position (Fig. 1).
þ
MS (EI, 70eV): m=z (%) ¼ 186 (8) [M] ꢂ, 159 (25), 130 (14),
105 (12), 91 (100), 77 (43).
3-(N-Acetyl-N-benzylamino)-2-formylprop-2-enenitrile
(3, C13H12N2O2)
A three-necked round-bottomed flask (250 cm3) was equipped
with a stirrer, fitted with a thermometer, sealed with a septum,
and placed under an argon atmosphere. The flask was charged
with 1.9 g 2 (10 mmol), 30cm3 anh. CH2Cl2, 15 cm3 anh.
diethyl ether, and 1.2 cm3 pyridine (15 mmol). Freshly dis-
tilled acetyl chloride (1.4cm3, 15mmol) was added by syringe
at 0ꢀC. The reaction mixture was allowed to warm to room
temperature and stirring was continued for 3 h. The precipitat-
ed ammonium salt of pyridine was filtered off, washed with
diethyl ether (10 cm3), and the combined organic layers were
evaporated on vacuum. The residue was purified by column
chromatography on silica gel using chloroform=methanol
(20=1) as eluent. Crystallization from cyclohexane=ethyl
acetate 3=1 gave (1.48 g) colorless crystals; mp 95ꢀC; yield
65%; IR (HCB=nujol): ꢃꢀ¼ 3020, 2933, 2844 (CH), 2213
In conclusion, the present results indicate that
3-(N-acetyl-N-benzylamino)-2-formylprop-2-eneni-
trile 3 and 2-benzoyl-3-heteroaromaticprop-2-eneni-
triles 7a–7c can act as valuable heterodienes in
inverse electron demand HDA reaction with enol
ethers. Enaminocarbaldehyde 3 was found to be less
reactive than propenenitriles 7a–7c because reac-
tions 7a–7c with enol ethers occurred at room tem-
perature whereas reactions with 3 required heating in
boiling toluene.
(CN), 1720, 1690 (C¼O), 1600 (C¼C) cmꢁ1
;
1H NMR
(300.18 MHz, CDCl3): ꢂ ¼ 2.45 (s, 3 COCH3), 5.41 (s, 2
CH2Ph), 7.13–7.50 (m, 5 PhH), 8.55 (s, 1 3-H), 9.38 (s, 1
CHO) ppm; 13C NMR (75.48 MHz, CDCl3): ꢂ ¼ 22.0
(COCH3), 48.9 (NCH2), 94.7 (C-2), 113.5 (CN), 126.0, 127.6,
128.3, 129.3, 134.1 (PhC), 158.8 (C-3), 170.7 (COCH3), 186.1
Experimental
Melting points were determined on a Boetius hot stage appa-
ratus. IR spectra: Bruker IFS 48 in HCB=nujol, KBr pellets.
1H NMR, 13C NMR, COSY and HETCOR spectra: Bruker
Avance II 300 (1H: 300.18MHz, 13C: 75.48 MHz), in CDCl3
with TMS as an internal standard. Mass spectra: Finningan
Mat 95 (70 eV). Microanalyses were performed with Euro
EA 3000 Elemental Analyzer, their results agreed satisfactori-
ly with the calculated values. 3-N,N-Dimethylamino-2-formyl-
propenenitrile (1) was obtained according to the procedure
reported in Ref. [20]. Enol ethers 4a–4e were commercially
available. 2-Benzoyl-3-(2-thienyl)prop-2-enenitrile (7a), 2-
benzoyl-3-(2-furyl)prop-2-enenitrile (7b), and 2-benzoyl-3-
(4-cyanophenyl)prop-2-enenitrile (7c) were prepared by
procedures described in Refs. [13, 26].
þ
(CHO) ppm; MS (EI, 70 eV): m=z (%) ¼ 228 (4) [M] ꢂ, 186
(56), 158 (26), 149 (5), 106 (7), 91 (100), 43 (76).
Procedures for the synthesis of 3,4-dihydro-2H-pyran-5-
carbonitriles 5a–5e and 8a–8e
A solution of 2 mmol 3 in 10cm3 anh. toluene, 20 mmol
appropriate vinyl ethers 4a–4e (10 equivalents), and some
crystals of hydroquinone was heated at 110ꢀC in a pressure
flask for the time given in Table 1. A solution of 2 mmol 7a–
7c in 10cm3 anh. CH2Cl2 and 20mmol vinyl ether 4a, 4b,
and 4d (10 equiv.) was kept at room temp. for the time given
in Table 1. The progress of the reactions was monitored by
TLC. The solvent and excess of ethers were evaporated and

652
A. Pałasz, K. Bogdanowicz-Szwed
the mixture was separated and purified by column chromatog-
raphy on silica gel using ethyl acetate=petrol ether: 1=1 (5a–
5c), t-butyl methyl ether (5d and 5e), t-butyl methyl ether=
petrol ether: 1=3 (8a and 8c), 1=1 (8b and 8e), 1=2 (8d) as an
eluent. Recrystallization from cyclohexane=ethyl acetate: 5=2
(5a–5e) or petrol ether=t-butyl methyl ether: 3=1 (8a–8d),
petrol ether=t-butyl methyl ether: 2=1 (8e) gave 5a–5e and
8a–8e with yields listed in Table 1.
OCH2CH(CH3)2), 4.39 (d, J ¼ 18.0Hz, 1 CH2Ph), 4.73 (d,
J ¼ 18.0 Hz, 1 CH2Ph), 5.09 (dd, J ¼ 2.0, 9.0 Hz, 1 2-H),
5.78 (dd, J ¼ 6.5, 8.8Hz, 1 4-H), 7.15–7.40 (m, 6 6-H,
PhH) ppm; 13C NMR (75.48 MHz, CDCl3): ꢂ ¼ 19.1, 19.2
(OCH2CH(CH3)2), 22.3 (COCH3), 28.3 (OCH2CH(CH3)2),
31.6 (C-3), 46.4 (C-4), 48.0 (NCH2), 77.6 (OCH2CH(CH3)2),
90.3 (C-5), 101.3 (C-2), 116.7 (CN), 125.6, 125.5, 129.0, 137.4
(PhC), 157.6 (C-6),þ172.7 (COCH3) ppm; MS (EI, 70eV): m=z
(%) ¼ 328 (12) [M] ꢂ, 237 (38), 211 (10), 195 (76), 163 (15),
148 (35), 139 (14), 106 (42), 91 (100).
