Copper-Catalyzed Oxirane-Opening Reaction with Aryl Iodides and Se Powder

Article abstract of DOI:10.1021/acs.joc.6b01274

Using Se powder as the selenating reagent, the copper-catalyzed double C-Se cross-coupling of aryl iodides, epoxides, and elemental selenium has been developed. This strategy provides a straightforward approach to the synthesis of β-hydroxy phenylselenides with excellent regioselectivity of the ring opening reaction. This process proceeds in generally good yields and is compatible with a broad range of functional groups.

Full text of DOI:10.1021/acs.joc.6b01274

Subscriber access provided by University of Pennsylvania Libraries
Article
Copper-Catalyzed Oxirane-Opening Reaction with Aryl Iodides and Se Powder
Lin Min, Ge Wu, Miaochang Liu, Wenxia Gao, Jinchang Ding, Jiuxi Chen, Xiaobo Huang, and Huayue Wu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01274 • Publication Date (Web): 04 Aug 2016
Downloaded from http://pubs.acs.org on August 8, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 24
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Copper-Catalyzed Oxirane-Opening Reaction with Aryl Iodides and Se Powder
Lin Min,† Ge Wu,*,‡ Miaochang Liu,† Wenxia Gao,† Jinchang Ding,† Jiuxi Chen,† Xiaobo Huang, †
and Huayue Wu*, †
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
†College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035,
People’s Republic of China
‡School of Pharmacy, Wenzhou Medical University, Wenzhou 325035, People’s Republic of China
Abstract: Using Se powder as the selenating reagent, the copperꢀcatalyzed double CꢀSe
crossꢀcoupling of aryl iodides, epoxides and elemental selenium has been developed. This strategy
provides a straightforward approach to synthesisβꢀhydroxy phenylselenides with excellent
regioselectivity of ring opening reaction. This process proceeds in generally good yields and
compatible with a broad range of functional groups.
Introduction
Organoselenium chemistry has gained increasingly attention, because seleniumꢀcontain chemicals
are prevalence in many drug candidates, biologically active compounds, functional organic
materials as well as in food chemistry.1 Considering the significance of organoselenium
compounds, especiallyβꢀhydroxy phenylselenides, these compounds are valuable intermediates
in the synthesis of allylic alcohols,2 olefins3 and vinyl selenides.4 Therefore, the development of
new synthetic route for the introduction of stable, economical selenium reagent into organic
skeletons would be of significant synthetic value.
In recent years, the utilization of element selenium as linkage atom has received considerable
attention due to their commercial available, stable and easily handled as compared to commonly
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 24
1
2
3
4
5
6
7
8
9
employed as aryl selenium reagents. Unlike the use of diaryl diselenides, a limited knowledge has
been acquired when using transitionꢀmetal catalyzed transformation of selenium powder with aryl
halides. This is probably due to the selenium has the high activation energy to destroy the structure
of high polymer catenation, and the proclivity of elemental selenium for transition metal easily
form the stability transitionꢀmetal selenium clusters,5 which attenuate the activity of catalysts. In
2005, Taniguchi6 realized the first selenation of aryl iodides using aluminum as reductant and
MgCl2 as additive in combination with CuI / bpy to provide the symmetrical diaryl selenides.7
More recently, contributions have been extended to synthesis of ebselen,8 seleniumꢀcontaining
heterocycles,9 and trifluoromethylselenolation.10 Despite the encouraging advancements,
achieving direct crossꢀcoupling of elemental selenium in a general way remains a daunting
challenge. Lately, our group has established the copperꢀcatalyzed 3ꢀphenylselenation of indoles
through double C−Se bonds formation of indoles with (hetero) aryl iodides and elemental
selenium.11 Inspired by this result, we envisioned thatβꢀhydroxy phenylselenides, valuable
synthetic intermediates of considerable interest in important natural compounds,12 could be within
achieved by transitionꢀmetal catalyzed selenation of aryl halides with elemental selenium and
consequently further react with epoxides to afford the corresponding product under certain
reaction conditions (Scheme 1).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 1. Strategies for CrossꢀCoupling Reactions of Epoxides
Double C-Se bonds formation
OH
Se
O
[Cu] (cat.)
R1
R2
R1
R2
Se
I
Electrophile
Electrophile
Selenating reagent:
42 examples
up to 95%
(+) Avoiding prepare phenylselenation reagent
(+) Excellent regioselectivity
(+) Broad substrate scope and compatible with various functional group
Such a methodology would constitute an alternative to the commonly ring opening reactions
ACS Paragon Plus Environment

Page 3 of 24
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
of epoxides with selenolate anions.13 The drawback of these reactions is the functional group
tolerance and the loss of one equivalent of PhSe as waste. Clearly, such a single atom Se bridging
different crossꢀcoupling pratners strategy will be widely accepted and used for complex
pharmaceutical compounds synthesis by synthetic chemists. Herein, we report the discovery of
copperꢀcatlayzed double CꢀSe bond formation that allow for regioselectivity ring opening of
epoxides with (hetero) aryl iodides and elemental selenium.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Results and Discussion
Table 1. Reaction Optimizationa
entry
1
[Cat]
Pd(OAc)2
Pd(PPh3)4
Ni(acac)2
Ni(PPh3)2Cl2
Cu
base
K3PO4
K3PO4
K3PO4
K3PO4
Cs2CO3
Na2CO3
K2CO3
K3PO4
KOH
solvent
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
yield %b
0
2
0
3
0
4
0
5
32
6
Cu
0
7
Cu
20
8
Cu
45
9
Cu
5
10
11
12
13
14
15c
16d
17
18
19
20
21
22
23
Cu
tBuOK
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
4
CuO
74
CuI
64
CuBr
CuCl
76
83
CuCl
0
CuCl
33
Cu(OAc)2
CuCl2
CuCl
70
79
64
CuCl
HMPA
DCE
Trace
Trace
trace
trace
CuCl
CuCl
toluene
CH3CN
CuCl
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 24
1
2
3
4
5
24e
25f
CuCl
CuCl
K3PO4
K3PO4
DMSO
DMSO
45
60
aReaction conditions unless specified otherwise: 0.4 mmol of Iodobenzene, 0.8 mmol of Se, 1.2
mmol of Cyclohexene oxide, 0.04 mmol of [Cu], 1.2 mmol of base, 2 mL of solvent, under N2,
140 ℃, 24 h. bIsolated yield. cUnder O2. dUnder air. eAt 90 oC. fAt 110 oC.
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
We commenced our study by examining the reaction between iodobenzene 1a and 1,
2ꢀepoxycyclohexane 2a in the presence of elemental selenium (Table 1). It’s observed that three
critical reaction parameters have a remarkable effect on the reaction outcomes. First, the
examination of different transition metals, copper was found to be the only efficient catalyst
species for this transformation (entries 1ꢀ5). We were pleased to find that the desired product was
isolated in 45% yield under Cu as the catalyst, and K3PO4 as the base in DMSO stirred at 140 oC
for 24 h (entry 8). Different copper catalysts were screened, which showed that CuCl was the best
choice (entry 14). Second, a strong base was necessary for the model reaction to occur probably
because bases were required to activate the selenium powder and therefore trigger the reaction.
The effect of bases on the reaction was also observed to depend on the amounts of bases and their
anions (entries 7ꢀ10). The best result was obtained when 3 equiv K3PO4 was used (entry 8).
Finally, the choice of suitable solvent is critical successful for this transformation. When the
reaction was conducted in polar solvent DMF, the starting material was not completely converted.
No product was detected when apolar solvent toluene, DCE or weak coordination CH3CN were
used instead of DMSO (entry 21ꢀ23). An N2 atmosphere is essential for this reaction. No product
was detected when the reaction was conducted under O2 and air afforded the much lower 33 %
yield (entry 15, 16). This is due to the fact that O2 can intercept intermediates in the catalytic
process. A control experiment showed that the copper catalyst is essential for this transformation
and no coupling product was detected in the absence of copper.
Scheme 2. Aryl Iodide Scopea
ACS Paragon Plus Environment

