Iodosobenzene-Mediated Three-Component Selenofunctionalization of Olefins

Article abstract of DOI:10.1021/acs.joc.1c00257

A three-component reaction of olefin, diselenide and water, alcohols, phenol, carboxylic acid, or amine by a commercially available hypervalent iodine(III) reagent, PhIO, was developed. This method provides access to a wide range of vicinally functionalized selenoderivatives under ambient conditions with mostly excellent yields and high diastereoselectivity. The developed reaction displays high levels of functional group compatibility and is suitable for the late-stage functionalization of styrene-functionalized biomolecules. Preliminary investigations on the mechanism of the reaction are also presented.

Full text of DOI:10.1021/acs.joc.1c00257

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Iodosobenzene-Mediated Three-Component
Selenofunctionalization of Olefins
Zhi-Peng Liang, Wei Yi,† Peng-Fei Wang,† Gong-Qing Liu,* and Yong Ling*
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ABSTRACT: A three-component reaction of olefin, diselenide and water, alcohols, phenol, carboxylic acid, or amine by a
commercially available hypervalent iodine(III) reagent, PhIO, was developed. This method provides access to a wide range of
vicinally functionalized selenoderivatives under ambient conditions with mostly excellent yields and high diastereoselectivity. The
developed reaction displays high levels of functional group compatibility and is suitable for the late-stage functionalization of styrene-
functionalized biomolecules. Preliminary investigations on the mechanism of the reaction are also presented.
Scheme 1. β-Hydroxy Selenides: State-of-the-Art
INTRODUCTION
■
The introduction of selenium into organic molecules has
recently been the subject of intense research, as selenium-
containing molecules have found widespread applications in
the fields of organic synthesis and drug discovery.1 Within the
wide variety of organoselenium compounds, β-hydroxy
selenides represent particularly versatile manifolds, as docu-
mented in access to some of the extremely biologically
important natural products, such as pancratistatin,2 sphingo-
sine,3 and schweinfurthin B.4 Additionally, these compounds
can be readily converted to allylic alcohols,5 olefins,6 vinyl
selenides,7 and heterocyclic compounds8 through classical
reactions. Consequently, numerous attempts have been made
to determine the synthetic route to access β-hydroxy selenides.
Traditional approaches to synthesize this class of compounds
involve the ring-opening reactions of epoxides with selenolate
anions, such as (phenylseleno)silanes,9 aluminum seleno-
lates,10 zinc selenolates,11 selenoboranes,12 benzeneselenol13
selenostannanes,14 and selenium powder15 (Scheme 1a). Most
selenolate anions are relatively unstable and are usually formed
in situ by reductive cleavage of the Se−Se bond or by the
insertion of selenium into organometallic reagents under
controlled anhydrous conditions. Furthermore, these ap-
proaches are commonly implemented under acidic conditions
and, thus, suffer from poor tolerance to base-sensitive
functional groups as well as low regioselectivity. Another
common synthetic strategy toward β-hydroxy selenides
involves the nucleophilic addition of α-selenoalkyllithiums or
analogues to carbonyl compounds (Scheme 1b).5a,16 The
preparations and reactions of α-selenoalkyllithiums, however,
often require very low temperature (usually at −78 °C) and
anhydrous conditions, which causes inconvenient handling
procedures.
In recent years, the selenofunctionalization of simple alkenes
has developed into a powerful tool for the preparation of
selenocompounds because this process enables the simulta-
neous introduction of selenium functional groups and other
synthetically useful functionalities across the π system in an
Received: February 2, 2021
Published: March 11, 2021
https://dx.doi.org/10.1021/acs.joc.1c00257
© 2021 American Chemical Society
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a
Scheme 2. Scope of Alkenes
a
Reactions were performed in the presence of alkene 1 (0.25 mmol), Ph2Se2 2a (0.25 mmol), PhIO (0.25 mmol), and CH3CN/H2O (3:1, 2.0 mL)
b
c
in an open flask at room temperature for 20 h. Five mmol scale. ORTEP drawing of 3s with the thermal ellipsoids at 30% probability. Hydrogen
atoms were omitted for clarity.
atom-economical fashion with increasing molecular complex-
ity.17 In this context, oxyselenation of alkenes has been proven
to be a step- and atom-economical route for the preparation of
β-hydroxy selenides (Scheme 1c). Mechanistically, this process
occurs via the formation of seleniranium intermediate I and
subsequent nucleophilic attack of water at the more electro-
philic carbon. In recent decades, great attention has been
devoted to seeking suitable selenium sources, which can serve
as reactive electrophilic intermediates to induce the generation
of seleniranium ion I. From a conceptual point of view, two
different strategies have been chosen: directly using electro-
philic selenenylating agents, such as phenylselenenyl halides,18
phenyl selenocyanate,19 or N-phenylselenophthalimide,20 or
preparing electrophilic selenium species in situ by the
oxidation of diselenides through electrochemical processes21
or by the use of oxidants, such as Oxone,22 2,3-dichloro-5,6-
dicyanobenzoquinone (DDQ),23 hypervalent iodine reagent,24
ammonium persulfate,25 or m-chloroperbenzoic acid.26
Although they represent useful platforms for β-hydroxy
selenides, the preparation and handling of toxic and
moisture-sensitive selenylating agents,18 the necessity to
perform the reactions in the presence of transition metals18a,19
and nonoptimal chemical yields26 narrow the practical
applicability of these methods.
products by the treatment of diphenyl diselenide (Ph2Se2) with
iodobenzene diacetate in acetonitrile.24a The limitation of this
procedure was that acetoxyphenylselenenylation products were
obtained for intermolecular variant reactions because of the
presence of the nucleophilic acetate anion as an iodine(III)
ligand, and only isolated examples have been demonstrated on
the preparation of β-hydroxy selenides; the scope of
diselenides was confined to Ph2Se2. Moreover, a detailed
understanding of mechanistic aspects still needs to be
illuminated.
From the careful analysis of these drawbacks and limitations
and in continuation of our ongoing work toward the
hypervalent iodine-promoted difunctionalization of olefins,27
we conjecture that the in situ generated active electrophilic
selenium species from iodosobenzene (PhIO) and diselenide
would form seleniranium ion I with alkene and subsequent
intermolecular attack by an array of nucleophiles including
water, alcohol, acid or amine, generating vicinal difunctional
compounds that may overcome the aforementioned limitations
and provide an efficient and modular approach for the
formation of diverse selenium-containing compounds.