(2RS,4RS)-4-(N-Acetyl-N-benzylamino)-2-ethoxy-3,4-di-
hydro-2H-pyran-5-carbonitrile (cis-5a, C17H20N2O3)
Colorless crystals; mp 102ꢀC; yield 50.5%; IR (HCB=nujol):
ꢃꢀ¼ 2973, 2920, 2880 (CH), 2200 (CN), 1640 (C¼O), 1610
(2RS,4SR)-4-(N-Acetyl-N-benzylamino)-3,4-dihydro-2-iso-
butoxy-2H-pyran-5-carbonitrile (trans-5b, C19H24N2O3)
Colorless oil; yield 18%; IR (film): ꢃꢀ¼ 2960, 2920, 2882
(C¼C) cmꢁ1
;
1H NMR (300.18 MHz, CDCl3): ꢂ ¼ 1.17
(CH), 2200 (CN), 1659 (C¼O), 1620 (C¼C) cmꢁ1
;
1H
(t, J ¼ 7.1 Hz, 3 OCH2CH3), 1.84 (m, 1 3-H), 1.99 (s, 2.7
COCH3), 2.09 (ddd, J ¼ 2.1, 6.3, 13.5Hz, 1 3-H), 2.27 (s,
0.3 COCH3), 3.55 (dq, J ¼ 7.1, 9.5 Hz, 1 OCH2CH3), 3.84
(dq, J ¼ 7.1, 9.5 Hz, 1 OCH2CH3), 4.36 (d, J ¼ 18.0Hz, 1
CH2Ph), 4.68 (d, J ¼ 18.0 Hz, 1 CH2Ph), 5.09 (dd, J ¼ 2.1,
8.3 Hz, 1 2-H), 5.72 (dd, J ¼ 6.3, 9.0Hz, 1 4-H), 7.08–7.36
(m, 6 6-H, PhH) ppm; 13C NMR (75.48 MHz, CDCl3):
ꢂ ¼ 14.8 (OCH2CH3), 22.3 (COCH3), 31.7 (C-3), 46.2 (C-4),
47.9 (NCH2), 65.6 (OCH2CH3), 90.4 (C-5), 100.7 (C-2), 116.6
(CN), 125.5, 127.7, 128.9, 137.4 (PhC), 157.5 (C-6), 172.7
NMR (300.18 MHz, CDCl3): ꢂ ¼ 0.86 (d, J ¼ 6.5 Hz, 6
OCH2CH(CH3)2), 1.83 (m, 1 OCH2CH(CH3)2), 1.88 (m, 1
3-H), 2.15 (s, 2.4 COCH3), 1.97 (ddd, J ¼ 3.0, 6.0, 13.5Hz,
1 3-H), 2.35 (s, 0.6 COCH3), 3.22 (dd, J ¼ 6.5, 9.5Hz,
1 OCH2CH(CH3)2), 3.49 (dd, J ¼ 6.6, 9.5 Hz, 1 OCH2-
CH(CH3)2), 3.92 (br, 0.2 CH2Ph), 4.43 (d, J ¼ 18.0Hz, 0.8
CH2Ph), 4.74 (d, J ¼ 18.0Hz, 0.8 CH2Ph), 4.89 (br, 0.2 4-H),
5.05 (t, J ¼ 3.0 Hz, 1 2-H), 5.30 (br, 0.2 CH2Ph), 5.51 (dd,
J ¼ 6.9, 9.9Hz, 0.8 4-H), 7.10–7.40 (m, 6 6-H, PhH) ppm;
13C NMR (75.48 MHz, CDCl3): ꢂ ¼ 19.0, 19.1 (OCH2-
CH(CH3)2), 22.4 (COCH3), 28.3 (OCH2CH(CH3)2), 30.9 (C-
3), 44.5 (C-4), 49.3 (NCH2), 76.1 (OCH2CH(CH3)2), 91.8
(C-5), 99.1 (C-2), 116.8 (CN), 125.9, 127.5, 127.6 (PhC),
157.7 (C-6), 172.3 þ(COCH3) ppm; MS (EI, 70eV): m=z
(%) ¼ 328 (15) [M] ꢂ, 237 (39), 211 (13), 195 (67), 163
þ
ꢂ,
(COCH3) ppm; MS (EI, 70 eV): m=z (%) ¼ 300 (10) [M]
209 (40), 167 (87), 148 (33), 139 (13), 106 (44), 91 (100), 72
(11), 43 (61).
(2RS,4SR)-4-(N-Acetyl-N-benzylamino)-2-ethoxy-3,4-di-
hydro-2H-pyran-5-carbonitrile (trans-5a, C17H20N2O3)
Colorless crystals; mp 154ꢀC; yield 19.5%; IR (HCB=nujol):
ꢃꢀ¼ 2973, 2920, 2880 (CH), 2200 (CN), 1626 (C¼O), 1613
(18), 148 (41), 139 (12), 106 (46), 91 (100).