Page 5 of 24
The Journal of Organic Chemistry
1
2
3
4
5
6
OH
CuCl (10 mol%)
K3PO4 (3 equiv)
Se
I
R
Se
O
DMSO, N2, 140 C, 24 h
R
7
8
9
OH
CN
OH
CH3 OH
Se
Se
Se
Se
OH
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3a, 83%
3b, 57%
3c, 81%
3d, 83%
OH
OH
OH
OH
R
Se
Se
Se
Se
R
R
OHC
3e (R=F), 73%
3h (R=Me), 86%
3i (R=OMe), 81%
3j (R=F), 80%
3k (R=Cl), 79%
3l (R=Br), 85%
3m, 38%
3f
(R=CF3), 74%
(R=NO2), 65%
3g
OH
OH
OH
OH
Se
Se
Se
Cl
Se
N
S
MeO2C
H2N
3q
, 75%
3p, 70%
3n, 35%
3o, 78%
aReaction conditions unless specified otherwise: aryl iodides (0.4 mmol), Se8 (0.8 mmol),
Cyclohexene oxide (1.2 mmol), CuCl (0.04 mmol), K3PO4 (1.2 mmol), DMSO (2 mL), 140 °C, 24
h, N2. Isolated yields are given.
With the optimal conditions in hand, the scope of the reaction was explored. A wide range of
aryl iodides were employed and the reaction generally proceeds smoothly, affording the
corresponding products in good to excellent yields (Scheme 2). When the iodobenzenes bearing a
variety of electronꢀdonating groups were used, such as methyl (3c, 3h) and methoxy (3i) were
highly reactive coupling partner gave the high yield. The reaction of iodobenzenes bearing the
electronꢀwithdrawing groups such as fluoro (3e, 3j), chloro (3k), bromo (3l), cyan (3b),
trifluoromethyl (3f) and nitro (3g) all gave the corresponding products in the excellent yield.
However, the efficiency of this transformation was comparatively low when aldehyde and ester
group at the C4 position of iodobenzene, affored the corresponding product in 38 % and 35 %
isolated respective yield. Probably the low electron density on the phenyl ring would reduce the
tendency of CꢀI oxidative addition. The compatibility of these transformation groups in this
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 24
1
2
3
4
5
6
7
8
9
reaction provided a platform for the further elaboration of the complex products. To our delight,
substrates contain active hydrogen group amino (3o) also could be tolerated, which is a great
challenge in many coupling reactions. This is in sharp contrast to the previous results,13 in which
the phenylselenium nuclephilic reagents are very sensitive to these functional groups. Thus, the
current reaction features the advantage of the versatile and operational simplicity. It’s remarkable
that heterocyclic iodides such as pyridine and thiophene are competent coupling partners and
could also provide the corresponding products (3p, q) in good yield.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 3. Epoxides Scope
aReaction conditions unless specified otherwise: Iodobenzene (0.4 mmol), Se8 (0.8 mmol),
epoxides (1.2 mmol), CuCl (0.04 mmol), K3PO4 (1.2 mmol), DMSO (2 mL), 140 °C, 24 h, N2.
Isolated yields are given.
Next, the scope of epoxides was further investigated under the optimized reaction conditions.
As demonstrated in Scheme 3, the reaction worked well in regionꢀselectivity and the great
ACS Paragon Plus Environment

Page 7 of 24
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
functional group tolerance. Cyclic epoxides (4a, b) are efficiently opened to give corresponding
product in excellent yield. The reaction can be applied to the linear and branched aliphatic oxirane
all provided the products (4cꢀf) in good to excellent yields. Notably, double bond (4g, h) and ester
(4i) substituents could afford the desired products. We found that different electronic property of
substituents on the aromatic ring of 2ꢀ(phenoxymenthyl)oxirane were compatible, such as
methoxy (4n), fluoride(4k), chloride (4l), bromide (4m), and trifluoromethyl (4o), to a certain
extent, these functional groups have affected the substrates reactivity. Investigation of
functionalized styrene oxides were high indispensable, as the resulting αꢀhydroxyꢀ2ꢀphenylethyl
phenyl selenides is complement of the contrary products obtained by the previously reported
methods that employed PhSeZnCl reagent as coupling partner.13e
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 4. Preliminary Mechanism Investigation
To understand the reaction mechanism, control experiments were conducted (Scheme 4).
First, a stoichiometric reaction of PhSeCu6 with 1,2ꢀepoxycyclohexane no matter whether under
an N2 or under an O2 atmosphere did not promote the reaction (Scheme 4, eq 1). An interesting
phenomenon was observed, the desired product 3a was obtained in 89% isolated yield, when 1
equiv of selenium powder was added under standard reaction condition (eq 2); These experiments
indicates that elemental selenium play a critical role in the process of oxirane opening reaction.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 24
1
2
3
4
5
6
7
8
9
Secondly, As shown in eq 3, PhSeCu may be a chemically competent intermediate produced in
situ during the catalytic cycle. It could also rationalize why a small amount of diphenyl diselenides
were detected in the reaction. Finally, when the radical inhibitor TEMPO was added to the
reaction conditions, product 3a was still obtained in 76 % yield (eq 4), which return suggested that
a radicalꢀinvolved mechanism could be ruled out. Although, the details of the reaction mechanism
remains unclear at the present time, we assume that the epoxides ring opening reaction is likely to
involve a SN2ꢀtype by the phenylseleniumꢀcopper complex intermediate generated in situ from the
aryl iodide and elemental selenium.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
In summary, we have demonstrated the synthesis of a broad range of β ꢀhydroxy
phenylselenides through a convergent threeꢀcomponent copperꢀcatalyzed coupling approach.
Commercially available, stable, easily handled elemental selenium was used as selenating reagent.
The important feature of this method was operationally simple to perform and applied to broad
substrate scope. Further studies to develop related transformations and deeply understand the
mechanism are underway.
Experimental Section
General Remarks. 1H NMR (500 MHz), 13C NMR (125 MHz) and 19F NMR (470 MHz) spectra
were recorded in CDCl3 solutions using a 500 MHz spectrometer. Highꢀresolution mass spectra
were recorded on an ESIꢀQꢀTOF mass spectrometer. All reactions were conducted using standard
Schlenk techniques. Column chromatography was performed using EM silica gel 60 (300−400
1
mesh). H NMR and 13C NMR spectra are provided as Supporting Information. 4ꢀbromo styrene
oxide,14
2ꢀchloro
styrene
oxide,14
2ꢀ[(4ꢀchlorophenoxy)methyl]oxirane,14
2ꢀ[(4ꢀfluorophenoxy)methyl]oxirane,14
2ꢀ[(4ꢀbromophenoxy)methyl]oxirane,14
ACS Paragon Plus Environment

