Synthesis of dihydropyrano[3,2-c]pyrazoles via double bond migration and ring-closing metathesis

Article abstract of DOI:10.3390/molecules24020296

Three types of pyrazole-fused heterobicycles, i.e., 1,5-, 1,7-, and 2,5-dihydropyrano[3,2-c] pyrazoles, were synthesized from 4-allyloxy-1H-pyrazoles. A sequence of the Claisen rearrangement of 4-allyloxy-1H-pyrazoles, ruthenium-hydride-catalyzed double b

Full text of DOI:10.3390/molecules24020296

molecules
Article
Synthesis of Dihydropyrano[3,2-c]pyrazoles via
Double Bond Migration and Ring-Closing Metathesis
Yoshihide Usami * , Kodai Sumimoto, Azusa Kishima, Yuya Tatsui, Hiroki Yoneyama and
Shinya Harusawa
Department of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1
Nasahara, Takatsuki, Osaka 569-1094, Japan; e12241@gap.oups.ac.jp (K.S.); e13307@gap.oups.ac.jp (A.K.);
e18902@gap.oups.ac.jp (Y.T.); yoneyama@gly.oups.ac.jp (H.Y.); harusawa@gly.oups.ac.jp (S.H.)
* Correspondence: usami@gly.oups.ac.jp; Tel.: +81-726-90-1087
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀꢁꢂꢃꢄꢅꢆ
Received: 25 December 2018; Accepted: 11 January 2019; Published: 15 January 2019
Abstract: Three types of pyrazole-fused heterobicycles, i.e., 1,5-, 1,7-, and 2,5-dihydropyrano[3,2-c]
pyrazoles, were synthesized from 4-allyloxy-1H-pyrazoles. A sequence of the Claisen rearrangement
of 4-allyloxy-1H-pyrazoles, ruthenium-hydride-catalyzed double bond migration, O-allylation, and
ring-closing metathesis was employed in this study.
Keywords: dihydropyrano[3,2-c]pyrazole; synthesis; double bond migration; ruthenium hydride
catalyst; ring-closing metathesis
1. Introduction
The synthesis of substituted or functionalized pyrazoles has been studied extensively thus far
because they show or are expected to show important and diverse bioactivities [1,2]. Celecoxib, a
non-steroidal anti-inflammatory drug (NSAID), is a representative pyrazole-containing compound,
which acts through selective cyclooxygenase (COX)-2 inhibition. Whereas the late-stage construction
of a pyrazole ring through some cycloadditions of already-substituted components is the basis for most
syntheses of substituted pyrazoles [3,4], direct functionalization of pyrazoles has not been investigated
satisfactorily to date. As investigations on it seem rare, we have been interested in and studied the
direct functionalization of pyrazoles through coupling reactions of halogenated analogues derived
from commercially available pyrazole [
been synthesized for reasons similar to those described above or because of characteristic activities not
seen in monocyclic substituted pyrazoles [ ]. Many pyrazole-fused heterocyclic compounds possess
5–8]. In addition, pyrazole-fused heterocycles have recently
9
unique and important biological activities [10]. Some examples of pyrano[2,3-c]pyrazoles [11
pyrano[3,2-c]pyrazoles [15,16], and furo[3,2-c]pyrazoles [17,18] are presented in Figure 1.
–14],
The Claisen rearrangement followed by ring-closing metathesis (RCM) is an effective sequence
for constructing various polycyclic systems [19 20]. On the basis of our previous work on the synthesis
of withasomnines [21 22], we recently reported the synthesis of dihydrooxepino[3,2-c]pyrazoles (
and its isomers) via a combination of the Claisen rearrangement of 4-allyloxy-1H-pyrazoles (1a
O-allylation of Claisen rearrangement product into , and subsequent RCM of
the construction of pyrazole-containing 5,7-bicyclic system 4, shown in Scheme 1.
,
,
4
–
d),
2
3
3 [23]. This realized
Molecules 2019, 24, 296; doi:10.3390/molecules24020296
www.mdpi.com/journal/molecules

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Figure 1. Examples of bioactive pyrano[2,3-c]pyrazoles, pyrano[3,2-c]pyrazoles, and furo[3,2-c]pyrazoles.
After the migration of the double bond in the side chain of intermediate
product can be O-allylated to . The subsequent RCM of may provide a pyrazole-containing
5,6-bicyclic system, i.e., a dihydropyrano[3,2-c]pyrazole. These are expected to show various types of
activities. There have been many reports of syntheses of pyrano[2,3-c]pyrazoles [10 14], but very few
for pyrano[3,2-c]pyrazoles [15 16 24 25]. In addition, the development of a new synthetic method for
2 in Scheme 1, expected
5
6
6
–
,
, ,
furo[3,2-c]pyrazoles, which are extremely important as mentioned above, seems possible if both double
bond migration and dehydrohalogenation occur on a 5-allyl-4-(2-haloethyl)oxy-1H-1-tritylpyrazole.
Described herein is a new and selective synthesis of three types of dihydropyrano[3,2-c]pyrazoles,
namely
7, 8, and 20, with pyrazole-fused heterocyclic skeletons from 1 via the combination of Claisen
rearrangements and RCM, along with efforts toward furo[3,2-c]pyrazoles (17).

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Scheme 1. Preparation of 5-allyl-4-allyloxy-1H-pyrazoles (6) from 4-allyloxy-1H-pyrazoles (2).
2. Results
2.1. Synthesis of 1,5-Dihydropyrano[3,2-c]pyrazoles
Our initial efforts in the synthesis of 1,5-dihydropyrano[3,2-c]pyrazoles (
7) are presented
in Scheme 1 and Table 1.
In our earlier efforts for double bond migration for the
conversion of 2a to 5a with potassium tert-butoxide (t-BuOK) as a base, every trial under
microwave (MW) irradiation in a different solvent (tetrahydrofuran (THF), EtOH, MeCN, acetone,
1,2-dimethoxyethane (DME), toluene, THF-toluene) failed to give the desired product 5a
Alternatively, carbonylchlorohydridotris(triphenylphosphine)ruthenium(II) [(RuClH(CO)(PPh3)3]
was applied to the double bond migration for the conversion of to , as shown in
Scheme 1 [27]. MW irradiation of the reaction mixture of and 5 mol% of the ruthenium
hydride catalyst in toluene gave the desired product , whereas the same reaction at room
temperature (rt) did not occur. Starting compounds 2a are known compounds [21 23],
[20,26].
2
5
2
5
–
d
–
and 1-benzyl-4-hydroxy-5-((1-methoxycarbonyl)-2-propen-1-yl)-1H-pyrazole (2e) is the Claisen
rearrangement product of 1e, which was newly prepared from 1-benzyl-4-iodo-1H-pyrazole for
this work and already contained a small part of 5e (see Experimental section).
Then, the C4-hydroxyl groups in 4-hydroxy-5-(1-propenyl)-1H-pyrazoles 5a and 5b were treated
with aqueous NaOH followed by alkenyl halides in order to prepare the RCM substrates 6a and 6b
Conversion of 5c and 5d, which have a substituent, to 6c and 6d using the same condition took a
long time with poor yields. So, alternative transformation of 5c and 5d to 6c and 6d was carried out
using K2CO3 in acetone under MW irradiation, respectively. The reactions proceeded smoothly and
the chemical yields of 6c and 6d are presented in Scheme 1a. In a separate experiment, compound
2e, which already contains a small part of 5e as noted above, was transformed directly to 6e through
treatment with K2CO3 and allyl bromide in acetone under MW irradiation in 63% yield, since the yield
from 2e to 5e was not satisfactory. The yield of the MW-aided transformation of 2e to 6e was improved
to 85% by applying acetone-water (9:1) as the solvent system (Scheme 1b).
.

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Table 1. Ring-closing metathesis (RCM) of 5-allyl-4-allyloxy-1H-pyrazoles.
Time
(min)
0
◦
Entry Substrate
R
R
Temp. ( C)
Product Yield (%)
1
2
3
4
5
6
7
8
9
10
11 a
12
13
14
15 b
16 c
17 d
18
6a
6a
6a
6a
6a
6a
6a
6b
6b
6b
6c
6c
6d
6d
6e
6e
6e
6e
Tr
H
rt
rt
rt
5
30
60
120
3
0.5
10
30
7a (89) e
7a (92)
7a (83)
7a (44)
7a (87)
7a (71)
7a (65)
7b (96)
7b (91)
7b (75)
7c (10)
7c (24)
-
rt
80 (MW)
100 (MW)
140 (MW)
rt
80 (MW)
140 (MW)
rt
140 (MW)
rt
140 (MW)
Bn
H
3
10
8b (15)
Bn
Bn
Bn
Me
Ph
overnight
60
9c (45)
overnight
-
-
60
-
-
-
10d (30)
COOMe
rt
overnight
-
-
80 (MW)
100 (MW)
140 (MW)
60
60
60
7e (2)
7e (7)
7e (15)
10e (29)
10e (30)
a. 60% of starting material 6c was recovered. b. 50% of 6e was recovered. c. Undesired 11e (2%) was obtained
during the recovery of 6e (21%). d. 11e was obtained (4%). e. A small amount of 6a was detected in the NMR
spectrum and was inseparable from 7a.
RCM substrates 6
were treated with 5 mol% Grubbs0 second-generation catalyst (Grubbs2nd) in
CH2Cl2. The results of the RCM reactions are summarized in Table 1. With substrate 6a, reaction at rt
afforded the desired RCM product 7a within 30 min (entry 2). A shorter reaction time also led to 7a, but
with an inseparable trace amount of 6a (entry 1). In contrast, extended reaction times led to reduced
product yields (entries 3 and 4). The MW-aided reaction was also examined in an attempt to reduce
the reaction time (entries 5–7). In these trials, only 7a was formed and double bond migration product
◦
8a could not be detected [23]. Moreover, higher temperatures above 100 C reduced the reaction yield
(entry 7). The optimal reaction conditions in entries 2 and 5 for substrate 6a were applied to the RCM
of 6b and gave similar results producing 7b (entries 8 and 9, respectively). The MW reaction of 6b at a
higher temperature of 140 ◦C led to partial double bond migration to produce 8b (entry 10). When
0
the substrate had an R substituent, different results were obtained, as shown by the following entries.
Substrates 6d and 6e did not react at rt (entries 13 and 15, respectively).
The MW-aided reaction (140 ◦C) of 6c afforded RCM product 7c as a minor product (24%) and
9c (45%) with an exomethylene moiety as the major product (entry 12). The structure of 9c was
determined through the heteronuclear single quantum coherence (HSQC) correlations between a
carbon signal at
δ 107.2 ppm and two proton signals at δ 4.78 and 4.96 ppm. Generally, endo-cyclic
alkene is considered to be more stable than the corresponding exo-alkene. But in this case, 7c is thought

