Iridium-catalyzed asymmetric hydroalkynylation reactions of oxabenzonorbornadienes

Article abstract of DOI:10.1039/c2ob26775f

Oxabenzonorbornadienes were found to be suitable substrates for asymmetric hydroalkynylation reactions. Catalyzed by the complex of [Ir(COD)Cl]₂ and (R)-SYNPHOS, oxabenzonorbornadienes and terminal alkynes could react smoothly to give the alkyn

Full text of DOI:10.1039/c2ob26775f

Organic &
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Iridium-catalyzed asymmetric hydroalkynylation
reactions of oxabenzonorbornadienes†
Cite this: Org. Biomol. Chem., 2013, 11,
814
Jun Hu,a Qingjing Yang,a Jianbin Xu,a Chao Huang,a Baomin Fan,*a Jun Wang,b
Chengyuan Lin,b Zhaoxiang Bianb,c and Albert S. C. Chan*c
Received 10th September 2012,
Accepted 13th November 2012
Oxabenzonorbornadienes were found to be suitable substrates for asymmetric hydroalkynylation reac-
tions. Catalyzed by the complex of [Ir(COD)Cl]2 and (R)-SYNPHOS, oxabenzonorbornadienes and terminal
alkynes could react smoothly to give the alkynylated products in moderate to good yields (up to 93%
yield) and enantioselectivities (up to 85% ee).
DOI: 10.1039/c2ob26775f
www.rsc.org/obc
Introduction
Caused by the coexistence of a carbon–carbon double bond in
the strained cycle and an oxygen bridge at the allylic position,
oxabenzonorbornadienes have not only high chemical reacti-
vities but also high reactive diversities. Promoted by different
catalysts, the isomerization,1,2 dimerization,3,4 hydroamina-
tion,5 carbometalation,6 hydroarylation,7 chloroacetonylation,8
carbocyclization9–15 and ring-opening16 reactions of oxabenzo-
norbornadienes have been realized. Furthermore, the reactions
of oxabenzonorbornadienes and terminal alkynes are particu-
larly interesting. Under different reaction conditions, oxabenzo-
norbornadienes and terminal alkynes can undergo [2 + 1]
(Scheme 1A and B),17 [2 + 2] (Scheme 1C),18 and [2 + 2 + 2]
(Scheme 1D)19 cycloaddition reactions respectively, leading to
various cyclic products. In addition, some non-cyclization reac-
tions can also take place between oxabenzonorbornadienes
and terminal alkynes. For example, in the presence of
Ni(dppe)Cl2, PPh3, ZnCl2, and Zn powder in toluene at 90 °C,
the reaction of oxabenzonorbornadienes with terminal acety-
lenes gives the ring-opening products in good yields
(Scheme 1E).20 When catalyzed by Herrmann–Beller phospha-
palladacycle, addition of trimethylsilylethyne to the carbon–
carbon double bond of 7-oxa-benzonorbornadiene (hydroalky-
nylation reaction) proceeds readily (Scheme 1F).21 However,
Scheme 1 The catalytic reactions of oxabenzonorbornadienes and terminal
alkynes.
unlike the other reactions of oxabenzonorbornadienes,3,16 few
improvements have been achieved in the asymmetric version
of these catalytic reactions between oxabenzonorbornadienes
and terminal alkynes (Scheme 2).
Our group has been interested in the asymmetric reactions
of norbornadienes and terminal alkynes for some time. We
had found that the complex of iridium and chiral xylyl-phane-
phos is an efficient catalyst for the [2 + 2] cycloadditions of
oxabenzonorbornadienes and terminal alkynes, with which
the cyclobutene products can be constructed in a single step
with up to 99% ee.22 Recently, we also reported that changing
the chiral diphosphine ligand from (R)-xylyl-phanephos to (R)-
SYNPHOS (also named as BisbenzodioxanPhos), resulted in an
iridium catalyst that can promote the asymmetric addition of
the carbon–hydrogen bond of terminal alkynes to the carbon–
carbon double bond of norbornadienes smoothly, and the
hydroalkynylation products are generated with good yields (up
to 92%) and high enantioselectivities (up to 97% ee).23 During
aKey Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs
Commission and Ministry of Education, Yunnan University of Nationalities,
Kunming, 650500, China. E-mail: adams.bmf@hotmail.com;
Fax: (+86)-871-5910017
bSchool of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
cInstitute of Creativity, Hong Kong Baptist University, Hong Kong, China.
