Synthesis of 3,6-Dihydro-2 H-1,2-oxazines via Dimethylsulfoxonium Methylide Addition to α,β-Unsaturated Nitrones

Article abstract of DOI:10.1021/acs.joc.0c01349

A unique and efficient formation of 3,6-dihydro-2H-1,2-oxazines starting from α,β-unsaturated nitrones has been achieved. The nucleophilic addition of dimethylsulfoxonium methylide to the C-N bond of an α,β-unsaturated nitrone to form an aziridine N-oxide followed by the Meisenheimer rearrangement affords 3,6-dihydro-2H-1,2-oxazine in up to 70% yield. Methylene was confirmed to be incorporated at the C3 position of the ring. A wide range of β-aryl-substituted α,β-unsaturated nitrones were applicable to this reaction.

Full text of DOI:10.1021/acs.joc.0c01349

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Article
Synthesis of 3,6-Dihydro-2H-1,2-oxazines via Dimethylsulfoxonium
Methylide Addition to #,#-Unsaturated Nitrones
Megumi Hasegawa, Takuya Suga, Takahiro Soeta, and Yutaka Ukaji
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01349 • Publication Date (Web): 03 Aug 2020
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Synthesis of 3,6-Dihydro-2H-1,2-oxazines
via Dimethylsulfoxonium Methylide Addition to α,β-Unsaturated Nitrones
Megumi Hasegawa, Takuya Suga, Takahiro Soeta, and Yutaka Ukaji*
Division of Material Chemistry, Graduate School of Natural Science and Technology,
Kanazawa University, Kakuma, Kanazawa, Ishikawa 920-1192, Japan
E-mail: ukaji@staff.kanazawa-u.ac.jp
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R3
N
O
R3
N
O
CH2
CH2 S(O)Me2
R1
R1
THF
40 °C
R2
R2
1) regioselective 1,3-addition
2) ring closure by nitrogen
3) Meisenheimer rearrangement
ABSTRACT: Unique and efficient formation of 3,6-dihydro-2H-1,2-oxazines starting from α,β-
unsaturated nitrones has been achieved. The nucleophilic addition of dimethylsulfoxonium
methylide to the C=N bond of an α,β-unsaturated nitrone to form an aziridine N-oxide followed by
Meisenheimer rearrangement affords the 3,6-dihydro-2H-1,2-oxazine up to 70% yield. Methylene
was confirmed to be incorporated at the C3-position of the ring. A wide range of β-aryl-substituted
α,β-unsaturated nitrones was applicable to this reaction.
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INTRODUCTION
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Sulfur ylides are one of the most important and widely applied reagents since the pioneering work
of Corey and Chaykovsky in the 1960s (Corey–Chaykovsky reaction).1 These impressive successes
are attributed to the inherent properties of sulfur ylides that enable them to function as nucleophilic
1,1-dipolar species. They have long been used as one-carbon synthons in transformations with
different electron-deficient unsaturated functional groups, providing a variety of significant
carbocyclic and heterocyclic compounds.2 One of the most widespread uses of sulfur ylides is the
reaction with aldehydes and ketones, which yields betaine intermediates that collapse to give
epoxides. In the case of α,β-unsaturated ketones, dimethylsulfonium methylide was reported to
prefer 1,2-addition while the reaction of dimethylsulfoxonium methylide tended to give the
cyclopropane derivatives via 1,4-addition.1,2,3 In the case of imines, sulfonium and sulfoxonium
ylides reacted smoothly to form aziridines.1,2 The reaction of sulfonium ylides with α,β-unsaturated
imine substrates preferred 1,2-addition onto imine-carbons to produce the corresponding
aziridines.4 However, 1,4-addition was dominant depending on the protecting group on the imine
nitrogen and characteristics of the ylide.5 Among the imine derivatives, the reaction of sulfur ylides
to nitrones has scarcely been reported. The nucleophilic addition of dimethylsulfoxonium ylide to
o-hydroxy-benzaldehyde-based nitrones followed by cyclization gave dihydrobenzofuran
derivatives.6 As part of our investigation into the reactions of 1,3-dipoles and sulfur ylides,7 we
planned to examine the reaction of sulfur ylides to α,β-unsaturated nitrones. By the 1,3-addition to
an α,β-unsaturated nitrone, aziridine I or azetidine II formation might occur by nucleophilic
substitution of dimethylsulfide or dimethylsulfoxide in the betaine intermediate (pathways (i) and
(ii), respectively). In contrast, cyclopropane III formation or 5,6-dihydro-2H-1,2-oxazine IV
formation might be possible by the addition to the β-carbon of the α,β-unsaturated nitrone (1,5-
addition) via ring closure (pathways (iii) and (iv), respectively). The present report describes the
unique formation of 3,6-dihydro-2H-1,2-oxazines by a sequential addition and rearrangement
starting from α,β-unsaturated nitrones with dimethylsulfoxonium methylide via aziridine N-oxide
intermediate I (Scheme 1).
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Scheme 1. Possible Pathways for Sulfur Ylide-Mediated Transformations from α,β-
4
5
Unsaturated Nitrone
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Me
7
8
9
O+
N
N
O
CH2
Me
this work
(i)
Ph
CH2
Ph
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I
O
Me
2a
(ii)
Ph
N
1,3-
(i)
C+H2
S(O)nMe2
Me
O
Me
N
N O
CH2
(ii)
Ph
Ph
II
1a
+
(iii)
O
H2C
Me
Me
+
–
N
N
CH2 S(O)nMe2
+ (iv)
O
1,5-
Me2(O)nS
Me
Ph
(n = 0 or 1)
CH2
N
III
O
(iii)
Ph
(iv)
H2C
Ph
IV
RESULTS AND DISCUSSION
The initial reaction of α,β-unsaturated nitrone 1a with dimethylsulfonium methylide derived in situ
from trimethylsulfonium iodide with NaH in THF was examined at 60 °C (oil bath temperature) for
1
5 h. By H NMR analysis of the crude products, unreacted 1a was recovered in 59% yield.
Although several products were indicated by TLC analysis during the reaction, clear and sharp
singlet signals, which could be assigned to the N-CH3 group, were scarcely observed in the area
from 2 to 4 ppm except N-methyl protons of 1a in the 1H NMR spectrum (Table 1, Entry 1). When
dimethylsulfoxonium methylide generated in situ from trimethylsulfoxonium iodide and NaH was
employed, most of the nitrone 1a was consumed within 6 h. After aqueous workup, two rather sharp
1
proton resonances were observed around 3 ppm in the H NMR spectrum of the crude products.