1
(C¼C) cmꢁ1; H NMR (300.18 MHz, CDCl3): ꢂ ¼ 1.18 (t,
(2RS,4RS)-4-(N-Acetyl-N-benzylamino)-3,4-dihydro-2-n-
butoxy-2H-pyran-5-carbonitrile (cis-5c, C19H24N2O3)
Colorless crystals; mp 92ꢀC; yield 44%; IR (film): ꢃꢀ¼ 2963,
2938, 2874 (CH), 2211 (CN), 1653 (C¼O), 1628 (C¼C)
J ¼ 7.1 Hz, 3 OCH2CH3), 1.86 (ddd, J ¼ 2.7, 10.2, 13.0 Hz,
1 3-H), 1.97 (ddd, J ¼ 2.6, 6.1, 13.0Hz, 1 3-H), 2.13 (s, 2.4
COCH3), 2.35 (s, 0.6 COCH3), 3.53 (dq, J ¼ 7.1, 9.6 Hz, 1
OCH2CH3), 3.78 (dq, J ¼ 7.1, 9.6 Hz, 1 OCH2CH3), 3.90 (br,
0.2 CH2Ph), 4.41 (d, J ¼ 18.0Hz, 0.8 CH2Ph), 4.74 (d, J ¼
18.0Hz, 0.8 CH2Ph), 4.87 (dd, J ¼ 5.6, 10.4Hz, 0.2 4-H), 5.04
(t, J ¼ 2.7 Hz, 1 2-H), 5.31 (br, 0.2 CH2Ph), 5.52 (dd, J ¼ 6.3,
10.2Hz, 0.8 4-H), 7.10-7.39 (m, 6 6-H, PhH) ppm; 13C NMR
(75.48 MHz, CDCl3): ꢂ ¼ 14.8 (OCH2CH3), 22.2, 22.3
(COCH3), 30.1, 31.6 (C-3), 44.4 (C-4), 47.7, 49.1 (NCH2),
65.0, 65.2 (OCH2CH3), 91.5, 91.7 (C-5), 98.4, 98.7 (C-2),
116.1, 116.8 (CN), 125.7, 126.6, 126.9, 127.6, 128.5, 128.9,
137.3, 138.6 (PhC), 155.9, 156.4 (C-6), 171.1, 17þ2.2 (COCH3)
ppm; MS (EI, 70eV): m=z (%) ¼ 300 (20) [M] ꢂ, 209 (32),
cmꢁ1
;
1H NMR (300.18 MHz, CDCl3): ꢂ ¼ 0.86 (t, J ¼
7.5 Hz, 3 O(CH2)3CH3), 1.28 (sext, 2 O(CH2)2CH2CH3),
1.48 (quit, 2 OCH2CH2CH2CH3), 1.87 (ddd, J ¼ 8.5, 9.0,
13.5Hz, 1 3-H), 2.00 (s, 2.8 COCH3), 2.13 (ddd, J ¼ 2.5,
6.5, 13.5Hz, 1 3-H), 2.31 (s, 0.2 COCH3), 3.48 (dt, J ¼ 7.5,
9.5 Hz, 1 OCH2(CH2)2CH3), 3.79 (dt, J ¼ 7.5, 9.5 Hz, 1
OCH2(CH2)2CH3), 4.36 (d, J ¼ 18.0Hz, 1 CH2Ph), 4.68 (d,
J ¼ 18.0 Hz, 1 CH2Ph), 5.08 (dd, J ¼ 2.5, 8.5 Hz, 1 2-H), 5.76
(ddd, J ¼ 1.3, 6.5, 9.0 Hz, 1 4-H), 7.06–7.40 (m, 6 6-H, PhH)
ppm; 13C NMR (75.48MHz, CDCl3): ꢂ ¼ 13.7 (OCH2-
(CH2)2CH3), 19.1 (OCH2CH2CH2CH3), 22.3 (COCH3), 30.9
(OCH2CH2CH2CH3), 31.3 (C-3), 46.3 (C-4), 48.0 (NCH2),
70.1 (OCH2(CH2)2CH3), 90.4 (C-5), 101.0 (C-2), 116.7
(CN), 125.6, 127.5, 129.0, 137.5 (PhC), 157.6 (C-6), 172.7
167 (59), 148 (31), 139 (8), 106 (54), 91 (100), 72 (11), 43 (66).
(2RS,4RS)-4-(N-Acetyl-N-benzylamino)-3,4-dihydro-2-iso-
butoxy-2H-pyran-5-carbonitrile (cis-5b, C19H24N2O3)
Colorless oil; yield 30%; IR (film): ꢃꢀ¼ 2950, 2920, 2870
(CH), 2200 (CN), 1650 (C¼O), 1615 (C¼C) cmꢁ1; 1H NMR
(300.18MHz, CDCl3): ꢂ ¼ 0.87 (d, J ¼ 6.5 Hz, 6 OCH2-
CH(CH3)2), 1.81 (m, 1 OCH2CH(CH3)2), 1.89 (ddd, J ¼ 8.8,
9.0, 13.5Hz, 1 3-H), 2.06 (s, 2.8 COCH3), 2.16 (ddd, J ¼ 2.0,
6.5, 13.5 Hz, 1 3-H), 2.32 (s, 0.2 COCH3), 3.23 (dd, J ¼ 6.5,
9.5 Hz, 1 OCH2CH(CH3)2), 3.63 (dd, J ¼ 6.5, 9.5 Hz, 1
þ
ꢂ,
(COCH3) ppm; MS (EI, 70 eV): m=z (%) ¼ 328 (14) [M]
237 (35), 211 (8), 195 (71), 163 (13), 148 (35), 106 (44),
91 (100).