Page 9 of 24
The Journal of Organic Chemistry
1
2
3
4
2ꢀ[(4ꢀmethoxyphenoxy)methyl]oxirane14 and 2ꢀ[(4ꢀtrifluromethylphenoxy)methyl]oxirane14 were
5
6
7
1
prepared according to the reported procedures. H and 13C spectra of known compounds were in
8
9
accordance with those described in the literature.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Procedure for Intermolecular Phenylselenation of epoxides-opening Reactions. In a 25 mL
Schlenk tube equipped with a stir bar were placed aryl iodides 1 (0.4 mmol), epoxides 2 (1.2
mmol), Se (0.8 mmol), CuCl (10 mol %), and K3PO4 (1.2 mmol) in DMSO (2 mL). The tube was
o
evacuated and refilled with N2 three times. The reaction mixture was stirred at 140 C for 24 h.
After it was colled, the reaction mixture was diluted with 10 mL of ethyl ether, and filtered
through a pad of silica gel, followed by washing the pad of silica gel with the same solvent (20
mL). The filtrate was washed with water (3×15 mL). The organic phase was dried over Na2SO4,
filtered, and concentrated under reduced pressure. The residue was then purified by flash
chromatography on silica gel to provide the corresponding product.
Preliminary Mechanism Investigation. In Two 10 mL of Schlenk tubes equipped with a stir bar
were placed with PhSeCu (0.4 mmol), Cyclohexene oxide (1.2 mmol), and K3PO4 (1.2 mmol) in
DMSO (2 mL). The first tube, was evacuated and refilled N2 three times. The other tube, was
fitted with a rubber septum, and then it was evacuated and refilled with O2 three times. These
o
reaction mixtures were stirred at 140 C for 24 h (see Scheme 4, eq 1). To a 10 mL Schlenk tube
equipped with a stir bar were placed PhSeCu (0.4 mmol), Se (0.4 mmol), Cyclohexene oxide (1.2
mmol), and K3PO4 (1.2 mmol) in DMSO (2 mL). The tube was evacuated and refilled with N2
three times. The reaction mixture was stirred at 140 oC for 24 h (see Scheme 4, eq 2). In a 10 mL
Schlenk tube equipped with a stir bar were placed iodobenzene (0.4 mmol), Cyclohexene oxide
(1.2 mmol), Se (0.8 mmol), PhSeCu (10 mol %), and K3PO4 (1.2 mmol) in DMSO (2 mL). The
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 24
1
2
3
4
5
6
7
8
9
tube was evacuated and refilled with N2 three times. The reaction mixture was stirred at 140 oC for
24 h (see Scheme 4, eq 3). After it was cooled, the reaction mixture was diluted with 10 mL of
ethyl ether, and filtered through a pad of silica gel, followed by washing the pad of silica gel with
the same solvent (20 mL). The filtrate was washed with water (3×15 mL). The organic phase was
dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was then
purified by flash chromatography on silica gel to provide the corresponding product.
Characterization Data of Compounds 3 and 4:
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2ꢀphenylselenocyclohexanꢀ1ꢀol (3a). Following the general procedure, using 8/1 petroleum ether
/ethyl acetate as the eluant to afford yellow oil liquid (85.0 mg, 83 % yield). The 1H and 13C NMR
spectra were in accordance with those described in the literature.14
2ꢀ(2ꢀcyano)phenylselenocyclohexanꢀ1ꢀol (3b). Following the general procedure, using 8/1
1
petroleum ether/ethyl acetate as the eluant to afford yellow oil liquid (64.1 mg, 57 % yield). H
NMR (500 MHz, CDCl3): δ 7.79 ꢀ 7.77 (m, 1H), 7.70 ꢀ 7.68 (m, 1H), 7.51 ꢀ 7.48 (m, 1H), 7.44 ꢀ
7.41 (m, 1H), 3.48 ꢀ 3.42 (m, 1H), 3.13 ꢀ 3.08 (m, 1H), 2.77 (d, J = 2.5 Hz, 1H), 2.27 ꢀ 2.13 (m,
2H), 1.77 ꢀ 1.65 (m, 2H), 1.44 ꢀ 1.25 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 137.2, 133.7, 132.7,
131.9, 128.5, 119.5, 118.5, 73.0, 54.8, 34.3, 33.3, 26.8, 24.4. HRMS (ESI): calcd for
C13H15NOSeNa [M+Na]+ 304.0212, found 304.0218.
2ꢀ(oꢀtolylseleno)cyclohexanꢀ1ꢀol (3c). Following the general procedure, using 8/1 petroleum
1
ether/ethyl acetate as the eluant to afford yellow oil liquid (87.5 mg, 81 % yield). H NMR (500
MHz, CDCl3): δ 7.59 (d, J = 7.5 Hz, 1H), 7.24 ꢀ 7.18 (m, 2H), 7.09 (t, J = 7.5 Hz, 1H), 3.46 ꢀ 3.41
(m, 1H), 3.00 ꢀ 2.95 (m, 1H), 2.82 (s, 1H), 2.48 (s, 3H), 2.19 ꢀ 2.12 (m, 2H), 1.75 ꢀ 1.19 (m, 1H),
1.50 ꢀ 1.43 (m, 1H), 1.36 ꢀ 1.22 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 141.5, 135.9, 130.1,
ACS Paragon Plus Environment

Page 11 of 24
The Journal of Organic Chemistry
1
2
3
4
5
6
128.9, 128.1, 126.5, 73.1, 53.4, 34.1, 33.4, 26.8, 24.4, 23.3. HRMS (ESI): calcd for C13H18OSeNa
[M+Na]+ 293.0416, found 293.0413.
7
8
9
2ꢀ(naphthalenꢀ1ꢀylseleno)cyclohexanꢀ1ꢀol (3d). Following the general procedure, using 8/1
petroleum ether/ethyl acetate as the eluant to afford yellow oil liquid (101.6 mg, 83 % yield). The
1H and 13C NMR spectra were in accordance with those described in the literature.14
2ꢀ(3ꢀfluoro)phenylselenocyclohexanꢀ1ꢀol (3e). Following the general procedure, using 8/1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
petroleum ether/ethyl acetate as the eluant to afford yellow oil liquid (80.0 mg, 73 % yield). H
NMR (500 MHz, CDCl3): δ 7.36 ꢀ 7.30 (m, 2H), 7.25 ꢀ 7.22 (m, 1H), 7.01 (t, J = 8.5 Hz, 1H), 3.38
ꢀ 3.34 (m, 1H), 2.98 ꢀ 2.93 (m, 1H), 2.80 (s, 1H), 2.20 ꢀ 2.13 (m, 2H), 1.76 ꢀ 1.64 (m, 2H), 1.48 ꢀ
1.20 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 162.4 (d, JF = 248.8 Hz), 131.2 (d, JF = 2.5 Hz),
130.2 (d, JF = 7.5 Hz), 128.8 (d, JF = 6.3 Hz), 122.3 (d, JF = 21.3 Hz), 115.1 (d, JF = 21.3 Hz), 72.6,
53.9, 34.1, 33.5, 26.8, 24.4. 19F NMR (470 MHZ, CDCl3): δ ꢀ111.92 (s, 1F). HRMS (ESI): calcd
for C12H15FOSeNa [M+Na]+ 297.0165, found 297.0166.
2ꢀ(3ꢀ(trifluoromethyl)phenylseleno)cyclohexanꢀ1ꢀol (3f). Following the general procedure, using
8/1 petroleum ether/ethyl acetate as the eluant to afford yellow oil liquid (95.9 mg, 74 % yield). 1H
NMR (500 MHz, CDCl3): δ 7.52 (d, J = 8.0 Hz, 1H), 7.46 (s, 1H), 7.30 (t, J = 8.5 Hz, 1H), 7.17 (d,
J = 8.0 Hz, 1H), 3.40 ꢀ 3.34 (m, 1H), 3.00 ꢀ 2.94 (m, 1H), 2.77 (s, 1H), 2.20 ꢀ 2.13 (m, 2H), 1.79 ꢀ
1.74 (m, 1H), 1.68 ꢀ 1.64 (m, 1H), 1.48 ꢀ 1.20 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 149.1,
133.8, 130.8, 129.1, 127.8, 120.5 (q, JF = 256.3 Hz), 120.4, 72.7, 53.9, 34.2, 33.47, 26.8, 24.4. 19
F
NMR (470 MHz, CDCl3): δ ꢀ57.81 (s, 3F). HRMS (ESI): calcd for C13H15F3OSeNa [M+Na]+
347.0133, found 347.0134.
2ꢀ(3ꢀnitro)phenylselenocyclohexanꢀ1ꢀol (3g). Following the general procedure, using 8/1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 24
1
2
3
4
5
6
7
8
9
1
petroleum ether/ethyl acetate as the eluant to afford yellow oil liquid(78.3 mg, 65 % yield). H
NMR (500 MHz, CDCl3): δ 8.44 (s, 1H), 8.15 (d, J = 8.0 Hz, 1H), 7.91 (d, J = 7.5 Hz, 1H), 7.46 (t,
J = 8.0 Hz, 1H), 3.5 ꢀ 3.40 (m, 1H), 3.09 ꢀ 3.04 (m, 1H), 2.67 (s, 1H), 2.22 ꢀ 2.14 (m, 2H), 1.79 ꢀ
1.67 (m, 2H), 1.50 ꢀ 1.27 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 148.2, 140.9, 129.9, 129.6,
129.5, 122.7, 72.9, 54.1, 34.4, 33.5, 26.7, 24.3. HRMS (ESI): calcd for C12H16NO3Se [M+H]+
302.0290, found 302.0297.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2ꢀ(pꢀtolylseleno)cyclohexanꢀ1ꢀol (3h). Following the general procedure, using 8/1 petroleum
ether/ ethyl acetate as the eluant to afford yellow oil liquid (92.9 mg, 86 % yield). 1H NMR (500
MHz, CDCl3): δ 7.47 (d, J = 8.0 Hz, 2H), 7.09 (d, J = 8.0 Hz, 2H), 3.32 ꢀ 3.27 (m, 1H), 2.97 (s,
1H), 2.85 ꢀ 2.80 (m, 1H), 2.34 (s, 3H), 2.17 ꢀ 2.11 (m, 2H), 1.73 ꢀ 1.70 (m, 1H), 1.63 ꢀ 1.59 (m,
1H), 1.40 ꢀ 1.18 (m, 4H); 13C NMR (125 MHZ, CDCl3): δ 138.3, 136.5, 129.8, 122.6, 72.2, 58.5,
33.9, 33.3, 26.9, 24.5, 21.2. HRMS (ESI): calcd for C13H18OSeNa [M+Na]+ 293.0416, found
293.0418.
2ꢀ(pꢀmethoxy)phenylselenocyclohexanꢀ1ꢀol (3i). Following the general procedure, using 8/1
1
petroleum ether/ethyl acetate as the eluant to afford yellow oil liquid (92.7 mg, 81 % yield). H
NMR (500 MHz, CDCl3): δ 7.50 (d, J = 9.0 Hz, 2H), 6.82 (d, J = 8.5 Hz, 2H), 3.81 (s, 3H), 3.27 ꢀ
3.23 (m, 1H), 2.98 (s, 1H), 2.79 ꢀ 2.73 (m, 1H), 2.13 ꢀ 2.10 (m, 2H), 1.72 ꢀ 1.59 (m, 2H), 1.33 ꢀ
1.19 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 159.9, 138.4, 115.9, 114.7, 71.9, 55.3, 53.4, 33.8,
33.2, 26.9, 24.5. HRMS (ESI): calcd for C13H18O2SeNa [M+Na]+ 309.0365, found 309.0362.
2ꢀ(pꢀfluoro)phenylselenocyclohexanꢀ1ꢀol (3j). Following the general procedure, using 8/1
1
petroleum ether/ethyl acetate as the eluant to afford yellow oil liquid (87.7 mg, 80 % yield). H
NMR (500 MHz, CDCl3): δ 7.57 (t, J = 6.5 Hz, 2H), 6.99 (t, J = 8.5 Hz, 2H), 3.29 (s, 1H), 2.87 ꢀ
ACS Paragon Plus Environment