Purification by silica gel column chromatography furnished unexpected 3,6-dihydro-2H-1,2-
1
13
oxazine 2a in 33% yield (Entry 2). The structure of the product was confirmed by its H and C
NMR spectra, which were identical to the reported data.8 The sharp signals at 2.71 and 3.30 ppm
could be assigned to methyl protons on nitrogen and C3 methylene protons, respectively. Using
NaOH as a base instead of NaH, 2a was obtained in only 4% yield (Entry 3). The use of KOH
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afforded the product in 25% yield (Entry 4). When pre-prepared dimethylsulfoxonium methylide
was used,9 the α,β-unsaturated nitrone 1a remained in the reaction mixture for a longer time than in
the reactions via the in situ ylide generation. However, the final yield was not improved (Entry 5).
When the temperature was slightly decreased, the dihydrooxazine 2a was obtained in improved
chemical yield of 43% yield (Entry 6). Monitoring the reactions by TLC suggested that various by-
products, whose structures were not confirmed, were gradually produced. One reason for this might
be the decomposition of dimethylsulfoxonium methylide to generate a reactive carbene, which
caused undesired reactions with the organic materials.10 To prevent this interference, several
alkenes were examined as scavengers to consume the methylene carbene as it was formed.11 When
2-methyl-2-butene was employed,12 the chemical yield was improved up to 54% yield (Entry 7).13
The reaction proceeded well even at 25 ºC, albeit with slight decrease of the yield (Entry 8).
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Table 1. Reaction of Sulfur Ylides with α,β-Unsaturated Nitrone 1a
Me
N
O
Me
base (3 equiv)
N
O
(CH3)3S(O)nI
(3 equiv)
THF, T °C, time
Ph
Ph
1a
2a
Entry
Sulfur ylide
T/°C
time
5 h
6 h
2 h
6 h
22 h
2 d
2 d
3 d
Yield/% Recovery of 1a/%a
1
(CH3)3SI / NaH
65
65
65
65
65
40
40
25
--
59
3
2
(CH3)3S(O)I / NaH
(CH3)3S(O)I / NaOH
(CH3)3S(O)I / KOH
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4
3
82
5
4
25
36
43
54
49
b
5
CH2S(O)(CH3)2
2
6
3
7c
8c
2
1
aRecovery of 1a was measured by 1H NMR of the crude products using CH2Br2 as
b
c
an internal standard. Pre-prepared dimethylsulfoxonium methylide was used. 10
Equiv of 2-methyl-2-butene was added.
With the optimal reaction conditions in hand, we examined the substrate scope of the reaction as
shown in Table 2. A series of β-tolyl-substituted α,β-unsaturated nitrones 1b-d were tolerated
(Entries 2-4). Notably, β-mesityl-substituted α,β-unsaturated nitrone 1e underwent the present
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addition-rearrangement transformation to afford 3,6-dihydro-2H-1,2-oxazine 2e in 70% yield (Entry
5). β-(4-Methoxyphenyl) nitrone 1f gave 2f in 56% yield (Entry 6). β-(Di- and trimethoxyphenyl)
substituted nitrones 1g-j were tolerated to furnish the products 2g-j in moderate yields (Entries 7–
10). The structure of 2j was unambiguously determined by X-ray crystallographic analysis (see
Experimental section). N,N-Dimethylamino and chloro groups could be introduced to the aromatic
ring of the nitrones to give 3,6-dihydro-2H-1,2-oxazines 2k and 2l in about 40% yields (Entries 11
and 12). In the case of nitrone 1m with aliphatic substituents, the chemical yield was rather low
(Entry 13). An α-methyl-substituted nitrone 1n could be a substrate in the present transformation
(Entry 14). Although the reaction of 1o with a benzyl substituent on nitrogen produced several
byproducts which were not observed in the case of N-methyl substituted nitrone 1e, the
dihydrooxazine 2o was obtained in 42% yield (Entry 15).
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Table 2. Reaction of Dimethylsulfoxonium Methylide with α,β-Unsaturated Nitrones
R3
O
R3
N
N
O
(10 equiv)
CH2 S(O)Me2
(3 equiv)
R1
R1
THF, 40 °C, 2–4 d
R2
R2
1
2
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Entry
R1
Ph
R2
H
R3
Yield/%
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1
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5a
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Me
a
b
c
2-MeC6H4
3-MeC6H4
50
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4-MeC6H4
d
e
61
2,4,6-Me3C6H2
4-(MeO)C6H4
2,3-(MeO)2C6H3
2,4-(MeO)2C6H3
2,5-(MeO)2C6H3
70
f
56
g
h
i
52
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43
10a 2,4,6-(MeO)3C6H2
j
55
11a
4-(Me2N)C6H4
4-ClC6H4
Ph(CH2)2
Ph
k
l
40
12
42
13
m
n
o
14
14
Me
Me
54
15b
2,4,6-Me3C6H2
H
PhCH2
42
aReaction was carried out at 60 °C. Reaction was carried out at
b
25 °C using 10 equiv of dimethylsulfoxonium methylide.
In order to gain insight into the present transformation, the nitrone 1a was treated with deuterated
dimethylsulfoxonium methylide generated in situ from trimethylsulfoxonium-d9 iodide and NaH in
THF.14 It was confirmed that deuterated methylene was incorporated at the C3 position by 1H NMR
analysis of the obtained 3,6-dihydro-2H-1,2-oxazine 2a-d2 (eq 1). Based on this result, the present
reaction was proposed to proceed via 1,3-addition of dimethylsulfoxonium methylide to the nitrone
1a followed by ring closure by nitrogen to produce aziridine N-oxide I. The subsequent
rearrangement (Meisenheimer rearrangement)15 produced 3,6-dihydro-2H-1,2-oxazine 2a as shown
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in Scheme 2.