E-mail: ascchan@hkbu.edu.hk; Fax: +852-34112123
†Electronic supplementary information (ESI) available: Copies of 1H and
13C NMR spectra of new compounds, and HPLC chromatograms. See DOI:
10.1039/c2ob26775f
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Table 1 Iridium-catalyzed asymmetric addition of phenylacetylene 2a to
7-oxabenzonorbornadiene 1a with different chiral ligandsa
Temp
Entry (°C)
Time
Ligand (h)
Solvent
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
70
90
90
90
90
90
90
90
90
90
90
90
90
90
90
50
rt
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
THF
DME
Toluene
iPrOH
4
5
6
7
8
9
10
11
12
13
14
15
16
17
4
4
4
4
4
24
18
18
18
24
18
18
18
12
12
18
18
18
12
6
60
60
24
24
24
24
63
Trace
6
NR
Complex result
Trace
22
80
70
64
51
69
48
68
67
47
<10
68
77 (96)d
N.D.
N.D.
/
/
N.D.
<10
43
48
38
67
66
61
70
73
76
/
66
68
62
69
9
10
11
12
13
14
15
16
17
18
19
20
21
Scheme 2 The Ir catalyzed asymmetric reactions of norbornadiene derivatives
and terminal alkynes.
the course of our further investigation on this iridium-
catalyzed asymmetric hydroalkynylation reaction, we wondered
if oxabenzonorbornadienes can serve as substrates for this
reaction, and how the oxygen atom at the bridge chain would
affect the reaction. Herein, we wish to report the results of our
exploration of oxabenzonorbornadienes as substrates in the
iridium-catalyzed asymmetric hydroalkynylation reactions.
70
70
70
70
52
27
50
4
4
a Reaction conditions: 1a (0.3 mmol), 1a : 2a:[Ir(COD)Cl]2 : bidentate
ligand (1 : 2 : 0.025 : 0.065) and 1a : 2a:[Ir(COD)Cl]2 : monodentate
ligand (1 : 2 : 0.025 : 0.13), in solvent (2 mL) under Ar for indicated
period of time. b Isolated yield by column chromatography. c ee % were
determined by chiral HPLC using a Chiralcel OD-H column. d The ee
value was determined after one simple recrystallization.
Results and discussion
In our initial trial, oxabenzonorbornadiene 1a was treated with
phenylacetylene 2a (2 equiv.) under the conditions which had
been optimized for the asymmetric hydroalkynylation reaction
of norbornadienes. Using the complex of [Ir(COD)Cl]2 and (R)-
SYNPHOS 4 as catalyst, DCE as solvent, the reaction was com-
pleted after 24 hours’ stirring at 70 °C, and the hydroalkynyla-
tion product 3aa was separated with 63% yield and 77% ee
(Table 1, entry 1). Just like in the iridium-catalyzed [2 + 2]
cycloaddition reaction of oxabenzonorbornadienes and term-
inal alkynes, only the carbon–carbon double bond in oxaben-
zonorbornadiene 1a was involved here, and the oxygen bridge
chain was maintained without any transformation.! After one
simple recrystallization, the ee value of 3aa could be increased
to 96%.
Since the catalytic reactions of oxabenzonorbornadienes
and terminal alkynes are quite sensitive to reaction conditions,
it is necessary to investigate the effect of various reaction para-
meters on this iridium-catalyzed asymmetric hydroalkynyla-
tion reaction of oxabenzonorbornadiene 1a. The chiral ligand
was the main focus, and several types of chiral ligands were
examined (Fig. 1). As shown in Table 1, the monodentate
chiral ligands, (R)-MONOPHOS 6 and (S)-NMDPP 8, were
proved useless in this reaction (Table 1, entries 3 and 5), since
Fig. 1 Chiral ligands tested in the addition of terminal alkynes to 7-oxabicyclic
alkenes.
the former gave the desired product in a very poor yield and
the latter resulted a quite complex mixture. The chiral diphos-
phinite ligand 5, N,P-ligand (R)-iPr-PHOX 7 and diphosphine
ligand (R,R)-BDPP 9 were also invalid in this reaction (Table 1,
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entries 2, 4 and 6). (R,R)-iPr-DUPHOS 10 showed low efficiency all terminal aromatic alkynes could react with 1a smoothly to
in this reaction (Table 1, entry 7). However, we determined provide the corresponding products in moderate to good
that biaryl diphosphine ligands were more efficient in this yields and enantioselectivities (Table 2, entries 1–10). Substitu-
reaction (Table 1, entries 8–15). The BINAP ligands 11–13, ents with different electronic and steric properties on the aro-
PyPhos ligands 14 and 15, (R)-DIFLUORPHOS 16 and (S)-MeO- matic rings of terminal alkynes 2b–j were well tolerated by this
BIPHEP 17 could all make the desired product 3aa in moderate addition reaction. It should be noted that the terminal alkyne
to good yields and enantioselectivities. (R)-SYNPHOS 4 was with CH2OH on the aromatic ring afforded the hydroalkynyla-
optimal in all of these chiral ligands tested and could promote tion product in good enantioselectivity (73% ee) and moderate
the best enantioselectivity along with good yield. Just like in yield (54%) (entry 7), and no competitive reactions of the
the asymmetric hydroalkynylation reaction of norbornadienes, hydroxy group adding to oxabenzonorbornadiene 1a were
the screening of temperature and solvent showed 70 °C and observed. In addition, the aliphatic terminal alkyne 2k could
DCE were the best ones (Table 1, entries 1 and 15–21).