(2RS,4SR)-4-(N-Acetyl-N-benzylamino)-3,4-dihydro-2-n-
butoxy-2H-pyran-5-carbonitrile (trans-5c, C19H24N2O3)
Colorless crystals; mp 82ꢀC; yield 30%; IR (film): ꢃꢀ¼ 2961,
2948, 2873 (CH), 2215 (CN), 1647 (C¼O), 1626 (C¼C)

Hetero-Diels-Alder reaction
653
(2RS,3SR,4RS)-4-(N-Acetyl-N-benzylamino)-2-ethoxy-3,4-di-
cmꢁ1; 1H NMR (300.18 MHz, CDCl3): ꢂ ¼ 0.87 (t, J ¼ 7.5 Hz,
3O(CH2)3CH3), 1.28 (sext, 2 O(CH2)2CH2CH3), 1.49 (quit, 2
OCH2CH2CH2CH3), 1.80 (m, 1 3-H), 1.93 (ddd, J ¼ 2.5,
6.5, 13.5Hz, 1 3-H), 2.09 (s, 2.45 COCH3), 2.30 (s, 0.55
COCH3), 3.44 (dt, J ¼ 7.5, 9.5 Hz, 1 OCH2(CH2)2CH3), 3.68
(dt, J ¼ 7.5, 9.5 Hz, 1 OCH2(CH2)2CH3), 3.85 (br, 0.2 CH2Ph),
4.38 (d, J ¼ 18.0Hz, 0.8 CH2Ph), 4.70 (d, J ¼ 18.0Hz, 0.8
CH2Ph), 4.82 (br, 0.2 4-H), 5.04 (t, J ¼ 2.5 Hz, 1 2-H), 5.26
(br, 0.2 CH2Ph), 5.49 (dd, J ¼ 6.6, 9.9 Hz, 0.8 4-H), 7.00–7.40
(m, 6 6-H, PhH) ppm; 13C NMR (75.48 MHz, CDCl3): ꢂ ¼
13.7 (OCH2(CH2)2CH3), 19.1 (OCH2CH2CH2CH3), 22.4
(COCH3), 30.2 (OCH2CH2CH2CH3), 31.7 (C-3), 44.5 (C-
4), 49.2 (NCH2), 69.4 (OCH2(CH2)2CH3), 91.7 (C-5), 99.0
(C-2), 116.8 (CN), 125.8, 127.6, 128.5, 137.4 (PhC), 155.9
(C-6), 172.3 (COCH3) ppm; MS (EI, 70 eV): m=z (%) ¼ 328
hydro-3-methyl-2H-pyran-5-carbonitrile (5e, C18H22N2O3)
Colorless crystals; mp 117ꢀC; yield 48%; IR (KBr): ꢃꢀ¼
3056, 2976, 2912 (CH), 2224 (CN), 1648 (C¼O), 1622
(C¼C) cmꢁ1
;
1H NMR (300.18 MHz, CDCl3): ꢂ ¼ 1.01
(d, J ¼ 7.5 Hz, 3 3-CH3), 1.12 (t, J ¼ 7.0 Hz, 3 OCH2-
CH3), 2.00 (s, 2.8 COCH3), 2.31 (m, 1 3-H), 2.32 (s, 0.2
COCH3), 3.55 (dq, J ¼ 7.0, 9.5 Hz, 1 OCH2CH3), 3.82 (dq,
J ¼ 7.0, 9.5 Hz, 1 OCH2CH3), 4.49 (d, J ¼ 18.0 Hz, 1
CH2Ph), 4.81 (d, J ¼ 18.0 Hz, 1 CH2Ph), 4.95 (d, J ¼
3.5 Hz, 1 2-H), 5.68 (d, J ¼ 6.0 Hz, 1 4-H), 7.15–7.39
(m, 6 6-H, PhH) ppm; 13C NMR (75.48 MHz, CDCl3):
ꢂ ¼ 11.5 (3-CH3), 14.7 (OCH2CH3), 23.0 (COCH3), 36.4
(C-3), 47.1 (C-4), 49.5 (NCH2), 65.7 (OCH2CH3), 89.2
(C-5), 100.0 (C-2), 117.9 (CN), 126.0, 126.9, 128.6,
138.3 (PhC), 157.7 (C-6), 174.4 (CþOCH3) ppm; MS
(EI, 70 eV): m=z (%) ¼ 314 (17) [M] ꢂ, 223 (49), 181
þ
(15) [M] ꢂ, 237 (38), 211 (11), 195 (74), 163 (13), 148
(31), 106 (47), 91 (100).
(100), 153 (19), 148 (39), 135 (40), 106 (26), 91 (65), 86
(30), 43 (36).
(2RS,4RS)-4-(N-Acetyl-N-benzylamino)-3,4-dihydro-2-
methoxy-2-methyl-2H-pyran-5-carbonitrile
(cis-5d, C17H20N2O3)
Colorless crystals; mp 111ꢀC; yield 58.5%; IR (KBr):
ꢃꢀ¼ 2992, 2960, 2848 (CH), 2224 (CN), 1664 (C¼O),
(2RS,4SR)-2-Ethoxy-3,4-dihydro-6-phenyl-4-(2-thienyl)-2H-
pyran-5-carbonitrile (cis-8a, C18H17NO2S)
Colorless crystals; mp 70ꢀC; yield 72%; IR (KBr): ꢃꢀ¼
1638 (C¼C) cmꢁ1
;
1H NMR (300.18 MHz, CDCl3): ꢂ ¼
3087, 2975, 2935, 2890 (CH), 2200 (CN), 1601 (C¼C),
1146 (C–O) cmꢁ1
;
1H NMR (300.18 MHz, CDCl3): ꢂ ¼
1.48 (s, 2.4 2-CH3), 1.80 (s, 0.6 2-CH3), 1.90 (dd, J ¼ 6.5,
14.0 Hz, 1 3-H), 2.05 (s, 2.4 COCH3), 2.07 (dd, J ¼ 8.3,
14.0 Hz, 1 3-H), 2.32 (s, 0.6 COCH3), 3.20 (s, 3 OCH3),
4.43 (d, J ¼ 18.0 Hz, 1 CH2Ph), 4.72 (d, J ¼ 18.0 Hz, 1
CH2Ph), 5.59 (ddd, J ¼ 1.5, 6.6, 8.1 Hz, 1 4-H), 7.19–7.38
(m, 6 6-H, PhH) ppm; 13C NMR (75.48 MHz, CDCl3):
ꢂ ¼ 21.6 (2-CH3), 22.5 (COCH3), 35.4 (C-3), 46.6 (C-4),
48.6 (NCH2), 49.6 (2-OCH3), 89.1 (C-5), 103.4 (C-2),
116.9 (CN), 125.7, 127.4, 128.9, 137.7 (PhC), 157.6 (C-
6), 172.7 (COCH3) ppm; MS (EI, 70 eV): m=z (%) ¼ 300
1.29 (t, J ¼ 7.05 Hz, 3 OCH2CH3), 2.24 (ddd, J ¼ 8.1, 9.9,
13.8 Hz, 1 3-H), 2.51 (ddd, J ¼ 2.1, 6.9, 13.8 Hz, 1 3-H),
3.73 (dq, J ¼ 7.05, 9.5 Hz, 1 OCH2CH3), 4.07 (dq, J ¼ 7.05,
9.5 Hz, 1 OCH2CH3), 4.21 (dd, J ¼ 6.9, 9.6 Hz, 1 4-H), 5.31
(dd, J ¼ 2.1, 8.1 Hz, 1 2-H), 6.97 (dd, J ¼ 3.6, 5.1 Hz, 1 40-
H), 7.05 (dd, J ¼ 1.2, 3.6 Hz, 1 30-H), 7.23 (dd, J ¼ 1.2,
5.1 Hz, 1 50-H), 7.44 (m, 3 PhH), 7.77 (m, 2 PhH); 13C
NMR (75.48 MHz, CDCl3): ꢂ ¼ 15.1 (OCH2CH3), 35.5
(C-3), 36.5 (C-4), 65.4 (OCH2CH3), 88.6 (C-5), 100.8 (C-
2), 119.1 (CN), 124.7 (C-50), 126.0 (C-30), 126.8 (C-40),
128.2, 128.3, 128.4, 131.0, 132.9 (PhC), 144.0 (C-20),
163.2 (C-6) ppm; MS (EI, 70 eV): m=z (%) ¼ 311 (16)
þ
(19) [M] ꢂ, 209 (15), 177 (85), 167 (53), 150 (55), 148
(37), 136 (14), 135 (21), 120 (23), 106 (35), 91 (100), 72
(98), 43 (68).