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7
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9
Me
N
D
D
O
Me
NaH (3 equiv)
(CD3)3S(O)I
THF, 65 °C, 3 h
O
N
(1)
(3 equiv)
Ph
Ph
1a
2a-d2 42%
(86%-D)
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Scheme 2. Plausible Reaction Mechanism for Sulfur Ylide-Mediated Formation of 3,6-
Dihydro-2H-1,2-oxazine 2a
Me
O
Me
O
N
N
CH2 S(O)Me2
Ph
CH2
Ph
1a
S(O)Me2
Me
N
O
Me
O
CH2
N
Ph
CH2
Ph
2a
I
In conclusion, we developed the unique synthesis of 3,6-dihydro-2H-1,2-oxazines via 1,3-addition
of dimethylsulfoxonium methylide to α,β-unsaturated nitrones. 3,6-Dihydro-2H-1,2-oxazines, often
obtained by hetero Diels-Alder reactions of nitroso compounds with 1,3-dienes,16 are useful
heterocycles especially for the synthesis of biologically active nitrogen-containing compounds.16,17
α,β-Unsaturated nitrones could be readily available from α,β-unsaturated aldehydes and are slightly
more stable than 1,3-dienes. The present method provides a useful, unique, and alternative way to
provide 3,6-dihydro-2H-1,2-oxazines.
EXPERIMENTAL SECTION
1
General Method. H 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, quint = quintet, m = multiplet),
coupling constant (J) and integration. 13C NMR spectra were recorded on a 100 MHz NMR
spectrometer. The chemical shifts are reported relative to CDCl3 (δ = 77.0 ppm). The wavenumbers
of maximum absorption peaks in IR spectra are presented in cm−1. All of the melting points were
measured with a micro melting point apparatus. HRMS (ESI and FAB) spectra were measured with
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quadrupole and TOF mass spectrometers. Dehydrated solvents were purchased for the reactions and
used without further desiccation.
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(Z)-N-((E)-3-Phenylallylidene)methanamine oxide (1a):18,19 To a stirred mixture of (E)-
cinnamaldehyde (3.96 g, 30 mmol), triethylamine (5.58 mL, 40 mmol) and anhydrous Na2SO4 (14.2
g, 100 mmol) in dichloromethane (60 mL) was added N-methylhydroxylamine hydrochloride (1.67
g, 20 mmol) at 0 °C. After stirring for 2 d at rt, the reaction mixture was partitioned between water
and CHCl3. The aqueous layer was extracted with CHCl3. The combined organic layers were dried
over anhydrous Na2SO4, filtered and evaporated under reduced pressure. The residue was purified
by silica gel column chromatography (AcOEt/MeOH = 6/1) to give the nitrone 1a (2.06 g, 64%
yield) as a solid. Mp. 86–87 °C. 1H NMR (CDCl3, 400 MHz): δ 7.52 (d, 2H, J = 6.9 Hz), 7.45 (dd,
1H, J = 16.5, 9.6 Hz), 7.38–7.29 (m, 3H), 7.25 (d, 1H, J = 9.6 Hz), 6.96 (d, 1H, J = 16.5 Hz), 3.77
(s, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 138.1, 137.6, 135.9, 129.2, 128.8, 127.3, 118.4, 52.4.
IR (KBr) 3056, 1591, 1403, 1191, 1139, 980, 947, 750, 697 cm–1. HRMS (ESI) m/z: [M+H]+ Calcd
for C10H12NO 162.0919; Found 162.0922.
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In a similar manner, nitrones 1b–1o were obtained from the corresponding α,β-unsaturated
aldehydes.
(Z)-N-((E)-3-(o-Tolyl)allylidene)methanamine oxide (1b): The compound 1b (2.00 g, 68% yield,
17 mmol scale) was obtained as a solid after purification by silica gel column chromatography
(AcOEt/MeOH = 6/1). Mp. 85–86 °C. 1H NMR (CDCl3, 400 MHz): δ 7.69–7.66 (m, 1H), 7.38 (dd,
1H, J = 16.0, 9.6 Hz), 7.28 (d, 1H, J = 9.6 Hz), 7.23–7.15 (m, 4H), 3.76 (s, 3H), 2.37 (s, 3H).
13C{1H} NMR (CDCl3, 100 MHz): δ 137.8, 136.4, 135.3, 134.6, 130.6, 129.0, 126.3, 125.6, 119.0,
52.3, 19.7. IR (KBr) 3043, 1561, 1407, 1184, 1146, 971, 955, 746 cm–1. HRMS (ESI) m/z: [M+H]+
Calcd for C11H14NO 176.1075; Found 176.1074.
(Z)-N-((E)-3-(m-Tolyl)allylidene)methanamine oxide (1c): The compound 1c (2.95 g, 99% yield,
16 mmol scale) was obtained as an oil after purification by silica gel column chromatography
(AcOEt/MeOH = 6/1). 1H NMR (CDCl3, 400 MHz): δ 7.43 (dd, 1H, J = 16.0, 9.6 Hz), 7.36 (s, 1H),
7.31 (d, 1H, J = 7.8 Hz), 7.26–7.22 (m, 2H), 7.13 (d, 1H, J = 7.3 Hz), 6.93 (d, 1H, J = 16.0 Hz),
13
3.76 (s, 3H), 2.35 (s, 3H). C{1H} NMR (CDCl3, 100 MHz): δ 138.4, 138.3, 137.7, 135.9, 130.1,
128.7, 127.8, 124.6, 118.2, 52.3, 21.3. IR (neat) 2943, 1560, 1484, 1395, 957, 778, 691 cm–1.
HRMS (ESI) m/z: [M+H]+ Calcd for C11H14NO 176.1075; Found 176.1076.
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(Z)-N-((E)-3-(p-Tolyl)allylidene)methanamine oxide (1d):19,20 The compound 1d (0.11 g, 60%
yield, 1.0 mmol scale) was obtained as a solid after purification by silica gel column
chromatography (AcOEt/MeOH = 6/1). Mp. 121–123 °C. 1H NMR (CDCl3, 400 MHz): δ 7.42–7.36
(m, 1H), 7.41 (d, 2H, J = 7.8 Hz), 7.22 (d, 1H, J = 9.6 Hz), 7.15 (d, 2H, J = 7.8 Hz), 6.92 (d, 1H, J
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= 16.0 Hz), 3.74 (s, 3H), 2.34 (s, 3H). C{1H} NMR (CDCl3, 100 MHz): δ 139.4, 138.2, 137.8,
133.1, 129.5, 127.2, 117.3, 52.1, 21.3. IR (KBr) 3013, 1553, 1510, 1392, 1174, 1144, 982, 789 cm–1.