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to be less stable than exo-diene 9c due to the strain caused by 6-membered endo-diene structure in the
thermodynamic condition.
However, the same MW conditions applied to substrate 6d did not result in 7d, but dimeric 10d
formed through intermolecular metathesis in 30% yield (entry 14). Mass spectrometry (MS) revealed
1
that compound 10d had an m/z of 632 (M+), which corresponds to C42H42N4O2. The H nuclear
magnetic resonance (NMR) spectrum of 10d suggested the presence of a =CHCH3 moiety through the
signals at
δ 6.29 (q, J = 7.1 Hz) and 1.51 ppm (d, J = 7.1 Hz) in a 1:3 integral ratio and the lack of an
exomethylene from the starting 6d. These data suggest that the intermolecular metathesis product 10d
formed by expelling an ethylene molecule [339 (6d
)
×
2
−
28 (CH2=CH2) = 632 ((M+) for 10d)]. The
0
presence of a bulky R substituent may lead to serious repulsion in the transition state for RCM. When
the substrate had a methoxycarbonyl group as R0, the results were confusing. The MW reaction of 6e
◦
at 140 C gave a complex mixture and only 7e was isolated in 15% yield (entry 18). The MW reactions
of 6e at lower temperatures (80 and 100 ◦C) gave 10e in similar yields (29% and 30%, respectively)
with 7e as a minor product (entries 16 and 17). In both of these entries, 11e, which is a metathesis
product of 6e and the Grubbs catalyst, was also isolated as a minor product. The structure of 11e
was confirmed through detailed NMR analysis and an M+ peak at m/z 388.1785 (C24H24N2O3) in the
high-resolution MS (HRMS) spectrum. However, our attention was focused on increasing the yields of
7e and decreasing the yields of 10e by increasing the reaction temperature (entries 16–18). Then, we
hypothesized that 10e transforms into 7e; 10e may be the initial product at lower reaction temperatures.
Therefore, the MW reaction of pure 10e with Grubbs2nd at 140 ◦C was examined independently in an
attempt to observe the formation of 7e as the major product in the reaction mixture.
2.2. Synthesis of 1,7-Dihydropyrano[3,2-c]pyrazoles
We attempted to expand this methodology to the syntheses of different types of pyrazole-fused
heterobicycles, i.e., 1,7-dihydropyrano[3,2-c]pyrazoles (8) and furo[3,2-c] pyrazoles (17), as illustrated
in Scheme 2. In order to realize this, 4-O-vinylation was required. First, the 4-hydroxyl group
of 2a was treated with 1,2-dichloroethane to obtain a pyrazole with a 2-chloroethoxy group at
C4, 12Cl
. However, dehydrochlorination of 12Cl did not occur under basic conditions. Then,
2-bromoethylation of the 4-hydroxyl group was examined, aimed at improving the leaving ability.
Desired 5-allyl-4-(2-bromoethyl)oxy-1H-1-tritylpyrazole (12a) was smoothly prepared through the
MW-aided reaction of 2a. The examination of the dehydrobromination of 12a is summarized in Table 2.
Whereas treatment of 12a with t-BuOK in toluene resulted in no reaction (entry 1), application of
THF-MeOH (4:1) led to the desired dehydrobromination (entries 2–5). The MW reaction at 100 ◦C for
30 min afforded only double bond migration product (E/Z)-5-allyl-4-vinyloxy-1H-1-tritylpyrazole
(13a) but in 14% yield (entry 2). Increasing the reaction time to 60 min resulted in an inseparable
mixture of 13a and 5-(1-propenyl)-4-vinyloxy-1H-1-tritylpyrazole (14a) in 19% combined yield (entry
3). A higher temperature of 130 ◦C resulted in only 14a in 30% yield (entry 4). A similar MW reaction
at 80 ◦C produced 13a in a similar yield (entry 5). In these trials (entries 2–5), the chemical yields of
desired 13a and 14a were not satisfactory. Close inspection of entries 4 and 5 led us to isolate and
elucidate the structures of side product 15 (28% yield), which should have formed via SN2 attack by
a methoxide on 12a, and 16 (17% yield) (see footnotes of Table 2). To improve the chemical yields,
inhibition of the SN2 attack on 12a by a nucleophile formed from the solvent under basic conditions
was required. Hence, t-BuOH was applied instead of MeOH as a co-solvent. Although the MW
reaction at 80 ◦C afforded only a trace amount of desired product 13a (entry 6), the same reaction at
130 ◦C afforded only 13a in 87% yield (entry 7). Inspired by the result in entry 4, the MW reaction
was attempted at a higher temperature of 180 ◦C and afforded 14a selectively in 67% yield (entry 8).
Treatment of the N-benzyl derivative 12b with t-BuOK at 130 ◦C resulted in only 14b (72%) (entry 9).
Then, the dehydrobromination of 12b was examined at a lower temperature (entry 10), but resulted in
an inseparable mixture of 12b and 14b.

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X
N
t-BuOK (5 eq.),
THF-ROH (4:1)
NaOH
XCH2CH2X
HO
O
O
O
MW
+
N
MW
Table 2
N
N
R
N
R
N
R
N
Tr
N
2a,b
14a
14b: R = Bn
: R = Tr
13a
: R = Tr
13b: R = Bn
12Cl: R = Tr, X = Cl (37%)
12a
: R = Tr, X = Br (66%)
12b: R = Bn, X = Br (35%)
Grubbs2nd (5 mol%)
CH2Cl2, rt
OMe
OMe
O
O
O
O
N
N
R
8a: R = Tr (95%)
R
N
N
N
N
Tr
Tr
N
N
17a
: R = Tr
17b: R = Bn
16
15
Scheme 2. Challenges in the syntheses of 1,7-dihydropyrano[3,2-c]pyrazoles (8) and
furo[3,2-c]pyrazoles (19).
Table 2. Potassium t-butoxide promoted dehydrohalogenation of 12.
◦
Entry
Substrate
Solvent
Time (min)
Temp. ( C)
Product Yield (%)
1
2
3
12a
12a
12a
12a
12a
12a
12a
12a
12b
12b
THF
30
30
60
60
60
60
60
60
60
60
100
100
100
130
80
No reaction
THF:MeOH (4:1)
THF:MeOH (4:1)
THF:MeOH (4:1)
THF:MeOH (4:1)
THF:t-BuOH (4:1)
THF:t-BuOH (4:1)
THF:t-BuOH (4:1)
THF:t-BuOH (4:1)
THF:t-BuOH (4:1)
13a (14)
14a (0)
13a + 14a (19) a
4 b
5 c
6
13a (0)
14a (30)
14a (0)
14a (0)
14a (0)
14a (67)
14b (72)
13a (27)
13a (trace)
13a (87)
13a (0)
13b (0)
13b (0)
80
7
8
130
180
130
80
9
14b (31) e
10 d
a. Combined yield of 13a and 14a. b. Formation of side product 15 (28%) was observed. c. Formation of side
product 16 (17%) was observed. d. An inseparable mixture of 12b and 14b was obtained. e. Combined yields of
(E)-14b (25%) and (Z)-14b (6%) calculated from the 1H NMR spectrum with unreacted 12b (6%).
The RCM of prepared substrates 13a, 14a, and 14b were examined. Treatment of 13a with
Grubbs2nd (5 mol%) at rt gave the desired product 8a in 95% yield. However, the corresponding
reactions of 14a and 14b did not afford the desired products 17a and 17b, even with MW assistance.
Further examinations of 14a with alternative catalysts, such as the Grubbs1st, Hoveyda-Grubbs, and
Schrock catalysts, also did not lead to 17a. Our synthesis of 17 will be continued in a future study.
2.3. Synthesis of 2,5-Dihydropyrano[3,2-c]pyrazoles
The synthesis of 2,5-dihydropyrano[3,2-c]pyrazoles (20) was examined and the results are
summarized in Scheme 3. For this purpose, selective preparation of 3-alkenyl-4-allyloxy-1H-pyrazoles
19 is required since 3-allyl-4-hydroxy-1H-1-tritylpyrazole is a minor Claisen rearrangement product of
1a, and the corresponding 3-allyl-1-benzyl-4-hydroxy-1H-pyrazole could not be obtained by heating
1b [21,22]. Hence, an alternative method of preparing 19 via a deprotection-reprotection sequence was
examined. 4-Allyloxy-5-(1-propenyl)-1H-1-tritylpyrazole (6a) was deprotected with aqueous HCl to
give 18, which was then treated with trityl chloride or benzyl bromide under basic conditions. An
E/Z mixture of 4-allyloxy-3-(1-propenyl)-1H-1-tritylpyrazole (19a) was obtained exclusively owing
to the steric repulsion between the propenyl group on the pyrazole ring and an introduced bulky
trityl group. However, N-benzylation of 18 afforded a mixture of 19b and 6b in a ca. 4:1 ratio in 60%
combined yield, and separation gave pure 19b in 25% yield. The obtained substrates 19a and 19b were