RESULTS AND DISCUSSION
■
With this in mind, we investigated the oxyselenation of styrene
(1a) with Ph2Se2 (2a) in the presence of PhIO in a mixture of
water and acetonitrile. To our delight, the title reaction
Tingoli et al. demonstrated the synthesis of phenylseleno-
acetoxylation, hydroxylation, etherification, and lactonization
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a
Scheme 3. Scope of Vinylarenes Derived from Biomolecules
a
Reactions were performed in the presence of alkene 1 (0.25 mmol), Ph2Se2 2a (0.25 mmol), PhIO (0.25 mmol), and CH3CN/H2O (3:1, 2.0 mL)
in an open flask at room temperature for 20 h.
proceeded readily and provided a Markovnikov product
exclusively, β-hydroxy selenide 3a, with an 88% yield and
complete regioselectivity.28 Notably, the present reaction can
be scaled up to a 5 mmol scale without significant decreases in
the yield, suggesting that this simple protocol could be
employed as a practical method to access β-hydroxy selenides.
Encouraged by these results, other alkenes were then subjected
to the same conditions to test the scope of the reaction, and
the results are summarized in Scheme 2.
As shown in Scheme 2, an array of substituted vinylarenes
readily underwent oxyselenation to produce the corresponding
β-hydroxy selenides 3a−3q with yields up to 95%. The
electronic effect of the arenes had little impact on the course of
the reaction, and terminal vinylarenes bearing either electron-
donating or electron-withdrawing substituents all delivered the
corresponding products in good to excellent yields. Notably, a
large variety of functional groups at the styrene aromatic core
could be tolerated, including halide, ester, carboxyl, formyl,
trifluoromethyl, and nitro groups. The resulting products from
this transformation provide a facile approach toward the
synthesis of versatile motifs of many biologically active
selenium-containing compounds. For example, the use of Cl-
and Br-substituted styrenes allows for the further modification
of products 3f−3g and 3o−3p by means of classical Pd-
catalyzed cross-couplings. In addition, ester, carboxyl, formyl,
and nitro groups can be manipulated readily to give various
functionalized selenoderivatives using conventional reactions.
Next, more rigid alkenes, such as 1,2-dihydronaphthalene 1r
and indene 1s, were examined under the optimized conditions
and gave the desired products 3r−3s exclusively with trans-
diastereoselectivity and good yields. The relative configuration
of 3s was elucidated based on X-ray crystallography.29
Furthermore, naphthalene-derived substrates and heteroaro-
matic olefins, such as 4-vinylpyridine, 5-vinylthiazole 2-
vinylthiophene, and vinylferrocene, were subjected to the
same reaction to test the scope of the reaction and gave the
corresponding products at acceptable yields (3t−3x). Sub-
sequently, the possibility of performing these reactions with
1,1-disubstituted (1y−1z) and internal alkenes (1aa−1ab) was
investigated. The cis-stilbene 1aa, however, resulted in a drastic
reduction in the reaction yield, probably due to the steric
hindrance of this substrate. Finally, aliphatic alkenes were also
suitable substrates for the current transformation and produced
desired products 3ac−3ah′ in good yields, but resulted in a
mixture of regioisomers corresponding to Markovnikov-type
hydroxyselenated product (3ah) and an anti-Markovnikov-
type adduct (3ah′) in a relative ratio of 1.7:1 in the case of 1-
octene. The total yield and the isomer ratio of 3ah and 3ah′
were hardly affected by the reverse addition of the reactants.
Comparison of regioselectivity in the case of aryl alkenes 1a−
1ab with alkyl alkene 1ah clearly demonstrates predominant
intermediate stabilization over steric interaction for cases of
1a−1ab; however, 1ah gave a mixture of Markovnikov and
anti-Markovnikov adducts, which could be ascribed to the
variation in the charge density on the two carbons leading to a
nonregiospecific ring-opening of the seleniranium ion inter-
mediate with water. Thus, the seleniranium intermediate was
attacked by H2O at the less sterically hindered C atom yielding
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a
Scheme 4. Scope of Diselenides
a
Reactions were performed in the presence of styrene 1a (0.25 mmol), R2Se2 2 (0.25 mmol), PhIO (0.25 mmol), and CH3CN/H2O (3:1, 2.0 mL)
in an open flask at room temperature for 20 h.
a
Scheme 5. Scope of Other Nucleophiles
a
For 5a−5e, reactions were performed in the presence of styrene 1a (0.25 mmol), Ph2Se2 2a (0.25 mmol), PhIO (0.25 mmol), and CH3CN/ROH
(3:1, 2.0 mL) in an open flask at room temperature for 20 h. For 5f−5h, reactions were performed in the presence of styrene 1a (0.25 mmol),
Ph2Se2 2a (0.25 mmol), PhIO (0.25 mmol), nucleophile (1.0 mmol), and CH2Cl2 (2.0 mL) in an open flask at room temperature for 20 h.
an anti-Markovnikov adduct. Remarkably, all reactions
described here displayed excellent diastereoselectivity, produc-
ing one single diastereomer (3aa−3af). The stereochemical
course of title reaction was disclosed to be trans from the
oxyselenation of trans- and cis-alkene, which afforded the
erythro- and threo-type hydroxyselenated product, respectively.
For example, hydroxyselenation of trans-β-methylstyrene
afforded erythro-3ab, while cis-alkene, such as 1aa and 1af,
yielded threo-3aa and 3af. The high diastereoselectivity may be
attributed to the stereospecific ring-opening of the putative
seleniranium ion intermediate I.18c,30
To further evaluate the synthetic utility and generality of the
current procedure, more complex styrene-functionalized
biomolecules were investigated. As shown in Scheme 3, the
late-stage oxyselenation of biologically active molecules was
successful, giving the corresponding β-hydroxy selenides. For
instance, natural product derivatives, such as coumarin (1aj),
L-menthol (1ak), galactose (1al), formononetin (1an), and
vanillylacetone (1aq), and pharmaceutical intermediates, such
as estrone (1ai), naproxen (1am), and tocopherol (1ap), and
peptide (1ao) derivatives, were tolerated and produced desired
products 3ai−3aq with good yields.
straightforward transformation. As expected, the title reaction
system proceeded readily in a mixture of different alcohols and
acetonitrile and gave β-alkoxy selenides in good yields
exclusively with Markovnikov selectivity (Scheme 5). Notably,
this protocol is also effective for the synthesis of deuterated
functionalized selenide compound 5d through the utilization of
deuterated methanol as a nucleophilic solvent. Next, other
tested nucleophiles, such as phenol, carboxylic acid, and amine,
were further examined. Gratifyingly, slight modifications to the
optimal reaction conditions allowed the preparation of a
variety of vicinally functionalized selenoderivatives (5f−5h)
with good yields.