HRMS (ESI) m/z: [M+H]+ Calcd for C11H14NO 176.1075; Found 176.1072.
(Z)-N-((E)-3-Mesitylallylidene)methanamine oxide (1e): The compound 1e (2.25 g, 73% yield,
15.2 mmol scale) was obtained as a solid after purification by silica gel column chromatography
1
(AcOEt/MeOH = 6/1). Mp. 130–131 °C. H NMR (CDCl3, 400 MHz): δ 7.26 (d, 1H, J = 8.2 Hz),
7.09 (d, 1H, J = 16.9 Hz), 7.02 (dd, 1H, J = 16.9, 8.2 Hz), 6.88 (s, 2H), 3.76 (s, 3H), 2.34 (s, 6H),
2.27 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 138.1, 137.7, 136.5, 131.92, 131.85, 129.2, 123.3,
52.3, 21.3, 21.0. IR (KBr) 3002, 1574, 1398, 1194, 1141, 979, 855, 724 cm–1. HRMS (ESI) m/z:
[M+Na]+ Calcd for C13H17NONa 226.1208; Found 226.1223.
(Z)-N-((E)-3-(4-Methoxyphenyl)allylidene)methanamine oxide (1f):19,20 The compound 1f (1.46
g, 51% yield, 15.0 mmol scale) was obtained as a solid by recrystalization (AcOEt/hexane). Mp.
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101–102 °C. H NMR (CDCl3, 400 MHz): δ 7.47 (d, 2H, J = 8.7 Hz), 7.31 (dd, 1H, J = 16.0, 9.6
Hz), 7.24 (d, 1H, J = 9.6 Hz), 6.93 (d, 1H, J = 16.0 Hz), 6.88 (d, 2H, J = 8.7 Hz), 3.83 (s, 3H), 3.76
(s, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 160.9, 138.7, 138.2, 129.0, 128.6, 116.0, 114.3, 55.4,
52.0. IR (KBr) 2950, 1599, 1510, 1401, 1301, 1257, 1172, 1140, 1026, 974, 946, 812 cm–1. HRMS
(ESI) m/z: [M+H]+ Calcd for C11H14NO2 192.1025; Found 192.1029.
(Z)-N-((E)-3-(2,3-Dimethoxyphenyl)allylidene)methanamine oxide (1g): The compound 1g
(1.23 g, 34% yield, 16.6 mmol scale) was obtained as a solid after purification by silica gel column
chromatography (AcOEt/MeOH = 6/1). Mp. 85–86 °C. 1H NMR (CDCl3, 400 MHz): δ 7.45 (dd, 1H,
J = 16.0, 9.6 Hz), 7.33 (d, 1H, J = 16.0 Hz), 7.32–7.29 (m, 2H), 7.06 (t, 1H, J = 8.0 Hz), 6.89 (d, 1H,
J = 7.8 Hz), 3.88 (s, 3H), 3.83 (s, 3H), 3.77 (s, 3H). C{1H} NMR (CDCl3, 100 MHz): δ 152.9,
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147.3, 138.2, 132.3, 130.1, 124.3, 119.2, 118.1, 112.8, 61.3, 55.8, 52.3. IR (KBr) 2940, 1557, 1476,
1387, 1268, 1178, 1146, 1061, 998, 983, 744 cm–1. HRMS (ESI) m/z: [M+Na]+ Calcd for
C12H15NO3Na 244.0950; Found 244.0963.
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(Z)-N-((E)-3-(2,4-Dimethoxyphenyl)allylidene)methanamine oxide (1h): The compound 1h
(2.29 g, 65% yield, 15.9 mmol scale) was obtained as a solid after purification by silica gel column
chromatography (AcOEt/MeOH = 3/1). Mp. 99–100 °C. 1H NMR (CDCl3, 400 MHz): δ 7.58 (d, 1H,
J = 8.2 Hz), 7.35 (dd, 1H, J = 15.6, 9.6 Hz), 7.27–7.20 (m, 2H), 6.51 (d, 1H, J = 8.2 Hz), 6.43 (s,
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1H), 3.85 (s, 3H), 3.83 (s, 3H), 3.73 (s, 3H). C{1H} NMR (CDCl3, 100 MHz): δ 161.9, 158.6,
138.9, 133.0, 128.2, 118.1, 116.3, 105.3, 98.3, 55.5, 55.4, 52.0. IR (KBr) 3004, 1594, 1505, 1450,
1391, 1315, 1274, 1297, 1181, 1027, 945, 828 cm–1. HRMS (FAB+) m/z: [M+H]+ Calcd for
C12H16NO3 222.1130; Found 222.1131.
(Z)-N-((E)-3-(2,5-Dimethoxyphenyl)allylidene)methanamine oxide (1i): The compound 1i (2.33
g, 81% yield, 13.0 mmol scale) was obtained as a solid after purification by silica gel column
chromatography (AcOEt/MeOH = 6/1). Mp. 68–70 °C. 1H NMR (CDCl3, 400 MHz): δ 7.43 (dd, 1H,
J = 16.5, 9.6 Hz), 7.32 (d, 1H, J = 16.5 Hz), 7.27 (d, 1H, J = 9.6 Hz), 7.17 (d, 1H, J = 2.8 Hz), 6.86
(dd, 1H, J = 9.2, 2.8 Hz), 6.82 (d, 1H, J = 9.2 Hz), 3.83 (s, 3H), 3.80 (s, 3H), 3.76 (s, 3H). 13C{1H}
NMR (CDCl3, 100 MHz): δ 153.7, 151.8, 138.5, 132.7, 125.4, 118.4, 116.9, 112.4, 110.6, 56.1,
55.8, 52.3. IR (KBr) 2943, 1563, 1496, 1413, 1281, 1221, 1188, 1039, 969, 824, 801, 707 cm–1.
HRMS (ESI) m/z: [M+Na]+ Calcd for C12H15NO3Na 244.0950; Found 244.0965.