Molecules 2019, 24, 296
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independently treated with 5 mol% Grubbs2nd at rt to afford the desired RCM products 20a and 20b
,
respectively, in good yields.
Scheme 3. Synthesis of 2,5-dihydropyrano[3,2-c]pyrazoles (20).
3. Conclusions
We synthesized 1,5-, 1,7-, and 2,5-dihydropyrano[3,2-c]pyrazoles (
5-allyl-4-hydroxy-1H-1-tritylpyrazoles via combination of the Claisen rearrangement,
ruthenium-hydride-catalyzed double bond isomerization, O-alkenylation, and RCM. In the
synthesis of 1,5-dihydropyrano[3,2-c]pyrazoles , the presence of a substituent on the 5-alkenyl group
inhibited smooth RCM through steric hindrance. In these cases, MW-aided reactions were effective, but
7, 8, and 20) from
a
7
gave various products. Towards the selective synthesis of 1,7-dihydro-1-tritylpyrano[3,2-c]pyrazole 8a
temperature-dependent selective dehydrobromination was effective for preparing the RCM substrate
13b. For the synthesis of 2,5-dihydropyrano[3,2-c]pyrazoles 20, a deprotection-reprotection sequence
was applied to obtain the RCM substrate 19.
,
4. Materials and Methods
Infrared (IR) spectra were obtained using a Perkin Elmer 1720X FT-IR spectrometer (Perkin Elmer,
Wattham, MA, USA). HRMS was performed using a JEOL JMS-700 (2) mass spectrometer (JEOL,
Tokyo, Japan). NMR spectra were recorded at 27 ◦C using Agilent 300, 400-MR-DD2, and 600-DD2
spectrometers in CDCl3 using tetramethylsilane (TMS) as the internal standard. Liquid column
chromatography was conducted using silica gel BW127ZH (Fuji Silysia Chemical Ltd., Tokyo, Japn).
Analytical and preparative thin layer chromatography (TLC) analyses were performed using pre-coated
Merck glass plates (silica gel 60 F254), and the compounds were visualized by dipping the plates in
an ethanol solution of phosphomolybdic acid followed by heating (Merk & Co., Inc., Darmstadt,
Germany). MW-assisted reactions were carried out using a Biotage Initiator® (Basel, Switzerland).
Anhydrous CH2CH2 was purchased from Wako Pure Chemical Industries (Osaka, Japan).
4.1. Synthesis of (E)-Methyl 4-((1-Benzyl-1H-pyrazol-4-yl)oxy)but-2-enoate (1e)
To 1-benzyl-4-formyl-1H-pyrazole (200 mg, 1.07 mmol) in CH2Cl2 (5 mL) was added 70%
meta-chloroperoxybenzoic acid (397.6 mg, 1.61 mmol) at 0 ◦C. After it was stirred overnight at room
temperature, the mixture was quenched by adding aqueous NaHCO3 and then extracted with CH2Cl2.
The organic layer was dried over MgSO4, filtered, and evaporated to give a crude residue. The crude
material was dissolved in t-BuOH-CH2Cl2 (5 mL/5 mL) at 40 ◦C, and then potassium tert-butoxide
(428.6 mg, 3.82 mmol) was added to the solution. After it was stirred overnight at 40 ◦C, the mixture
was quenched with saturated aqueous NH4Cl and extracted with CH2Cl2. The separated organic layer
was dried over MgSO4, filtered, and evaporated under reduced pressure to afford a crude residue,
which was purified using silica gel column chromatography (eluent: EtOAc:hexane = 1:3) to afford
(E/Z)-1e (128.1 mg, 44%): oil; IR (film) vmax 1724 (C=O), 1574 (C=C), 1437 (C=C) cm−1; 1H NMR (400
MHz, CDCl3):
15.9 Hz, -COCH=CH-), 6.99 (1H, dt, J = 15.9, 4.1 Hz, -CH2CH=CH-), 7.05 (1H, d, J = 0.6 Hz, pyrazole-H),
7.18 (2H, br d, J = 8.0 Hz, Bn-H), 7.30–7.35 (4H, m, Bn-H, pyrazole-H); 13C NMR (100 MHz, CDCl3):
δ 3.74 (3H, s, -COOMe), 4.52 (2H, dd, J = 4.1, 1.9 Hz, -OCH2CH=CH-), 6.13 (1H, br d, J =
δ

Molecules 2019, 24, 296
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51.6, 56.6, 70.0, 115.1, 121.4, 127.2, 127.5, 128.0, 128.7, 136.3, 142.5, 145.2, 166.4; high-resolution electron
ionization mass spectrometry (HREIMS) m/z calcd. for C15H16N2O3 (M+) 272.1161, found 272.1163.
*(E)-Methyl 4-((1-trityl-1H-pyrazol-4-yl)oxy)but-2-enoate (1f) was synthesized in a similar manner
as 1e, but it was not rearranged under the thermal condition described below. 1f: colorless crystals
(CH2Cl2); mp 155–158 ◦C; IR (film) vmax 1725 (C=O), 1572 (C=C), 1492 (C=C), 1442 (C=C) cm−1; 1H
NMR (400 MHz, CDCl3):
δ 3.76 (3H, s, -COOMe), 4.53 (2H, dd, J = 4.1, 2.0 Hz, -OCH2CH=CH-),
5.20 (2H, s, ArCH2Ph), 6.14 (1H, dt, J = 15.9, 1.9 Hz, -COCH=CH-), 7.00 (1H, dt, J = 15.9, 4.1 Hz,
-CH2CH=CH-), 7.05 (1H, s, pyrazole-H), 7.13–7.18 (6H, m, Tr-H), 7.30–7.35 (9H, m, Tr-H), 7.42 (1H, s,
pyrazole-H); 13C NMR (100 MHz, CDCl3):
δ 51.7, 70.0, 78.7, 118.4, 121.5, 127.68, 127.71, 127.9, 130.1,
142.5, 143.0, 143.8, 166.4; HREIMS m/z calcd. for C27H24N2O3 (M+) 424.1786, found 424.1779.
4.2. Synthesis of Methyl 2-(1-Benzyl-4-hydroxy-1H-pyrazol-5-yl)but-3-enoate (2e)
A sealed microwave vial containing a solution of 1e (128.1 mg, 0.47 mmol) in 1,2-dimethoxyethane
◦
(DME) (2 mL) was heated under microwave irradiation at 200 C for 30 min. After it had cooled,
the reaction mixture was quenched with saturated aqueous NH4Cl and extracted with CH2Cl2. The
separated organic layer was dried over MgSO4, filtered, and evaporated under reduced pressure
to afford a crude residue, which was purified using silica gel column chromatography (eluent:
EtOAc:hexane = 1:1) to afford 2e with a small amount of the isomer, 5e (53.9 mg, 42%).
2e (major) and 5e (minor) in ca. 2:1 ratio: oil; IR (film) vmax 1716 (C=O), 1497 (C=C), 1435
1
(C=C) cm−1; H NMR (400 MHz, CDCl3):
δ 1.65 (1H, d, J = 7.3 Hz, =CHCH3 of 5e), 3.64 (1H, s,
-COOMe of 5e), 3.68 (2H, s, -COOMe of 2e), 4.37 (0.7H, br d, J = 7.0 Hz, ArCH(COOMe)CH=), 4.93
(0.7H, dd, J = 17.0, 1.5 Hz, -CH=CHH), 5.01 (0.6H, s, ArCH2Ph), 5.12 (0.7H, dd, J = 10.3, 1.5 Hz,
-CH=CHH of 2e), 5.19 (0.7H, br d, J = 16.1 Hz, ArCHHPh of 2e), 5.25 (0.7H, br d, J = 16.1 Hz, ArCHHPh
of 2e), 5.86 (1H, ddd, J = 17.0, 10.3, 6.5 Hz, -CH(COOMe)CH=CH2 of 2e), 6.83 (0.6H, br s, -OH of
2e), 7.03–7.05 (2H, m, Ph-H), 7.19–7.31 (3H, m, Ph-H; 0.3H, m, overlapped, =CHCH3 of 5e), 7.30 (1H,
br s, pyrazole-H); 13C NMR (150 MHz, CDCl3):
δ 15.8 (5e), 46.4, 52.3 (5e), 53.2, 54.4 (5e), 54.6, 118.7,
120.6, 122.4 (5e), 122.9 (5e), 126.6, 127.2 (5e), 127.6 (5e), 127.9, 128.2 (5e), 128.40 (5e), 128.44, 129.1, 130.7,
136.9 (5e), 139.8 (5e), 140.9, 147.0, 166.5 (5e), 173.2; HREIMS m/z calcd. for C15H16N2O3 (M+) 272.1161,
found 272.1162.
4.3. Double Bond Migration of 5-Allyl-4-hydroxy-1H-pyrazoles (Scheme 1)
General procedure: To a toluene solution (10 mL) of 5-allyl-4-hydroxy-1-trityl-1H-pyrazole (2a
)
(0.434 g, 1.19 mmol) in a microwave vial (5–20 mL), RuCl◦H(CO)(PPh3)3 (56.6 mg, 0.059 mmol) was
added. The reaction vial was sealed and then heated at 150 C for 15 min under microwave irradiation.
The cooled reaction mixture was evaporated to give a crude residue, which was purified using column
chromatography (eluent: hexane:EtOAc = 1:1) to afford 4-hydroxy-5-(1-propenyl)-1-trityl-1H-pyrazole
(5a) (0.323 g, 74% yield) as an E/Z mixture.
**Pure starting material gave the desired product as described above, but a small contamination
inhibited the isomerization. In that case, a toluene-MeOH (9:1) solvent system was effective for
isolating the desired product.
5a: oil; IR (film) vmax 3268 (-OH), 1597 (C=C), 1494 (C=C), 1446 (C=C) cm−1; 1H NMR (400 MHz,
CDCl3):
δ 1.43 (3H, dd, J = 6.5, 1.2 Hz, =CHCH3), 5.17 (1H, dd, J = 11.4, 1.4 Hz, ArCH=CH-), 5.23 (1H,
dq, J = 11.4, 6.6 Hz, -CH=CHCH3), 7.09–7.34 (16H, m, Tr-H, pyrazole-H); 13C NMR (100 MHz, CDCl3):
δ
14.9, 78.8, 118.3, 126.2, 127.3, 127.4, 127.6, 127.8, 129.6, 130.0, 130.1, 130.28, 130.34, 142.6; HREIMS m/z
calcd. for C25H22N2O (M+) 366.1732, found 366.1731.
(E/Z)-1-Benzyl-4-hydroxy-5-(1-propenyl)-1H-pyrazole (5b): E/Z mixture in ca. 5:1 ratio (X); oil;
IR (film) vmax 3031 (-OH), 1589 (C=C), 1496 (C=C), 1454 (C=C) cm−1; 1H NMR (600 MHz, CDCl3):
δ
1.72 (0.5H, dd, J = 6.8, 1.5 Hz, -CH=CHCH3 of (E)-isomer), 1.83 (2.5H, dd, J = 6.8, 1.8 Hz, -CH=CHCH3
of (Z)-isomer), 5.15 (0.3H, s, -NCH2Ph of (Z)-isomer), 5.24 (1.5H, s, -NCH2Ph of (E)-isomer), 5.93 (0.15H,
dq, J = 10.1, 6.8 Hz, -CH=CHCH3 of (Z)-isomer), 5.99 (0.15H, dq, J = 10.1, 1.5 Hz, ArCH=CHCH3 of