With regard to the mechanism of the title transformation,
the following observations from control experiments are
noteworthy. First, when iodohydrin 6 was stirred for 20 h in
a mixture of water and acetonitrile, it remained intact and was
totally recovered, and no trace of 3a was detected (Scheme 6,
eq 1). These results indicate that a cascade process of
iodohydroxylation of styrene and subsequent nucleophilic
substitution of the C−I bond by arylselenide is less likely.
Second, no significant effect on the reaction outcomes was
observed after the addition of the radical scavenger 2,2,6,6-
tetramethyl-1-piperidinyloxy (TEMPO), which indicates that a
radical process seems very unlikely (Scheme 6, eq 2). Ph2Se2
has been documented to be readily oxidized to phenylseleninic
acid (PhSeO2H) 7 in the presence of an oxidant,31 and thus,
whether 7 the active electrophilic species in the present
reaction was investigated. None of the β-hydroxy selenide 3a
was, however, detected when commercially available PhSeO2H
7 was used (Scheme 6, eq 3). These studies suggest that acid 7
might not be the intermediate of the developed transformation.
Interestingly, when 1,3,5-trimethoxybenzene 8 was employed
as a nucleophile under the title reaction condition, a yield of
Inspired by these results, we next explored the versatility of
the title reaction by probing diverse diselenides. As depicted in
Scheme 4, aliphatic diselenides were efficiently engaged in this
process, with styrene 1a delivering desired products (4a−4d)
with good yields. The other substituted diphenyl diselenides
and heteroaryl diselenide were also good reaction partners and
produced the corresponding selenides (4e−4i) in moderate to
good yields.
Encouraged by the successful application of a water
nucleophile, we then switched the solvent system to alcohol,
which would enable the synthesis of β-alkoxy selenides in a
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172.95033 was detected from the reaction of Ph2Se2 and
PhIO, implying the generation of PhSeOH 12 during the
reaction (Figure S5). Additionally, its anhydride 13 was also
detected on ESI-MS (Figure S6). To further certify whether
PhSeOH 12 could be the active electrophilic species in the
reaction, alkyl phenyl selenides were subjected to the reaction
because PhSeOH is the side product of the well-known
selenoxide syn-elimination of these selenides.36 As shown in
Scheme 6, eq 6, i-BuSePh gave a trace amount of the desired
3a probably due to difficulties in the oxidation of i-BuSePh to
the corresponding selenoxide under the title conditions. As
expected, PhSePh failed to produce any β-hydroxy selenide 3a
because PhSePh is incapable of undergoing selenoxide syn-
elimination to generate PhSeOH. Thus, these results implied
that putative intermediate PhSeOH 12, generated in situ from
PhIO and Ph2Se2, should be involved in this reaction.
Scheme 6. Experiments for Mechanistic Studies
On the basis of the above results and previous literature
reports,24a,37 a preliminary reaction pathway is proposed in
Scheme 7. First, Ph2Se2 is oxidized by PhIO to generate
Scheme 7. Tentative Reaction Pathway
26% of the desired carboselenenylation product 9 was obtained
along with some amounts of selenation product 10 (Scheme 6,
eq 4). Compound 10 probably arose from an electrophilic
attack of the phenylselenenyl cation (PhSe+) on the electron-
rich 1,3,5-trimethoxybenzene.32 These results suggest that the
current transformation should be an electrophilic process.
However, it is still necessary to identify the authentic active
electrophilic species in this transformation.
intermediate PhSeOH 12 and/or it anhydride 13. We believe
13 rather than 12 would serve as a reactive electrophilic
intermediate to react with alkene 1 to give seleniranium
intermediate 14 because extremely unstable PhSeOH 12 has
been documented to readily convert to anhydride 13 through
the self-condensation process.35 Finally, trapping of 14 with
various nucleophiles delivers the vicinally functionalized
selenoderivatives.
To examine true reactive organoselenium species in the
reaction, NMR experiments were carried out, and the results
showed no interaction of styrene with Ph2Se2 (Figure S1).
PhIO is insoluble in CDCl3 because it displays a zigzag
polymeric chain structure according to X-ray powder
diffraction and EXAFS studies,33 and the H NMR spectrum
1
of PhIO and its mixture with styrene thus cannot be recorded.
PhIO, however, could be mostly dissolved when Ph2Se2 was
added to the CDCl3 solution. This result indicates that PhIO
can react with Ph2Se2 to generate new reactive species during
the course of the reaction. This phenomenon was in
accordance with NMR observations, which showed that the
signal pattern for the aromatic protons of Ph2Se2 changed
significantly after the addition of PhIO, indicating the mutual
interaction between Ph2Se2 and PhIO and, thus, resulting in
changes in the electronic environment surrounding the phenyl
groups in Ph2Se2 (Figure S2). Based on our understanding of
hypervalent iodine chemistry, we assumed that PhIO can react
with Ph2Se2 to generate benzeneselenenic acid (PhSeOH) 12
and/or its anhydride 13 as the active species through the
reaction of Ph2Se2 with PhIO to give putative intermediate
11,34 followed by the elimination of iodobenzene (Scheme 6,
eq 5). The formation of iodobenzene was confirmed by 13C
NMR experiments and GC−MS analysis (Figures S3 and S4).
PhSeOH 12 cannot be isolated in analytically pure at this
stage, as it is a notoriously unstable compound,35 but it can be
detected by HRMS experiments. A mass peak at m/z
CONCLUSION
■
In conclusion, we have developed a PhIO-promoted three-
component coupling of olefin, diselenide and water, alcohols,
phenol, carboxylic acid, or amine for the synthesis of vicinally
functionalized selenoderivatives. The title transformation
allows for significant variation within each of the three
components and displays high diastereoselectivity. Mechanis-
tically, the process is believed to proceed through the transient
formation of an electrophilic selenium intermediate derived
from the oxidation of diselenide by PhIO. Owing to its mild
reaction conditions, easy operation, excellent functional group
tolerance, and suitability for the late-stage functionalization of
complex molecules of biological importance, we envisage that
the present protocol will have a widespread application in the
construction of diverse selenium-containing compounds.