Page 13 of 24
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
2.81 (m, 2H), 2.17 ꢀ 2.12 (m, 2H), 1.75 ꢀ 1.72 (m,1H), 1.63 ꢀ 1.62 (m, 1H), 1.38 ꢀ 1.19 (m, 4H);
13C NMR (125 MHz, CDCl3): δ 163.1 (d, JF = 247.5 Hz), 138.5 (d, JF = 8.8 Hz), 120.9, 116.3 (d,
JF = 21.3 Hz), 72.1, 53.7, 33.9, 33.3, 26.8, 24.5. 19F NMR (470 MHz, CDCl3): δ ꢀ113.07 (s, 1F).
HRMS (ESI): calcd for C12H16FOSe [M+H]+ 275.0345, found 275.0347.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2ꢀ((4ꢀchlorophenyl)seleno)cyclohexanꢀ1ꢀol (3k). Following the general procedure, using 8/1
1
petroleum ether/ethyl acetate as the eluant to afford yellow oil liquid (91.6 mg, 79 % yield). H
NMR (CDCl3, 500 MHz): δ 7.51 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.5 Hz, 2H), 3.34 ꢀ 3.29 (m, 1H),
2.91 ꢀ 2.87 (m, 1H), 2.84 (s, 1H), 2.17 ꢀ 2.12 (m, 2H), 1.74 ꢀ 1.62 (m, 2H), 1.43 ꢀ 1.22 (m, 4H);
13C NMR (CDCl3, 125 MHz): δ 137.4, 134.6, 129.2, 124.9, 72.3, 53.8, 34.0, 33.7, 26.8, 24.4.
HRMS (ESI): calcd for C12H15ClOSeNa [M+Na]+ 312.9870, found 312.9873.
2ꢀ((4ꢀbromophenyl)seleno)cyclohexanꢀ1ꢀol (3l). Following the general procedure, using 8/1
1
petroleum ether/ethyl acetate as the eluant to afford yellow oil liquid (113.6 mg, 85 % yield). H
NMR (500 MHz, CDCl3): δ 7.46 ꢀ 7.39 (m, 4H), 3.32 (s, 1H), 2.92 ꢀ 2.83 (m, 2H), 2.17 ꢀ 2.12 (m,
2H), 1.75 ꢀ 1.62 (m, 2H), 1.40 ꢀ 1.23 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 137.6, 132.2, 125.6,
122.8, 72.3, 53.8, 34.0, 33.4, 26.8, 24.4. HRMS (ESI): calcd for C12H15BrOSeNa [M+Na]+
356.9364, found 356.9368.
2ꢀ((4ꢀformylphenyl)seleno)cyclohexanꢀ1ꢀol (3m). Following the general procedure, using 4/1
1
petroleum ether/ethyl acetate as the eluant to afford yellow oil liquid (43.2 mg, 38 % yield). H
NMR (500 MHz, CDCl3): δ 9.97 (s, 1H), 7.77 ꢀ 7.70 (m, 4H), 3.47 ꢀ 3.44 (m, 1H), 3.17 ꢀ 3.11 (m,
1H), 2.68 (s, 1H), 2.25 ꢀ 2.15 (m, 2H), 1.79 ꢀ 1.67 (m, 2H), 1.57 ꢀ 1.27 (m, 4H); 13C NMR (125
MHz, CDCl3): δ 191.6, 137.9, 135.2, 133.9, 129.9, 73.1, 53.7, 34.3, 33.6, 26.8, 24.4. HRMS (ESI):
calcd for C13H16O2SeNa [M+Na]+ 307.0209, found 307.0211.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 24
1
2
3
4
5
6
7
8
9
2ꢀ(pꢀmethoxycarbonyl)phenylselenocyclohexanꢀ1ꢀol (3n). Following the general procedure, using
4/1 petroleum ether/ethyl acetate as the eluant to afford yellow oil liquid (44.0 mg, 35 % yield). 1H
NMR (500 MHz, CDCl3): δ 7.92 (d, J = 8.5 Hz, 2H), 7.63 (d, J = 8.5 Hz, 2H), 3.91 (s, 3H), 3.43 ꢀ
3.38 (m, 1H), 3.08 ꢀ 3.03 (m, 1H), 2.75 (s, 1H), 2.22 ꢀ 2.13 (m, 2H), 1.77 ꢀ 1.66 (m, 2H), 1.49 ꢀ
1.26 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 166.7, 134.7, 134.3, 129.9, 129.3, 72.8, 53.7, 52.22,
34.2, 33.5, 26.8, 24.4. HRMS (ESI): calcd for C14H18O3SeNa [M+Na]+ 337.0314, found 337.0316.
2ꢀ((3ꢀchloroꢀ4ꢀamino)phenylseleno)cyclohexanꢀ1ꢀol (3o). Following the general procedure, using
4/1 petroleum ether/ethyl acetate as the eluant to afford yellow oil liquid(95.2 mg, 78 % yield). 1H
NMR (500 MHz, CDCl3): δ 7.24 ꢀ 7.21 (m, 1H), 7.16 (d, J = 8.5 Hz, 1H), 6.69 (t, J = 8.5 Hz, 1H),
3.85 (s, 2H), 3.27 ꢀ 3.22 (m, 1H), 2.95 (s, 1H), 2.77 ꢀ 2.71 (m, 1H), 2.13 ꢀ 2.11 (m, 2H), 1.73 ꢀ
1.70 (m, 1H), 1.62 ꢀ 1.60 (m, 1H), 1.36 ꢀ 1.17 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 151.7,
149.8, 135.3, 133.7, 123.9, 116.9, 71.8, 53.5, 33.8, 33.1, 26.8, 24.5. HRMS (ESI): calcd for
C12H16ClNOSeNa [M+Na]+ 327.9979, found 327.9980.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2ꢀ(thiophenꢀ3ꢀylseleno)cyclohexanꢀ1ꢀol (3p). Following the general procedure, using 8/1
1
petroleum ether/ethyl acetate as the eluant to afford yellow oil liquid (73.4 mg, 70 % yield). H
NMR (500 MHz, CDCl3): δ 7.44 ꢀ 7.42 (m, 1H), 7.32 ꢀ 7.30 (m, 1H), 7.12 (d, J = 5.0 Hz, 1H),
3.29 ꢀ 3.25 (m, 1H), 2.92 (s, 1H), 2.79 ꢀ 2.74 (m, 1H), 2.18 ꢀ 2.10 (m, 2H), 1.74 ꢀ 1.63 (m, 2H),
1.40 ꢀ 1.18 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 134.3, 131.1, 126.3, 118.9, 72.2, 53.4, 33.9,
33.3, 26.9, 24.5. HRMS (ESI): calcd for C10H15OSSe [M+H]+ 263.0004, found 263.0008.
2ꢀ(oꢀpyridylseleno)cyclohexanꢀ1ꢀol (3q). Following the general procedure, using 2/1 petroleum
1
ether/ethyl acetate as the eluant to afford yellow oil liquid (77.1 mg, 75 % yield). H NMR (500
MHz, CDCl3): δ 8.39 ꢀ 8.37 (m, 1H), 7.50 ꢀ 7.44 (m, 2H), 7.09 ꢀ 7.06 (m, 1H), 6.24 (s, 1H), 3.66 ꢀ
ACS Paragon Plus Environment

