Development of a One-Pot Synthetic Method for Multifunctional Oxazole Derivatives Using Isocyanide Dichloride

Article abstract of DOI:10.1021/acs.joc.7b00296

A one-pot synthetic method was developed for multifunctional dihydrooxazole and oxazole derivatives. New reaction sequences were developed involving the formation of isocyanide dichloride, an aldol-type reaction with aldehydes, and a nucleophilic addition-elimination reaction, which efficiently afforded the dihydrooxazole and oxazole scaffolds.

Full text of DOI:10.1021/acs.joc.7b00296

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Note
Development of a One-Pot Synthetic Method for Multifunctional
Oxazole Derivatives Using Isocyanide Dichloride
Takahiro Soeta, Akihiro Matsumoto, Yoko Sakata, and Yutaka Ukaji
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b00296 • Publication Date (Web): 12 Apr 2017
Downloaded from http://pubs.acs.org on April 12, 2017
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The Journal of Organic Chemistry
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Development of a One-Pot Synthetic Method for
Multifunctional Oxazole Derivatives Using Isocyanide Dichloride
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Takahiro Soeta*, Akihiro Matsumoto, Yoko Sakata, Yutaka Ukaji*
Division of Material Sciences, Graduate School of Natural Science and Technology,
Kanazawa University, Kakuma, Kanazawa 920-1192, Japan.
soeta@se.kanazawa-u.ac.jp; ukaji@staff.kanazawa-u.ac.jp
Abstract
One-Pot, 3 Components Coupling
R
R
R
R
NucH
O
H
Cl
Cl
Ts
SO2Cl2
base
Ts
Ts
base
Ts
+
O
O
or
O
N
N
–C
N
N
N
Nuc
Nuc
Cl
A one-pot synthetic method was developed for multifunctional dihydrooxazole and
oxazole derivatives. New reaction sequences were developed involving the formation of
isocyanide dichloride, an aldol-type reaction with aldehydes, and a nucleophilic
addition-elimination reaction, which efficiently afforded the dihydrooxazole and
oxazole scaffolds.
Isocyanides have been found useful as polyfunctional molecules, due to their molecular
diversity, in fields such as drug discovery and natural product synthesis.1 Isocyanide
was first synthesized in 1859 by Lieke, in the form of an allyl isocyanide, by alkylation
of silver cyanide.2 These compounds remained laboratory curiosities for decades, as
their strong and unpleasant smell discouraged many chemists from working with them.
In 1921, a breakthrough achievement by Passerini allowed the use of isocyanide, along
with aldehydes and carboxylic acids, to synthesize α-hydroxyamides.3 After another 40
years, Ugi developed multi-component reactions using isocyanides, aldehydes, amines,
and carboxylic acids to afford α-aminoamides.4 Isocyanides have also been used for
their oligo- and polymerization5 properties, as well as acting as two-electron-donating
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ligands in organometallic chemistry.6 However, the most important application of
isocyanides is in the synthesis of versatile heterocycles.7,8 Zhu and other groups
independently developed reactions of α-isocyanoacetamides with aldehydes or imines
leading to the corresponding oxazoles, including asymmetric versions.9 Our research
group is involved in extending Ugi-type reactions using 1,n-dipoles (E–Nu), which are
composed of an electrophilic moiety (E) and a nucleophilic moiety (Nu), as substrates
to afford various types of heterocycle (Eq. 1, path a).10 We envisioned that isocyanides
might be converted to active species which would allow alternative access to
heterocycles. Therefore, we focused on the use of isocyanide dihalides, which are
relatively stable derivatives readily formed by addition of chlorine or bromine to
isocyanides.11 The existence of the two halogen atoms renders the C=N double bond
more reactive toward nucleophiles, with double addition in a sequential manner (Eq. 1,
path b). In this work, we demonstrate the use of isocyanide dichloride to afford
multifunctional 1,4-dihydrooxazole derivatives from three components in a one-pot
reaction.
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Oxazoles and their derivatives have long attracted attention due to their functionality as
chiral ligands for Lewis acids and as building blocks for natural product synthesis, as
well as their biological activity.12 There are many approaches to the synthesis of
oxazoles derivatives.13 Furthermore, dihydrooxazoles can easily be transformed into
other functional groups such as carboxylic acids and amines. We sought a strategy that
would provide a valuable synthetic method for the preparation of functionalized
dihydrooxazoles. The existing method for the synthesis of oxazoles is through
dehydration of α-acylaminocarbonyls, as demonstrated by van Leusen14, Gannesan15,
and Schöllkopf;16 these strategies have been greatly enriched by the use of isocyanides.
General interest in the synthesis and reactivity of dihydrooxazoles is reflected in the
extensive works published on this subject over the past few decades.
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E
7
8
9
E
Nu
R
N
N
C
path a
path b
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Nu
+
N
–
C
(1)
R
Nu1
X
Nu1
Nu2
X
Nu1
Nu2
X2
R
C
R
R
N
N
C
C
X
We initially examined whether isocyanide dichloride 2, which was easily prepared from
the corresponding 4-toluenesulfonylmethyl isocyanide (TosMIC) (1a) with SO2Cl2, was
capable of participating in an aldol-type reaction with an aldehyde to afford the
2-chloro-4,5-dihydrooxazole derivatives 4 (Eq. 1, step 1).17 We further investigated the
reaction of the resulting 2-chloro-4,5-dihydrooxazole derivatives 4 with a nucleophile to
generate the 4,5-dihydrooxazole derivatives 5 in a one-pot operation (Eq. 2, step 2).
One-Pot?
R
O
H
3
R
Ph
Cl
Cl
Ts
Ts
SO2Cl2
NucH
base
+
Ts
–C
N
Ts
(2)
O
O
N
step1
step 2
N
N
Cl
Nuc
1
2a
4
5
In our initial studies, we examined the aldol-type reaction of isocyanide dichloride 2a
with benzaldehyde (3a) in the presence of LDA as a base using THF as a solvent (Table
1). Fortunately, the reaction proceeded smoothly at room temperature, affording the
2-chloro-4,5-dihydrooxazole 4aa in 54% yield (Table 1, entry 1). In view of these
results, bases other than LDA were evaluated for their ability for an aldol-type reaction
in THF (entries 2–4). Thus, with the use of LHMDS, dihydrooxazole 4aa was obtained
in relatively good yield; however, DBU and TBD were not effective in this reaction
(entries 3 and 4). A significant increase in yield was observed when 1.2, 1.5, and 2.0
equiv of 2a were used at –30 °C, and the product 4aa was isolated in 90%, 85%, and
90% yields, respectively (entry 5–7). Unfortunately, the use of isocyanide dichlorides
2b–2e resulted in no reaction.