EXPERIMENTAL SECTION
■
General Experimental Information. Reagents were used as
received without further purification unless otherwise indicated.
Solvents were dried and distilled prior to use. Petroleum ether used
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had a boiling point range of 60−90 °C. Diselenides were prepared
from the corresponding iodides with elemental selenium, according to
Braga’s report.38 Chromatographic purification of products was
performed as flash column chromatography on silica gel (200−300
meshes). Thin-layer chromatography (TLC) was carried out on silica
plates (TLC Silica GF254). Visualization of the compounds was
accomplished by projecting UV light onto the developed plates.
Nuclear magnetic resonance spectra were recorded at an ambient
temperature (unless otherwise stated) at 400 MHz (100 MHz for
13C) in CDCl3. Chemical shifts were reported in ppm (δ) using TMS
as an internal standard, and spin−spin coupling constants (J) were
given in hertz. Multiplicities of NMR signals are abbreviated as
follows: br = broad, s = singlet, d = doublet, t = triplet, q = quartet, m
= multiplet. High-resolution mass spectrometry (HRMS) analyses
were carried out on a Thermo Fisher Q Exactive Mass Spectrometer,
and the mass analyzer type is Orbitrap. The crystal of compound 3s
was obtained by slowly evaporating a mixture of ethyl acetate and n-
hexane solution (1:5) at an ambient temperature. The data were
collected at 100 K on a Rigaku Oxford Diffraction Supernova Dual
Source, Cu at Zero, equipped with an AtlasS2 CCD using Cu Kα
radiation. Melting points were determined on glass slides using a
digital display microscopic melting point apparatus and were
presented uncorrected.
General Procedure for Selenofunctionalization of Olefins.
The reaction was carried out in an open air system at an ambient
temperature. To a 10 mL vessel with a magnetic stir bar were added
0.25 mmol alkene, 0.25 mmol diselenide, 0.25 mmol PhIO, and 2 mL
of CH3CN/water or CH3CN/alcohol (3:1). The reaction mixture was
stirred overnight. The reaction was monitored by TLC. After
completion of the reaction (ca. 20 h), the mixture was added to 5
mL of H2O and extracted with ethyl acetate (15 mL) three times. The
combined organic layer was dried (Na2SO4) and concentrated to give
the crude residue, which was purified by flash column chromatog-
raphy to give the corresponding product.
13C{1H} NMR (100 MHz, CDCl3): δ 149.8, 138.4, 131.9, 128.3,
128.1, 126.2, 124.5, 124.4, 71.1, 37.1, 33.5, 30.3. Spectral data are in
agreement with literature values.26
1-(4-Fluorophenyl)-2-(phenylselanyl)ethan-1-ol (3e). Com-
pound 3e was prepared according to the general procedure and
isolated as an oil (66 mg, 89% yield) after flash chromatography
(petroleum ether/ethyl acetate = 16:1). 1H NMR (400 MHz,
CDCl3): δ 7.50−7.42 (m, 2H), 7.27−7.11 (m, 5H), 6.91 (t, J = 8.7
Hz, 2H), 4.62 (dt, J = 9.2, 3.2 Hz, 1H), 3.16 (dd, J = 12.8, 3.9 Hz,
1H), 3.00 (dd, J = 12.8, 9.3 Hz, 1H), 2.87 (d, J = 2.7 Hz, 1H).
13C{1H} NMR (100 MHz, CDCl3): δ 161.3 (d, C−F,1JC−F = 246.0
Hz), 137.2 (d, C−F, 3JC−F = 3.1 Hz), 132.1, 128.2, 127.9, 126.5, 126.4
(d, C−F, 3JC−F = 3.1 Hz), 114.3 (d, C−F, 2JC−F = 21.5 Hz) 70.5, 37.4.
19F NMR (376 MHz, CDCl3): δ −114.3. Spectral data are in
agreement with literature values.15a
1-(4-Chlorophenyl)-2-(phenylselanyl)ethan-1-ol (3f). Com-
pound 3f was prepared according to the general procedure and
isolated as an oil (66 mg, 85% yield) after flash chromatography
(petroleum ether/ethyl acetate = 20:1). 1H NMR (400 MHz,
CDCl3): δ 7.65−7.29 (m, 2H), 7.30−7.00 (m, 7H), 4.60 (dt, J = 9.2,
3.1 Hz, 1H), 3.16 (dd, J = 12.8, 3.8 Hz, 1H), 2.98 (dd, J = 12.8, 9.3
Hz, 1H), 2.88 (d, J = 2.7 Hz, 1H). 13C{1H} NMR (100 MHz,
CDCl3): δ 139.9, 132.5, 132.2, 128.3, 127.8, 127.6, 126.5, 126.2, 70.4,
37.3. Spectral data are in agreement with literature values.22
1-(4-Bromophenyl)-2-(phenylselanyl)ethan-1-ol (3g). Com-
pound 3g was prepared according to the general procedure and
isolated as an oil (81 mg, 91% yield) after flash chromatography
(petroleum ether/ethyl acetate = 16:1). 1H NMR (400 MHz,
CDCl3): δ 7.49−7.39 (m, 2H), 7.34 (d, J = 8.4 Hz, 2H), 7.22−7.16
(m, 3H), 7.09 (d, J = 8.4 Hz, 2H), 4.58 (dt, J = 9.1, 3.3 Hz, 1H), 3.14
(dd, J = 12.8, 3.9 Hz, 1H), 2.97 (dd, J = 12.8, 9.2 Hz, 1H), 2.91 (d, J
= 2.8 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 140.4, 132.2,
130.5, 128.3, 127.7, 126.5, 120.6, 70.5, 37.2. Spectral data are in
agreement with literature values.15a
1-Phenyl-2-(phenylselanyl)ethan-1-ol (3a). Compound 3a was
prepared according to the general procedure and isolated as an oil (61
mg, 88% yield) after flash chromatography (petroleum ether/ethyl
4-(1-Hydroxy-2-(phenylselanyl)ethyl)phenyl acetate (3h).