þ
[M] ꢂ, 265 (56), 239 (67), 212 (52), 105 (100), 77 (47),
72 (13).
(2RS,4SR)-4-(N-Acetyl-N-benzylamino)-2-methoxy-2-
methyl-3,4-dihydro-2H-pyran-5-carbonitrile
(2RS,4RS)-2-Ethoxy-3,4-dihydro-6-phenyl-4-(2-thienyl)-2H-
(trans-5d, C17H20N2O3)
Colorless crystals; mp 110ꢀC; yield 18.5%; IR (KBr):
ꢃꢀ¼ 3008, 2960, 2848 (CH), 2224 (CN), 1664 (C¼O), 1630
(C¼C) cmꢁ1; 1H NMR (300.18 MHz, CDCl3): ꢂ ¼ 1.40 (s, 2.9
2-CH3), 1.65 (dd, J ¼ 11.5, 13.5Hz, 1 3-H), 1.70 (s, 0.1 2-
CH3), 1.92 (dd, J ¼ 6.5, 13.5Hz, 1 3-H), 2.10 (s, 2.25
COCH3), 2.32 (s, 0.75 COCH3), 3.30 (s, 3 OCH3), 3.85 (d,
J ¼ 18.0Hz, 0.25 CH2Ph), 4.42 (d, J ¼ 18.0Hz, 0.75 CH2Ph),
4.73 (d, J ¼ 18.0Hz, 0.75 CH2Ph), 4.90 (dd, J ¼ 6.5, 11.5 Hz,
0.25 4-H), 5.25 (d, J ¼ 18.0Hz, 0.25 CH2Ph), 5.95 (br, 0.75 4-
H), 6.90-7.45 (m, 6 6-H, PhH) ppm; 13C NMR (75.48 MHz,
CDCl3): ꢂ ¼ 21.7 (2-CH3), 22.2 (COCH3), 35.5 (C-3), 46.7
(C-4), 48.6 (NCH2), 49.7 (2-OCH3), 92.2 (C-5), 102.5 (C-
2), 117.0 (CN), 125.7, 127.4, 129.0, 137.7 (PhC), 157.7 (C-
6), 172.7 (COCH3) ppm; MS (EI, 70 eV): m=z (%) ¼ 300
pyran-5-carbonitrile (trans-8a, C18H17NO2S)
Colorless oil; yield 7%; IR (KBr): ꢃꢀ¼ 3087, 2975, 2935,
2890 (CH), 2200 (CN), 1601 (C¼C), 1146 (C–O) cmꢁ1; 1H
NMR (300.18 MHz, CDCl3): ꢂ ¼ 1.30 (t, J ¼ 7.05 Hz, 3
OCH2CH3), 2.16 (ddd, J ¼ 2.4, 9.3, 13.5 Hz, 1 3-H), 2.35
(ddd, J ¼ 4.2, 6.0, 13.5 Hz, 1 3-H), 3.74 (dq, J ¼ 7.05,
9.5 Hz, 1 OCH2CH3), 4.03 (dq, J ¼ 7.05, 9.5 Hz, 1 OCH2-
CH3), 4.24 (dd, J ¼ 6.0, 9.3 Hz, 1 4-H), 5.35 (dd, J ¼ 2.4,
4.5 Hz, 1 2-H), 7.00 (dd, J ¼ 3.6, 5.1 Hz, 1 40-H), 7.04 (dd,
J ¼ 1.2, 3.6 Hz, 1 30-H), 7.26 (dd, J ¼ 1.2, 5.1 Hz, 1 50-H),
7.44 (m, 3 PhH), 7.77 (m, 2 PhH); 13C NMR (75.48 MHz,
CDCl3): ꢂ ¼ 15.1 (OCH2CH3), 32.6 (C-3), 35.5 (C-4), 65.1
(OCH2CH3), 88.5 (C-5), 98.1 (C-2), 119.2 (CN), 124.8 (C-
50), 126.0 (C-30), 127.1 (C-40), 128.2, 128.3, 128.4, 130.2
(PhC), 144.6 (C-20),þ162.5 (C-6) ppm; MS (EI, 70 eV): m=z
(%) ¼ 311 (14) [M] ꢂ, 265 (48), 239 (68), 212 (40), 105
þ
(15) [M] ꢂ, 209 (8), 177 (62), 167 (23), 150 (42), 148 (23),
135 (18), 135 (18), 120 (53), 106 (32), 91 (100), 72 (68),
43 (67).
(100), 77 (42), 72 (12).