also be used in this catalytic system with 1a, giving the corres-
Under the best reaction conditions for asymmetric hydro- ponding hydroalkynylation product with comparable yield and
alkynylation reaction of oxabenzonorbornadiene 1a, which are ee value (entry 11).
the same as those for asymmetric hydroalkynylation reaction
To extend the substrate scope of this transformation,
of norbornadienes, a series of terminal alkynes 2a–k were several substituted oxabenzonorbornadiene derivatives 1b–i
tested, and the results are summarized in Table 2. Generally, were also examined (Table 3). It can be seen that the electronic
properties of the substituents on the phenyl ring have obvious
effect on the enantioselectivities of the reactions. Electron-
Table 2 Iridium-catalyzed asymmetric addition of various alkynes 2a–k to
7-oxabenzonorbornadiene 1aa
withdrawing groups are preferred in this catalytic system, since
higher enantioselectivities can be obtained. For example,
when employing dibromo-oxabenzonorbornadiene 1d, an 85%
ee was achieved, which represented the highest enantioselec-
tivity for the asymmetric hydroalkynylation reaction of oxa-
benzonorbornadienes (entry 3). However, electron-donating
groups slightly decrease the enantioselectivities of the reac-
tions (entry 2, and entries 4–6). Bulky substituents in oxa-
benzonorbornadiene derivatives have a negative effect on the
reactions, and the closer the substituents to the carbon–
carbon double bonds, the greater the negative effect on the
reactions. This was proved by the fact that the methoxy
groups in 1b caused the decrease of the reaction’s enantio-
selectivity (entry 1), however the methyl groups on the bridge-
heads in 1h and 1i blocked the reactions completely (entry 7
and entry 8).
Entry
1
Alkyne
Time (h)
24
Yieldb (%)
63
eec (%)
77
2
3
4
5
6
7
24
10
30
60
60
15
87
90
90
82
89
54
78
74
69
62
75
73
Conclusions
In summary, it was found that oxabenzonorbornadienes could
also be served as substrates for the iridium-catalyzed asym-
metric hydroalkynylation reactions. Under the best reaction
conditions, which were same as those for norbornadienes,
most of the tested oxabenzonorbornadienes reacted with term-
inal alkynes smoothly, generating the addition products of
carbon–hydrogen bonds in terminal alkynes across the
carbon–carbon double bonds in oxabenzonorbornadienes.
Though the oxygen bridges were maintained without any
transformation in these reactions, compared with carbon
bridges,23 they did affect the enantioselectivities of the reac-
tions negatively. Generally, moderate to good ee values (up to
85%) were obtained. The influence of the electronic and
steric properties of substituents in substrates was also investi-
gated. Further improvements of this type of catalytic reactions
and detailed study of the reaction mechanism are still in
progress.
8
9
60
48
51
76
73
74
10
11
36
48
93
61
75
67
a Reaction conditions: 1a (0.3 mmol), 1a : 2a:[Ir(COD)Cl]2 : 4
=
1 : 1.5 : 0.025 : 0.065, in DCE (2 mL) at 70 °C under Ar for indicated
period of time. b Isolated yield by column chromatography. c ee % were
determined by chiral HPLC using a Chiralcel OD-H or AD-H column.
816 | Org. Biomol. Chem., 2013, 11, 814–820
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oxabenzonorbornadienes were synthesized according to the
reported procedures in literatures.24 1H NMR and 13C NMR
spectra were recorded on Bruker-Avance 400 or 500 MHz
spectrometer. CDCl3 was used as solvent. Chemical shifts (δ)
were reported in ppm with tetramethylsilane as internal stan-
dard, and J values were given in Hz. The enantioselective
excesses were determined by Agilent 1260 Series HPLC using
Daicel AD-H, OD-H, or OJ-H chiral columns eluted with a
mixture of isopropyl alcohol and hexane. Melting points were
measured on X-4 melting point apparatus and uncorrected.
High resolution mass spectra (HRMS) were performed on a VG
Autospec-3000 spectrometer. Column chromatography was
performed with silica gel (200–300 mesh).