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Table 1. Aldol-type reaction of isocyanide dichloride
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9
Ph
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11
12
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O
H
3a
Ph
Cl
Cl
Ts
base (1.2 equiv)
Ts
O
N
THF, temp., 7 h
N
Cl
2a
4aa
i-Pr
Cl
Cl
Cl
Cl
Cl
Cl
Ph
CO2Et
CO2t-Bu
Cl
Cl
Ts
N
N
N
N
2b
2c
2d
2e
Entry
2a/equiv
1.0
base
temp.
rt
yield of 4aa/%
1
2
3
4
5
6
7
LDA
63
1.0
LHMDS
DBU
TBD
rt
62
1.0
rt
complicated
1.0
rt
40
90
85
90
1.2
LDA
–30 °C
–30 °C
–30 °C
1.5
LDA
2.0
LDA
Next, we set out to evaluate the addition-elimination reaction nucleophiles of various
types using 2-chloro-4,5-dihydrooxazole derivatives 4aa. When 4-toluenethiol (7a) was
used, the addition-elimination reaction proceeded efficiently to afford the corresponding
dihydrooxazole 5aaa in 95% yield as a single diastereomer. The stereochemistry was
determined by X-ray crystallographic analysis of a single crystal of 5aea (see Table 3,
entry 5). However, oxazoles 6 were selectively obtained when the nitrogen nucleophiles
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8a and 9 were used (entries 2 and 3). Other nucleophiles such as alcohol, phosphine,
and carbanions resulted in no isolable product being obtained (entries 4–8).
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Table 2. Results of addition-elimination reaction using various nucleophiles.
Ph
Ph
Ph
Nucleophile (Nuc) (2.0 equiv)
Et3N (2.0 equiv)
Ts
Ts
O
O
O
or
solv., temp., 6-12 h
N
N
N
Nuc
Cl
Nuc
4aa
6aaa: Nuc = NEt2
6aab: Nuc = NHNHBn
5aaa: Nuc = 4-tolS
entry
1
Nucleophile
4-tolSH (7a)
Et2NH (8a)
solv.
CH2Cl2
THF
temp.
results
rt
95% (5aaa)
96 % (6aaa)
40 % (6aab)
complicated
no reaction
complicated
no reaction
no reaction
2
rt
3a
4b
5
BnNHNH2·HCl (9)
Guanidine (10)
MeOH (11)
THF
rt
toluene
CH2Cl2
THF
reflux
rt
6
Ph2PH (12a)
H3PO2 (12b)
rt
rt
7b
8 c
CH2Cl2
THF
EtMgBr (13)
rt to 60 °C
a
b
c
4.0 equiv of Et3N were used. NaH (2.0 equiv) was used as a base instead of Et3N.
Et3N was not used.
Having established an efficient method for an aldol-type reaction of isocyanide
dichloride 2a and benzaldehyde (3a), followed by an addition-elimination reaction, we
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then attempted to expand the range of aldehydes and nucleophiles, particularly in
one-pot reactions, as detailed in Table 3. Throughout these experiments, optimal
amounts of TosMIC (1a) (1.2 equiv), sulfenyl chloride (1.2 equiv), aldehydes 3 (1.0
equiv), LDA (1.2 equiv), thiophenol derivatives 7 (1.5 equiv), and triethylamine (3.0
equiv) were used. The results demonstrate that these conditions allowed the reaction to
proceed with a wide variety of aldehydes and thiophenols, and that most reactions were
completed smoothly in a one-pot manner. Benzaldehyde (3a), 1-naphthaldehyde (3b),
and 2-naphthaldehyde (3c) were found to be good substrates, and the products 5aaa,
5aba, and 5aca were obtained in 95%, 62% and 76% yields (entries 1–3).
4-Tolualdehyde (3d) was also a good substrate, and the product 5ada was obtained in
78% yield (entry 4). We examined substituted aldehydes bearing an
electron-withdrawing group at the 2- and 4-position of the phenyl group. The reactions
of 4-bromobenzaldehyde (3e), 4-chlorobenzaldehyde (3f), 2-chlorobenzaldehyde (3g)
and 4-nitrobenzaldehyde (3h) gave the corresponding dihydrooxazolines 5aea–5aha in
good yields (entries 5–8). The structure of the product was confirmed by X-ray
crystallographic analysis of a single crystal of 5aea. The reactions of 3i and 3j,
containing a heterocyclic 2-furyl and a heterocyclic 2-thienyl group, respectively, gave
5aia and 5aja in 89% and 69% yields (entries 9 and 10). In the case of cinnamaldehyde
(3k), the reactivity of the aldol-type reaction was slightly lower, furnishing the
corresponding product 5aka in 48% yield (entry 11). Aliphatic aldehydes 3l–3o were
also applicable to this reaction, affording the products in moderate to good yields
(entries 12–15). Other aromatic thiols, such as 2-toluenethiol (7b), 4-chlorobenzenethiol
(7c), and thiophenol (7d) were also good nucleophiles for the formation of the
dihydrooxazoles in good yields (entries 16–18).
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Table 3. One-pot synthesis of 3,4-dihydrooxazoles using various aldehydes.
8
9
R
10
11
12
13
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O
H
R
ArSH 7
(1.5 equiv)
3
Ts
SO2Cl2
(1.2 equiv)
(1.0 equiv)
LDA (1.2 equiv)
Ts
O
Et3N (3.0 equiv)
CN
1a
N
CHCl3, –45 °C
then evap.