Compound 3h was prepared according to the general procedure
and isolated as an oil (67 mg, 80% yield) after flash chromatography
(petroleum ether/ethyl acetate = 8:1). 1H NMR (400 MHz, CDCl3):
δ 7.53−7.37 (m, 2H), 7.26 (d, J = 8.6 Hz, 2H), 7.21−7.19 (m, 3H),
6.97 (d, J = 8.6 Hz, 2H), 4.65 (dt, J = 9.1, 3.0 Hz 1H), 3.19 (dd, J =
12.8, 3.7 Hz, 1H), 3.02 (dd, J = 12.8, 9.5 Hz, 1H), 2.85 (brs, 1H),
2.21 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 168.5, 149.1,
139.0, 132.1, 128.3, 128.0, 126.4, 125.9, 120.6, 70.7, 37.4, 20.1.
Spectral data are in agreement with literature values.26
1
acetate = 15:1). H NMR (400 MHz, CDCl3): δ 7.8−7.45 (m, 2H),
7.26−7.23 (m, 4H), 7.23−7.16 (m, 4H), 4.66 (dd, J = 9.4, 3.7 Hz,
1H), 3.22 (dd, J = 12.8, 3.7 Hz, 1H), 3.06 (dd, J = 12.8, 9.4 Hz, 1H),
2.75 (brs, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 141.4, 132.1,
128.2, 128.1, 127.5, 126.9, 126.4, 124.76, 71.2, 37.4. Spectral data are
in agreement with literature values.22
2-(Phenylselanyl)-1-(p-tolyl)ethan-1-ol (3b). Compound 3b
was prepared according to the general procedure and isolated as an oil
(65 mg, 89% yield) after flash chromatography (petroleum ether/
ethyl acetate = 18:1). 1H NMR (400 MHz, CDCl3): δ 7.46−7.44 (m,
2H), 7.23−7.17 (m, 3H), 7.16−7.10 (m, 2H), 7.05 (d, J = 7.7 Hz,
2H), 4.63 (dt, J = 8.9, 3.0 Hz, 1H), 3.19 (dd, J = 12.7, 3.9 Hz, 1H),
3.05 (dd, J = 12.7, 9.2,Hz, 1H), 2.76 (d, J = 2.6 Hz, 1H), 2.25 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3): δ 138.5, 136.6, 132.0, 128.2,
128.15, 128.13, 126.3, 124.7, 71.0, 37.3, 20.1. Spectral data are in
agreement with literature values.22
1-(4-Methoxyphenyl)-2-(phenylselanyl)ethan-1-ol (3c).
Compound 3c was prepared according to the general procedure
and isolated as an oil (54 mg, 70% yield) after flash chromatography
(petroleum ether/ethyl acetate = 10:1). 1H NMR (400 MHz,
CDCl3): δ 7.58−7.39 (m, 2H), 7.31−7.07 (m, 5H), 6.79 (d, J = 8.7
Hz, 2H), 4.64 (dt, J = 9.3, 3.2 Hz, 1H), 3.72 (s, 3H), 3.20 (dd, J =
12.7, 3.8 Hz, 1H), 3.07 (dd, J = 12.7, 9.3 Hz, 1H), 2.68 (d, J = 2.7 Hz,
1H). 13C{1H} NMR (100 MHz, CDCl3): δ 158.3, 133.6, 132.0, 128.2,
128.1, 126.3, 126.0, 112.7, 70.8, 54.3, 37.4. Spectral data are in
agreement with literature values.22
1-([1,1′-Biphenyl]-4-yl)-2-(phenylselanyl)ethan-1-ol (3i).
Compound 3i was prepared according to the general procedure and
isolated as a white solid (84 mg, 95% yield) after flash
chromatography (petroleum ether/ethyl acetate = 17:1). Mp: 70−
1
72 °C. H NMR (400 MHz, CDCl3): δ 7.49−7.38 (m, 6H), 7.35−
7.18 (m, 5H), 7.16−7.10 (m, 3H), 4.66 (dt, J = 9.2, 3.2 Hz, 1H), 3.19
(dd, J = 12.7, 3.9 Hz, 1H), 3.04 (dd, J = 12.7, 9.2 Hz, 1H), 2.91 (d, J
= 2.6 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 140.4, 139.7,
139.6, 132.0, 128.2, 128.1, 127.7, 126.3, 126.2, 126.1, 126.0, 125.2,
71.0, 37.2. HRMS (ESI): m/z [M + H]+ calcd for C20H19OSe,
355.0596; found, 355.0596.
1-(4-(Chloromethyl)phenyl)-2-(phenylselanyl)ethan-1-ol
(3j). Compound 3j was prepared according to the general procedure
and isolated as an oil (74 mg, 91% yield) after flash chromatography
(petroleum ether/ethyl acetate = 10:1). 1H NMR (400 MHz,
CDCl3): δ 7.47−7.41 (m, 2H), 7.29−7.07 (m, 7H), 4.63 (dd, J = 9.4,
3.8 Hz, 1H), 4.46 (s, 2H), 3.16 (dd, J = 12.8, 3.8 Hz, 1H), 3.00 (dd, J
= 12.8, 9.2 Hz, 1H), 2.90 (s, 1H). 13C{1H} NMR (100 MHz,
CDCl3): δ 141.7, 136.0, 132.0, 128.2, 128.0, 127.7, 126.4, 125.2, 70.8,
44.9, 37.2. HRMS (ESI): m/z [M + H − H2O]+ calcd for
C15H14ClSe, 308.9944; found, 308.9937.
1-(4-(tert-Butyl)phenyl)-2-(phenylselanyl)ethan-1-ol (3d).
Compound 3d was prepared according to the general procedure
and isolated as an oil (77 mg, 92% yield) after flash chromatography
(petroleum ether/ethyl acetate = 20:1). 1H NMR (400 MHz,
CDCl3): δ 7.48−7.36 (m, 2H), 7.31−7.20 (m, 2H), 7.18−7.16 (m,
5H), 4.64 (dt, J = 9.2, 3.2 Hz, 1H), 3.19 (dd, J = 12.7, 3.9 Hz, 1H),
3.06 (dd, J = 12.8, 9.2 Hz, 1H), 2.77 (d, J = 2.7 Hz, 1H), 1.21 (s, 9H).
4-(1-Hydroxy-2-(phenylselanyl)ethyl)benzoic acid (3k).