Page 15 of 24
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
3.61 (m, 1H), 3.49 ꢀ 3.43 (m, 1H), 2.28 ꢀ 2.21 (m, 2H), 1.80 ꢀ 1.73 (m, 1H), 1.71 ꢀ 1.70 (m, 1H),
1.61 ꢀ 1.53 (m, 1H), 1.42 ꢀ 1.27 (m, 3H); 13C NMR (125 MHz, CDCl3): δ 156.0, 149.4, 136.5,
126.6, 120.8, 76.1, 50.9, 36.7, 32.6, 26.9, 24.3. HRMS (ESI): calcd for C11H15NOSeNa [M+Na]+
280.0212, found 280.0211.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2ꢀ(phenylseleno)cyclopentanꢀ1ꢀol (4a). Following the general procedure, using 8/1 petroleum
1
ether/ethyl acetate as the eluant to afford yellow oil liquid (92.0 mg, 95 % yield). H NMR (500
MHz, CDCl3): δ 7.58 ꢀ 7.55 (m, 2H), 7.28 ꢀ 7.26 (m, 3H), 4.18 ꢀ 4.15 (m, 1H), 3.42 ꢀ 3.38 (m, 1H),
2.30 ꢀ 2.23 (m, 1H), 2.09 ꢀ 2.03 (m, 1H), 1.82 ꢀ 1.60 (m, 5H); 13C NMR (125 MHz, CDCl3) : δ
134.20, 129.36, 129.11, 127.48, 79.06, 49.29, 32.90, 31.12, 22.05. HRMS (ESI): calcd for
C11H14OSeNa [M+Na]+ 265.0103, found 265.0101.
4ꢀ((2ꢀhydroxycyclohexyl)seleno)tetrahydrofuranꢀ3ꢀol (4b). Following the general procedure,
using 4/1 petroleum ether/ethyl acetate as the eluant to afford yellow oil liquid (79.1 mg, 81 %
1
yield). H NMR (500 MHz, CDCl3): δ 7.57 ꢀ 7.54 (m, 2H), 7.30 ꢀ 7.27 (m, 3H), 4.37 ꢀ 4.31 (m,
2H), 4.02 (dd, J1 = 4.5 Hz, J2 = 9.5 Hz, 1H), 3.77 ꢀ 3.72 (m, 2H), 3.63 ꢀ 3.60 (m, 1H), 2.63 (s, 1H);
13C NMR (125 MHz, CDCl3): δ 134.1, 129.4, 128.7, 127.9, 77.8, 74.0, 72.2, 47.4. HRMS (ESI):
calcd for C10H12O2SeNa [M+Na]+ 266.9896, found 266.9898.
2ꢀmethylꢀ1ꢀ(phenylseleno)propanꢀ2ꢀol (4c). Following the general procedure, using 4/1 petroleum
1
ether/ethyl acetate as the eluant to afford yellow oil liquid (59.8 mg, 65 % yield). H NMR (500
MHz, CDCl3): δ 7.56 ꢀ 7.54 (m, 2H), 7.26 ꢀ 7.23 (m, 3H), 3.15 (s, 2H), 2.26 (s, 1H), 1.31 (s, 6H);
13C NMR (125 MHz, CDCl3): δ 132.5, 130.9, 129.2, 127.0, 70.4, 44.4, 29.0. HRMS (ESI) : calcd
for C10H14OSeNa [M+Na]+ 253.0103, found 253.0106.
1ꢀ(phenylseleno)butanꢀ2ꢀol (4d). Following the general procedure, using 8/1 petroleum ether/ethyl
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 24
1
2
3
4
1
acetate as the eluant to afford yellow oil liquid (85.6 mg, 93 % yield). The H and 13C NMR
5
6
7
spectra were in accordance with those described in the literature16.
8
9
3,3ꢀdimethylꢀ1ꢀ(phenylseleno)butanꢀ2ꢀol (4e). Following the general procedure, using 8/1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
petroleum ether/ethyl acetate as the eluant to afford yellow oil liquid (82.6 mg, 80 % yield). H
NMR (500 MHz, CDCl3): δ 7.52 ꢀ 7.50 (m, 2H), 7.27 ꢀ 7.25 (m, 3H), 3.27 (dd, J1 = 11.0 Hz, J2 =
26.0 Hz, 2H), 2.80 (t, J = 12.0 Hz, 1H), 2.49 (s, 1H), 0.92 (s, 9H); 13C NMR (125 MHz, CDCl3): δ
132.9, 129.4, 129.2, 127.2, 77.1, 34.9, 33.3, 25.8. HRMS (ESI): calcd for C12H18OSeNa [M+Na]+
281.0416, found 281.0417.
1ꢀbutoxylꢀ3ꢀ(phenylseleno)ꢀpropanꢀ2ꢀol (4f). Following the general procedure, after 12h, butyl
glycidyl ether (156 mg, 3 equiv, 1.2 mmol) was added using syringe, using 8/1 petroleum
ether/ethyl acetate as the eluant to afford yellow oil liquid (99.1 mg, 86 % yield). The H and 13
C
1
NMR spectra were in accordance with those described in the literature17.
4ꢀ(phenylseleno)butenꢀ3ꢀol (4g). Following the general procedure, using 8/1 petroleum ether/ethyl
acetate as the eluant to afford yellow oil liquid (52.9 mg, 58 % yield). The H and 13C NMR
1
spectra were in accordance with those described in the literature18.
1ꢀ(phenylseleno)ꢀ3ꢀ(2ꢀpropenꢀ1ꢀyloxy)ꢀpropanꢀ2ꢀol (4h). Following the general procedure, after
12h, allyl glycidyl ether (136.8 mg, 3 equiv, 1.2 mmol) was added using syringe, using 4/1
petroleum ether/ethyl acetate as the eluant to afford yellow oil liquid (77.2 mg, 71 % yield). The
1H and 13C NMR spectra were in accordance with those described in the literature17.
2‘ꢀpropenoic acidꢀ2ꢀhydroxyꢀ3ꢀ(phenylseleno)propyl ester (4i). Following the general procedure,
after 12h, glycidyl methacrylate (170.4 mg, 3 equiv, 1.2 mmol) was added using syringe, using 4/1
petroleum ether/ethyl acetate as the eluant to afford yellow oil liquid (36 mg, 30 % yield). The 1H
ACS Paragon Plus Environment