THF, rt, 7 h
rt, 20 h
ArS
(1.2 equiv)
5
entry
1
R
Ar
yield/%a
95 (5aaa)
62 (5aba)
76 (5aca)
78 (5ada)
53 (5aea)
69 (5afa)
73 (5aga)
63 (5aha)
89 (5aia)
69 (5aja)
48 (5aka)
35 (5ala)
C6H5 (3a)
1-naphthyl (3b)
2-naphthyl (3c)
4-MeC6H4 (3d)
4-BrC6H4 (3e)
4-ClC6H4 (3f)
2-ClC6H4 (3g)
4-O2NC6H4 (3h)
2-furyl (3i)
4-tol (7a)
4-tol (7a)
4-tol (7a)
4-tol (7a)
4-tol (7a)
4-tol (7a)
4-tol (7a)
4-tol (7a)
4-tol (7a)
4-tol (7a)
4-tol (7a)
4-tol (7a)
4-tol (7a)
4-tol (7a)
2
3
4
5
6
7
8
9
10
11
12
13
14
2-thienyl (3j)
2-phenylethenyl (3k)
t-Bu (3l)
i-Pr (3m)
81 (5ama)
94 (5ana)
c-Hex (3n)
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2-phenylethyl (3o)
4-tol (7a)
2-tol (7b)
59 (5aoa)
87 (5aab)
60 (5aac)
78 (5aad)
C6H5 (3a)
C6H5 (3a)
C6H5 (3a)
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4-ClC6H4 (7c)
C6H5 (7d)
a The stereochemistries of 5 were assigned as trans based on analogous reactions.
Next, we examined amines as nucleophiles for the synthesis of multi-substituted
oxazoles 6 (Table 4). Diethylamine (8a) and benzylhydrazine (8b), which had already
been examined (Table 2), proved also to be acceptable substrates in the one-pot reaction
(entries 1 and 2). Although the cyclic secondary amines 8c and 8d were not effective in
this reaction, oxazoles 6aac and 6aad were obtained in 20% and 17% yields,
respectively (entries 3 and 4). Aniline (8e), which is a weaker nucleophile, gave the
product 6aae in 25% yield (entry 5). Benzylamine derivatives 8f–8i were good
nucleophiles for this reaction, affording aminoxazoles 6aaf–6aai in moderate to good
yields (entries 6–9).
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Table 4. One-pot synthesis of oxazoles using various amines
8
9
Ph
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11
12
13
14
15
16
17
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R1R2NH 8
O
H
3a
Ph
(1.5 equiv)
SO2Cl2
(1.2 equiv)
(1.0 equiv)
LDA (1.2 equiv)
Ts
Et3N (3.0 equiv)
O
CN
1a
CHCl3, -45 °C
then evap.
THF, rt, 7 h
rt, 20 h
N
R1R2N
(1.2 equiv)
6
entry
R1R2NH/8
Et2NH (8a)
yield/%
96 (6aaa)
39 (6aab)
20 (6aac)
17 (6aad)
25 (6aae)
65 (6aaf)
87 (6aag)
46 (6aah)
37 (6aai)
1
2a
3
BnNHNH2 HCl (8b = 9)
piperidine (8c)
4
pyrrolidine (8d)
5
aniline (8e)
6
BnNH2 (8f)
7
4-MeOC6H4CH2NH2 (8g)
2-MeOC6H4CH2NH2 (8h)
4-O2NC6H4CH2NH2 (8i)
8
9
a 4.0 equiv of Et3N were used.
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Conclusion
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In summary, we developed a one-pot synthetic method for multifunctional
dihydrooxazole and oxazole derivatives. These included new synthetic sequences
involving the formation of isocyanide dichloride, aldol-type reactions of isocyanide
dichloride, and nucleophilic addition-elimination reactions, affording the products
efficiently in one-pot reactions. Based on these studies, isocyanide dihalides may be
considered as isocyanide surrogates suitable for construction of various kinds of
multifunctionalized heterocycles with easy operation. Further work is under
investigation to extend this work to multifunctionalized heterocycles.
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Experimental Section
General Method
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1H NMR spectra were recorded on a 400 MHz NMR spectrometer. Chemical shifts δ
are reported in ppm using TMS as an internal standard. Data are reported as follows:
chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m =
multiplet), coupling constant (J) and integration. 13C NMR spectra were recorded on
100 MHz NMR spectrometer. The chemical shifts were determined in the δ-scale
relative to CDCl3 (δ = 77.0 ppm). The wave numbers of maximum absorption peaks of
IR spectroscopy are presented in cm−1. HRMS (FAB positive, DART) was measured
with a quadrupole mass spectrometer and TOF mass spectrometers. All melting points
were measured using a micro melting point apparatus. Dehydrated solvents were
purchased for the reactions and used without further desiccation.
General procedure
2-Chloro-5-phenyl-4-tosyl-4,5-dihydrooxazole (4aa)
To a solution of the 2a (0.36 mmol) in THF (1.0 mL), benzaldehyde (3a) (0.30 mmol)
in THF (2.0 mL) and LDA (0.36 mmol) in THF (3.0 mL) were subsequently added at –
30 °C, then the whole was stirred at –30 °C for 7 h. The reaction mixture was filtered
through silica gel and the filtrate was concentrated. Silica gel column chromatography
(hexane/diethyl ether = 5/1) gave 4aa (96 mg, 90% yield) as a white solid of mp = 87–
1
90 °C (hexane/ethyl acetate). H NMR (CDCl3): 2.44 (s, 3H), 5.01 (d, J = 5.6 Hz, 1H),
6.22 (d, J = 5.6 Hz, 1H), 7.31–7.44 (m, 7H), 7.83 (d, J = 8.4 Hz, 2H). 13C NMR
(CDCl3): 21.7, 83.2, 91.9, 125.2, 129.3, 129.6, 130.0, 132.6, 136.6, 145.9, 158.7. IR
(KBr): 2980, 2250, 1740, 1460, 1370, 1250, 1150 cm–1. HRMS–ESI (m/z): Calcd for
C16H15ClNO3S [M+H]+: 336.0461. Found: 336.0456.
To a solution of 1a (0.36 mmol) in CHCl3 (1.0 mL), SO2Cl2 in CHCl3 (1.0 mL) was
added dropwise at –45 ℃. The reaction mixture was stirred for 10 min at –45 ℃, then
allowed to warm to room temperature. After removing the solvents, 2a was obtained
and was used without further purification. To a solution of the obtained 2a in THF (1.0
mL), aldehyde 3 (0.30 mmol) in THF (2.0 mL) and LDA (0.36 mmol) in THF (3.0 mL)
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were subsequently added at 0 °C, then the whole was stirred for 7 h at room
temperature. To the reaction mixture, nucleophile (0.45 mmol) in THF (1.0 mL) and
Et3N (0.90 mmol) were subsequently added and the whole was stirred at room
temperature. After 20 h, the reaction mixture was filtered through silica gel and the
filtrate was concentrated. The crude product was purified by silica gel column
chromatography.