(Z)-N-((E)-3-(2,4,6-Trimethoxyphenyl)allylidene)methanamine oxide (1j): The compound 1j
(0.94 g, 53% yield, 7.1 mmol scale) was obtained as a solid after purification by silica gel column
chromatography (AcOEt/MeOH = 6/1, 3/1). Mp. 147–148 °C. 1H NMR (CDCl3, 400 MHz): δ 7.69
(dd, 1H, J = 16.5, 10.1 Hz), 7.26 (d, 1H, J = 16.5 Hz), 7.17 (d, 1H, J = 10.1 Hz), 6.11 (s, 2H), 3.87
(s, 6H), 3.84 (s, 3H), 3.71 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 161.8, 160.3, 140.8, 130.0,
119.2, 107.2, 90.3, 55.7, 55.3, 51.9. IR (KBr) 2943, 1593, 1463, 1408, 1319, 1200, 1119, 1038, 976,
949, 822 cm–1. HRMS (ESI) m/z: [M+Na]+ Calcd for C13H17NO4Na 274.1055; Found 274.1074.
(Z)-N-((E)-3-(4-(Dimethylamino)phenyl)allylidene)methanamine oxide (1k): The compound 1k
(0.82 g, 86% yield, 4.7 mmol scale) was obtained as a solid by recrystalization (MeOH/hexane).
Mp. 105–106 °C. 1H NMR (CDCl3, 400 MHz): δ 7.42 (d, 2H, J = 8.7 Hz), 7.27–7.16 (m, 2H), 6.87
(d, 1H, J = 15.6 Hz), 6.66 (d, 2H, J = 8.7 Hz), 3.73 (s, 3H), 3.01 (s, 6H). C{1H} NMR (CDCl3,
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100 MHz): δ 151.0, 139.3, 138.8, 128.9, 123.9, 113.7, 111.9, 51.8, 40.1. IR (KBr) 1598, 1325, 1371,
1173, 809 cm–1. HRMS (ESI) m/z: [M+Na]+ Calcd for C12H16N2ONa 227.1160; Found 227.1173.
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(Z)-N-((E)-3-(4-Chlorophenyl)allylidene)methanamine oxide (1l):20,21 The compound 1l (1.26 g,
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chromatography (AcOEt/MeOH = 6/1). Mp. 130–132 °C. H NMR (CDCl3, 400 MHz): δ 7.44 (d,
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Hz), 6.93 (d, 1H, J = 16.0 Hz), 3.77 (s, 3H). C{1H} NMR (CDCl3, 100 MHz): δ 137.6, 136.8,
135.0, 134.5, 129.1, 128.4, 118.8, 52.4. IR (KBr) 3034, 1557, 1488, 1391, 1186, 1140, 972, 956,
803 cm–1. HRMS (ESI) m/z: [M+H]+ Calcd for C10H11NOCl 196.0529; Found 196.0524.
(Z)-N-((E)-5-Phenylpent-2-en-1-ylidene)methanamine oxide (1m): The compound 1m (0.59 g,
18% yield, 17.5 mmol scale) was obtained as an oil after purification by silica gel column
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chromatography (AcOEt/MeOH = 20/1, 10/1, 6/1). H NMR (CDCl3, 400 MHz): δ 7.32–7.13 (m,
5H), 7.03 (d, 1H, J = 9.6 Hz), 6.80 (dd, 1H, J = 16.0, 9.6 Hz), 6.24 (dt, 1H, J = 16.0, 6.9 Hz), 3.68
(s, 3H), 2.77 (t, 2H, J = 7.3 Hz), 2.55 (td, 2H, J = 7.3, 6.9 Hz). 13C{1H} NMR (CDCl3, 100 MHz): δ
141.9, 140.9, 137.4, 128.4, 128.3, 126.1, 121.4, 52.0, 34.89, 34.86. IR (neat) 3026, 2926, 1631,
1603, 1571, 1454, 1407, 1149, 977, 748, 701 cm–1; HRMS (ESI) m/z: [M+H]+ Calcd for C12H16NO
190.1232; Found 190.1237.
(Z)-N-((E)-2-Methyl-3-phenylallylidene)methanamine oxide (1n):22 The compound 1n (1.40 g,
53% yield, 15.0 mmol scale) was obtained as an oil after purification by silica gel column
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chromatography (AcOEt/MeOH = 10/1, 6/1). H NMR (CDCl3, 400 MHz): δ 8.26 (s, 1H), 7.36–
7.19 (m, 5H), 6.93 (s, 1H), 3.78 (s, 3H), 2.18 (s, 3H). C{1H} NMR (CDCl3, 100 MHz): δ 137.9,
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137.0, 134.5, 129.5, 128.1, 127.7, 127.4, 54.4, 17.7. IR (KBr) 3056, 1587, 1558, 1167, 957, 751,
699 cm–1. HRMS (ESI) m/z: [M+H]+ Calcd for C11H14NO 176.1075; Found 176.1074.
(Z)-N-((E)-3-Mesitylallylidene)-1-phenylmethanamine oxide (1o): The compound 1o (0.59 g,
88% yield, 2.4 mmol scale) was obtained as a solid after purification by silica gel column
chromatography (hexane/AcOEt = 2/1, 1/1, AcOEt only, then AcOEt/MeOH = 10/1). Mp. 180–
182 °C. 1H NMR (CDCl3, 400 MHz): δ 7.49–7.39 (m, 5H), 7.24–7.21 (m, 1H), 7.06–7.04 (m, 2H),
6.86 (s, 2H), 4.95 (s, 2H), 2.32 (s, 6H), 2.26 (s, 3H). C{1H} NMR (CDCl3, 100 MHz): δ 137.7,
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136.9, 136.8, 136.6, 132.9, 131.9, 129.4, 129.2, 128.9, 123.2, 69.2, 21.4, 21.0; one signal overlaps.
IR (KBr) 3061, 1608, 1556, 1433, 1331, 1205, 1185, 1119, 984, 938, 864, 765, 701 cm–1. HRMS
(ESI) m/z: [M+H]+ Calcd for C19H22NO 280.1701; Found 280.1699.
Representative Procedure for Synthesis of 3,6-Dihydro-2H-1,2-oxazines for 2d.
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Under an Ar atmosphere, a mixture of α,β-unsaturated nitrone 1d (175 mg, 1.0 mmol),
dimethylsulfoxonium methylide9 (4.8 mL, 0.63 M in THF, 3.0 mmol), and 2-methyl-2-butene (1.1
mL, 10 mmol) in THF (1.2 mL) was stirred at 40 °C (oil bath temperature) for 2 d. After cooling to
rt, brine was added and extracted with CHCl3. Combined organic layers were dried over Na2SO4
and concentrated. The residue was purified by column chromatography on silica gel (hexane/AcOEt
= 15/1, 10/1, 6/1) to give 2d (115 mg, 61% yield).