Page 17 of 24
The Journal of Organic Chemistry
1
2
3
4
and 13C NMR spectra were in accordance with those described in the literature17.
5
6
7
1ꢀphenoxyꢀ3ꢀ(phenylseleno)propanꢀ2ꢀol (4j). Following the general procedure, after 12h, glycidyl
8
9
phenyl ether (180.0 mg, 3 equiv, 1.2 mmol) was added using syringe, using 4/1 petroleum
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
ether/ethyl acetate as the eluant to afford yellow oil liquid (82.6 mg, 67 % yield). The H and 13
C
NMR spectra were in accordance with those described in the literature17.
1ꢀ(pꢀfluoro)phenoxyꢀ3ꢀ(phenylseleno)propanꢀ2ꢀol (4k). Following the general procedure, after
12h, (4ꢀfluoro)phenoxymethyl oxirane (201.6 mg, 3 equiv, 1.2 mmol) was added using syringe,
using 4/1 petroleum ether /ethyl acetate as the eluant to afford yellow oil liquid (122.6 mg, 94 %
1
yield). H NMR (500 MHz, CDCl3): δ 7.55 ꢀ 7.53 (m, 2H), 7.25 ꢀ 7.23 (m, 3H), 6.96 ꢀ 6.92 (m,
2H), 6.80 ꢀ 6.77 (m, 2H), 4.11 ꢀ 4.07 (m, 1H), 4.01 ꢀ 3.95 (m, 2H), 3.22 ꢀ 3.19 (m, 1H), 3.14 ꢀ 3.10
(m, 1H), 2.68 (s, 1H); 13C NMR (125 MHz, CDCl3): δδ 157.5 (d, JF = 237.5 Hz), 154.5 (d, JF =
1.3 Hz), 132.9, 129.3, 129.2, 127.4, 115.9 (d, JF = 23.8 Hz), 115.6 (d, JF = 8.8 Hz), 71.2, 69.0,
31.9. 19F NMR (470 MHz, CDCl3): δ ꢀ123.35 (s, 1F). HRMS (ESI): calcd for C15H15FO2SeNa
[M+Na]+ 349.0114, found 349.0120.
1ꢀ(pꢀchloro)phenoxyꢀ3ꢀ(phenylseleno)propanꢀ2ꢀol (4l). Following the general procedure, after 12h,
(4ꢀchloro)phenoxymethyl oxirane (220.8 mg, 3 equiv, 1.2 mmol) was added using syringe, using
4/1 petroleum ether /ethyl acetate as the eluant to afford yellow oil liquid (101.2 mg, 74 % yield).
1H NMR (500 MHz, CDCl3): δ 7.54 ꢀ 7.52 (m, 2H), 7.25 ꢀ 7.24 (m, 3H), 7.20 (d, J = 9.0 Hz, 2H),
6.77 (d, J = 9.0 Hz, 2H), 4.12 ꢀ 4.07 (m, 1H), 4.01 ꢀ 3.95 (m, 2H), 3.20 (dd, J1 = 5.5 Hz, J2 = 13.0
Hz, 1H), 3.12 (dd, J1 = 7.0 Hz, J2 = 13.0 Hz, 1H), 2.73 (d, J = 4.5 Hz, 1H); 13C NMR (125 MHz,
CDCl3): δ 157.0, 133.0, 129.4, 129.3, 129.1, 127.5, 126.1, 115.8, 70.8, 69.0, 31.9. HRMS (ESI):
calcd for C15H15ClO2SeNa [M+Na]+ 364.9819, found 364.9814.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 24
1
2
3
4
5
6
7
8
9
1ꢀ(pꢀbromo)phenoxyꢀ3ꢀ(phenylseleno)propanꢀ2ꢀol (4m). Following the general procedure, after
12h, (4ꢀbromo)phenoxymethyl oxirane (273.6 mg, 3 equiv, 1.2 mmol) was added using syringe,
using 4/1 petroleum ether / ethyl acetate as the eluant to afford yellow oil liquid (118.9 mg, 77 %
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
yield). H NMR (500 MHz, CDCl3): δ 7.54 ꢀ 7.52 (m, 2H), 7.36 ꢀ 7.33 (m, 2H), 7.25 ꢀ 7.24 (m,
3H), 6.74 ꢀ 6.71 (m, 2H), 4.11 ꢀ 4.07 (m, 1H), 4.00 ꢀ 3.95 (m, 2H), 3.20 (dd, J1 = 6.0 Hz, J2 = 13.0
Hz, 1H), 3.11 (dd, J1 = 7.0 Hz, J2 = 13.0 Hz, 1H), 2.67 (d, J = 4.5 Hz, 1H); 13C NMR (125 MHz,
CDCl3): δ 157.5, 133.0, 132.3, 129.3, 129.1, 127.5, 116.4, 113.4, 70.8, 68.9, 31.9. HRMS (ESI):
calcd for C15H15BrO2SeNa [M+Na]+ 408.9314, found 408.9310.
1ꢀ(pꢀmethoxyl)phenoxyꢀ3ꢀ(phenylseleno)propanꢀ2ꢀol (4n). Following the general procedure, after
12h, (4ꢀmethoxy)phenoxymethyl oxirane (216.0 mg, 3 equiv, 1.2 mmol) was added using syringe,
using 4/1 petroleum ether / ethyl acetate as the eluant to afford yellow oil liquid (117.6 mg, 87 %
1
yield). H NMR (500 MHz, CDCl3): δ 7.54 ꢀ 7.52 (m, 2H), 7.24 ꢀ 7.23 (m, 3H), 6.81 ꢀ 6.75 (m,
4H), 4.10 ꢀ 4.07 (m, 1H), 4.00 ꢀ 3.93 (m, 2H), 3.75 (s, 3H), 3.20 (dd, J1 = 6.0 Hz, J2 = 13.0 Hz,
1H), 3.11 (dd, J1 = 7.0 Hz, J2 = 13.0 Hz, 1H), 2.81 (d, J = 4.5 Hz, 1H); 13C NMR (125 MHz,
CDCl3): δ 154.2, 152.5, 132.9, 129.4, 129.3, 127.4, 115.6, 114.7, 71.3, 69.2, 55.8, 31.9. HRMS
(ESI): calcd for C16H18O3SeNa [M+Na]+ 361.0314, found 361.0318.
1ꢀ(pꢀtrifluoromethyl)phenoxyꢀ3ꢀ(phenylseleno)propanꢀ2ꢀol (4o). Following the general procedure,
after 12h, (4ꢀtrifluoromethyl)phenoxymethyl oxirane (261.6 mg, 3 equiv, 1.2 mmol) was added
using syringe, using 4/1 petroleum ether/ ethyl acetate as the eluant to afford yellow oil liquid
(93.3 mg, 62 % yield). 1H NMR (500 MHz, CDCl3): δ 7.54 ꢀ 7.50 (m, 4H), 7.24 ꢀ 7.23 (m, 3H),
6.89 (d, J = 8.55 Hz, 2H), 4.14 ꢀ 4.11 (m, 1H), 4.07 ꢀ 4.01 (m, 2H), 3.22 (dd, J1 = 5.5 Hz, J2 = 13.0
Hz, 1H), 3.13 (dd, J1 = 7.0 Hz, J2 = 13.0 Hz, 1H), 2.78 (s, 1H); 13C NMR (125 MHz, CDCl3):
ACS Paragon Plus Environment