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5-Phenyl-2-(p-tolylthio)-4-tosyl-4,5-dihydrooxazole (5aaa)
Silica gel column chromatography (hexane/diethyl ether = 6/1) gave 5aaa (121 mg,
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95% yield) as a white solid of mp = 110–111 °C (hexane/ethyl acetate). H NMR
(CDCl3): 2.31 (s, 3H), 2.41 (s, 3H), 4.94 (dd, J = 1.6, 4.8 Hz, 1H), 6.11 (d, J = 4.8 Hz,
1H), 7.19–7.26 (m, 6H), 7.30–7.37 (m, 3H), 7.50 (d, J = 6.4 Hz, 2H), 7.70 (d, J = 6.4
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Hz, 2H). C NMR (CDCl3): 21.4, 21.7, 82.1, 93.4, 123.1, 125.2, 129.0, 129.6, 129.7,
130.1, 133.0, 135.0, 137.7, 140.4, 145.3, 172.6. IR (KBr): 2950, 1580, 1490, 1450,
1400, 1320, 1230, 1150, 1090, 1030 cm–1. HRMS–DART (m/z): Calcd for
C23H22NO3S2 [M+H]+: 424.1041. Found: 424.1039.
5-(Naphthalen-1-yl)-2-(p-tolylthio)-4-tosyl-4,5-dihydrooxazole (5aba)
Silica gel column chromatography (hexane/diethyl ether = 6/1) gave 5aba (88 mg, 62%
1
yield) as a white solid of mp = 178–179 °C (hexane/ethyl acetate). H NMR (CDCl3):
2.33 (s, 3H), 2.35 (s, 3H), 4.99 (d, J = 4.0 Hz, 1H), 6.79 (d, J = 4.0 Hz, 1H), 7.13–7.19
(m, 4H), 7.25 (d, J = 7.2 Hz, 1H), 7.36 (t, J = 8.0 Hz, 1H), 7.45–7.49 (m, 3H), 7.54 (t, J
= 8.0 Hz, 1H), 7.64 (d, J = 8.4 Hz, 2H), 7.78 (d, J = 8.4 Hz, 1H), 7.82 (d, J = 8.4 Hz,
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1H), 8.26 (d, J = 8.4 Hz, 1H). C NMR (CDCl3): 21.4, 21.7, 80.4, 92.3, 122.8, 123.1,
123.4, 125.1, 126.2, 127.2, 129.0, 129.4, 129.5, 129.7, 129.8, 130.1, 132.0, 133.3, 133.9,
135.2, 140.4, 145.3, 173.3. IR (KBr): 2920, 1580, 1490, 1400, 1300, 1290, 1230, 1200,
1160, 1080, 1020 cm–1. HRMS–DART (m/z): Calcd for C27H24NO3S2 [M+H]+:
474.1198. Found: 474.1207.
5-(Naphthalen-2-yl)-2-(p-tolylthio)-4-tosyl-4,5-dihydrooxazole (5aca)
Silica gel column chromatography (hexane/diethyl ether = 6/1) gave 5aca (108 mg,
1
76% yield) as a white solid of mp = 147–149 °C (hexane/ethyl acetate). H NMR
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(CDCl3): 2.40 (s, 3H), 2.42 (s, 3H), 5.03 (d, J = 4.4 Hz, 1H), 6.27 (d, J = 4.4 Hz, 1H),
7.22–7.34 (m, 5H), 7.49–7.55 (m, 4H), 7.71–7.86 (m, 6H). 13C NMR (CDCl3): 21.3,
21.7, 82.3, 93.4, 122.2, 123.2, 124.8, 126.7, 126.8, 127.8, 128.2, 129.3, 129.6, 129.7,
130.1, 132.9, 133.1, 133.4, 134.8, 135.1, 140.4, 145.3, 172.7. IR (KBr): 2940, 1590,
1490, 1380, 1310, 1290, 1230, 1160, 1080, 1030 cm–1. HRMS–DART (m/z): Calcd for
C27H24NO3S2 [M+H]+: 474.1198. Found: 474.1184.
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5-(p-Tolyl)-2-(p-tolylthio)-4-tosyl-4,5-dihydrooxazole (5ada)
Silica gel column chromatography (hexane/diethyl ether = 6/1) gave 5ada (106 mg,
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78% yield) as a yellow solid of mp = 136–137 °C (hexane/ethyl acetate) H NMR
(CDCl3): 2.32 (s, 3H), 2.38 (s, 3H), 2.41 (s, 3H), 4.93 (d, J = 4.4 Hz, 1H), 6.06 (s, J =
4.4 Hz, 1H), 7.11–7.26 (m, 8H), 7.49 (d, J = 8.4 Hz, 2H), 7.70 (d, J = 8.4 Hz, 2H) .13C
NMR (CDCl3): 21.2, 21.3, 21.7, 82.2, 93.4, 123.2, 125.3, 129.5, 129.7, 129.8, 130.0,
133.1, 134.7, 135.0, 139.1, 140.3, 145.3, 172.6. IR (KBr): 2920, 1590, 1490, 1450,
1400, 1310, 1230, 1160, 1080, 1030 cm–1. HRMS–DART (m/z): Calcd for
C24H24NO3S2 [M+H]+: 438.1198. Found: 438.1179.
5-(4-Bromophenyl)-2-(p-tolylthio)-4-tosyl-4,5-dihydrooxazole (5aea)
Silica gel column chromatography (hexane/diethyl ether = 6/1) gave 5aea (81 mg, 53%
1
yield) as a white solid of mp = 132–133 °C (hexane/ethyl acetate) H NMR (CDCl3):
2.37 (s, 3H), 2.41 (s, 3H), 5.04 (d, J = 4.8 Hz, 1H), 6.39 (d, J = 4.8 Hz, 1H), 7.16–7.31
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(m, 7H), 7.37–7.39 (m, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.71 (d, J = 8.4 Hz, 2H). C
NMR (CDCl3): 21.3, 21.7, 80.2, 92.1, 123.0, 127.4, 128.3, 129.5, 129.7, 130.1, 130.4,
130.6, 132.5, 133.2, 134.3, 135.1, 140.4, 145.3, 172.7. IR (KBr): 2950, 1590, 1490,
1450, 1410, 1310, 1290, 1240, 1150, 1080, 1030 cm–1. HRMS–DART (m/z): Calcd for
C23H21BrNO3S2 [M+H]+: 502.0146. Found: 502.0149.