Table 3 Iridium-catalyzed asymmetric addition of 4-methoxy-phenyl-acetylene
2b to substituted oxabenzonorbornadiene derivatives 1b–ga
Substituted
Time
(h)
Yieldb
(%)
eec
(%)
Entry
1
oxabenzonorbornadiene
19
92
67 (87)d
2
3
4
5
19
19
60
65
81
84
66
75
75
Typical procedure for the iridium-catalyzed asymmetric
hydroalkynylations of oxabenzonorbornadienes
85e
Under the protection of argon, [Ir(COD)Cl]2 (5.1 mg,
0.0075 mmol), (R)-SYNPHOS 4 (12.5 mg, 0.0195 mmol) and
1.0 mL 1,2-dichloroethane were added to a Schlenk tube. The
solution obtained was stirred at room temperature. 30 minutes
later, 7-oxa-benzonorbornadiene 1a (43.2 mg, 0.3 mmol) and
another 1.0 mL 1,2-dichloroethane were added, and the stir-
ring was continued for additional 20 minutes. After the
addition of phenylacetylene 2a (61.2 mg, 0.6 mmol), the
Schlenk tube was sealed with a rubber septum and moved to
an oil bath. The mixture was stirred at 70 °C (bath tempera-
ture) until the reaction was complete. After vacuum evapo-
ration of the reaction solvent, the residue was purified by
column chromatography on silica gel eluting with hexane/
ethyl acetate (15 : 1), and a white solid was obtained as product
3aa (46.5 mg, 63% yield). The enantioselective excess of the
product was determined to be 77% by chiral HPLC. After one
simple recrystallization, the ee value increased to 96%.
76 (98)d
73
6
7
46
60
70
72
/
NR
8
60
NR
/
2-(Phenylethynyl)-1,2,3,4-tetrahydro-1,4-epoxynaphthalene
(3aa). White solid, 63% yield, mp 96–97 °C, 77% ee (96% ee
1
a Reaction conditions: 1a (0.3 mmol), 1a : 2a:[Ir(COD)Cl]2 : 4
=
after one simple recrystallization). H NMR (400 MHz, CDCl3):
1 : 1.5 : 0.025 : 0.065, in DCE (2 mL) at 70 °C under Ar for indicated
period of time. b Isolated yield by column chromatography. c ee % were
determined by chiral HPLC using a Chiralcel OD-H, OJ-H or AD-H
column. d The ee value was determined after one simple
recrystallization. e The other two repeated experiments showed 84%
and 84.5% ee values respectively.
δ 7.45–7.43 (m, 2H), 7.29–7.27 (m, 5H), 7.25–7.22 (m, 2H),
5.52–5.51 (d, J = 4.9 Hz, 1H), 5.47 (s, 1H), 2.75–2.72 (dd, J =
8.36, 4.00 Hz, 1H), 2.29–2.24 (dt, J = 11.56, 4.78 Hz, 1H),
1.95–1.90 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 145.3, 144.4,
131.6, 128.2, 127.8, 127.1, 126.8, 123.5, 119.3, 119.1, 92.0,
84.4, 81.3, 79.2, 36.7, 32.3; HRMS (ESI) calcd for C18H14ONa
[M + Na]+, 269.0942, found 269.0948; HPLC (Chiralcel OD-H,
i-propanol/hexane = 10/90, flow rate 1.0 mL min−1, λ = 254 nm):
tminor = 8.0 min, tmajor = 18.9 min.
Experimental section
General remarks
2-((4-Methoxyphenyl)ethynyl)-1,2,3,4-tetrahydro-1,4-epoxy-
naphthalene (3ab). White solid, 87% yield, mp 124–125 °C,
78% ee. 1H NMR (400 MHz, CDCl3): δ 7.40–7.31 (m, 2H),
The reactions and manipulations were performed under an
atmosphere of argon by using standard Schlenk techniques
and Drybox (Mikrouna, Supper 1220/750). Anhydrous toluene, 7.30–7.17 (m, 4H), 6.85–6.82 (m, 2H), 5.54–5.53 (d, J = 4.9 Hz,
DME and THF were distilled from sodium benzophenone ketyl
prior to use. Anhydrous DCE was distilled from calcium
1H), 5.47 (s, 1H), 3.81 (s, 3H), 2.75–2.72 (dd, J = 8.38, 4.12 Hz,
1H), 2.29–2.24 (dt, J = 11.54, 4.46 Hz, 1H), 1.97–1.92 (m, 1H);
hydride and stored under argon. Absolute isopropyl alcohol 13C NMR (100 MHz, CDCl3): δ 159.2, 145.3, 144.4, 133.0, 127.1,
was distilled from magnesium and stored under argon.