654
A. Pałasz, K. Bogdanowicz-Szwed
(2RS,4SR)-3,4-Dihydro-2-isobutoxy-6-phenyl-4-(2-thienyl)-
2H-pyran-5-carbonitrile (cis-8b, C20H21NO2S)
(2RS,4SR)-3,4-Dihydro-2-methoxy-2-methyl-6-phenyl-4-(4-
thienyl)-2H-pyran-5-carbonitrile (trans-8c, C18H17NO2S)
Colorless oil; yield 14%; IR (KBr): ꢃꢀ¼ 3105, 3083, 2987,
2972, 2939, 2836 (CH), 2205 (CN), 1615 (C¼C), 1169,
Colorless crystals; mp 70ꢀC; yield 73%; IR (KBr): ꢃꢀ¼ 3087,
2975, 2935, 2890 (CH), 2200 (CN), 1601 (C¼C), 1146 (C–O)
cmꢁ1
;
1H NMR (300.18 MHz, CDCl3): ꢂ ¼ 0.91 (d, J ¼
1049 (C–O) cmꢁ1
;
1H NMR (300.18 MHz, CDCl3): ꢂ ¼
6.9 Hz, 6 OCH2CH(CH3)2), 1.89 (m, J ¼ 6.6 Hz, 1 OCH2-
CH(CH3)2), 2.28 (ddd, J ¼ 7.8, 9.0, 13.8Hz, 1 3-H), 2.50
(ddd, J ¼ 2.1, 6.9, 13.8Hz, 1 3-H), 3.39 (dd, J ¼ 6.6, 9.0 Hz,
1 OCH2CH(CH3)2), 3.78 (dd, J ¼ 6.3, 9.0 Hz, 1 OCH2-
CH(CH3)2), 4.20 (dd, J ¼ 6.9, 9.3 Hz, 1 4-H), 5.29 (dd,
J ¼ 2.1, 7.8Hz, 1 2-H), 6.97 (dd, J ¼ 3.6, 5.1Hz, 1 40-H),
7.05 (dd, J ¼ 1.2, 3.6 Hz, 1 30-H), 7.23 (dd, J ¼ 1.0, 5.1 Hz,
1 50-H), 7.44 (m, 3 PhH), 7.77 (m, 2 PhH) ppm; 13C NMR
(75.48 MHz, CDCl3): ꢂ ¼ 19.1, 19.2 (OCH2CH(CH3)2), 28.5
(OCH2CH(CH3)2), 35.3 (C-3), 36.3 (C-4), 77.0 (OCH2-
CH(CH3)2), 88.3 (C-5), 101.2 (C-2), 119.2 (CN), 124.6 (C-
50), 125.9 (C-30), 126.8 (C-40), 128.2, 128.4, 131.0, 132.9
(PhC), 144.2 (C-20),þ163.3 (C-6) ppm; MS (EI, 70eV): m=z
(%) ¼ 339 (13) [M] ꢂ, 265 (76), 239 (99), 212 (33), 105
1.62 (s, 3 2-CH3), 2.00 (dd, J ¼ 12.3, 13.8Hz, 1 3-H), 2.42
(dd, J ¼ 6.0, 13.8Hz, 1 3-H), 3.46 (s, 3 OCH3), 4.27 (dd, J ¼
6.0, 12.3Hz, 1 4-H), 7.00 (dd, J ¼ 3.3, 5.1 Hz, 1 40-H),
7.05 (dd, J ¼ 1.2, 3.6 Hz, 1 30-H), 7.25 (dd, J ¼ 1.2, 5.1 Hz,
1 50-H), 7.44 (m, 3 PhH), 7.78 (m, 2 PhH) ppm; 13C NMR
(75.48MHz, CDCl3): ꢂ ¼ 22.4 (2-CH3), 33.0 (C-3), 41.6 (C-
4), 49.9 (2-OCH3), 90.0 (C-5), 101.8 (C-2), 119.2 (CN), 124.6
(C-50), 126.0 (C-30), 127.0 (C-40), 128.7, 128.8, 130.8, 133.3
(PhC), 144.0 (C-20),þ162.0 (C-6) ppm; MS (EI, 70eV): m=z
(%) ¼ 311 (16) [M] ꢂ, 279 (24), 239 (57), 212 (23), 105
(100), 77 (62), 72 (71).
(2RS,4SR)-2-Ethoxy-4-(2-furyl)-3,4-dihydro-6-phenyl-2H-
pyran-5-carbonitrile (cis-8d, C18H17NO3)
Colorless crystals; mp 66ꢀC; yield 70%; IR (KBr): ꢃꢀ¼ 3143,
(100), 100 (5), 77 (38), 73 (54).
3115, 2981, 2917, 2883 (CH), 2206 (CN), 1618 (C¼C), 1141
(2RS,4RS)-3,4-Dihydro-2-isobutoxy-6-phenyl-4-(2-thienyl)-
2H-pyran-5-carbonitrile (trans-8b, C20H21NO2S)
(C–O) cmꢁ1
;
1H NMR (300.18 MHz, CDCl3): ꢂ ¼ 1.24
(t, J ¼ 7.05Hz, 3 OCH2CH3), 2.35 (m, 2 3-H), 3.69 (dq,
J ¼ 7.05, 9.5Hz, 1 OCH2CH3), 4.02 (dq, J ¼ 7.05, 9.5 Hz, 1
OCH2CH3), 3.99 (t, J ¼ 7.3 Hz, 1 4-H), 5.31 (t, J ¼ 5.0 Hz,
1 2-H), 6.29 (d, J ¼ 3.3 Hz, 1 30-H), 6.35 (dd, J ¼ 3.3,
1.8 Hz, 1 40-H), 7.42 (m, 4 50-H, PhH), 7.77 (m, 2 PhH)
ppm; 13C NMR (75.48 MHz, CDCl3): ꢂ ¼ 15.0 (OCH2CH3),
32.1 (C-3), 33.4 (C-4), 65.2 (OCH2CH3), 85.7 (C-5), 100.5
(C-2), 107.0 (C-30), 110.5 (C-40), 119.2 (CN), 128.2, 128.4,
130.9, 132.9, 141.9 (PhC), 153.0 (C-50), 163.8 (C-6) ppm; MS
Colorless crystals; mp 76ꢀC; yield 8%; IR (KBr): ꢃꢀ¼ 3087,
2975, 2935, 2890 (CH), 2200 (CN), 1601 (C¼C), 1146 (C–O)
cmꢁ1
;
1H NMR (300.18 MHz, CDCl3): ꢂ ¼ 0.95 (d, J ¼