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In a similar manner, syntheses of 3,6-dihydro-2H-1,2-oxazines 2a–2c, and 2e–2o were carried out.
2-Methyl-6-phenyl-3,6-dihydro-2H-1,2-oxazine (2a):8 The compound 2a (47 mg, 54% yield, 0.5
mmol scale) was obtained as an oil after purification by silica gel column chromatography
(hexane/AcOEt = 6/1). 1H NMR (CDCl3, 400 MHz): δ 7.40–7.28 (m, 5H), 6.02–5.87 (m, 2H), 5.45
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(brs, 1H), 3.30 (brs, 2H), 2.71 (s, 3H). C{1H} NMR (CDCl3, 100 MHz): δ 139.2, 128.8, 128.4,
128.1, 127.8, 124.1, 79.5, 56.3, 46.1. IR (neat) 3033, 2953, 2919, 2852, 2805, 1656, 1493, 1454,
1436, 1274, 1097, 1056, 994, 957, 924, 884, 792, 753, 700, 680 cm–1. HRMS (ESI) m/z: [M+H]+
Calcd for C11H14NO 176.1075; Found 176.1080.
2-Methyl-6-(o-tolyl)-3,6-dihydro-2H-1,2-oxazine (2b): The compound 2b (47 mg, 50% yield, 0.5
mmol scale) was obtained as an oil after purification by silica gel column chromatography
(hexane/AcOEt = 6/1). 1H NMR (CDCl3, 400 MHz): δ 7.33 (d, 1H, J = 6.4 Hz), 7.24–7.06 (m, 3H),
6.05–5.97 (m, 1H), 5.93 (d, 1H, J = 10.1 Hz), 5.71 (br, 1H), 3.31 (brs, 2H), 2.71 (s, 3H), 2.43 (s,
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3H). C{1H} NMR (CDCl3, 100 MHz): δ 150.0, 136.9, 130.5, 128.6, 128.2, 127.8, 125.9, 124.3,
76.6, 56.3, 46.1, 19.0. IR (neat) 2953, 2853, 2804, 1652, 1490, 1462, 1437, 1096, 1058, 995, 952,
888, 751, 670 cm–1. HRMS (ESI) m/z: [M+H]+ Calcd for C12H16NO 190.1232; Found 190.1233.
2-Methyl-6-(m-tolyl)-3,6-dihydro-2H-1,2-oxazine (2c): The compound 2c (43 mg, 45% yield, 0.5
mmol scale) was obtained as an oil after purification by silica gel column chromatography
(hexane/AcOEt = 6/1). 1H NMR (CDCl3, 400 MHz): δ 7.30–7.10 (m, 4H), 6.06–5.86 (m, 2H), 5.43
(br, 1H), 3.31 (brs, 2H), 2.72 (s, 3H), 2.35 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 150.0,
138.1, 137.6, 129.0, 128.5, 128.3, 124.9, 124.0, 79.8, 56.3, 46.1, 21.4. IR (neat) 2953, 2920, 2853,
2805, 1657, 1608, 1489, 1461, 1437, 1098, 1058, 994, 967, 853, 785, 761, 702, 677 cm–1. HRMS
(ESI) m/z Calcd for C12H16NO [M+H]+ 190.1232; Found 190.1231.
2-Methyl-6-(p-tolyl)-3,6-dihydro-2H-1,2-oxazine (2d): The compound 2d (115 mg, 61% yield,
1.0 mmol scale) was obtained as an oil after purification by silica gel column chromatography
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(hexane/AcOEt = 6/1). 1H NMR (CDCl3, 400 MHz): δ 7.27 (d, 2H, J = 8.1 Hz), 7.15 (d, 2H, J = 8.1
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Hz), 6.00–5.83 (m, 2H), 5.42 (br, 1H), 3.29 (brs, 2H), 2.70 (s, 3H), 2.33 (s, 3H). C{1H} NMR
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(CDCl3, 100 MHz): δ 138.0, 136.1, 129.1, 127.9, 124.1, 79.5, 56.3, 46.1, 21.2. IR (neat) 2953, 2920,
2852, 1654, 1615, 1514, 1436, 1097, 1057, 994, 957, 888, 813, 659 cm–1. HRMS (ESI) m/z:
[M+H]+ Calcd for C12H16NO 190.1232; Found 190.1227.
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6-Mesityl-2-methyl-3,6-dihydro-2H-1,2-oxazine (2e): The compound 2e (76 mg, 70% yield, 0.5
mmol scale) was obtained as an oil after purification by silica gel column chromatography
(hexane/AcOEt = 6/1). 1H NMR (CDCl3, 400 MHz): δ 6.74 (s, 2H), 5.92–5.81 (m, 2H), 5.74 (d, 1H,
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J = 10.1 Hz), 3.40–3.18 (m, 2H), 2.66 (s, 3H), 2.30 (s, 6H), 2.15 (s, 3H). C{1H} NMR (CDCl3,
100 MHz): δ 137.6, 137.5, 131.4, 129.8, 128.9, 123.1, 76.2, 56.1, 46.2, 20.7, 20.6. IR (neat) 2952,
2918, 2852, 1658, 1611, 1459, 1435, 994, 869, 797 cm–1. HRMS (ESI) m/z: [M+H]+ Calcd for
C14H20NO 218.1545; Found 218.1548.
6-(4-Methoxyphenyl)-2-methyl-3,6-dihydro-2H-1,2-oxazine (2f): The compound 2f (57 mg, 56%
yield, 0.5 mmol scale) was obtained as an oil after purification by silica gel column chromatography
(hexane/AcOEt = 6/1). 1H NMR (CDCl3, 400 MHz): δ 7.30 (d, 2H, J = 8.2 Hz), 6.87 (d, 2H, J = 8.2
Hz), 6.02–5.95 (m, 1H), 5.90 (d, 1H, J = 10.1 Hz), 5.41 (br, 1H), 3.79 (s, 3H), 3.29 (brs, 2H), 2.70
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(s, 3H). C{1H} NMR (CDCl3, 100 MHz): δ 159.5, 131.3, 129.3, 128.9, 124.1, 113.8, 79.1, 56.3,
55.2, 46.1. IR (neat) 2953, 2836, 1653, 1611, 1513, 1462, 1248, 1173, 1096, 1056, 1035, 995, 887,
833, 660 cm–1. HRMS (ESI) m/z: [M+H]+ Calcd for C12H16NO2 206.1181; Found 206.1178.