Compound 3k was prepared according to the general procedure
and isolated as a yellow solid (75 mg, 93% yield) after flash
chromatography (petroleum ether/ethyl acetate = 1:2). Mp: 90−92
1
°C. H NMR (400 MHz, CDCl3): δ 7.99 (d, J = 8.1 Hz, 2H), 7.48
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(dd, J = 6.6, 2.9 Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H), 7.26−7.15 (m,
3H), 4.72 (dd, J = 9.4, 3.6 Hz, 1H), 3.24 (dd, J = 12.9, 3.6 Hz, 1H),
3.02 (dd, J = 12.9, 9.4 Hz, 1H), 1.12(s, 2H). 13C{1H} NMR (100
MHz, CDCl3): δ 170.4, 147.3, 132.3, 129.4, 128.3, 127.7, 127.5,
126.7, 124.9, 70.6, 37.4. HRMS (ESI): m/z [M + H − H2O]+ calcd
for C15H13O2Se, 305.0075; found, 305.0072.
anti-2-(Phenylselanyl)-1,2,3,4-tetrahydronaphthalen-1-ol
(3r). Compound 3r was prepared according to the general procedure
and isolated as an oil (61 mg, 81% yield) after flash chromatography
(petroleum ether/ethyl acetate = 10:1). 1H NMR (400 MHz,
CDCl3): δ 7.61−7.45 (m, 2H), 7.46−7.33 (m, 1H), 7.26−7.15 (m,
3H), 7.16−7.05 (m, 2H), 7.01−6.83 (m, 1H), 4.59 (dd, J = 7.8, 3.4
Hz, 1H), 3.37 (ddd, J = 10.6, 7.7, 3.2 Hz, 1H), 2.96−2.54 (m, 3H),
2.31 (dtd, J = 14.2, 5.6, 3.2 Hz, 1H), 1.90−1.80 (m, 1H). 13C{1H}
NMR (100 MHz, CDCl3): δ 135.8, 134.54, 134.50, 128.1, 127.5,
127.2, 127.0, 126.6, 126.0, 125.4, 71.0, 47.6, 27.7, 26.5. Spectral data
are in agreement with literature values.40
4-(1-Hydroxy-2-(phenylselanyl)ethyl)benzaldehyde (3l).
Compound 3l was prepared according to the general procedure and
isolated as an oil (60 mg, 79% yield) after flash chromatography
(petroleum ether/ethyl acetate = 1:2). 1H NMR (400 MHz, CDCl3):
δ 9.91 (s, 1H), 7.77 (d, J = 8.2 Hz, 2H), 7.51−7.46 (m, 2H), 7.43 (d,
J = 8.2 Hz, 2H), 7.25−7.17 (m, 3H), 4.72 (dd, J = 9.4, 3.6 Hz, 1H),
3.24 (dd, J = 12.9, 3.6 Hz, 1H), 3.01 (dd, J = 12.9, 9.4 Hz, 1H), 3.00
(brs, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 190.9, 148.1, 134.9,
132.4, 129.0, 128.4, 127.5, 126.7, 125.4, 70.5, 37.4. HRMS (ESI): m/z
[M + H − H2O]+ calcd for C15H13OSe, 289.0126; found, 289.0125.
2-(Phenylselanyl)-1-(4-(trifluoromethyl)phenyl)ethan-1-ol
(3m). Compound 3m was prepared according to the general
procedure and isolated as an oil (76 mg, 88% yield) after flash
anti-2-(Phenylselanyl)-2,3-dihydro-1H-inden-1-ol (3s). Com-
pound 3s was prepared according to the general procedure and
isolated as a white solid (62 mg, 86% yield) after flash
chromatography (petroleum ether/ethyl acetate = 20:1). Mp: 93−
94 °C. 1H NMR (400 MHz, CDCl3): δ 7.55 (dd, J = 6.4, 3.0 Hz, 2H),
7.34−7.24 (m, 1H), 7.25−7.18 (m, 3H), 7.19−7.13 (m, 2H), 7.12−
7.07 (m, 1H), 5.08 (t, J = 5.2 Hz, 1H), 3.67 (td, J = 7.7, 6.0 Hz, 1H),
3.35 (dd, J = 16.3, 7.8 Hz, 1H), 2.86 (dd, J = 16.3, 7.6 Hz, 1H), 2.28
(d, J = 5.1 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 142.0,
140.0, 133.6, 128.2, 127.6, 127.5, 126.7, 126.2, 123.5, 123.2, 80.4,
48.3, 36.6. Spectral data are in agreement with literature values.40
1-(Naphthalen-2-yl)-2-(phenylselanyl)ethan-1-ol (3t). Com-
pound 3t was prepared according to the general procedure and
isolated as a white solid (74 mg, 91% yield) after flash
chromatography (petroleum ether/ethyl acetate = 17:1). Mp: 52−
1
chromatography (petroleum ether/ethyl acetate = 15:1). H NMR
(400 MHz, CDCl3): δ 7.46 (d, J = 8.1 Hz, 2H), 7.44−7.39 (m, 2H),
7.32 (d, J = 8.1 Hz, 2H), 7.21−7.17 (m, 3H), 4.67 (dt, J = 9.2, 3.1 Hz,
1H), 3.18 (dd, J = 12.9, 3.8 Hz, 1H), 3.05−2.91 (m, 2H). 13C{1H}
2
NMR (100 MHz, CDCl3): δ 145.3, 132.2, 128.9 (q, C−F, JC−F
=
32.4 Hz), 128.3, 127.6, 126.6, 125.1, 124.4 (q, 3JC−F = 3.8 Hz), 121.7
(q, C−F,1JC−F = 270.4 Hz), 70.5 37.3. 19F NMR (376 MHz, CDCl3):
δ −62.4. HRMS (ESI): m/z [M + H − H2O]+ calcd for C15H12F3Se,
329.0051; found, 329.0045.
1
53 °C. H NMR (400 MHz, CDCl3): δ 7.77−7.57 (m, 4H), 7.51−
7.39 (m, 2H), 7.38−7.31 (m, 2H), 7.29 (dd, J = 8.5, 1.8 Hz, 1H),
7.20−7.09 (m, 3H), 4.77 (dt, J = 9.2, 3.1 Hz, 1H), 3.23 (dd, J = 12.8,
3.8 Hz, 1H), 3.08 (dd, J = 12.8, 9.3 Hz, 1H), 2.96 (d, J = 2.6 Hz, 1H).
13C{1H} NMR (100 MHz, CDCl3): δ 138.8, 132.1, 132.1, 132.0,
128.2, 128.1, 127.3, 126.9, 126.6, 126.3, 125.1, 124.9, 123.6, 122.7,
71.3 37.2. HRMS (ESI): m/z [M + H − H2O]+ calcd for C18H15Se,
311.0333; found, 311.0327.