6.9 Hz, 6 OCH2CH(CH3)2), 1.85 (m, J ¼ 6.6 Hz, 1 OCH2-
CH(CH3)2), 2.15 (ddd, J ¼ 2.4, 9.6, 13.8Hz, 1 3-H), 2.36
(ddd, J ¼ 4.2, 6.0, 13.8Hz, 1 3-H), 3.46 (dd, J ¼ 6.6, 9.0 Hz,
1 OCH2CH(CH3)2), 3.72 (dd, J ¼ 6.9, 9.0 Hz, 1 OCH2-
CH(CH3)2), 4.24 (dd, J ¼ 6.0, 9.6 Hz, 1 4-H), 5.34 (dd,
J ¼ 2.4, 4.2Hz, 1 2-H), 7.00 (dd, J ¼ 3.6, 5.1Hz, 1 40-H),
7.05 (dd, J ¼ 1.2, 3.0 Hz, 1 30-H), 7.24 (dd, J ¼ 0.9, 5.1 Hz,
1 50-H), 7.44 (m, 3 PhH), 7.77 (m, 2 PhH) ppm; 13C NMR
(75.48 MHz, CDCl3): ꢂ ¼ 19.3, 19.5 (OCH2CH(CH3)2), 29.7
(OCH2CH(CH3)2), 32.5 (C-3), 35.5 (C-4), 77.0 (OCH2CH-
(CH3)2), 88.3 (C-5), 98.4 (C-2), 119.2 (CN), 124.6 (C-50),
124.7 (C-30), 125.9 (C-40), 127.1, 128.2, 130.8, 133.0 (PhC),
144.2 (C-20), 163.3 (C-6) ppm; MS (EI, 70eV): m=z (%) ¼
þ
(EI, 70eV): m=z (%) ¼ 295 (9) [M] ꢂ, 249 (67), 223 (100),
195 (10), 169 (7), 105 (98), 77 (38), 72 (14).
(2RS,4RS)-2-Ethoxy-4-(2-furyl)-3,4-dihydro-6-phenyl-2H-
pyran-5-carbonitrile (trans-8d, C18H17NO3)
Colorless oil; yield 7%; IR (KBr): ꢃꢀ¼ 3143, 3115, 2981,
2917, 2883 (CH), 2206 (CN), 1618 (C¼C), 1141 (C–O)
cmꢁ1
7.05Hz, 3 OCH2CH3), 2.27 (m, 2 3-H), 3.73 (dq, J 7.05,
;
1H NMR (300.18 MHz, CDCl3): ꢂ ¼ 1.29 (t, J ¼
þ
339 (13) [M] ꢂ, 265 (76), 239 (94), 212 (36), 105 (100), 100
¼
(7), 77 (38), 73 (2).
9.5 Hz, 1 OCH2CH3), 4.00 (dq, J ¼ 7.05, 9.5 Hz, 1 OCH2-
CH3), 4.03 (dd, J ¼ 6.7, 8.9 Hz, 1 4-H), 5.35 (dd, J ¼ 2.7,
4.8 Hz, 1 2-H), 6.29 (d, J ¼ 3.3 Hz, 1 30-H), 6.35 (dd,
J ¼ 3.3, 1.8 Hz, 1 40-H), 7.42 (m, 4 50-H, PhH), 7.77 (m, 2
PhH) ppm; 13C NMR (75.48MHz, CDCl3): ꢂ ¼ 15.1
(OCH2CH3), 29.7 (C-3), 31.4 (C-4), 65.1 (OCH2CH3), 85.8
(C-5), 98.4 (C-2), 107.6 (C-30), 110.5 (C-40), 119.1 (CN),
128.1, 128.3, 130.8, 133.2, 142.4 (PhC), 153.3 (C-50), 163.1
(2RS,4SR)-3,4-Dihydro-2-methoxy-2-methyl-6-phenyl-4-(4-
thienyl)-2H-pyran-5-carbonitrile (cis-8c, C18H17NO2S)
Colorless crystals; mp 85ꢀC; yield 62%; IR (KBr): ꢃꢀ¼ 3108,
3085, 2990, 2971, 2942, 2836 (CH), 2202 (CN), 1613 (C¼C),
1163, 1054 (C–O) cmꢁ1 1H NMR (300.18 MHz, CDCl3):
;
ꢂ ¼ 1.61 (s, 3 2-CH3), 2.26 (dd, J ¼ 7.2, 13.8Hz, 1 3-H),
2.37 (dd, J ¼ 7.5, 13.8 Hz, 1 3-H), 3.41 (s, 3 OCH3), 4.13 (t,
J ¼ 7.2 Hz, 1 4-H), 6.97 (dd, J ¼ 3.3, 5.1 Hz, 1 40-H), 7.05 (dd,
J ¼ 1.2, 3.6 Hz, 1 30-H), 7.23 (dd, J ¼ 1.2, 5.1 Hz, 1 50-H), 7.44
(m, 3 PhH), 7.78 (m, 2 PhH) ppm; 13C NMR (75.48 MHz,
CDCl3): ꢂ ¼ 21.8 (2-CH3), 35.2 (C-3), 39.3 (C-4), 49.6 (2-
OCH3), 87.8 (C-5), 102.5 (C-2), 119.4 (CN), 124.8 (C-50),
126.0 (C-30), 126.7 (C-40), 128.2, 128.4, 130.9, 133.1 (PhC),
144.5 (C-20), 163.2 (C-6) ppm; MS (EI, 70eV): m=z
þ
(C-6) ppm; MS (EI, 70eV): m=z (%) ¼ 295 (7) [M] ꢂ, 249
(59), 223 (100), 195 (8), 169 (6), 105 (92), 77 (35), 72 (13).
(2RS,4SR)-4-(Cyanophenyl)-2-ethoxy-3,4-dihydro-6-phenyl-
2H-pyran-5-carbonitrile (cis-8e, C21H18N2O2)
Colorless crystals; mp 140ꢀC; yield 81%; IR (KBr): ꢃꢀ¼ 3064,
2979, 2940, 2903 (CH), 2228, 2201 (CN), 1606 (C¼C), 1144
(C–O) cmꢁ1
;
1H NMR (300.18MHz, CDCl3): ꢂ ¼ 1.21 (t,
þ
(%) ¼ 311 (35) [M] ꢂ, 279 (35), 239 (33), 212 (18), 105
J ¼ 7.05 Hz, 3 OCH2CH3), 2.13 (ddd, J ¼ 6.9, 7.8, 13.8Hz,
(52), 77 (34), 72 (100).