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(Z)-isomer), 6.15 (0.85H, dq, J = 16.1, 1.5 Hz, ArCH=CHCH3 of (E)-isomer), 6.38 (0.85H, dq, J = 16.1,
6.8 Hz, -CH=CHCH3 of (E)-isomer), 7.06–7.09 (6H, m, Tr-H), 7.16 (1H, s, pyrazole-H), 7.22–7.31 (9H, m,
Tr-H); 13C NMR of (E)-isomer (150 MHz, CDCl3):
δ
19.2, 53.7, 116.7, 126.6, 127.6, 127.9, 128.7, 130.3,
137.1, 138.9 (two carbon signals were deduced to have overlapped); (Z)-isomer: 15.4, 54.0, 115.4,
δ
126.8, 126.9, 127.9, 128.6, 133.4, 137.0, 138.4 (two carbon signals were deduced to have overlapped);
HREIMS m/z calcd. for C13H14N2O (M+) 214.1106, found 214.1104.
(E/Z)-1-Benzyl-4-hydroxy-5-(1-(1-methyl)propen-1-yl)-1H-pyrazole (5c): E/Z ratio = ca. 1:1; oil;
IR (film) vmax 3063 (OH), 1563 (C=C), 1497 (C=C), 1456 (C=C) cm−1; 1H NMR of E/Z mixture (400 MHz,
CDCl3):
δ 1.41 (1.6H, dd, J = 6.9, 1.5 Hz, -CH=CHCH3), 1.73 (1.4H, dd, J = 6.8, 1.2 Hz, -CH=CHCH3),
1.79 (3H, br s, CqCH3), 4.30 (0.47H, br s, -OH), 4.43 (0.53H, br s, -OH), 5.08 (0.9H, s, -NCH2Ph), 5.15
(1.1H, s, -NCH2Ph), 5.57 (0.47H, qq, J = 6.8, 1.6 Hz, -CCH=CHCH3), 5.78 (0.53H, qq, J = 6.9, 1.6 Hz,
-CCH3=CHCH3), 7.03 (0.94H, br d, J = 6.7 Hz, Ph-H), 7.07 (1.06H, br d, J = 6.7 Hz, Ph-H), 7.06–7.09
(6H, m, Ph-H), 7.16–7.36 (3H, m, Ph-H), 7.21 (1H, s, pyrazole-H); 13C NMR of E/Z mixture (100 MHz,
CDCl3):
δ 14.0, 15.0, 16.2, 32.0, 53.9, 54.1, 124.2, 124.6, 126.8, 127.2, 127.4, 127.5, 127.91, 127.94, 128.46,
128.49, 128.6, 129.8, 130.0, 132.6, 137.3, 137.6, 137.8; HREIMS m/z calcd. for C14H16N2O (M+) 228.1263,
found 228.1260.
(E/Z)-1-Benzyl-4-hydroxy-5-(1-(1-phenyl)propenyl)-1H-pyrazole (5d): isomer ratio = ca. 5:1; oil;
IR (film) vmax 3031 (OH), 1573 (C=C), 1496 (C=C) cm−1; 1H NMR (100 MHz, CDCl3):
δ 1.55 (2.5H, d,
J = 7.0 Hz, =CHCH3), 1.85 (0.5H, d, J = 7.3 Hz, =CHCH3), 4.61 (1H, br s, J = 14.8 Hz, -NCHHPh), 4.95
(1H, br s, J = 15.3 Hz, -NCHHPh), 5.94 (0.16H, q, J = 7.2 Hz, Cq=CHCH3), 6.31 (0.84H, br q, J = 7.0 Hz,
Cq=CHCH3), 6.87–6.90 (0.66H, m, Ph-H), 6.93–6.96 (1.34H, m, Ph-H), 7.06–7.34 (4H, m, Ph-H), 7.32 (1H,
s, pyrazole-H); 13C NMR (100 MHz, CDCl3):
δ 15.7, 54.3, 126.2, 127.0, 127.38, 127.45, 127.6, 128.3, 128.4,
128.6, 128.9, 129.3, 131.1, 136.9, 139.9 (minor isomer: 15.4, 54.0, 126.4, 127.68, 127.8); HREIMS m/z calcd.
for C19H18N2O (M+) 290.1419, found 290.1417.
(E/Z)-1-Benzyl-4-hydroxy-5-(1-(1-methoxycarbonyl)propenyl)-1H-pyrazole (5e): E/Z mixture
in ca. 13:1 ratio; oil; IR (film) vmax 3090 (OH), 1716 (C=O), 1507 (C=C), 1436 (C=C) cm−1; 1H NMR
(400 MHz, CDCl3):
δ 1.72 (2.6H, d, J = 7.3 Hz, -CH=CHCH3 of major isomer), 1.83 (0.4H, d, J = 7.2 Hz,
-CH=CHCH3 of minor isomer), 3.66 (2.6H, s, -OCH3 of major isomer), 3.71 (0.4H, s, -OCH3 of minor
isomer), 4.73 (1H, s, -OH), 5.06 (1.86H, s, -NCH2Ph of major isomer), 5.17 (0.14H, s, -NCH2Ph of minor
isomer), 7.04 (2H, br d, J = 6.6 Hz, Ph-H), 7.19–7.30 (4H, m, Ph-H, =CHCH3), 7.33 (1H, s, pyrazole-H);
13C NMR (100 MHz, CDCl3):
δ 15.8, 52.3, 54.5, 122.2, 122.9, 127.3, 127.6, 128.1, 128.4, 136.7, 140.0, 147.5,
166.5; HREIMS m/z calcd. for C15H16N2O3 (M+) 272.1161, found 272.1160.
4.4. O-Allylation of 1-Protected 5- or 3-Allyl-4-allyloxy-1H-pyrazoles (Scheme 1)
General procedure: To a solution of an E/Z mixture of 4-hydroxy-5-(1-propenyl)-1H-
1-tritylpyrazole (5a) (0.410 g, 1.12 mmol) in acetone (2 mL), 20% aqueous NaOH (1 mL) and allyl
bromide (142
µL, 1.68 mmol) were added. The reaction mixture was stirred for 1 h and then
quenched with saturated aqueous NH4Cl and extracted with CH2Cl2. The organic layer was dried
over anhydrous MgSO4, filtered, and evaporated. The crude residue was purified with column
chromatography (eluent: hexane:EtOAc = 3:1) to afford 4-allyloxy-5-(1-propenyl)-1H-1-tritylpyrazole
(6a) (E/Z mixture in ca. 3:1 ratio, 0.334 g, 73% yield).
(E)-6a: mp 152–155 ◦C; IR (KBr) vmax 1567 (C=C), 1491 (C=C), 1446 (C=C) cm−1; 1H NMR (400
MHz, CDCl3):
δ 1.40 (3H, dd, J = 6.7, 1.5 Hz, CH3CH=), 4.50 (2H, dt, J = 5.3, 1.5 Hz, -OCH2CH=CH2),
5.26 (1H, dq, J = 15.8, 1.4 Hz, -CH2CH=CHH), 5.37 (1H, dq, J = 17.2, 1.5 Hz, -CH2CH=CHH), 5.46
(1H, dq, J = 15.8, 1.4 Hz, ArCH=CHCH3), 6.04 (1H, ddt, J = 17.2, 10.5, 5.3 Hz, -OCH2CH=CH2), 6.14
(1H, dq, J = 15.8, 6.7 Hz, ArCH=CHCH3), 7.07–7.16 (6H, m, Tr-H), 7.24–7.39 (9H, m, Tr-H), 7.32 (1H,
s, pyrazole-H); 13C NMR (100 MHz, CDCl3):
δ 18.9, 72.0, 79.0, 117.5, 120.0, 124.7, 127.3, 127.4, 127.6,
128.5, 130.3, 133.5, 142.◦9, 143.5; HREIMS m/z calcd. for C28H26N2O (M+) 406.2055, found 406.2047.
(Z)-6a: mp 82–86 C; IR (KBr) vmax 1567 (C=C), 1491 (C=C), 1446 (C=C) cm−1; 1H NMR (400 MHz,
CDCl3):
δ 1.42 (3H, d, J = 5.1 Hz, CH3CH=), 4.47 (2H, dt, J = 5.5, 1.6 Hz, -OCH2CH=CH2), 5.16–5.20