5-(4-Chlorophenyl)-2-(p-tolylthio)-4-tosyl-4,5-dihydrooxazole (5afa)
Silica gel column chromatography (hexane/diethyl ether = 6/1) gave 5afa (95 mg, 69%
1
yield) as a white solid of mp = 147–148 °C (hexane/ethyl acetate) H NMR (CDCl3):
2.38 (s, 3H), 2.42 (s, 3H), 4.87 (d, J = 4.8 Hz, 1H), 6.06 (d, J = 4.8 Hz, 1H), 7.18–7.27
(m, 6H), 7.30 (d, J = 8.4 Jz, 2H), 7.49 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H). 13C
NMR (CDCl3): 21.4, 21.7, 81.4, 93.4, 123.0, 126.5, 129.3, 129.6, 129.7, 130.1, 132.9,
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134.9, 135.0, 136.2, 140.5, 145.5, 172.5. IR (KBr): 2940, 1590, 1490, 1420, 1380, 1230,
1150, 1010 cm–1. HRMS–DART (m/z): Calcd for C23H21ClNO3S2 [M+H]+: 458.0651.
Found: 458.0639.
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5-(2-Chlorophenyl)-2-(p-tolylthio)-4-tosyl-4,5-dihydrooxazole (5aga)
Silica gel column chromatography (hexane/diethyl ether = 6/1) gave 5aga (103 mg,
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73% yield) as a white solid of mp = 123–124 °C (hexane/ethyl acetate). H NMR
(CDCl3): 2.38 (s, 3H), 2.41 (s, 3H), 5.05 (d, J = 4.8 Hz, 1H), 6.39 (d, J = 4.8 Hz, 1H),
7.19–7.30 (m, 7H), 7.31–7.39 (m, 1H), 7.49 (d, J = 8.0 Hz, 2H), 7.71 (d, J = 8.0 Hz,
2H). 13C NMR (CDCl3): 21.3, 21.7, 80.2, 92.1, 123.0, 127.4, 128.3, 129.5, 129.7, 130.1,
130.4, 130.6, 132.5, 133.2, 134.3, 135.1, 140.4, 145.3, 172.7. IR (KBr): 2920, 1580,
1490, 1470, 1440, 1400, 1310, 1230, 1150, 1080, 1020 cm–1. HRMS–DART (m/z):
Calcd for C23H21ClNO3S2 [M+H]+: 458.0651. Found: 458.0662.
5-(4-Nitrophenyl)-2-(p-tolylthio)-4-tosyl-4,5-dihydrooxazole (5aha)
Silica gel column chromatography (hexane/diethyl ether = 6/1) gave 5aha (89 mg, 63%
1
yield) as a white solid of mp = 209–210 °C (hexane/ethyl acetate). H NMR (CDCl3):
2.34 (s, 3H), 2.41 (s, 3H), 5.04 (d, J = 4.8 Hz, 1H), 6.39 (d, J = 4.8 Hz, 1H), 7.17–7.30
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(m, 7H), 7.37–7.40 (m, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.71 (d, J = 8.4 Hz, 2H). C
NMR (CDCl3): 21.4, 21.7, 80.2, 92.2, 123.0, 127.4, 128.3, 129.5, 129.7, 130.1, 130.4,
130.6, 132.6, 133.2, 134.3, 135.1, 140.4, 145.3, 172.7. IR (KBr): 2950, 1580, 1490,
1350, 1230, 1160, 1080, 1030 cm–1. HRMS–DART (m/z): Calcd for C23H21N2O5S2
[M+H]+: 469.0892. Found: 469.0895.
5-(Furan-2-yl)-2-(p-tolylthio)-4-tosyl-4,5-dihydrooxazole (5aia)
Silica gel column chromatography (hexane/diethyl ether = 6/1) gave 5aia (110 mg, 89%
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yield) as a yellow solid of mp = 129–131 °C (hexane/ethyl acetate) H NMR (CDCl3):
2.32 (s, 3H), 2.36 (s, 3H), 5.18 (d, J = 4.8 Hz, 1H), 6.03 (d, J = 4.8 Hz, 1H), 6.29–6.30
(m, 1H), 6.40 (d, J = 3.6 Hz, 1H), 7.14 (d, J = 7.6 Hz, 2H), 7.20 (d, J = 7.6 Hz, 2H),
7.34 (s, 1H), 7.39 (d, J = 7.6 Hz, 2H), 7.63 (d, J = 7.6 Hz, 2H). 13C NMR (CDCl3): 21.3,
21.7, 75.6, 89.6, 110.7, 110.8, 123.1, 129.5, 129.7, 130.0, 132.8, 134.9, 140.2, 144.2,
145.4, 148.8, 172.1. IR (KBr): 2960, 1580, 1490, 1400, 1300, 1230, 1180, 1150, 1080,
1020 cm–1. HRMS–DART (m/z): Calcd for C21H20NO4S2 [M+H]+: 414.0834. Found:
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414.0840.
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5-(Thiophen-2-yl)-2-(p-tolylthio)-4-tosyl-4,5-dihydrooxazole (5aja)
Silica gel column chromatography (hexane/diethyl ether = 6/1) gave 5aja (89 mg, 69%
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yield) as a white solid of mp = 133–134 °C (hexane/ethyl acetate). H NMR (CDCl3):
2.38 (s, 3H), 2.42 (s, 3H), 5.10 (d, J = 4.4 Hz, 1H), 6.32 (d, J = 4.4 Hz, 1H), 6.97 (dd, J
= 3.2, 5.2 Hz, 1H), 7.08 (d, J = 3.2 Hz, 1H), 7.20 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.4
Hz, 2H), 7.30 (dd, J = 1.6, 5.2 Hz, 1H), 7.48 (d, J = 8.0 Hz, 2H), 7.70 (d, J = 8.0 Hz,
2H). 13C NMR (CDCl3): 21.3, 21.7, 78.5, 92.9, 123.0, 126.5, 127.0, 127.2, 129.6, 129.7,
130.0, 132.9, 135.0, 139.8, 140.3, 145.4, 172.3. IR (KBr): 2930, 1580, 1490, 1440,
1310, 1250, 1230, 1190, 1150, 1080, 1040 cm–1. HRMS–DART (m/z): Calcd for
C21H20NO3S3 [M+H]+: 430.0605. Found: 430.0616.