Page 19 of 24
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
δ160.8, 133.1, 129.3, 128.9, 127.6, 127.0, 126.9, 126.8, 125.4, 123.4 (q, JF = 31.3 Hz), 114.5, 70.6,
68.9, 31.9. 19F NMR (470MHz, CDCl3): δ ꢀ61.55 (s, 3F). HRMS (ESI): calcd for C16H15F3O2SeNa
[M+Na]+ 399.0082, found 399.0084.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1ꢀphenylꢀ2ꢀ(phenylseleno)ethanꢀ1ꢀol (4p). Following the general procedure, after 12h, phenyl
oxirane (144mg, 3equiv, 1.2mmol) was added using syringe, using petroleum ether/ ethyl acetate
as the eluant to afford yellow oil liquid (84.5 mg, 76 % yield). The 1H and 13C NMR spectra were
in accordance with those described in the literature18.
1ꢀ(4ꢀfluoro)phenyl ꢀ2ꢀphenylselenoethanꢀ1ꢀol (4q). Following the general procedure, after 12h,
(4ꢀ fluoro)phenyl oxirane (184.8 mg, 3 equiv, 1.2 mmol) was added using syringe, using 4/1
1
petroleum ether / ethyl acetate as the eluant to afford yellow oil liquid (92.4 mg, 78 % yield). H
NMR (500 MHz, CDCl3): δ 7.55 ꢀ 7.52 (m, 2H), 7.31 ꢀ 7.27 (m, 5H), 7.01 (t, J = 8.5 Hz, 2H), 4.72
ꢀ 4.70 (m, 1H), 3.26 (dd, J1 = 3.5 Hz, J2 = 13.0 Hz, 1H), 3.09 (dd, J1 = 9.5 Hz, J2 = 13.0 Hz, 1H),
2.85 (s,1H); 13C NMR (125 MHz, CDCl3): δ 162.4 (d, JF = 248.7 Hz), 138.2 (d, JF = 3.7 Hz),
133.2, 129.3, 128.9, 127.5, 127.5, 115.4 (d, JF = 21.2 Hz), 71.6, 38.6. 19F NMR (470 MHz,
CDCl3): δ ꢀ114.40 (s, 1F). HRMS (ESI): calcd for C14H14FOSe [M+H]+ 297.0189, found
297.0183.
1ꢀ(4ꢀchloro)phenyl ꢀ2ꢀphenylselenoethanꢀ1ꢀol (4r). Following the general procedure, after 12h,
(4ꢀchloro)phenyl oxirane (184.8 mg, 3 equiv, 1.2 mmol) was added using syringe, using 4/1
1
petroleum ether /ethyl acetate as the eluant to afford yellow oil liquid(93.6 mg, 75 % yield). H
NMR (500 MHz, CDCl3): δ 7.52 ꢀ 7.50 (m, 2H), 7.28 ꢀ 7.23 (m, 7H), 4.68 (d, J = 9.0 Hz, 1H),
3.24 (dd, J1 = 3.5 Hz, J2 = 13.0 Hz, 1H), 3.05 (dd, J1 = 9.0 Hz, J2 = 13.0 Hz, 1H), 2.93 (s, 1H); 13
C
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 24
1
2
3
4
5
6
NMR (125 MHz, CDCl3): δ 140.9, 133.6, 133.3, 129.4, 128.9, 128.7, 127.6, 127.3, 71.5, 38.4.
HRMS (ESI): calcd for C14H14ClOSe [M+H]+ 312.9893, found 312.9891.
7
8
9
1ꢀ(4ꢀbromo)phenylꢀ2ꢀphenylselenoethanꢀ1ꢀol (4s). Following the general procedure, after 12h,
(4ꢀbromo)phenyl oxirane (237.6 mg, 3 equiv, 1.2 mmol) was added using syringe, using 4/1
petroleum ether/ ethyl acetate as the eluant to afford yellow oil liquid (102.5 mg, 72 % yield). 1H
NMR (500 MHz, CDCl3): δ 7.54 ꢀ 7.50 (m, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.29 ꢀ 7.27 (m, 3H),
7.19 (d, J = 8.5 Hz, 2H), 4.69 ꢀ 4.66 (m, 1H), 3.25 (dd, J1 = 3.5 Hz, J2 = 12.5 Hz, 1H), 3.06 (dd, J1
= 9.0 Hz, J2 = 12.5 Hz, 1H), 2.87 (d, J = 3.0 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ 141.5, 133.3,
131.6, 129.4, 128.8, 127.6, 127.6, 121.7, 71.6, 38.4. HRMS (ESI): calcd for C14H14BrOSe [M+H]+
356.9388, found 356.9390.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1ꢀ(2ꢀchloro)phenylꢀ2ꢀphenylselenoethanꢀ1ꢀol (4t). Following the general procedure, after 12h,
(2ꢀchloro)phenyl oxirane (184.8 mg, 3 equiv, 1.2 mmol) was added using syringe, using 4/1
1
petroleum ether /ethyl acetate as the eluant to afford yellow oil liquid (84.9 mg, 68 % yield). H
NMR (500 MHz, CDCl3): δ 7.64 ꢀ 7.56 (m, 3H), 7.29 ꢀ 7.17 (m, 6H), 5.12 ꢀ 5.09 (m, 1H), 3.47 (dd,
J1 = 2.5 Hz, J2 = 13.0 Hz, 1H), 2.95 (dd, J1 = 9.5 Hz, J2 = 13.0 Hz, 1H), 2.92 (s, 1H); 13C NMR
(125 MHz, CDCl3): δ 139.8, 133.2, 131.7, 129.4, 129.2, 128.8, 128.7, 127.5, 127.2, 127.01, 68.7,
36.6. HRMS (ESI): calcd for C14H14ClOSe [M+H]+ 312.9893, found 312.9890.
1ꢀ(phenylmethoxy)ꢀ3ꢀ(phenylseleno)ꢀpropanꢀ2ꢀol (4u). Following the general procedure, after 12h,
benzyl glycidyl ether (196.8 mg, 3 equiv, 1.2 mmol) was added using syringe, using 4/1 petroleum
1
ether / ethyl acetate as the eluant to afford yellow oil liquid (109. 5 mg, 85 % yield). H NMR
(500 MHz, CDCl3): δ 7.52 ꢀ 7.50 (m, 2H), 7.35 ꢀ 7.30 (m, 2H), 7.30 ꢀ 7.28 (m, 3H), 7.24 ꢀ 7.23 (m,
3H), 4.49 (s, 2H), 3.94 ꢀ 3.90 (m, 1H), 3.56 (dd, J1 = 4.0 Hz, J2 = 9.5 Hz, 1H), 3.51 (dd, J1 = 6.0
ACS Paragon Plus Environment