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(2H, m), 5.22 (1H, dq, J = 10.6, 1.4 Hz, -CH2CH=CHH), 5.34 (1H, dq, J = 17.2, 1.5 Hz, -CH2CH=CHH),
6.00 (1H, ddt, J = 17.2, 10.6, 5.6 Hz, -OCH2CH=CH2), 7.03–7.17 (6H, m, Tr-H), 7.21–7.32 (9H, m, Tr-H),
7.37 (1H, s, pyrazole-H); 13C NMR (100 MHz, CDCl3):
δ 15.4, 72.0, 78.9, 117.4, 117.9, 124.9, 127.2,
127.3, 127.9, 129.8, 130.1, 133.7, 142.6, 142.9; HREIMS m/z calcd. for C28H26N2O (M+) 406.2046, found
406.2050.
(E/Z)-4-Allyloxy-1-benzyl-5-(1-propenyl)-1H-pyrazole (6b) (an inseparable E/Z mixture in a ca.
8:2 ratio, 0.334 g, 73% yield): oil; IR (film) vmax 1566 (C=C), 1495 (C=C), 1452 (C=C) cm−1; HREIMS
1
m/z calcd. for C16H18N2O (M+) 254.1419, found 254.1421. (E)-isomer: H NMR (600 MHz, CDCl3):
δ
1.82 (3H, d, J = 6.7, 1.8 Hz, CH3CH=), 4.50 (2H, dt, J = 5.4, 1.4 Hz, -OCH2CH=CH2), 5.26 (1H, dq, J =
10.6, 1.4 Hz, -CH2CH=CHH), 5.28 (2H, s, NCH2Ph), 5.39 (1H, ddd, J = 17.3, 3.2, 1.8 Hz, -CH2CH=CHH),
6.05 (1H, ddt, J = 17.3, 10.6, 5.4 Hz, -OCH2CH=CH2), 6.16 (1H, br d, J = 15.8 Hz, ArCH=CHCH3),
6.46 (1H, dq, J = 15.8, 6.7 Hz, -CH=CHCH3), 7.07 (2H, br d, J = 7.6 Hz, Ph-H), 7.24 (1H, br t, J = 7.6
Hz, Ph-H), 7.26 (1H, s, pyrazole-H), 7.30 (2H, br t, J = 7.6 Hz, Ph-H); 13C NMR (150 MHz, CDCl3):
δ
19.3, 53.9, 72.2, 116.6, 117.5, 125.8, 126.5, 126.8, 127.5, 128.6, 128.7, 129.6, 133.5, 137.2; (Z)-isomer:
1H NMR (600 MHz, CDCl3):
δ
1.72 (3H, dd, J = 6.8, 1.8 Hz, CH3CH=), 4.46 (2H, dt, J = 5.6, 1.5 Hz,
-OCH2CH=CH2), 5.18 (2H, s, NCH2Ph), 5.24 (1H, dq, J = 10.5, 1.5 Hz, -CH2CH=CHH), 5.36 (1H, dq, J
= 17.1, 1.5 Hz, -CH2CH=CHH), 5.91 (1H, dq, J = 11.2, 6.8 Hz, -CH=CHCH3), 6.01 (1H, ddt, J = 17.1,
10.5, 5.6 Hz, -OCH2CH=CH2), 6.01 (1H, br d, J = 11.2 Hz, ArCH=CHCH3, overlapped), 7.07 (2H, br d, J
= 7.6 Hz, Ph-H), 7.24 (1H, br t, J = 7.6 Hz, Ph-H), 7.28 (1H, s, pyrazole-H), 7.30 (2H, br t, J = 7.6 Hz,
Ph-H); 13C NMR (150 MHz, CDCl3):
δ 15.7, 53.9, 72.4, 115.4, 117.4, 126.59, 126.64, 127.5, 133.2, 137.1,
142.7 (three signals should be overlapped with signals of the (E)-isomer).
(E/Z)-4-Allyloxy-1-benzyl-5-(1-(1-methyl)propenyl)-1H-pyrazole (6c): isomer ratio = ca. 1:1; oil;
IR (film) vmax 1562 (C=C), 1496 (C=C), 1455 (C=C) cm−1; 1H NMR (400 MHz, CDCl3):
δ 1.43 (1.6H,
dd, J = 6.7, 1.4 Hz, CH3CH=), 1.72 (1.4H, dd, J = 6.9, 1.2 Hz, CH3CH=), 4.414 (1.06H, d, J = 5.5 Hz,
-OCH2CH=), 4.417 (0.94H, d, J = 5.5 Hz, -OCH2CH=), 5.08 (0.94H, s, NCH2Ph), 5.19 (1.06H, s, NCH2Ph),
5.19–5.36 (2H, m, =CH2), 5.54 (0.44H, qq, J = 6.9, 1.6 Hz, -C(CH3)H=CH3), 5.75 (0.56H, qq, J = 6.8,
1.6 Hz, -C(CH3)H=CH3), 5.92–6.04 (1H, m, -CH2CH=CH2), 7.02 (0.94H, br d, J = 7.3 Hz, Ph-H), 7.07
(1.06H, br d, J = 7.2 Hz, Ph-H), 7.18–7.29 (3H, m, Ph-H), 7.29 (1H, s, pyrazole-H); 13C NMR (100 MHz,
CDCl3):
δ 13.9, 15.2, 16.0, 23.1, 53.7, 54.0, 72.8, 117.45, 117.54, 125.0, 126.77, 126.86, 127.21, 127.3, 127.5,
128.46, 128.49, 129.0, 129.2, 129.5, 133.2, 133.7, 133.8, 137.3, 137.8, 141.6, 141.7; HREIMS m/z calcd. for
C17H20N2O (M+) 268.1576, found 268.1575.
(E/Z)-4-Allyloxy-1-benzyl-5-(1-(1-phenyl)propenyl)-1H-pyrazole (6d): isomer ratio = ca. 7:1; oil;
IR (film) vmax 1556 (C=C), 1500 (C=C) cm−1; 1H NMR (400 MHz, CDCl3):
δ 1.55 (2.7H, d, J = 6.9 Hz,
CH3CH=), 1.85 (0.3H, d, J = 7.3 Hz, CH3CH=), 4.38 (0.25H, br d, J = 5.5 Hz, -OCH2CH=), 4.44
(1.75H, br d, J = 3.9 Hz, -OCH2CH=CH2), 4.64 (1H, br d, J = 14.9 Hz, NCHHPh), 4.94 (1H, br d,
J = 14.8 Hz, NCHHPh), 5.19 (1H, dd, J = 10.5, 1.3 Hz, -CH2CH=CHH), 5.29 (1H, dq, J = 17.2, 1.6 Hz,
-CH2CH=CHH), 5.89–6.99 (1H, m, -OCH2CH=CH2 overlaps with 0.12H, m, =CHCH3), 6.31 (0.88H,
q, J = 7.0 Hz, =CHCH3), 6.89–6.90 (2H, m, Ph-H), 7.08–7.49 (8H, m, Ph-H), 7.39 (1H, s, pyrazole-H);
13C NMR (100 MHz, CDCl3):
δ 15.8, 54.3, 72.7, 117.5, 126.2, 127.0, 127.1, 127.4, 128.27, 128.33, 128.5,
129.2, 129.3, 131.2, 133.7, 137.0, 139.7, 143.3; HREIMS m/z calcd. for C22H22N2O (M+) 330.1732,
found 330.1729.
Synthesis of (E/Z)-4-allyloxy-1-benzyl-5-(1-(1-methoxycarbonyl)propenyl)-1H-pyrazole (6e) from
2e: To an acetone solution (4.5 mL) of 2e with a small amount of 5e (121.8 mg, 0.45 mmol) in a
microwave vial were added K2CO3 (61.8 mg, 0.45 mmol) in water (0.5 mL) and allyl bromide (0.04 mL,
0.45 mmol). After the reaction vial was sealed, the mixture was heated under microwave irradiation at
60 ◦C for 1 h. After it had cooled, the reaction was quenched by adding aqueous NH4Cl. Then, the
reaction mixture was extracted with EtOAc three times. The organic layer was washed with brine,
dried over MgSO4, filtered, and then evaporated to give a crude residue, which was purified using
column chromatography (eluent: hexane:EtOAc = 2:1) to give pure 6e (117.1 mg, 84%).

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1
6e (isomer ratio = ca. 13:1): oil; IR (film) vmax 1717 (C=O), 1500 (C=C) cm−1; H NMR:
δ 1.54
(2.6H, d, J = 7.2 Hz, CH3CH= of major isomer), 2.12 (0.4H, d, J = 7.2 Hz, CH3CH= of minor isomer),
3.52 (0.4H, s, -OCH3 of minor isomer), 3.60 (2.6H, s, -OCH3 of major isomer), 4.92 (0.93H, br d,
J = 15.3 Hz, NCHHPh of major isomer), 5.01 (0.14H, s, NCH2Ph of minor isomer), 5.03 (0.93H, br d,
J = 15.3 Hz, NCHHPh of major isomer), 5.11 (0.93H, dq, J = 10.6, 1.4 Hz, -CH2CH=CHH of major
isomer), 5.14 (0.07H, dq, J = 10.6, 1.5 Hz, -CH2CH=CHH of minor isomer), 5.22 (0.93H, dq, J = 17.5,
1.6 Hz, -CH2CH=CHH of major isomer), 5.23 (1H, dq, J = 17.4, 1.6 Hz, -CH2CH=CHH of minor isomer),
5.87–5.93 (1H, m, -OCH2CH=CH2), 6.46 (0.07H, q, J = 7.3 Hz, -Cq=CHCH3 of minor isomer), 7.06
(2H, br d, J = 6.6 Hz, Ph-H), 7.17–7.30 (3H, m, Ph-H), 7.20 (0.07H, q, J = 7.2 Hz, -Cq=CHCH3 of major
isomer), 7.32 (1H, s, pyrazole-H); 13C NMR (100 MHz, CDCl3):
δ 15.7, 52.0, 54.6, 72.5, 117.6, 122.0,
123.2, 126.4, 127.4, 127.6, 128.4, 133.4, 136.7, 143.2, 147.9, 165.9 (minor isomer: 16.2, 51.5, 54.1, 72.8, 121.5,
123.1, 126.6, 127.5, 136.9, 147.7); HREIMS m/z calcd. for C18H20N2O3 (M+) 312.1474, found 312.1467.
4.5. Ring-Closing Metathesis of 6 to 1H-1,5-Dihydropyrano[3,2-c]pyrazoles 7 (Table 1)
General procedure (Table 1, entry 3): To a solution of 6a (21.8 mg, 0.054 mmol) in CH2Cl2 (2 mL)
was added Grubbs2nd (1.7 mg, 2.7 mmol) at rt. The reaction mixture was stirred at rt for 1 h, and then
the solvent was removed under reduced pressure, affording a crude residue, which was purified using
silica gel column chromatography (eluent: EtOAc:hexane = 1:3) to afford 7a (16.2 mg, 83%).
*General procedure for MW-aided reaction (Table 1, entry 5): To a solution of 6a (16.4 mg,
0.04 mmol) in CH2Cl2 (2 mL) was added Grubbs2nd (2.3 mg, 2.0 mmol) in a microwave vial. The
◦
reaction mixture was heated under microwave irradiation at 80 C for 3 min. After the reaction
mixture had cooled, the solvent was removed under reduced pressure, affording a crude residue,
which was purified using silica gel column chromatography (eluent: EtOAc:hexane = 1:4) to afford 7a
(12.8 mg, 87%).
1,5-Dihydro-1-tritylpyrano[3,2-c]pyrazole (7a): oil; IR (film) vmax 1677 (C=C), 1581 (C=C), 1493
(C=C), 1447 (C=C) cm−1; 1H NMR (400 MHz, CDCl3):
δ 4.64 (2H, dd, J = 3.8, 1.8 Hz, -OCH2CH=CH-),
5.15 (1H, dt, J = 10.2, 3.7 Hz, -OCH2CH=CH-), 5.28 (1H, dtd, J = 10.2, 1.8, 0.8 Hz, -OCH2CH=CH-),
7.08–7.17 (6H, m, Tr-H), 7.18 (1H, d, J = 0.8 Hz, pyrazole-H), 7.23–7.32 (9H, m, Tr-H); 13C NMR (100
MHz, CDCl3):
δ 66.9, 78.0, 117.7, 118.6, 124.3, 127.55, 127.57, 130.1, 141.4, 142.7; HREIMS m/z calcd. for
C25H20N2O (M+) 364.1575, found 364.1585.
1-Benzyl-1,5-dihydropyrano[3,2-c]pyrazole (7b): oil; IR (film) vmax 1566 (C=C), 1495 (C=C), 1452
1
(C=C) cm−1; H NMR (400 MHz, CDCl3):
δ 4.75 (2H, dd, J = 3.9, 1.8 Hz, -OCH2CH=), 5.21 (2H, s,
ArCH2Ph), 5.53 (1H, dt, J = 10.0, 3.9 Hz, -OCH2CH=CH-), 6.34 (1H, br d, J = 10.0 Hz, -OCH2CH=CH-),
7.10 (1H, d, J = 0.8 Hz, pyrazole-H), 7.10–7.14 (2H, d, J = 6.6 Hz, Ph-H), 7.26–7.32 (3H, m, Ph-H); 13
NMR (100 MHz, CDCl3): 54.0, 67.2, 115.5, 119.7, 124.5, 127.1, 127.9, 128.8, 136.6, 140.9; HREIMS m/z
calcd. for C13H12N2O (M+) 212.0950, found 212.0949.
C
δ
1-Benzyl-1,5-dihydro-7-methylpyrano[3,2-c]pyrazole (7c): oil; IR (film) vmax 1732 (C=O), 1541
1
(C=C) cm−1; H NMR (400 MHz, CDCl3):
δ 1.96 (3H, br s, CqCH3), 4.64 (2H, dq, J = 3.3, 1.6 Hz,
-OCH2CH=), 5.23–5.26 (1H, m, -OCH2CH=), 5.39 (2H, s, NCH2Ph), 7.01 (2H, br d, J = 7.0 Hz, Ph-H),
7.17 (1H, s, pyrazole-H), 7.24–7.32 (3H, m, Ph-H); 13C NMR (100 MHz, CDCl3):
δ 18.1, 55.3, 67.6,
116.5, 124.7, 126.0, 127.6, 127.3, 128.7, 137.7, 141.4; HREIMS m/z calcd. for C15H14N2O3 (M+) 270.1004,
found 270.1003.
1-Benzyl-1,5-dihydro-7-methoxycarbonylpyrano[3,2-c]pyrazole (7e): oil; IR (film) vmax 1732 (C=O),
1
1541 (C=C) cm−1; H NMR (400 MHz, CDCl3):
δ 3.76 (3H, s, -COOCH3), 4.72 (2H, d, J = 4.5 Hz,
-OCH2CH=), 5.57 (2H, s, ArCH2Ph), 6.45 (1H, t, J = 4.5 Hz, -OCH2CH=Cq), 6.33 (1H, br d, J = 10.0 Hz,
-OCH2CH=CH-), 7.04 (2H, br d, J = 6.5 Hz, Ph-H), 7.23 (1H, s, pyrazole-H), 7.23–7.31 (3H, m, Ph-H);
13C NMR (100 MHz, CDCl3):
δ 52.3, 56.4, 66.9, 124.0, 124.7, 127.0, 127.4, 128.4, 128.7, 137.5, 142.4, 163.8;
HREIMS m/z calcd. for C15H14N2O3 (M+) 270.1004, found 270.1003.
1-Benzyl-1,7-dihydropyrano[3,2-c]pyrazole (8b): oil; IR (film) vmax 1607 (C=C), 1586 (C=C), 1557
1
(C=C) cm−1; H NMR (400 MHz, CDCl3):
δ 3.23 (2H, dd, J = 3.3, 2.0 Hz, ArCH2CH=), 4.77 (1H,