5-Styryl-2-(p-tolylthio)-4-tosyl-4,5-dihydrooxazole (5aka)
Silica gel column chromatography (hexane/diethyl ether = 6/1) gave 5aka (65 mg, 48%
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yield) as a white solid of mp = 130–132 °C (hexane/ethyl acetate). H NMR (CDCl3):
2.38 (s, 3H), 2.42 (s, 3H), 4.89 (d, J = 4.4 Hz, 1H), 5.73–5.76 (m, 1H), 6.10 (dd, J = 7.2,
15.6 Hz, 1H), 6.68 (d, J = 15.6 Hz, 1H), 7.19–7.36 (m, 9H), 7.46 (d, J = 8.0 Hz, 2H),
7.70 (d, J = 8.0 Hz, 2H). 13C NMR (CDCl3): 21.4, 21.7, 82.0, 91.3, 123.1, 123.5, 126.9,
128.6, 128.7, 129.6, 129.7, 130.0, 133.1, 134.6, 135.0, 135.1, 140.3, 145.3, 172.4. IR
(KBr): 2930, 1590, 1490, 1450, 1400, 1310, 1200, 1150, 1080, 1030 cm–1. HRMS–
DART (m/z): Calcd for C25H24NO3S2 [M+H]+: 450.1198. Found: 450.1192.
5-(tert-Butyl)-2-(p-tolylthio)-4-tosyl-4,5-dihydrooxazole (5ala)
Silica gel column chromatography (hexane/diethyl ether = 6/1) gave 5ala (42 mg, 35%
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yield) as a white solid of mp = 103–106 °C (hexane/ethyl acetate) H NMR (CDCl3):
0.80 (s, 9H), 2.33 (s, 3H), 2.36 (s, 3H), 4.71 (d, J = 4.8 Hz, 1H), 4.77 (d, J = 4.8 Hz,
1H), 7.14 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 7.39 (d, J = 8.0 Hz, 2H), 7.62 (d,
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J = 8.0 Hz, 2H). C NMR (CDCl3): 20.3, 20.7, 23.4, 33.4, 86.3, 88.1, 122.3, 128.5,
128.7, 128.9, 132.3, 134.1, 139.2, 144.1, 171.9. IR (KBr): 2970, 1590, 1490, 1460,
1400, 1310, 1240, 1180, 1160, 1080, 1030 cm–1. HRMS–DART (m/z): Calcd for
C21H26NO3S2 [M+H]+: 404.1354. Found: 404.1352.
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5-Isopropyl-2-(p-tolylthio)-4-tosyl-4,5-dihydrooxazole (5ama)
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yield) as a white solid of mp = 106–108 °C (hexane/ethyl acetate). H NMR (CDCl3):
0.92 (d, J = 7.6 Hz, 3H), 0.97 (d, J = 7.6 Hz, 3H), 1.89 (m, 1H), 2.38 (s, 3H), 2.41 (s,
3H), 4.73 (d, J = 4.4 Hz, 1H), 4.94 (dd, J = 4.4, 5.2 Hz, 1H), 7.20 (d, J = 7.6 Hz, 2H),
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7.25 (d, J = 7.6 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.67 (d, J = 8.0 Hz, 2H). C NMR
(CDCl3): 16.5, 17.1, 21.3, 21.7, 32.0, 86.3, 88.5, 123.3, 129.5, 129.6, 129.9, 133.2,
135.0, 140.1, 145.1, 172.7. IR (KBr): 2960, 1590, 1490, 1470, 1380, 1300, 1250, 1170,
1150, 1080, 1030 cm–1. HRMS–DART (m/z): Calcd for C20H24NO3S2 [M+H]+:
390.1198. Found: 390.1191.
5-Cyclohexyl-2-(p-tolylthio)-4-tosyl-4,5-dihydrooxazole (5ana)
Silica gel column chromatography (hexane/diethyl ether = 6/1) gave 5ana (121 mg,
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94% yield) as a white solid of of mp = 108–109 °C (hexane/ethyl acetate). H NMR
(CDCl3): 0.96–1.77 (m, 11H), 2.39 (s, 3H), 2.42 (s, 3H), 4.78 (d, J = 4.4 Hz, 1H), 4.95
(dd, J = 4.4, 6.0 Hz, 1H), 7.20 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H), 7.45 (d, J =
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8.4 Hz, 2H), 7.67 (d, J = 8.4 Hz, 2H). C NMR (CDCl3): 21.3, 21.7, 25.4, 25.5, 26.0,
26.9, 27.6, 41.5, 85.7, 88.6, 123.4, 129.4, 129.6, 129.9, 133.2, 135.0, 140.1, 145.1,
172.6. IR (KBr): 2920, 1590, 1490, 1450, 1400, 1380, 1310, 1220, 1170, 1080, 1040
cm–1. HRMS–DART (m/z): Calcd for C23H28NO3S2 [M+H]+: 430.1511. Found:
430.1502.
5-Phenethyl-2-(p-tolylthio)-4-tosyl-4,5-dihydrooxazole (5aoa)
Silica gel column chromatography (hexane/diethyl ether = 6/1) gave 52aoa (80 mg,
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59% yield) as a white solid of mp = 138–140 °C (hexane/ethyl acetate). H NMR
(CDCl3): 1.88–1.94 (m, 2H), 2.33 (s, 3H), 2.36 (s, 3H), 2.59–2.64 (m, 2H), 4.68 (d, J =
5.2 Hz, 1H), 5.10 (ddd, J = 1.2, 5.2, 6.4, 1H), 7.07–7.23 (m, 9H), 7.39 (d, J = 8.4 Hz,
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2H), 7.60 (d, J = 8.4 Hz, 2H). C NMR (CDCl3): 21.3, 21.7, 30.5, 36.4, 81.2, 90.6,
123.2, 126.3, 128.4, 128.6, 129.5, 129.6, 129.9, 132.9, 135.0, 140.0, 140.3, 145.2, 172.5.
IR (KBr): 2920, 1600, 1490, 1450, 1400, 1310, 1230, 1180, 1160, 1090, 1010 cm–1.