Alkynes were purchased from Sigma-Aldrich company, chiral
126.8, 119.3, 119.1, 115.7, 113.8, 90.4, 84.5, 81.1, 79.2, 55.2,
36.8, 32.3; HRMS (ESI) calcd for C19H16O2Na [M + Na]+,
ligands were purchased from Strem company, and 299.1048, found 299.1062; HPLC (Chiralcel OD-H, i-propanol/
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hexane = 10/90, flow rate 1.0 mL min−1, λ = 254 nm): tminor
10.1 min, tmajor = 19.7 min.
=
(m, 1H), 1.74–1.71 (t, J = 5.96 Hz, 1H); 13C NMR (100 MHz,
CDCl3): δ 145.3, 144.3, 140.5, 131.9, 127.2, 126.9, 126.7, 122.8,
N,N-Dimethyl-4-((1,2,3,4-tetrahydro-1,4-epoxynaphthalen-2-yl)- 119.3, 119.1, 92.1, 84.4, 81.1, 79.2, 65.0, 36.8, 32.4; HRMS (ESI)
ethynyl)aniline (3ac). White solid, 92% yield, mp 115–116 °C, calcd for C19H16O2Na [M + Na]+, 299.1048, found 299.1050;
74% ee. 1H NMR (400 MHz, CDCl3): δ 7.30–7.21 (m, 4H), HPLC (Chiralcel AD-H, i-propanol/hexane = 10/90, flow rate
7.16–7.14 (m, 2H), 6.60–6.58 (d, J = 8.8 Hz, 2H), 5.50–5.49 (d, 1.0 mL min−1, λ = 254 nm): tmajor = 18.0 min, tminor = 22.0 min.
J = 4.8 Hz, 1H), 5.43 (s, 1H), 2.94 (s, 6H), 2.73–2.70 (dd, J =
2-((4-(Trifluoromethyl)phenyl)ethynyl)-1,2,3,4-tetrahydro-
8.00, 4.00 Hz, 1H), 2.26–2.21 (dt, J = 11.56, 4.78 Hz, 1H), 1,4-epoxynaphthalene (3ah). White solid, 51% yield, mp
1.93–1.88 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 149.8, 145.4, 129–130 °C, 73% ee. 1H NMR (400 MHz, CDCl3): δ 7.53–7.50
144.6, 132.7, 127.1, 126.8, 119.3, 119.1, 111.8, 110.6, 89.4, 84.6, (m, 4H), 7.31–7.24 (m, 2H), 7.21–7.17 (m, 2H), 5.54–5.53 (d, J =
82.0, 79.2, 40.3, 36.9, 32.5; HRMS (ESI) calcd for C20H19NONa 4.2 Hz, 1H), 5.48 (s, 1H), 2.76–2.73 (dd, J = 8.37, 4.00 Hz, 1H),
[M + Na]+, 312.1364, found 312.1360; HPLC (Chiralcel AD-H, 2.30–2.25 (dt, J = 11.56, 4.76 Hz, 1H), 1.98–1.93 (m, 1H); 13C
i-propanol/hexane = 10/90, flow rate 1.0 mL min−1, λ = NMR (100 MHz, CDCl3): δ 145.3, 144.2, 131.9, 129.7, 129.4,
254 nm): tmajor = 9.7 min, tminor = 11.2 min.
127.4, 127.3, 126.9, 125.20, 125.16, 125.13, 125.09, 122.6,
2-(p-Tolylethynyl)-1,2,3,4-tetrahydro-1,4-epoxynaphthalene 119.3, 119.2, 94.8, 84.3, 80.2, 79.2, 36.7, 32.4; HRMS (ESI)
(3ad). White solid, 90% yield, mp 107–108 °C, 69% ee. 1H calcd for C19H13F3ONa [M + Na]+, 337.0816, found 337.0813;
NMR (500 MHz, CDCl3): δ 7.36–7.35 (m, 2H), 7.32–7.21 (m, (Chiralcel OD-H, i-propanol/hexane = 10/90, flow rate 1.0 mL
4H), 7.20–7.11 (m, 2H), 5.55–5.54 (d, J = 5.0 Hz, 1H), 5.48 (s, min−1, λ = 254 nm): tmajor = 6.1 min, tminor = 7.9 min.