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dt, J = 6.3, 3.4 Hz, -CH2CH=CH-), 5.17 (2H, s, ArCH2Ph), 6.42 (1H, dt, J = 6.2, 2.0 Hz, =CH=CHO-),
7.06–7.20 (2H, m, Ph-H), 7.22–7.33 (4H, m, Ph-H, pyrazole-H); 13C NMR (100 MHz, CDCl3):
δ 19.5,
53.8, 97.1, 125.1, 126.4, 127.0, 127.9, 128.8, 129.0, 136.6, 141.3; HREIMS m/z calcd. for C13H12N2O (M+)
212.0950, found 212.0947.
1-Benzyl-1,7-dihydro-7-methylenepyrano[3,2-c]pyrazole (9c): oil; IR (film) vmax 1644 (C=C), 1556
(C=C), 1401 (C=C) cm−1; 1H NMR (400 MHz, CDCl3):
δ
2.54 (2H, br t, J = 5.6 Hz, -OCH2CH2Cq), 4.17
(2H, t, J = 5.7 Hz, -OCH2CH2-), 4.78 (1H, br s, CqCHH), 4.96 (1H, br s, CqCHH), 5.43 (2H, s, NCH2Ph),
7.02 (2H, d, J = 7.0 Hz, Ph-H), 7.22–7.32 (4H, m, Ph-H, pyrazole-H); 13C NMR (100 MHz, CDCl3):
32.2,
δ
55.4, 68.3, 107.2, 124.0, 125.3, 126.2, 127.5, 128.7, 129.7, 136.9, 142.6; HREIMS m/z calcd. for C14H14N2O
(M+) 226.1106, found 226.1102.
1,4-Bis((1-benzyl-5-(1-phenylprop-1-en-1-yl)-1H-pyrazol-4-yl)oxy)but-2-ene (10d): oil; IR (film)
v
max 1569 (C=C), 1496 (C=C) cm−1; 1H NMR (400 MHz, CDCl3):
δ 1.51 (6H, d, J = 7.1 Hz, =CHCH3),
4.40 (4H, br s, -OCH2CH=), 4.62 (2H, br d, J = 14.8 Hz, ArCHHPh), 4.92 (2H, br d, J = 14.4 Hz,
ArCHHPh), 5.82–5.84 (2H, m, -OCH2CH=), 6.29 (2H, q, J = 7.1 Hz, =CHCH3), 6.92–6.95 (4H, m, Ph-H),
7.06–7.25 (6H, m, Ph-H), 7.35 (2H, s, pyrazole-H); 13C NMR (100 MHz, CDCl3):
δ 15.8, 54.3, 71.6,
126.1, 127.1, 127.35, 127.42, 128.3, 128.7, 129.1, 129.2, 131.2, 137.0, 140.0, 143.2 (three carbon signals
overlapped); HREIMS m/z calcd. for C42H40N4O2 (M+) 632.3151, found 632.3145.
1,4-Bis((1-benzyl-5-(1-(methoxycarbonyl)prop-1-en-1-yl)-1H-pyrazol-4-yl)oxy)but-2-ene (10e): oil;
IR (film) vmax 1722 (C=O), 1712 (C=O), 1642 (C=C), 1573 (C=C) cm−1; 1H NMR (400 MHz, CDCl3):
δ
1.54 (5.4H, d, J = 7.0 Hz, =CHCH3 of major isomer), 2.14 (0.6H, d, J = 7.2 Hz, =CHCH3 of minor
isomer), 3.61 (0.6H, s, -OCH3 of minor isomer), 3.62 (5.4H, s, =CHCH3 of major isomer), 4.42 (3.6H,
br s, -OCH2CH= of major isomer), 4.48 (0.4H, br s, -OCH2CH= of minor isomer), 5.08 (1.8H, br d,
J = 13.3 Hz, ArCHHPh of major isomer), 5.11 (0.4H, s, ArCH2Ph of minor isomer), 5.12 (1.8H, br d,
J = 13.3 Hz, ArCHHPh of major isomer), 5.77 (3.6H, br t, J = 3.7 Hz, -OCH2CH= of minor isomer),
5.88 (0.4H, br t, J = 3.7 Hz, -OCH2CH= of major isomer), 6.28 (0.2H, q, J = 7.5 Hz, =CHCH3 of minor
isomer), 7.08 (4H, d, J = 6.8 Hz, Ph-H), 7.20–7.32 (7.8H, m, Ph-H, =CHCH3 of major isomer), 7.33 (2H, s,
pyrazole-H); 13C NMR (100 MHz, CDCl3):
δ 15.7, 52.1, 54.6, 71.5, 122.1, 123.2, 126.4, 127.4, 127.6, 128.4,
128.5, 136.7, 147.9, 165.9; HREIMS m/z calcd. for C34H36N4O6 (M+) 596.2635, found 596.2634.
Methyl 2-(1-benzyl-4-(cinnamyloxy)-1H-pyrazol-5-yl)but-2-enoate (11e): oil; IR (film) vmax 1716
(C=O), 1644 (C=C), 1574 (C=C) cm−1; 1H NMR (600 MHz, CDCl3):
δ 1.58 (3H, d, J = 7.3 Hz, =CHCH3),
3.58 (3H, s, -COOCH3), 4.58 (2H, d, J = 6.2 Hz, -OCH2CH=), 5.02 (1H, br d, J = 15.2 Hz, ArCHHPh),
5.12 (1H, br d, J = 15.2 Hz, ArCHHPh), 6.30 (1H, dt, J = 15.9, 6.2 Hz, -OCH2CH=CH-), 6.62 (1H, d, J =
15.9 Hz, -CH=CHPh), 7.09 (2H, d, J = 7.3 Hz, Ph-H), 7.20–7.38 (8H, m, Ph-H), 7.30 (1H, q, J = 7.3 Hz,
-Cq=CHCH3), 7.40 (1H, s, pyrazole-H); 13C NMR (150 MHz, CDCl3):
δ 15.8, 52.0, 54.7, 72.7, 122.2, 123.6,
124.7, 126.6, 126.9, 127.4, 127.6, 127.9, 128.4, 128.6, 133.1, 136.4, 136.7, 143.2, 147.9, 165.9; HREIMS m/z
calcd. for C24H24N2O3 (M+) 388.1787, found 388.1785.
4.6. Synthesis of 5-Allyl-4-(2-haloethoxy)-1H-pyrazoles (12) (Scheme 2)
General procedure: To a solution of 2a (50.8 mg, 0.14 mmol) in acetone (2 mL) in a microwave vial
were added 1,2-dibromoethane (0.05 mL, 0.56 mmol), 20% aqueous NaOH (0.11 mL, 0.56 mmol), and
a catalytic amount of tetrabutylammonium bromide. The sealed reaction vial was MW irradiated at
140 ◦C for 30 min. After it had cooled, the reaction mixture was quenched with saturated aqueous
NH4Cl and extracted with CH2Cl2. The separated organic layer was dried over MgSO4, filtered, and
evaporated under reduced pressure to afford a crude residue. The residue was purified using silica gel
column chromatography (eluent: EtOAc:hexane = 1:3) to afford 12a (42.9 mg, 65%) as an oil.
5-Allyl-4-(2-bromoethoxy)-1H-1-tritylpyrazole (12a): pale yellow crystals (CH2Cl2); mp
1
135–140 ◦C; IR (film) vmax 1581 (C=C), 1491 (C=C), 1446 (C=C) cm−1; H NMR (500 MHz, CDCl3):
δ
2.85 (2H, dt, J = 6.5, 1.2 Hz, ArCH2CH=CH2), 3.56 (2H, t, J = 6.2 Hz, -OCH2CH2CBr), 4.20 (2H, t,
J = 6.2 Hz, -OCH2CH2Br), 4.63 (1H, dq, J = 17.0, 1.6 Hz, -CH=CHH), 4.66 (1H, dq, J = 10.0, 1.4 Hz,
-CH=CHH), 4.97 (1H, ddt, J = 17.0, 10.0, 6.5 Hz, -CH2CH=CH2), 7.10–7.13 (6H, m, Tr-H), 7.25–7.30