HRMS–DART (m/z): Calcd for C25H26NO3S2 [M+H]+: 452.1354. Found: 452.1336.
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5-Phenyl-2-(o-tolylthio)-4-tosyl-4,5-dihydrooxazole (5aab)
Silica gel column chromatography (hexane/diethyl ether = 6/1) gave 5aab (111 mg,
87% yield) as a white solid of mp = 94–96 °C (hexane/ethyl acetate). 1H NMR (CDCl3):
2.40 (s, 3H), 2.52 (s, 3H), 4.92 (d, J = 5.2 Hz, 1H), 6.11 (d, J = 5.2 Hz, 1H), 7.20–7.38
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(m, 10H), 7.62 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 8.0 Hz, 2H). C NMR (CDCl3): 21.1,
21.6, 82.0, 93.5, 125.1, 126.2, 126.7, 129.1, 129.5, 130.7, 130.8, 133.1, 136.6, 137.7,
142.9, 145.3, 171.9. IR (KBr): 2920, 1600, 1490, 1450, 1400, 1380, 1310, 1290, 1230,
1170, 1140, 1080, 1040 cm–1. HRMS–DART (m/z): Calcd for C23H22NO3S2 [M+H]+:
424.1041. Found: 424.1040.
2-((4-Chlorophenyl)thio)-5-phenyl-4-tosyl-4,5-dihydrooxazole (5aac)
Silica gel column chromatography (hexane/diethyl ether = 6/1) gave 5aac (80 mg, 60%
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yield) as a white solid of mp = 140–142 °C (hexane/ethyl acetate). H NMR (CDCl3):
2.40 (s, 3H), 4.93 (d, J = 5.2 Hz, 1H), 6.14 (d, J = 5.2 Hz, 1H), 7.24–7.39 (m, 9H), 7.56
(d, J = 8.8 Hz, 2H), 7.67 (d, J = 8.8 Hz, 2H). 13C NMR (CDCl3): 21.7, 82.3, 93.2, 125.2,
125.3, 129.1, 129.2, 129.4, 129.5, 129.6, 133.1, 136.2, 136.5, 137.5, 145.5, 171.7. IR
(KBr): 2970, 1610, 1450, 1400, 1380, 1320, 1220, 1140, 1080, 1030 cm–1. HRMS–
DART (m/z): Calcd for C22H19ClNO3S2 [M+H]+: 444.0495. Found: 444.0490.
5-Phenyl-2-(phenylthio)-4-tosyl-4,5-dihydrooxazole (5aad)
Silica gel column chromatography (hexane/diethyl ether = 6/1) gave 5aad (98 mg, 78%
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yield) as a white solid of mp = 116–117 °C (hexane/ethyl acetate). H NMR (CDCl3):
2.41 (s, 3H), 4.93 (d, J = 4.8 Hz, 1H), 6.13 (d, J = 4.8 Hz, 1H), 7.24–7.43 (m, 10H),
7.62–7.65 (m, 2H), 7.70 (d, J = 8.4 Hz, 2H). 13C NMR (CDCl3): 21.6, 82.1, 93.4, 125.2,
126.8, 129.1, 129.3, 129.5, 129.6, 129.9, 133.1, 135.0, 137.6, 145.3, 172.2. IR (KBr):
2930, 1580, 1490, 1470, 1390, 1320, 1230, 1170, 1150, 1090, 1010 cm–1. HRMS–
DART (m/z): Calcd for C22H20ClNO3S2 [M+H]+: 410.0885. Found: 410.0878.
N,N-Diethyl-5-phenyloxazol-2-amine (6aaa)
Silica gel column chromatography (hexane/diethyl ether = 5/1) gave 6aaa (62 mg, 96%
yield) as a brown oil. 1H NMR (CDCl3): 1.18 (t, J = 7.6 Hz, 6H), 3.44 (q, J = 7.6 Hz,
4H), 6.97 (s, 1H), 7.08–7.40 (m, 5H). 13C NMR (CDCl3): 13.4, 42.8, 122.3, 126.3,
128.7, 129.0, 144.6, 161.0. IR (KBr): 2970, 1610, 1450, 1450, 1380, 1320, 1220, 1140,
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1080, 1030 cm–1. HRMS–DART (m/z): Calcd for C13H17N2O [M+H]+: 217.1341.
Found: 217.1335.
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2-(2-Benzylhydrazineyl)-5-phenyloxazole (6aab)
Silica gel column chromatography (hexane/diethyl ether = 5/1) gave 6aab (31 mg, 39%
yield) as a white solid of mp = 74–75°C (hexane/ethyl acetate). 1H NMR (CDCl3): 4.09
(brs, 1H), 4.69 (s, 2H), 7.03 (s, 1H), 7.16–7.31 (m, 8H), 7.44 (d, J = 7.6 Hz, 2H). NH
proton was not appear clearly.13C NMR (CDCl3): 56.9, 122.2, 122.7, 127.0, 127.8,
128.4, 128.5, 128.7, 128.8, 136.4, 146.5, 162.9. IR (KBr): 2920, 1580, 1490, 1450,
1360, 1300, 1220, 1150, 1050, 1030 cm–1. HRMS–DART (m/z): Calcd for C16H16N3O
[M+H]+: 266.1293. Found: 266.1292.
5-Phenyl-2-(piperidin-1-yl)oxazole (6aac)
Silica gel column chromatography (hexane/diethyl ether = 5/1) gave 6aac (14 mg, 20%
yield) as a brown oil. 1H NMR (CDCl3): 1.34–1.66 (m, 6H), 3.46–3.48 (m, 4H), 6.99 (s,
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1H), 7.12 (t, J = 7.2 Hz, 1H), 7.27 (t, J = 7.2 Hz, 2H), 7.41 (d, J = 7.2 Hz, 2H). C
NMR (CDCl3): 24.0, 25.0, 46.7, 122.2, 122.5, 126.5, 128.6, 128.9, 144.8, 161.2. IR
(KBr): 2940, 1600, 1490, 1450, 1400, 1300, 1260, 1150, 1020 cm–1. HRMS–DART
(m/z): Calcd for C14H17N2O [M+H]+: 229.1341. Found: 229.1336.