1H), 2.76–2.74 (dd, J = 8.50, 4.50 Hz, 1H), 2.35 (s, 3H),
2-((3-Methoxyphenyl)ethynyl)-1,2,3,4-tetrahydro-1,4-epoxy-
2.30–2.26 (dt, J = 11.50, 4.88 Hz, 1H), 1.97–1.93 (m, 1H); 13C naphthalene (3ai). White solid, 76% yield, mp 100–101 °C,
NMR (125 MHz, CDCl3): δ 145.6, 144.7, 138.1, 131.8, 129.2, 74% ee. 1H NMR (400 MHz, CDCl3): δ 7.28–7.25 (m, 2H),
127.4, 127.1, 120.7, 119.6, 119.3, 91.5, 84.7, 81.7, 79.5, 37.0, 7.22–7.14 (m, 4H), 7.02–6.99 (m 1H), 6.83–6.80 (m, 1H),
32.6, 21.7; HRMS (ESI) calcd for C19H17O [M + 1]+, 261.1279, 5.51–5.50 (d, J = 4.8 Hz, 1H), 5.45 (s, 1H), 3.77 (s, 3H),
found 261.1283; HPLC (Chiralcel OD-H, i-propanol/hexane = 2.73–2.70 (dd, J = 8.40, 4.16 Hz, 1H), 2.26–2.21 (dt, J = 11.60,
5/95, flow rate 1.0 mL min−1, λ = 254 nm): tminor = 8.5 min, 4.56 Hz, 1H), 1.92–1.89 (m, 1H); 13C NMR (100 MHz, CDCl3): δ
tmajor = 14.1 min.
159.3, 145.3, 144.4, 129.3, 127.2, 126.9, 124.6, 124.2, 119.3,
2-((4-Bromophenyl)ethynyl)-1,2,3,4-tetrahydro-1,4-epoxynaphtha- 119.1, 116.4, 114.6, 91.9, 84.4, 81.3, 79.2, 55.3, 36.8, 32.4;
1
lene (3ae). White solid, 82% yield, mp 88–89 °C, 62% ee. H HRMS (ESI) calcd for C19H16O2Na [M + Na]+, 299.1048,
NMR (400 MHz, CDCl3): δ 7.46–7.44 (m, 2H), 7.33–7.28 (m, found 299.1045; (Chiralcel OD-H, i-propanol/hexane = 10/90,
4H), 7.22–7.20 (m, 2H), 5.56 (d, J = 4.8 Hz, 1H), 5.49 (s, 1H), flow rate 1.0 mL min−1, λ = 254 nm): tminor = 10.3 min, tmajor
2.76–2.73 (dd, J = 8.37, 4.10 Hz, 1H), 2.31–2.26 (dt, J = 11.58, 25.2 min.
=
4.8 Hz, 1H), 2.00–1.95 (m, 1H); 13C NMR (100 MHz, CDCl3): δ
2-((2-Methoxyphenyl)ethynyl)-1,2,3,4-tetrahydro-1,4-epoxy-
145.3, 144.3, 133.1, 131.5, 127.3, 126.9, 122.5, 122.0, 119.3, naphthalene (3aj). White solid, 93% yield, mp 109–110 °C,
1
119.1, 93.3, 84.3, 80.4, 79.2, 36.7, 32.4; HRMS (ESI) calcd for 75% ee. H NMR (400 MHz, CDCl3): δ 7.37 (m, 1H), 7.25–7.19
C18H13BrONa [M + Na]+, 347.0047, found 347.0050; HPLC (m, 3H), 7.14–7.12 (m, 2H), 6.87–6.81 (m, 2H), 5.49 (d, J =
(Chiralcel OD-H, i-propanol/hexane = 10/90, flow rate 1.0 mL 4.8 Hz, 1H), 5.46 (s, 1H), 3.84 (s, 3H), 2.77 (dd, J = 8.36,
min−1, λ = 254 nm): tmajor = 6.7 min, tminor = 8.5 min.
4.16 Hz, 1H), 2.29–2.23 (dt, J = 11.56, 4.68 Hz, 1H), 1.90 (m,
2-((4-Fluorophenyl)ethynyl)-1,2,3,4-tetrahydro-1,4-epoxy- 1H); 13C NMR (100 MHz, CDCl3): δ 159.9, 145.4, 144.5, 133.8,
naphthalene (3af). White solid, 89% yield, mp 128–129 °C, 129.3, 127.1, 126.8, 120.4, 119.3, 119.1, 112.6, 110.5, 96.2,
75% ee. 1H NMR (500 MHz, CDCl3): δ 7.43–7.41 (m, 2H), 84.5, 79.3, 55.8, 36.9, 32.7; HRMS (ESI) calcd for C19H16O2Na
7.31–7.25 (m, 2H), 7.21–7.18 (m, 2H), 7.01–6.98 (m, 2H), [M + Na]+, 299.1048, found 299.1043; (Chiralcel AD-H, i-propa-
5.54–5.53 (d, J = 5.0 Hz, 1H), 5.47 (s, 1H), 2.74–2.72 (dd, J = nol/hexane = 10/90, flow rate 1.0 mL min−1, λ = 254 nm):
8.52, 4.02 Hz, 1H), 2.28–2.25 (dt, J = 9.52, 4.50 Hz, 1H), tmajor = 14.2 min, tminor = 15.6 min.