1 3-H), 2.42 (ddd, J ¼ 2.4, 7.2, 13.8Hz, 1 3-H), 3.68 (dq,

Hetero-Diels-Alder reaction
655
J ¼ 7.05, 9.5 Hz, 1 OCH2CH3), 3.94 (t, J ¼ 7.5 Hz, 1 4-H),
4.02 (dq, J ¼ 7.05, 9.5 Hz, 1 OCH2CH3), 5.35 (dd, J ¼ 2.4,
6.9 Hz, 1 2-H), 7.46 (m, 5 ArH), 7.66 (m, 2 ArH), 7.80 (m,
2 ArH) ppm; 13C NMR (75.48MHz, CDCl3): ꢂ ¼ 15.0
(OCH2CH3), 35.2 (C-3), 39.7 (C-4), 65.3 (OCH2CH3), 86.2
(C-5), 100.2 (C-2), 111.4 (ArC), 118.7 (CN), 119.2 (CN),
128.1, 128.5, 128.8, 131.2, 132.6, 132.7, 146.7 (ArC), 164.6
4. Tietze LF, Harfiel U, Hubsch T, Voss E, Wichmann J
(1991) Chem Ber 124:881
5. Ager DJ, East MB (1993) Tetrahedron 49:5683
6. Tietze LF (1990) J Heterocycl Chem 27:45
7. John RA, Schmidt V, Wyler H (1987) Helv Chim Acta
70:600
8. Zhuo JC, Wyler H (1995) Helv Chim Acta 78:151
9. Yamauchi M, Katajama S, Baba O, Watanabe T (1983)
J Chem Soc Chem Commun:281
10. Dvorak D, Arnold Z (1982) Tetrahedron Lett 23:4401
11. Haag-Zeino B, Schmidt RR (1990) Liebigs Ann Chem:
1197
12. Dujardin G, Rossignol S, Brown E (1996) Tetrahedron
52:4007
13. Bogdanowicz-Szwed K, Pałasz A (1995) Monatsh Chem
126:1341
14. Bogdanowicz-Szwed K, Pałasz A (1997) Monatsh Chem
128:1157
15. Bogdanowicz-Szwed K, Pałasz A (2001) Z Naturforsch
56b:416
þ
(C-6) ppm; MS (EI, 70eV): m=z (%) ¼ 330 (30) [M] ꢂ, 284
(15), 105 (35), 77 (26), 72 (100).
(2RS,4RS)-4-(Cyanophenyl)-2-ethoxy-3,4-dihydro-6-phenyl-
2H-pyran-5-carbonitrile (trans-8e, C21H18N2O2)
Colorless crystals; mp 186ꢀC; yield 7%; IR (KBr): ꢃꢀ¼ 3087,
2975, 2935, 2890 (CH), 2200 (CN), 1601 (C¼C), 1146 (C–O)
cmꢁ1
;
1H NMR (300.18MHz, CDCl3): ꢂ ¼ 1.31 (t, J ¼
7.05Hz, 3 OCH2CH3), 1.97 (ddd, J ¼ 2.7, 11.1, 13.8Hz, 1
3-H), 2.29 (ddd, J ¼ 3.0, 6.3, 13.8Hz, 1 3-H), 3.77 (dq,
J ¼ 7.05, 9.5 Hz, 1 OCH2CH3), 4.02 (dd, J ¼ 6.3, 11.1Hz, 1
4-H), 4.03 (dq, J ¼ 7.05, 9.5Hz, 1 OCH2CH3), 5.39 (br t,
J ¼ 2.7 Hz, 1 2-H), 7.46 (m, 5 ArH), 7.69 (m, 2 ArH), 7.78
(m, 2 ArH) ppm; 13C NMR (75.48MHz, CDCl3): ꢂ ¼ 15.1
(OCH2CH3), 34.9 (C-3), 36.9 (C-4), 65.1 (OCH2CH3), 87.2
(C-5), 97.6 (C-2), 111.7 (ArC), 118.6 (CN), 119.0 (CN),
128.1, 128.5, 128.6, 131.1, 132.9, 133.0, 146.9 (ArC), 163.6
16. Pałasz A (2005) Org Biomol Chem 3:3207
17. Bogdanowicz-Szwed K, Pałasz A (1999) Monatsh Chem
130:795
18. Bogdanowicz-Szwed K, Pałasz A (2001) Monatsh Chem
132:395
þ
(C-6) ppm; MS (EI, 70eV): m=z (%) ¼ 330 (24) [M] ꢂ, 284
19. Meyer zu Reckendorf W, Bischof E (1971) Angew Chem
Int Ed Engl 10:660
(11), 105 (34), 77 (26), 72 (100).
20. Reichardt C, Kermer WD (1970) Synthesis:538
21. Tietze LF, Voss E (1986) Tetrahedron Lett 27:6181
22. Bushweller CH, O’Neil JW (1969) Tetrahedron Lett:
4713
23. Sankararaman S (2005) Pericyclic Reactions – A Text-
book. Wiley-VCH
24. Guilbert CC, Johnson SL (1971) Biochemistry 10:2313
25. Bonnetaud D, Queguinger G, Pastour P (1972) J Hetero-
cycl Chem 9:165
References
1. Boger DL, Weinreb SN (1987) Hetero Diels-Alder Meth-
odology in Organic Synthesis. Academic Press, San Diego
2. Tietze LF, Kettschau G (1997) Topics in Current Chem-
istry. Stereoselective Heterocyclic Synthesis I, vol. 189,
Springer
3. Tietze LF, Hartfiel U, Hubsch T, Voss E, Bogdanowicz-
Szwed K, Wichmann J (1991) Liebigs Ann Chem: 275
26. Kauffmann K (1951) Chem Ber 50:527