5-Phenyl-2-(pyrrolidin-1-yl)oxazole (6aad)
Silica gel column chromatography (hexane/diethyl ether = 5/1) gave 6aad (11 mg, 17%
yield) as a brown oil. 1H NMR (CDCl3): 1.92–1.96 (m, 4H), 3.49–3.53 (m, 4H), 6.99 (s,
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1H), 7.11 (t J = 7.6 Hz, 1H), 7.27 (t, J = 7.6 Hz, 2H), 7.41 (d, J = 7.6 Hz, 2H). C
NMR (CDCl3): 25.6, 47.3, 122.2, 122.3, 126.3, 128.6, 128.9, 144.8, 160.0. IR (KBr):
2970, 1620, 1490, 1460, 1400, 1350, 1300, 1230, 1190, 1140, 1050, 1020 cm–1.
HRMS–DART (m/z): Calcd for C13H15N2O [M+H]+: 215.1184. Found: 215.1181.
N,5-Diphenyloxazol-2-amine (6aae)
Silica gel column chromatography (hexane/diethyl ether = 5/1) gave 6aae (18 mg, 25%
1
yield) as a white solid of mp = 170–172 °C (hexane/ethyl acetate). H NMR (CDCl3):
1.84 (brs, 1H), 7.00 (t, J = 7.6 Hz, 1H), 7.18 (s, 1H), 7.22 (d, J = 7.6 Hz, 1H), 7.29–7.35
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(m, 4H), 7.44 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H). C NMR (CDCl3): 117.5,
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120.4, 122.8, 123.1, 127.6, 127.9, 128.9, 129.4, 138.0, 145.4. IR (KBr): 2930, 1660,
1590, 1500, 1390, 1300, 1210, 1140, 1050, 1020 cm–1. HRMS–DART (m/z): Calcd for
C15H13N2O [M+H]+: 237.1028. Found: 237.1025.
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N,N-Dibenzyl-5-phenyloxazol-2-amine (6aaf)
Silica gel column chromatography (hexane/diethyl ether = 5/1) gave 6aaf (55 mg, 65%
1
yield) as a white solid of mp = 130–131 °C (hexane/ethyl acetate). H NMR (CDCl3):
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4.50 (d, J = 4.8 Hz, 2H), 5.41 (brs, 1H), 6.94 (s, 1H), 7.13–7.40 (m, 10H). C NMR
(CDCl3): 47.3, 121.8, 122.6, 126.7, 127.6, 127.7, 128.6, 128.7, 128.8, 138.1, 145.1,
160.6. IR (KBr): 2950, 1640, 1490, 1450, 1390, 1350, 1300, 1250, 1190, 1160, 1070,
1020 cm–1. HRMS–DART (m/z): Calcd for C16H15N2O [M+H]+: 251.1184. Found:
251.1178.
2-(4-Methoxybenzyl)-5-phenyloxazole (6aag)
Silica gel column chromatography (hexane/diethyl ether = 5/1) gave 6aag (74 mg, 87%
1
yield) as a white solid of mp = 113–114 °C (hexane/ethyl acetate). H NMR (CDCl3):
3.78 (s, 3H), 4.05 (s, 2H), 5.55 (brs, 1H), 6.88 (d, J = 8.4 Hz, 2H), 7.03 (s, 1H), 7.20–
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7.34 (m, 5H), 7.45 (d, J = 7.6 Hz, 2H). C NMR (CDCl3): 46.8, 55.3, 114.1, 121.8,
122.6, 126.7, 128.6, 128.7, 129.0, 130.2, 145.0, 159.1, 160.5. IR (KBr): 3010, 2870,
1620, 1510, 1470, 1440, 1370, 1300, 1250, 1150, 1100, 1050, 1030 cm–1. HRMS–
DART (m/z): Calcd for C17H17N2O2 [M+H]+: 281.1290. Found: 281.1291.
2-(2-Methoxybenzyl)-5-phenyloxazole (6aah)
Silica gel column chromatography (hexane/diethyl ether = 5/1) gave 6aah (39 mg, 46%
1
yield) as a white solid of mp = 106–107 °C (hexane/ethyl acetate). H NMR (CDCl3):
3.86 (s, 3H), 4.54 (d, J = 6.0 Hz, 2H), 5.27 (brs, 1H), 6.88 (d, J = 8.0 Hz, 1H), 6.92 (d, J
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= 8.0 Hz, 1H), 6.99 (s, 1H), 7.16–7.35 (m, 5H), 7.44 (d, J = 7.6 Hz, 2H). C NMR
(CDCl3): 43.5, 55.3, 110.3, 120.6, 121.9, 122.6, 126.2, 126.7, 128.7, 128.8, 129.1, 129.6,
144.9, 157.6, 160.8. IR (KBr): 2940, 1650, 1490, 1460, 1380, 1340, 1280, 1250, 1160,
1120, 1050, 1030 cm–1. HRMS–DART (m/z): Calcd for C17H17N2O2 [M+H]+: 281.1290.
Found: 281.1286.
2-(4-Nitrobenzyl)-5-phenyloxazole (6aai)
Silica gel column chromatography (hexane/diethyl ether = 5/1) gave 6aai (33 mg, 37%
1
yield) as a white solid of mp = 101–103 °C (hexane/ethyl acetate). H NMR (CDCl3):
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4.59 (s, 2H), 6.17 (brs, 1H), 6.89 (s, 1H), 7.13 (t, J = 8.0 Hz, 1H), 7.25 (t, J = 8.0 Hz,
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2H), 7.35 (d, J = 8.0 Hz, 2H), 7.46 (d, J = 8.0 Hz, 2H). 8.10 (d, J = 8.0 Hz, 2H). C
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NMR (CDCl3): 46.2, 121.2, 122.6, 123.8, 127.1, 127.9, 128.1, 128.7, 145.4, 145.9,
147.3, 160.1. IR (KBr): 3030, 1620, 1520, 1450, 1400, 1350, 1220, 1150, 1050, 1020
cm–1. HRMS–DART (m/z): Calcd for C16H14N3O3 [M+H]+: 296.1035. Found:
296.1031.
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ACKNOWLEDGEMENTS
This work was supported by a Grant-in-Aid for Young Scientists (B) (24750037), a
Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of
Science (24350022), Kanazawa University CHOZEN Project, and Kanazawa University
SAKIGAKE.Project.
SUPPORTING INFORMATION Copies of 1H NMR and 13C NMR spectra of
products.
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