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(9H, m, Tr-H), 7.33 (1H, s, pyrazole-H); 13C NMR (125 MHz, CDCl3):
δ
29.4, 31.2, 71.6, 78.7, 115.9,
125.6, 127.4, 127.6, 129.9, 130.1, 132.4, 142.8, 143.6; HREIMS m/z calcd. for C27H25BrN2O (M+) 472.1151,
found 472.1149.
5-Allyl-1-benzyl-4-(2-bromoethoxy)-1H-pyrazole (12b): oil; IR (film) vmax 1583 (C=C), 1496 (C=C)
cm−1; 1H NMR (400 MHz, CDCl3):
δ 3.29 (2H, dd, J = 4.7, 1.7 Hz, ArCH2CH=), 3.56 (2H, br t, J = 6.2 Hz,
-OCH2CH2Br), 4.20 (2H, br t, J = 6.2 Hz, -OCH2CH2Br), 5.00 (1H, dd, J = 7.0, 1.4 Hz, -CH=CHH), 5.07
(1H, dd, J = 10.2, 1.4 Hz, -CH=CHH), 5.73–5.83 (1H, m, -CH2CH=CH2), 7.06 (2H, br d, J = 8.1 Hz,
Bn-H), 7.25–7.33 (4H, m, Ph-H, pyrazole-H); 13C NMR (100 MHz, CDCl3):
δ 27.1, 29.5, 53.9, 72.4, 116.5,
126.7, 127.2, 127.7, 127.8, 128.7, 133.6, 136.9, 141.6; HREIMS m/z calcd. for C15H17BrN2O (M+) 320.0524,
found 320.0520.
◦
5-Allyl-4-(2-chloroethoxy)-1H-1-tritylpyrazole (12Cl): white powder (CH2Cl2); mp 120–125 C; IR
(KBr) vmax 1580 (C=C), 1493 (C=C), 1446 (C=C) cm−1; 1H NMR (500 MHz, CDCl3):
δ 2.85 (2H, br d, J =
7.6 Hz, ArCH2CH=), 3.72 (2H, t, J = 5.7 Hz, -OCH2CH2Cl), 4.14 (2H, t, J = 5.7 Hz, -OCH2CH2CCl), 4.63
(1H, dq, J = 17.0, 1.6 Hz, -CH=CHH), 4.66 (1H, dq, J = 10.0, 1.4 Hz, -CH=CHH), 4.97 (1H, ddt, J = 17.0,
10.0, 6.7 Hz, -CH2CH=CH2), 7.10–7.14 (6H, m, Tr-H), 7.24–7.31 (9H, m, Tr-H), 7.34 (1H, s, pyrazole-H);
13C NMR (125 MHz, CDCl3):
δ 31.2, 42.1, 71.7, 78.6, 115.8, 125.5, 127.3, 127.6, 129.9, 130.0, 132.4, 142.8,
143.7; HREIMS m/z calcd. for C27H25ClN2O (M+) 428.1655, found 428.1654. *MW conditions: 160 ◦C,
30 min.
4.7. Reaction of 12 with Potassium Tert-Butoxide (Table 2, Scheme 2)
General procedure (Table 2, entry 7): To a solution of 12a (28.8 mg, 0.05 mmol) in anhydrous
THF:t-BuOH (2 mL:0.5 mL) in a microwave vial was added potassium tert-butoxide (28.8 mg,
◦
0.26 mmol). The sealed reaction vial was MW irradiated at 130 C for 1 h. After it had cooled,
the reaction mixture was quenched with saturated aqueous NH4Cl and extracted with CH2Cl2. The
separated organic layer was dried over MgSO4, filtered, and evaporated under reduced pressure to
afford a crude residue. The residue was purified using silica gel column chromatography (eluent:
EtOAc:hexane = 1:3) to afford 13a (20.8 mg, 87%).
◦
5-Allyl-1-trityl-1H-4-vinyloxypyrazole (13a): white powder (CH2Cl2); mp 75–80 C; IR (KBr)
1
vmax 1639 (C=C), 1624 (C=C), 1566 (C=C) cm−1; H NMR (600 MHz, CDCl3):
δ 2.81 (2H, ddd, J =
6.8, 1.5, 1.2 Hz, ArCH2CH=CH2), 4.23 (1H, dd, J = 5.4, 1.8 Hz, -OCH=CHH), 4.50 (1H, dd, J = 13.8,
2.1 Hz, -OCH2=CHH), 4.62 (1H, dq, J = 16.7, 1.5 Hz, -CH2CH=CHH), 4.68 (1H, dq, J = 10.9, 1.5 Hz,
-CH2CH=CHH), 4.99 (1H, ddt, J = 16.5, 10.9, 2.1 Hz, -CH2CH=CH2), 6.53 (1H, dd, J = 13.8, 6.5 Hz,
-OCH=CH2), 7.12–7.14 (6H, m, Tr-H), 7.25–7.31 (9H, m, Tr-H), 7.40 (1H, s, pyrazole-H); 13C NMR (150
MHz, CDCl3):
δ 31.1, 77.8, 91.3, 116.1, 127.4, 127.6, 128.3, 130.0, 131.7, 131.9, 140.4, 142.3, 150.7; HREIMS
m/z calcd. for C27H24N2O (M+) 392.1888, found 392.1880.
◦
5-(1-Propenyl)-1-trityl-1H-4-vinyloxypyrazole (14a): white powder (CH2Cl2); mp 133–135 C;
IR (KBr) vmax 1639 (C=C), 1560 (C=C), 1492 (C=C) cm−1; H NMR (600 MHz, CDCl3):
1
δ 1.39 (3H,
dd, J = 6.8, 1.8 Hz, -CH=CHCH3), 4.29 (1H, dd, J = 6.2, 2.0 Hz, -OCH=CHH), 4.59 (1H, dd, J = 13.8,
2.0 Hz, -OCH=CHH), 5.39 (1H, br dq, J = 15.8, 0.8 Hz, -CH=CHCH3), 5.98 (1H, dq, J = 15.8, 6.8 Hz,
-CH=CHCH3), 6.56 (1H, dd, J = 13.8, 6.2 Hz, -OCH=CH2), 7.11–7.15 (6H, m, Tr-H), 7.26–7.32 (9H,
m, Tr-H), 7.38 (1H, br s, pyrazole-H); 13C NMR (150 MHz, CDCl3):
δ 18.8, 79.8, 92.3, 119.1, 127.38,
127.44, 128.0, 129.1, 130.3, 131.2, 139.5, 142.7, 150.4; HREIMS m/z calcd. for C27H24N2O (M+) 392.1889,
found 392.1887.
(E/Z)-1-Benzyl-5-(1-propenyl)-1H-4-vinyloxypyrazole (14b): E/Z ratio = ca. 5:1; oil; IR (film)
v
max 1642 (C=C), 1562 (C=C), 1493 (C=C) cm−1; 1H NMR (400 MHz, CDCl3):
δ 1.68 (0.5H, d, J = 6.3 Hz,
=CHCH3 of (Z)-isomer), 1.82 (2.5H, dd, J = 6.6, 1.6 Hz, =CHCH3 of (E)-isomer), 4.22 (0.17H, dd, J =
6.3, 2.0 Hz, -CH=CHH of (Z)-isomer), 4.29 (0.83H, dd, J = 6.3, 2.0 Hz, -CH=CHH of (E)-isomer), 4.57
(0.17H, dd, J = 13.7, 2.0 Hz, -CH=CHH of (Z)-isomer), 4.59 (0.83H, dd, J = 13.7, 2.0 Hz, -CH=CHH of
(E)-isomer), 5.93 (0.17H, dq, J = 11.0, 6.5 Hz, -CH=CHCH3 of (Z)-isomer), 5.98 (0.17H, br d, J = 11.0 Hz,
ArCH=CHCH3 of (Z)-isomer), 6.11 (0.83H, br dq, J = 16.0, 1.6 Hz, ArCH=CHCH3 of (E)-isomer), 6.34