6-(2,3-Dimethoxyphenyl)-2-methyl-3,6-dihydro-2H-1,2-oxazine (2g): The compound 2g (61 mg,
52% yield. 0.5 mmol scale) was obtained as an oil after purification by silica gel column
chromatography (hexane/AcOEt = 3/1). 1H NMR (CDCl3, 400 MHz): δ 7.06–6.95 (m, 2H), 6.87 (d,
1H, J = 7.8 Hz), 5.99–5.81 (m, 3H), 3.88 (s, 3H), 3.86 (s, 3H), 3.30 (brs, 2H), 2.71 (s, 3H). 13C{1H}
NMR (CDCl3, 100 MHz): 152.6, 147.1, 133.1, 128.9, 124.0, 123.8, 120.2, 112.1, 73.4, 61.3, 56.3,
55.7, 46.1. IR (neat) 2936, 2834, 1657, 1586, 1480, 1431, 1277, 1055, 1008, 858, 574, 665 cm–1.
HRMS (ESI) m/z: [M+H]+ Calcd for C13H18NO3 236.1287; Found 236.1292.
6-(2,4-Dimethoxyphenyl)-2-methyl-3,6-dihydro-2H-1,2-oxazine (2h): The compound 2h (56 mg,
47% yield, 0.5 mmol scale) was obtained as an oil after purification by silica gel column
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chromatography (hexane/AcOEt = 3/1). H NMR (CDCl3, 400 MHz): δ 7.30–7.25 (m, 1H), 6.48–
6.45 (m, 1H), 6.45 (s, 1H), 5.97–5.83 (m, 3H), 3.81 (s, 3H), 3.79 (s, 3H), 3.28 (brs, 2H), 2.70 (s,
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3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 160.6, 158.1, 129.4, 123.5, 120.0, 104.2, 98.4, 72.6, 56.4,
55.5, 55.3, 46.1. IR (neat) 2953, 2834, 1613, 1588, 1506, 1464, 1288, 1208, 1157, 1038, 832, 665
cm–1. HRMS (FAB+) m/z: [M+H]+ Calcd for C13H18NO3 236.1287; Found 236.1280.
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6-(2,5-Dimethoxyphenyl)-2-methyl-3,6-dihydro-2H-1,2-oxazine (2i): The compound 2i (51 mg,
43% yield, 0.5 mmol scale) was obtained as an oil after purification by silica gel column
chromatography (hexane/AcOEt = 3/1). 1H NMR (CDCl3, 400 MHz): δ 7.03–6.93 (m, 1H), 6.81 (d,
1H, J = 9.2 Hz), 6.78 (dd, 1H, J = 9.2, 2.8 Hz), 5.96–5.81 (m, 3H), 3.80 (s, 3H), 3.76 (s, 3H), 3.29
(brs, 2H), 2.73 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 153.5, 151.0, 138.3, 129.0, 123.5,
114.1, 113.3, 111.9, 73.1, 56.3, 56.2, 55.6, 46.1. IR (neat) 2952, 2839, 1591, 1497, 1278, 1219,
1048, 806, 715 cm–1. HRMS (ESI) m/z: [M+H]+ Calcd for C13H18NO3 236.1287; Found 236.1282.
6-(2,4,6-Trimethoxyphenyl)-2-methyl-3,6-dihydro-2H-1,2-oxazine (2j): The compound 2j (73
mg, 55% yield, 0.5 mmol scale) was obtained as a solid after purification by silica gel column
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chromatography (hexane/AcOEt = 3/1). Mp 113–114 °C. H NMR (CDCl3, 400 MHz): δ 6.02 (s,
2H), 5.98 (brs, 1H), 5.72 (brs, 2H), 3.71 (s, 3H), 3.69 (s, 6H), 3.22 (brs, 2H), 2.65 (s, 3H). 13C{1H}
NMR (CDCl3, 100 MHz): δ 161.4, 160.5, 130.2, 120.6, 107.6, 91.3, 71.0, 56.2, 55.9, 55.2, 46.2. IR
(KBr) 2909, 2800, 1606, 1459, 1204, 1125, 957, 806 cm–1. HRMS (ESI) m/z: [M+H]+ Calcd for
C14H20NO4 266.1392; Found 266.1394.
Recrystallization from hexane/AcOEt gave the crystal 2j. Crystal data: C14H19NO4, Mr = 265.30,
monoclinic, P21/c, a = 10.5750(5), b = 8.7937(4), c = 14.6350(7) Å, β = 91.4380(10). V =
1360.53(11) Å3, Z = 4, Dcalcd = 1.295 g cm−3, R = 0.0419 (Rw = 0.1726) for 2658 reflections. CCDC
1991113 (2j) contains the supplementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
N,N-Dimethyl-4-(2-methyl-3,6-dihydro-2H-1,2-oxazin-6-yl)aniline (2k): The compound 2k (44
mg, 40% yield, 0.5 mmol scale) was obtained as an oil after purification by silica gel column
1
chromatography (hexane/AcOEt = 3/1). H NMR (CDCl3, 400 MHz): δ 7.24 (d, 2H, J = 8.7 Hz),
6.70 (d, 2H, J = 8.7 Hz), 6.02–5.84 (m, 2H), 5.38 (br, 1H), 3.28 (brs, 2H), 2.93 (s, 6H), 2.69 (s, 3H).
13C{1H} NMR (CDCl3, 100 MHz): 150.7, 129.4, 129.1, 126.8, 123.9, 112.4, 79.5, 56.3, 46.1, 40.6.
IR (neat) 2850, 2802, 1614, 1523, 1351, 1165, 1053, 812 cm–1. HRMS (ESI) m/z: [M+H]+ Calcd for
C13H19N2O 219.1497; Found 219.1494.