1.97–1.93 (m, 1H); 13C NMR (125 MHz, CDCl3): δ 163.4, 161.5,
2-(4-Phenylbut-1-yn-1-yl)-1,2,3,4-tetrahydro-1,4-epoxy-
1
145.5, 144.6, 133.8, 133.7, 127.5, 127.1, 119.9, 119.8, 119.6, naphthalene (3ak). Colorless oil, 61% yield, 67% ee. H NMR
119.3, 115.8, 115.6, 91.92, 91.91, 84.6, 80.5, 79.4, 37.0, 32.5; (500 MHz, CDCl3): δ 7.34–7.16 (m, 9H), 5.49–5.48 (d, J =
HRMS (ESI) calcd for C18H14OF [M + 1]+, 265.1029, found 5.5 Hz, 1H), 5.33 (s, 1H), 2.88–2.85 (t, J = 7.50 Hz, 2H),
265.1045; HPLC (Chiralcel AD-H, i-propanol/hexane = 10/90, 2.54–2.49 (m, 3H), 2.14–2.10 (m, 1H), 1.87–1.83 (m, 1H); 13C
flow rate 1.0 mL min−1, λ = 254 nm): tmajor = 6.8 min, tminor
=
NMR (125 MHz, CDCl3): δ 145.6, 144.7, 141.2, 128.8, 128.6,
9.8 min.
127.3, 127.0, 126.5, 119.5, 119.2, 84.8, 83.4, 80.9, 79.4, 37.0,
(4-((1,2,3,4-Tetrahydro-1,4-epoxynaphthalen-2-yl)ethynyl)phenyl)- 35.7, 31.9, 21.4; HRMS (EI) calcd for C20H18O [M]+, 274.1358,
methanol (3ag). White solid, 54% yield, mp 88–89 °C, 73% ee. found 274.1350; HPLC (Chiralcel AD-H, i-propanol/hexane =
1H NMR (400 MHz, CDCl3): δ 7.39–7.36 (m, 2H), 7.25–7.19 1/99, flow rate 1.0 mL min−1, λ = 254 nm): tmajor = 10.7 min,
(m, 4H), 7.16–7.12 (m, 2H), 5.48–5.47 (d, J = 5.0 Hz, 1H), 5.42 tminor = 12.8 min.
(s, 1H), 4.63–4.62 (d, J = 6.4 Hz, 2H), 2.71–2.68 (dd, J = 8.40,
5,8-Dimethoxy-2-((4-methoxyphenyl)ethynyl)-1,2,3,4-tetra-
4.16 Hz, 1H), 2.25–2.19 (dt, J = 11.56, 4.52 Hz, 1H), 1.92–1.87 hydro-1,4-epoxynaphthalene (3bb). White solid, 92% yield,
818 | Org. Biomol. Chem., 2013, 11, 814–820
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mp 105–107 °C, 67% ee (87% ee after one simple recrystalliza- 90.6, 84.4, 81.0, 79.1, 64.3, 55.3, 37.4, 32.8; HRMS (ESI) calcd
tion). 1H NMR (400 MHz, CDCl3): δ 7.41–7.39 (m, 2H), for C21H19O4 [M + 1]+, 335.1278, found 335.1272; HPLC (Chir-
6.85–6.83 (m, 2H), 6.69–6.68 (d, J = 0.7 Hz, 2H), 5.71–5.70 (d, alcel AD-H, i-propanol/hexane = 10/90, flow rate 1.0 mL min−1
J = 4.8 Hz, 1H), 5.64 (s, 1H), 3.84–3.82 (m, 9H), 2.78–2.75 (dd, λ = 254 nm): tmajor = 27.8 min, tminor = 33.6 min.
,
J = 8.45, 4.16 Hz, 1H), 2.27–2.23 (dt, J = 11.52, 4.52 Hz, 1H),
6-((4-Methoxyphenyl)ethynyl)-5,6,7,8-tetrahydro-5,8-epoxy-
2.00–1.95 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 159.2, 146.7, naphtho[2,3-d][1,3]dioxole (3gb). White solid, 70% yield, mp
146.6, 134.6, 133.6, 133.0, 115.8, 113.8, 111.5, 111.2, 90.6, 82.4, 189–190 °C, 72% ee. 1H NMR (400 MHz, CDCl3): δ 7.40–7.38
81.0, 56.1, 55.3, 36.4, 31.9; HRMS (ESI) calcd for C21H20O4Na (m, 2H), 6.85–6.82 (m, 3H), 6.78 (s, 1H), 5.99 (d, J = 1.2 Hz,
[M + Na]+, 359.1259, found 359.1256; HPLC (Chiralcel AD-H, 1H), 5.96–5.95 (d, J = 1.2 Hz, 1H), 5.46–5.45 (d, J = 4.8 Hz, 1H),
i-propanol/hexane = 10/90, flow rate 1.0 mL min−1, λ = 5.39 (s, 1H), 3.83 (s, 3H), 2.70–2.67 (dd, J = 8.40, 4.00 Hz, 1H),
254 nm): tminor = 11.0 min, tmajor = 16.3 min.