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(0.83H, dq, J = 15.8, 6.8 Hz, -CH=CHCH3 of (E)-isomer), 6.49 (0.17H, dd, J = 13.7, 6.3 Hz, -OCH=CH2 of
(Z)-isomer), 6.55 (0.83H, dd, J = 13.7, 6.3 Hz, -OCH=CH2 of (E)-isomer), 7.07 (2H, br d, J = 7.0 Hz, Ph-H),
7.23–7.37 (3H, m, Ph-H), 7.33 (1H, br s, pyrazole-H); 13C NMR (150 MHz, CDCl3):
δ 16.0 (minor), 19.3,
53.4 (minor), 54.0, 91.9 (minor), 92.3, 114.7 (minor), 115.9, 126.5, 126.9, 127.7, 128.7, 128.8, 129.0 (minor),
131.5, 134.2 (minor), 136.9, 138.5 (minor), 150.4 (minor), 150.5; HREIMS m/z calcd. for C15H16N2O
(M+) 240.1263, found 240.1256.
(E/Z)-4-(2-Methoxy)ethoxy-3-(1-propenyl)-2H-2-tritylpyrazole (15): oil; IR (film) vmax 1492 (C=C),
1446 (C=C) cm−1; 1H NMR (400 MHz, CDCl3):
δ 1.39 (3H, d, J = 6.7 Hz, =CHCH3), 3.65 (0.5H, br t, J =
4.1 Hz, -OCH2CH2Br), 3.7 (1.5H, br t, J = 4.1 Hz, -CH2CH2Br), 4.07 (0.5H, br t, J = 3.9 Hz, -CH2CH2Br),
3.70 (1.5H, br t, J = 4.1 Hz, -OCH2CH2Br), 5.44 (1H, br d, J = 15.8 Hz, (E)-ArCH=CH-), 6.09–6.18 (1H,
m, -CH=CHCH3), 7.11–7.20 (6H, m, Tr-H), 7.24–7.29 (9H, m, Tr-H), 7.32 (1H, s, pyrazole-H); 13C NMR
(150 MHz, CDCl3):
δ 18.9, 59.2, 70.6, 71.3, 79.0, 119.9, 124.8, 127.3, 127.4, 127.6, 130.1, 130.4, 142.9, 143.7;
HREIMS m/z calcd. for C28H28N2O2 (M+) 424.2151, found 424.2157.
4-(2-Methoxy)ethoxy-3-(2-propenyl)-2H-2-tritylpyrazole (16): oil; IR (film) vmax 1580 (C=C), 1447
(C=C) cm−1; 1H NMR (600 MHz, CDCl3):
δ 2.84 (2H, br d, J = 6.5 Hz, ArCH2CH=), 3.41 (3H, s, -OCH3),
3.66 (1H, br t, J = 5.0 Hz, -OCH2CH2O-), 4.05 (2H, br t, J = 5.0 Hz, -OCH2CH2O-), 4.60 (1H, dq, J =
17.0, 1.7 Hz, -CH=CHH), 4.64 (1H, dq, J = 10.5, 1.5 Hz, -CH=CHH), 7.10–7.13 (6H, m, Tr-H), 7.23–7.33
(9H, m, Tr-H), 7.34 (1H, s, pyrazole-H); 13C NMR (150 MHz, CDCl3):
δ 31.2, 59.2, 71.2, 71.4, 78.5, 115.6,
125.5, 127.3, 127.6, 127.9, 130.1, 132.6, 143.0, 144.4; HREIMS m/z calcd. for C28H28N2O2 (M+) 424.2151,
found 424.2157.
4.8. RCM of 13a and 14a and 14b
The RCM reactions of 13a and 14a and 14b in Scheme 2 were carried out as described above.
1,7-Dihydro-1-tritylpyrano[3,2-c]pyrazole (8a): oil; IR (film) vmax 1583 (C=C), 1493 (C=C), 1446
(C=C) cm−1; 1H NMR (600 MHz, CDCl3):
δ
2.27 (2H, dd, J = 3.5, 2.0 Hz, ArCH2CH=CH-), 4.49 (1H,
dt, J = 6.5, 3.5 Hz, -OCH=CHCH2-), 6.33 (1H, dt, J = 6.4, 2.0 Hz, -OCH=CHCH2-), 7.12–7.15 (6H, m,
Tr-H), 7.26–7.32 (9H, m, Tr-H), 7.32 (1H, s, pyrazole-H); 13C NMR (150 MHz, CDCl3):
δ 22.5, 29.7, 78.6,
98.2, 124.3, 127.6, 127.6, 127.9, 130.4, 140.3, 142.6; HREIMS m/z calcd. for C25H20N2O (M+) 364.1575,
found 364.1576.
4.9. Acid-Catalyzed Hydrolysis of 6a (Scheme 3)
To a solution of 6a (121.5 mg, 0.30 mmol) in acetone (10 mL) was added 1 N aqueous HCl (0.6 mL).
The reaction mixture was warmed under reflux for 90 min with stirring. After the reaction mixture had
cooled, it was treated with saturated aqueous NaHCO3 and extracted with CH2Cl2. The separated
organic layer was dried over MgSO4, filtered, and condensed under reduced pressure to give a crude
residue, which was purified using silica gel column chromatography (eluent: EtOAc:hexane = 1:2) to
afford (Z)-18 (9.1 mg, 20%) and (E)-18 (14.2 mg, 31%).
(E)-4-Allyloxy-5-(1-propenyl)-1H-pyrazole ((E)-18): oil; IR (film) vmax 1568 (C=C), 1516 (C=C)
cm−1; 1H NMR (600 MHz, CDCl3):
δ 1.89 (3H, br d, J = 6.0 Hz, CH3CH=), 4.60 (2H, dt, J = 5.5, 1.5 Hz,
-OCH2CH=CH2), 4.46 (1H, dq, J = 10.0, 1.5 Hz, -CH=CHH), 5.40 (1H, dq, J = 17.3, 1.5 Hz, -CH=CHH),
6.04 (1H, ddt, J = 17.3, 10.5, 5.5 Hz, -OCH2CH=CH2), 6.34 (1H, d, J = 16.7 Hz, ArCH=CH-), 6.35–6.41
(1H, m, -CH=CHCH3), 7.22 (1H, s, pyrazole-H); 13C NMR (150 MHz, CDCl3):
δ 18.9, 72.7, 117.7, 118.7,
127.6, 133.4, 142.0; HREIMS m/z calcd. for C9H12N2O (M+) 164.0950, found 164.0950.
(Z)-4-Allyloxy-5-(1-propenyl)-1H-pyrazole ((Z)-18): oil; IR (film) vmax 1570 (C=C), 1524 (C=C),
1
1450 (C=C) cm−1; H NMR (600 MHz, CDCl3):
δ 1.98 (3H, dd, J = 7.0, 1.8 Hz, CH3CH=), 3.49 (3H,
s, -OCH3), 4.45 (2H, dt, J = 5.2, 1.5 Hz, -OCH2CH=CH2), 5.27 (1H, dq, J = 10.6, 1.5 Hz, -CH=CHH),
5.38 (1H, dq, J = 17.0, 1.5 Hz, -CH=CHH), 5.82 (1H, dq, J = 11.4, 7.0 Hz, -CH=CHCH3), 6.03 (1H, ddt,
J = 17.3, 10.6, 5.3 Hz, -OCH2CH=CH2), 6.27 (1H, dq, J = 11.5, 1.5 Hz, ArCH=CHCH3), 7.27 (1H, s,
pyrazole-H); 13C NMR (150 MHz, CDCl3):
calcd. for C9H12N2O (M+) 164.0950, found 164.0949.
δ 69.1, 69.3, 117.7, 118.7, 127.6, 133.4, 142.0; HREIMS m/z

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4.10. Reprotection of 18 (Scheme 3)
General procedure: To a stereo mixture of (E/Z)-18 (15.9 mg, 0.10 mmol) in CH2Cl2 (10 mL) were
added TrCl (43.0 mg, 0.15 mmol) and Et3N (0.022 mL, 0.15 mmol) at 0 ◦C. The reaction mixture was
stirred at rt overnight, and then quenched with saturated aqueous NH4Cl and extracted with CH2Cl2.
The organic layer was dried over MgSO4, filtered, and condensed under reduced pressure to give a
crude residue, which was purified using silica gel column chromatography (eluent: EtOAc:hexane =
1:4) to afford 19a (28.9 mg, 68%) as an oil.
(E/Z)-4-Allyloxy-3-(1-propenyl)-1H-1-tritylpyrazole (19a): oil; IR (film) vmax 1560 (C=C), 1491
(C=C), 1445 (C=C) cm−1; 1H NMR of (E)-isomer (600 MHz, CDCl3):
δ 1.90 (3H, dd, J = 7.1, 1.8 Hz,
CH3CH=CH-), 4.27 (2H, dt, J = 5.6, 1.5 Hz, -OCH2CH=CH2), 5.20 (1H, ddd, J = 10.6, 3.2, 1.5 Hz,
-CH2CH=CHH), 5.28 (1H, ddd, J = 17.0, 3.2, 1.8 Hz, -CH2CH=CHH), 5.75 (1H, dq, J = 11.5, 7.1 Hz,
-CH=CHCH3), 5.95 (1H, ddt, J = 17.3, 10.7, 5.6 Hz, -OCH2CH=CH2), 6.29 (1H, dq, J = 11.5, 1.5 Hz,
ArCH=CHCH3), 6.84 (1H, s, pyrazole-H), 7.14–7.18 (6H, m, Tr-H), 7.26–7.30 (9H, m, Tr-H); 13C NMR
(150 MHz, CDCl3):
δ (14.2), 15.6, (60.4), 72.9, 78.6, (117.4), 117.6, 117.7, 127.4, 127.5, (127.6), 127.9, 130.4,
133.3, (138.6), (142.0), 143.4, signals in parentheses correspond to some of those of the (Z)-isomer;
HREIMS m/z calcd. for C28H26N2O (M+) 406.2045, found 406.2040.
(E)-4-Allyloxy-1-benzyl-3-(1-propenyl)-1H-pyrazole (19b): oil; IR (film) vmax 1566 (C=C), 1496
(C=C), 1445 (C=C) cm−1; 1H NMR (400 MHz, CDCl3):
δ 1.87 (3H, dd, J = 6.3, 1.2 Hz, CH3CH=CH-),
4.35 (2H, dt, J = 5.4, 1.5 Hz, -OCH2CH=CH2), 5.16 (2H, s, ArCH2Ph), 5.24 (1H, dq, J = 10.5,
1.5 Hz, -CH2CH=CHH), 5.36 (1H, dq, J = 17.2, 1.6 Hz, -CH2CH=CHH), 6.00 (1H, ddt, J = 17.2, 10.5,
5.4 Hz, -OCH2CH=CH2), 6.40 (1H, br d, J = 16.3 Hz, ArCH=CHCH3), 6.53 (1H, dq, J = 16.3, 6.3 Hz,
ArCH=CHCH3), 6.92 (1H, s, pyrazole-H), 7.18 (2H, br d, J = 8.0 Hz, Ph-H), 7.26–7.35 (3H, m, Ph-H);
13C NMR (100 MHz, CDCl3):
δ 18.9, 56.5, 72.6, 114.7, 117.6, 121.4, 127.4, 127.9, 128.7, 133.2, 136.8, 138.4,
143.1; HREIMS m/z calcd. for C16H18N2O (M+) 254.1419, found 254.1416.
4.11. RCM of 19
The RCM reactions of 19 were carried out in a similar manner to that described above to afford 20
.
2,5-Dihydro-2-tritylpyrano[3,2-c]pyrazole (20a): oil; IR (film) vmax 1492 (C=C), 1447 (C=C) cm−1
;
1H NMR (400 MHz, CDCl3):
3.5 Hz, -OCH2CH=CH-), 6.62 (1H, br d, J = 10.0 Hz, -OCH2CH=CHAr), 6.80 (1H, s, pyrazole-H),
δ 4.76 (2H, dd, J = 2.9, 1.9 Hz, -OCH2CH=CH-), 5.72 (1H, dt, J = 10.2,
7.18–7.20 (6H, m, Tr-H), 7.28–7.31 (9H, m, Tr-H); 13C NMR (150 MHz, CDCl3):
δ 67.2, 78.0, 116.5,
120.1, 122.7, 126.5, 127.6, 127.7, 137.5, 139.1, 143.3; HREIMS m/z calcd. for C25H20N2O (M+) 364.1575,
found 364.1584.
−1
2-Benzyl-2,5-dihydropyrano[3,2-c]pyrazole (20b): oil; IR (film) vmax 1660 (C=C), 1576 (C=C) cm
1H NMR (400 MHz, CDCl3):
3.5 Hz, -OCH2CH=CH-), 6.63 (1H, dt, J = 10.0, 1.9 Hz, -OCH2CH=CHAr), 6.84 (1H, s, pyrazole-H),
;
δ
4.77 (2H, dd, J = 3.5, 1.9 Hz, -OCH2CH=CH-), 5.73 (1H, dt, J = 10.0,
7.18–7.20 (2H, br d, J = 6.5 Hz, Ph-H), 7.27–7.36 (3H, m, Ph-H); 13C NMR (100 MHz, CDCl3):
δ 56.4,
67.2, 113.3, 119.5, 122.3, 127.5, 128.0, 128.8, 136.6, 137.2, 140.5; HREIMS m/z calcd. for C13H12N2O (M+)
212.0949, found 212.0950.
Author Contributions: Y.U. and K.S. conceived and designed the experiments; K.S., A.K., Y.T., and Y.U. performed
the experiments; Y.U., H.Y., and S.H. wrote the paper.
Funding: This research received no external funding.
Acknowledgments: The authors are grateful to K. Minoura and M. Fujitake for NMR and MS measurements,
respectively. Y. Suzuki, R. Nakamura, K. Hashimoto, and H. Matsukawa of our laboratory group are also
appreciated for their experimental assistance. We would like to thank Editage (www.editage.jp) for English
language editing.
Conflicts of Interest: The authors declare no conflicts of interest.

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