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6-(4-Chlorophenyl)-2-methyl-3,6-dihydro-2H-1,2-oxazine (2l): The compound 2l (44 mg, 42%
yield, 0.5 mmol scale) was obtained as an oil after purification by silica gel column chromatography
(hexane/AcOEt = 6/1). 1H NMR (CDCl3, 400 MHz): δ 7.32 (s, 4H), 6.01 (d, 1H, J = 9.6 Hz), 5.96–
5.84 (m, 1H), 5.41 (br, 1H), 3.30 (brs, 2H), 2.70 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 149.8,
137.8, 133.8, 129.2, 128.6, 124.6, 78.9, 56.2, 46.1. IR (neat) 2954, 2922, 2852, 1653, 1596, 1491,
1436, 1408, 1260, 1092, 1059, 1015, 995, 887, 807, 720 cm–1. HRMS (ESI) m/z: [M+H]+ Calcd for
C11H13NOCl 210.0686; Found 210.0685.
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2-Methyl-6-phenethyl-3,6-dihydro-2H-1,2-oxazine (2m): The compound 2m (14 mg, 14% yield,
0.5 mmol scale) was obtained as an oil after purification by silica gel column chromatography
(hexane/AcOEt = 6/1). 1H NMR (CDCl3, 400 MHz): δ 7.30–7.07 (m, 5H), 5.87–5.81 (m, 1H), 5.75
(d, 1H, J = 10.1 Hz), 4.45 (br, 1H), 3.25–3.14 (m, 2H), 2.82–2.67 (m, 2H), 2.70 (s, 3H), 1.84–1.72
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(m, 2H). C{1H} NMR (CDCl3, 100 MHz): 142.0, 129.4, 128.5, 128.3, 125.7, 123.7, 76.1, 56.4,
46.0, 35.3, 31.5. IR (neat) 3027, 2922, 2852, 1604, 1496, 1455, 1436, 1103, 1055, 993, 750, 699
cm–1. HRMS (ESI) m/z: [M+H]+ Calcd for C13H18NO 204.1388; Found 204.1389.
2,5-Dimethyl-6-phenyl-3,6-dihydro-2H-1,2-oxazine (2n): The compound 2n (51 mg, 54% yield,
0.5 mmol scale) was obtained as an oil after purification by silica gel column chromatography
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(hexane/AcOEt = 6/1). H NMR (CDCl3, 400 MHz): δ 7.35–7.28 (m, 5H), 5.71 (s, 1H), 5.25 (br,
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1H), 3.38–3.20 (m, 2H), 2.67 (s, 3H), 1.45 (s, 3H). C{1H} NMR (CDCl3, 100 MHz): δ 138.4,
135.1, 128.7, 128.33, 128.26, 119.6, 83.4, 56.6, 46.0, 18.7. IR (neat) 2916, 2852, 2801, 1493, 1454,
1437, 1379, 1270, 1087, 1039, 995, 942, 900, 850, 755, 701 cm–1. HRMS (ESI) m/z: [M+H]+ Calcd
for C12H16NO 190.1232; Found 190.1235.
2-Benzyl-6-mesityl-3,6-dihydro-2H-1,2-oxazine (2o): The compound 2o (16 mg, 42% yield, 0.13
mmol scale) was obtained as an oil after purification by preparative TLC (hexane/AcOEt = 10/1).
1H NMR (CDCl3, 400 MHz): δ 7.38 (d, 2H, J = 6.9 Hz), 7.32–7.20 (m, 3H), 6.79 (s, 2H), 5.95 (brs,
1H), 5.94–5.81 (m, 2H), 4.12 (d, 1H, J = 13.7 Hz), 3.87 (d, 1H, J = 13.7 Hz), 3.45–3.31 (m, 2H),
13
2.34 (s, 6H), 2.22 (s, 3H). C{1H} NMR (CDCl3, 100 MHz): δ 137.9, 137.5, 136.9, 131.6, 129.8,
129.5, 128.9, 128.7, 128.1, 128.0, 127.1, 123.2, 76.3, 62.7, 53.9, 20.8, 20.7. IR (neat) 3033, 2919,
2859, 2799, 1610, 1494, 1454, 1378, 1339, 1085, 1030, 970, 742, 698 cm–1. HRMS (FAB+) m/z:
[M+H]+ Calcd for C20H24NO 294.1858; Found 294.1853.
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2-Methyl-6-phenyl-3,6-dihydro-2H-(3,3-D2)1,2-oxazine (2a–d2): Under an Ar atmosphere, a
mixture of trimethylsulfoxonium-d9 iodide14 (344 mg, 1.50 mmol) and NaH (60 mg, 60% w/w
dispersion in mineral oil, 1.50 mmol) in THF (3 mL) was refluxed for 2 h. After cooling to 0 °C,
α,β-unsaturated nitrone 1a (81 mg, 0.50 mmol) in THF (2 mL) was added and the resulting mixture
was stirred for 3 h at 70 °C (oil bath temperature). After cooling to rt, sat aqueous NH4Cl solution
was added and extracted with CHCl3. Combined organic layers were dried over Na2SO4 and
concentrated. The residue was purified by column chromatography on silica gel (hexane/AcOEt =
15/1, 12/1, 8/1) to give a deuterated 3,6-dihydro-2H-1,2-oxazine 2a–d2 as an oil (37 mg, 42% yield,
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86%-D). H NMR (CDCl3, 400 MHz): δ 7.45–7.28 (m, 5H), 6.04–5.88 (m, 2H), 5.45 (brs, 1H),
3.32–3.27 (m, 0.27H), 2.72 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 138.9, 128.7, 128.4, 128.2,
127.8, 124.0, 79.6, 55.7 (quint, J = 18 Hz), 46.1. IR (neat) 3033, 2953, 2185, 2059, 1493, 1454,
1274, 1095, 1044, 921, 893, 748, 699 cm–1. HRMS (ESI) Calcd for C11H12D2NO [M+H]+: 178.1201,
found 178.1201.
AUTHOR INFORMATION
Takuya Suga: ORCID/0000-0002-7527-961
Takahiro Soeta: ORCID/0000-0001-9883-4772
Yutaka Ukaji: ORCID/0000-0003-3185-3113
ACKNOWLEDGEMENTS
This work was partially supported by Grants-in-Aid from the Japan Society for the Promotion of
Science (18K05102 and 17K05778), Kanazawa University SAKIGAKE Project, and the Kanazawa
University CHOZEN Project.
SUPPORTING INFORMATION
Copies of 1H NMR and 13C NMR spectra of products, cif files.
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