2.26–2.21 (dt, J = 11.60, 4.80 Hz, 1H), 1.92–1.87 (m, 1H); 13C
2-((4-Methoxyphenyl)ethynyl)-6,7-dimethyl-1,2,3,4-tetrahydro- NMR (100 MHz, CDCl3): δ 159.2, 146.7, 146.4, 139.1, 138.1,
1,4-epoxynaphthalene (3cb). White solid, 81% yield, mp 133.0, 115.7, 113.8, 101.6, 101.4, 101.2, 90.4, 84.6, 81.0, 79.3,
136–137 °C, 75% ee. 1H NMR (500 MHz, CDCl3): δ 7.38–7.37 55.3, 37.0, 32.5; HRMS (ESI) calcd for C20H16O4Na [M + Na]+,
(d, J = 8.5 Hz, 2H), 7.08 (br, 1H), 7.03 (br, 1H), 6.84–6.82 (d, J = 343.0946, found 343.0941; HPLC (Chiralcel AD-H, i-propanol/
8.5 Hz, 2H), 5.47–5.46 (d, J = 5 Hz, 1H), 5.40 (s, 1H), 3.81 (s, hexane = 10/90, flow rate 1.0 mL min−1, λ = 254 nm): tmajor
3H), 2.72–2.69 (dd, J = 8.00, 4.00 Hz, 1H), 2.25–2.21 (m, 7H), 22.3 min, tminor = 27.4 min.
1.93–1.89 (m, 1H); 13C NMR (125 MHz, CDCl3): δ 159.4, 143.5,
=
142.6, 135.4, 135.1, 133.3, 120.8, 120.6, 116.0, 114.0, 91.0, 84.7,
81.2, 79.4, 55.5, 37.5, 32.9, 20.23, 20.20; HRMS (ESI) calcd for
C21H21O2 [M + 1]+, 305.1542, found 305.1551; HPLC (Chiralcel
OD-H, i-propanol/hexane = 20/80, flow rate 1.0 mL min−1, λ =
254 nm): tminor = 8.2 min, tmajor = 11.9 min.
Acknowledgements
We thank the National Natural Science Foundation of China
(21162040, 20902080) and the Department of Education of
Yunnan Province (2010CI08) for financial support.
6,7-Dibromo-2-((4-methoxyphenyl)ethynyl)-1,2,3,4-tetrahydro-
1,4-epoxynaphthalene (3db). White solid, 92% yield, mp
190–192 °C, 85% ee. 1H NMR (500 MHz, CDCl3): δ 7.55 (s, 1H),
7.51 (s, 1H), 7.38–7.26 (m, 2H), 6.84–6.81 (m, 2H), 5.48–5.47
(d, J = 5 Hz, 1H), 5.40 (s, 1H), 3.79 (s, 3H), 2.75–2.72 (dd, J =
8.00, 3.96 Hz, 1H), 2.28–2.24 (dt, J = 9.50, 4.50, Hz, 1H),
1.95–1.91 (m, 1H); 13C NMR (125 MHz, CDCl3): δ 159.6, 146.6,
145.7, 133.3, 125.0, 124.8, 123.4, 123.0, 115.6, 114.1, 89.6, 84.1,
81.9, 79.0, 55.5, 36.7, 32.4; HRMS (ESI) calcd for C19H14O2Br2
[M]+, 431.9361, found 431.9363; HPLC (Chiralcel AD-H, i-pro-
panol/hexane = 10/90, flow rate 1.0 mL min−1, λ = 254 nm):
tmajor = 11.9 min, tminor = 13.1 min.
Notes and references
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1,4-epoxynaphthalene (3eb). White solid, 66% yield, mp
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1H NMR (500 MHz, CDCl3): δ 7.38–7.35 (m, 2H), 6.90–6.81 (m,
4H), 5.48–5.47 (d, J = 4.5 Hz, 1H), 5.41 (s, 1H), 3.89–3.87 (s,
6H), 3.80 (s, 3H), 2.68–2.65 (dd, J = 8.50, 4.00 Hz, 1H),
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=
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This journal is © The Royal Society of Chemistry 2013