Page 21 of 24
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Hz, J2 = 9.5 Hz, 1H), 3.08 (dd, J1 = 5.5 Hz, J2 = 12.5 Hz, 1H), 3.02 (dd, J1 = 7.0 Hz, J2 = 12.5 Hz,
1H), 2.72 (s, 1H); 13C NMR (125 MHz, CDCl3): δ 137.8, 132.9, 129.6, 129.2, 128.5, 127.9, 127.8,
127.2, 73.4, 72.9, 69.5, 31.9. HRMS (ESI): calcd for C16H18O2SeNa [M+Na]+ 345.0365, found
345.0369.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1ꢀ(furanꢀ2ꢀylmethoxy)ꢀ3ꢀ(phenylselanyl)propanꢀ2ꢀol (4v). Following the general procedure, after
12h, furfuryl glycidyl ether (184.8 mg, 3 equiv, 1.2 mmol) was added using syringe, using 4/1
1
petroleum ether / ethyl acetate as the eluant to afford yellow oil liquid (76.1 mg, 61 % yield). H
NMR (500 MHz, CDCl3): δ 7.52 ꢀ 7.50 (m, 2H), 7.39 (s, 1H), 7.26 ꢀ 7.24 (m, 3H), 6.34 ꢀ 6.33 (m,
1H), 6.30 ꢀ 6.29 (m, 1H), 4.44 (s, 2H), 3.91 ꢀ 3.86 (m, 1H), 3.56 (dd, J1 = 4.0 Hz, J2 = 9.5 Hz, 1H),
3.48 (dd, J1 = 6.0 Hz, J2 = 9.5 Hz, 1H), 3.06 (dd, J1 = 5.5 Hz, J2 = 12.5 Hz, 1H), 2.99 (dd, J1 = 7.0
Hz, J2 = 12.5 Hz, 1H), 2.61 (s, 1H); 13C NMR (125 MHz, CDCl3): δ 151.4, 142.9, 132.8, 129.6,
129.2, 127.2, 110.3, 109.5, 72.7, 69.4, 65.4, 31.9. HRMS: (ESI) calcd for C14H16O3SeNa [M+Na]+
335.0158, found 335.0155.
ASSOCIATED CONTENT
Supporting Information
1H, 13C and 19F NMR spectral data of all compounds reported. Supporting Information is available
free of charge the ACS Publications website at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail for G.W.: wuge@wmu.edu.cn.
*Eꢀmail for H.W.: huayuewu@wzu.edu.cn.
Notes
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 24
1
2
3
4
The authors declare no competing financial interest.
5
6
7
ACKNOWLEDGMENT
8
9
Financial support from the National Natural Science Foundation of China (21272176, 21372177
and 21472140), the Zhejiang Provincial Natural Science Foundation (LY14B020009,
LY15B020001, LY16B020011) and the Wenzhou Medical University startꢀup funding (QTJ15026)
is greatly appreciated.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
REFERENCES
(1) For selected reviews: (a) Mugesh, G.; Mont, W.; Sies, H. Chem. Rev. 2001, 101, 2125. (b)
Mugesh, G.; Singh, H. B. Acc. Chem. Res. 2002, 35, 226. (c) Nogueira, C. W.; Zeni, G.; Rocha, J.
B. T. Chem. Rev. 2004, 104, 6255. (d) Manjare, S. T.; Kim, Y. ; Churchill, D. G. Acc. Chem. Res.
2014, 47, 2985.
(2) Sharpless, K. B.; Lauer, R. F. J. Am. Chem. Soc. 1973, 95, 2697.
(3) (a) Rémion, J.; Dumont, W.; Krief, A. Tetrahedron Lett. 1976, 17, 1385. (b) Piers, E.;
Nagakura, I. Tetrahedron Lett. 1976, 17, 3237.
(4) (a) Van Ende, D.; Dumont, W.; Hevesi, L.; Krief, A. Angew. Chem. Int. Ed. 1975, 14, 700. (b)
Dumont, W.; Krief, A. Angew. Chem. Int. Ed. 1975, 14, 350. (c) Van Ende, D.; Krief, A.
Tetrahedron Lett. 1976, 17, 457.
(5) Zanella, R.; Ros, R.; Grazian, M. Inorg. Chem. 1973, 12, 2736.
(6) Taniguchi, N. Synlett, 2005, 11, 1687.
(7) (a)Singh, D.; Deobald, A. M.; Camargo, L. R. S.; Tabarelli, G.; Rodrigues, O. E. D. ; Braga, A.
L. Org. Lett. 2010, 12, 3288. (b) Li, Y.; Nie, C.; Wang, H.; Li, X.; Verpoort, F.; Duan, C. Eur. J.
Org. Chem. 2011, 7331. (c) Taniguchi, N. Tetrahedron, 2012, 68, 10510. (d) Li, Z.; Ke, F.; Deng,
ACS Paragon Plus Environment

Page 23 of 24
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
H.; Xu, H.; Xiang, H.; Zhou, X. Org. Biomol. Chem. 2013, 11, 2943. (e) Shibahara, F.; Kanai, T.;
Yamaguchi, E.; Kamei, A.; Yamauchi, T.; Murai, T. Chem. Asian J. 2014, 9, 237.
(8) Balkrishna, S. J.; Bhakuni, B. S.; Chopra, D.; Kumar, S. Org. Lett. 2010, 12, 5394.
(9) (a) Wu, B.; Yoshikai, N. Angew. Chem. Int. Ed. 2013, 52, 10496. (b) Fang, Y.; Wang, S.Y.;
Shen, X.ꢀB.; Ji, S.ꢀJ. Org. Chem. Front. 2015, 2, 1338.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(10) (a) Chen, C.; Hou, C.; Wang, Y.; Andy Hor, T. S.; Weng, Z. Org. Lett. 2014, 16, 524. (b)
Lefebvre, Q.; Pluta, R.; Rueping, M. Chem. Commun.2015, 51, 4394.
(11) Luo, D.; Wu, G.; Yang, H.; Liu, M.; Gao, W.; Huang, X.; Chen, J.; Wu, H. J. Org. Chem.
2016, 81, 4485.
(12) (a) Azuma, H.; Tamagaki, S.; Ogino, K. J. Org. Chem. 2000, 65, 3538. (b) Rigby, J. H.;
Maharoof, U. S. M.; Mateo, M. E. J. Am. Chem. Soc. 2000, 122, 6624. (c) Treadwell, E. M.;
Neighbors, J. D.; Wiemer, D. F. Org. Lett. 2002, 4, 3639. (d) Bagul, T. D.; Lakshmaiah, G.;
Kawabata, T.; Fuji, K. Org. Lett. 2002, 4, 249. (e) Knapp, S.; Zhao, D. L. Org. Lett. 2000, 2, 4037.
(13) (a) Liotta, D.; Sunay, U.; Santiesteban, H.; Markievicz, W. J. Org. Chem. 1981, 46, 2605. (b)
Nishiyama, Y.; Ohashi, H.; Itoh K.; Sonoda,N. Chem. Lett. 1998, 159. (c) Dowsland, J.; McKerlie,
F.; Procter, D. J. Tetrahedron Lett. 2000, 41, 4923. (d) Sridhar, R.; Srinivas, B.; Surendra, K.;
Krishnaveni, N. S.; Rao, K. R. Tetrahedron Lett. 2005, 46, 8837. (e) Santi, C.; Santoro, S.;
Battistelli, B.; Testaferri, L.; Tiecco, M. Eur. J. Org. Chem. 2008, 5387. (f) Freudendahl, D. M.;
Shahzad, S. A.; Wirth,T. Eur. J. Org. Chem. 2009, 1649. (g) Lv, G.; Li, T.; Hu, R.; Chen, J.; Ding,
J.; Wu, H. J. Chem. Res. 2010, 549.
(14) Lu, X. Y.; Yang, C. T.; Liu, J. H.; Zhang, Z. Q.; Lu, X.; Xiao, B.; Fu, Y. Chem. Commun.
2015, 51, 2388.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 24
1
2
3
4
5
6
7
8
9
(15) Yang, M. H.; Yan, G. B.; Zheng, Y. F. Tetrahedron Lett. 2008, 49, 6471.
(16) Sheng, S. R.; Luo, H. R.; Huang, Z. Z.; Sun, W. K.; Liu, X. L. Synth. Commun. 2007, 37,
2693.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(17) Lv, G. S.; Li, T.; Hu, R. J.; Chen, J. X.; Ding, J. C.; Wu, H. Y. J. Chem. Res. 2010, 34, 549.
(18) Gruttadauria, M.; Lo Meo, P.; Riela, S.; D’Anna, F.; Noto, R. Tetrahedron: Asymmetry 2006,
17, 2713.
ACS Paragon Plus Environment