1-(4-Nitrophenyl)-2-(phenylselanyl)ethan-1-ol (3n). Com-
pound 3n was prepared according to the general procedure and
isolated as an oil (65 mg, 81% yield) after flash chromatography
(petroleum ether/ethyl acetate = 8:1). 1H NMR (400 MHz, CDCl3):
δ 8.05 (d, J = 8.7 Hz, 2H), 7.50−7.42 (m, 2H), 7.39 (d, J = 8.7 Hz,
2H), 7.21−7.17 (m, 3H), 4.73 (dt, J = 9.2, 3.2 Hz, 1H), 3.20 (dd, J =
13.0, 3.9 Hz, 1H), 3.12 (d, J = 2.7 Hz, 2H), 2.98 (dd, J = 13.0, 9.1 Hz,
1H). 13C{1H} NMR (100 MHz, CDCl3): δ 148.6, 146.3, 132.3, 128.4,
127.3, 126.8, 125.6, 122.6, 70.16, 37.15. Spectral data are in
agreement with literature values.39
1-(2-Chlorophenyl)-2-(phenylselanyl)ethan-1-ol (3o). Com-
pound 3o was prepared according to the general procedure and
isolated as an oil (72 mg, 93% yield) after flash chromatography
(petroleum ether/ethyl acetate = 25:1). 1H NMR (400 MHz,
CDCl3): δ 7.54 (dd, J = 8.1, 1.7 Hz, 1H), 7.51−7.46 (m, 2H), 7.20−
7.17 (m, 5H), 7.14−7.06 (m, 1H), 5.02 (dt, J = 9.6, 2.9 Hz, 1H), 3.37
(dd, J = 12.9, 3.0 Hz, 1H), 2.95 (d, J = 3.0 Hz, 1H), 2.86 (dd, J =
12.9, 9.6 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 138.7, 132.1,
130.5, 128.3, 128.1, 127.7, 127.6, 126.4, 126.1, 126.0, 67.6, 35.5.
Spectral data are in agreement with literature values.15a
1-(3-Bromophenyl)-2-(phenylselanyl)ethan-1-ol (3p). Com-
pound 3p was prepared according to the general procedure and
isolated as an oil (80 mg, 90% yield) after flash chromatography
(petroleum ether/ethyl acetate = 20:1). 1H NMR (400 MHz,
CDCl3): δ 7.46−7.40 (m, 2H), 7.3.8−7.37 (m, 1H), 7.28 (dt, J = 7.7,
1.6 Hz, 1H), 7.21−7.16 (m, 2H), 7.16−7.03 (m, 2H), 4.57 (dt, J =
9.3, 3.2 Hz, 1H), 3.14 (dd, J = 12.9, 3.7 Hz, 1H), 3.04−2.84 (m, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ 143.7, 132.2, 129.9, 129.0,
128.3, 127.9, 127.7, 126.5, 123.4, 121.6, 70.4, 37.2. HRMS (ESI): m/z
[M + H − H2O]+ calcd for C14H12BrSe 338.9282; found, 338.9273.
1-(2,4-Dimethylphenyl)-2-(phenylselanyl)ethan-1-ol (3q).
Compound 3q was prepared according to the general procedure
and isolated as an oil (68 mg, 89% yield) after flash chromatography
(petroleum ether/ethyl acetate = 1:2). 1H NMR (400 MHz, CDCl3):
δ 7.61−7.46 (m, 2H), 7.33 (d, J = 7.9 Hz, 1H), 7.24−7.17 (m, 3H),
7.04−6.92 (m, 1H), 6.85 (d, J = 1.8 Hz, 1H), 4.82 (dt, J = 9.8, 2.9 Hz,
1H), 3.16 (dd, J = 12.9, 3.2 Hz, 1H), 2.96 (dd, J = 12.8, 9.8 Hz, 1H),
2.65 (d, J = 2.5 Hz, 1H), 2.22 (s, 3H), 2.03 (s, 3H). 13C{1H} NMR
(100 MHz, CDCl3): δ 136.4, 136.2, 133.3, 132.4, 130.2, 128.2, 128.0,
126.5, 126.0, 124.1, 67.5, 36.4, 20.0, 17.7. HRMS (ESI): m/z [M + H
− H2O]+ calcd for C16H17Se 289.0490; found, 289.0482.
2-(Phenylselanyl)-1-(pyridin-4-yl)ethan-1-ol (3u). Compound
3u was prepared according to the general procedure and isolated as an
oil (54 mg, 77% yield) after flash chromatography (petroleum ether/
1
ethyl acetate = 1:1). H NMR (400 MHz, CDCl3): δ 8.54−8.31 (m,
2H), 7.64−7.37 (m, 2H), 7.32−7.10 (m, 5H), 4.65 (dd, J = 9.2, 3.7
Hz, 1H), 3.23 (dd, J = 12.9, 3.7 Hz, 1H), 2.99 (dd, J = 12.9, 9.2 Hz,
1H), 2.57 (brs, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 150.5,
148.7, 132.44, 132.39, 128.4, 127.5, 126.8, 119.8, 69.6, 37.0. HRMS
(ESI): m/z [M + H]+ calcd for C13H14NOSe, 280.0235; found,
280.0235.
1-(4-Methylthiazol-5-yl)-2-(phenylselanyl)ethan-1-ol (3v).
Compound 3v was prepared according to the general procedure
and isolated as an oil (69 mg, 93% yield) after flash chromatography
(petroleum ether/ethyl acetate = 2:1). 1H NMR (400 MHz, CDCl3):
δ 8.44 (s, 1H), 7.45−7.36 (m, 2H), 7.25−7.15 (m, 3H), 4.95 (dd, J =
8.0, 5.3 Hz, 1H), 4.31 (brs, 1H), 3.44−2.91 (m, 2H), 2.15 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3): δ 150.0, 147.5, 133.5, 132.1,
128.3, 127.9, 126.5, 65.2, 36.5, 14.1. HRMS (ESI): m/z [M + H]+
calcd for C12H14NOSSe, 299.9956; found, 299.9950.
2-(Phenylselanyl)-1-(thiophen-2-yl)ethan-1-ol (3w). Com-
pound 3w was prepared according to the general procedure and
isolated as an oil (59 mg, 84% yield) after flash chromatography
(petroleum ether/ethyl acetate = 1:1). 1H NMR (400 MHz, CDCl3):
δ 7.48−7.40 (m, 2H), 7.26−7.06 (m, 4H), 6.92−6.81 (m, 2H), 4.91
(dt, J = 7.9, 3.6 Hz, 1H), 3.26 (dd, J = 12.8, 4.3 Hz, 1H), 3.16 (dd, J =
12.8, 8.6 Hz, 1H), 2.99 (d, J = 3.4 Hz, 1H). 13C{1H} NMR (100
MHz, CDCl3): δ 145.2, 132.1, 128.2, 128.0, 126.4, 125.7, 123.8,
123.0, 67.5, 37.1. Spectral data are in agreement with literature
values.40
1-Ferroceneyl-2-(phenylselanyl)ethan-1-ol (3x). Compound
3x was prepared according to the general procedure and isolated as an
oil (64 mg, 66% yield) after flash chromatography (petroleum ether/
ethyl acetate = 10:1). 1H NMR (400 MHz, CDCl3): δ 7.50−7.45 (m,
2H), 7.24−7.16 (m, 3H), 4.51−4.39 (m, 1H), 4.22−4.19 (m, 1H),
4.14−4.12 (m, 1H), 4.10 (s, 7H), 3.18 (dd, J = 12.5, 4.2 Hz, 1H),
3.09 (dd, J = 12.5, 8.5 Hz, 1H), 2.46 (d, J = 3.2 Hz, 1H). 13C{1H}
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NMR (100 MHz, CDCl3): δ 131.8, 128.9, 128.1, 126.1, 90.6, 67.6,
67.4, 67.1, 67.0, 66.0, 64.6, 35.7. HRMS (ESI): m/z [M + H]+ calcd
for C18H19FeOSe, 386.9945; found, 386.9890.
threo-4-(Phenylselanyl)hexan-3-ol (3af). Compound 3af was
prepared according to the general procedure and isolated as an oil (60
mg, 94% yield) after flash chromatography (petroleum ether/ethyl
acetate = 20:1). 1H NMR (400 MHz, CDCl3): δ 7.72−7.41 (m, 2H),
7.34−6.89 (m, 3H), 3.42 (dt, J = 9.1, 4.7 Hz, 1H), 2.97 (dt, J = 9.1,
5.2 Hz, 1H), 2.45 (s, 1H), 1.80−1.71 (m, 1H), 1.67−1.39 (m, 3H),
1.02 (t, J = 7.3 Hz, 3H), 0.85 (t, J = 7.4 Hz, 3H). 13C{1H} NMR (100
MHz, CDCl3): δ 133.8, 128.0, 127.9, 126.5, 73.3, 57.1, 26.7, 24.6,
12.0, 9.2. Spectral data are in agreement with literature values.43
2,3-Dimethyl-3-(phenylselanyl)butan-2-ol (3ag). Compound
3ag was prepared according to the general procedure and isolated as
an oil (48 mg, 75% yield) after flash chromatography (petroleum
2-Phenyl-1-(phenylselanyl)propan-2-ol (3y). Compound 3y
was prepared according to the general procedure and isolated as a
white solid (68 mg, 94% yield) after flash chromatography (petroleum
1
ether/ethyl acetate = 20:1). Mp: 88−89 °C. H NMR (400 MHz,
CDCl3): δ 7.39−7.29 (m, 4H), 7.22−7.18 (m, 2H), 7.16−7.06 (m,
4H), 3.48 (d, J = 12.5 Hz, 1H), 3.22 (d, J = 12.5 Hz, 1H), 2.87 br(s,
1H), 1.52 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 145.3,
131.8, 129.5, 128.0, 127.2, 126.0, 123.7, 72.6, 44.1, 28.7. Spectral data
are in agreement with literature values.39
1
ether/ethyl acetate = 20:1). H NMR (400 MHz, CDCl3): δ 7.66−
1,1-Diphenyl-2-(phenylselanyl)ethan-1-ol (3z). Compound
3z was prepared according to the general procedure and isolated as
an oil (73 mg, 83% yield) after flash chromatography (petroleum
7.50 (m, 2H), 7.37−7.25 (m, 1H), 7.24−7.16 (m, 2H), 2.31 (s, 1H),
1.33 (s, 6H), 1.27 (s, 6H). 13C{1H} NMR (100 MHz, CDCl3): δ
137.5, 127.7, 127.6, 127.0, 74.8, 58.8, 25.6, 24.8. Spectral data are in
agreement with literature values.18c
1
ether/ethyl acetate = 10:1). H NMR (400 MHz, CDCl3): δ 7.47−
7.40 (m, 2H), 7.38−7.31 (m, 4H), 7.26−7.18 (m, 4H), 7.16−7.11
(m, 5H), 3.78 (s, 2H), 3.50 (s, 1H). 13C{1H} NMR (100 MHz,
CDCl3): δ 144.3, 132.0, 129.7, 128.1, 127.3, 126.3, 126.2, 125.0, 76.4,
43.6. Spectral data are in agreement with literature values.41
threo-1,2-Diphenyl-2-(phenylselanyl)ethan-1-ol (3aa). Com-
pound 3aa was prepared according to the general procedure and
isolated as an oil (49 mg, 55% yield) after flash chromatography
(petroleum ether/ethyl acetate = 15:1). 1H NMR (400 MHz,
CDCl3): δ 7.38−7.28 (m, 2H), 7.24−7.05 (m, 8H), 7.05−7.01 (m,
3H), 6.96−6.87 (m, 2H), 4.96 (dd, J = 8.8, 2.3 Hz, 1H), 4.40 (d, J =
8.8 Hz, 1H), 3.13 (d, J = 2.6 Hz, 1H). 13C{1H} NMR (100 MHz,
CDCl3): δ 139.7, 138.8, 134.3, 127.9, 127.7, 127.4 127.1, 127.07,
127.03, 126.7, 126.0, 125.7, 75.5, 58.9. Spectral data are in agreement
with literature values.9a
1-(Phenylselanyl)octan-2-ol (3ah). Compound 3ah was pre-
pared according to the general procedure and isolated as an oil (38
mg, 53% yield) after flash chromatography (petroleum ether/ethyl
acetate = 40:1). 1H NMR (400 MHz, CDCl3): δ 7.47−7.44 (m, 2H),
7.20−7.18 (m, 3H), 3.59 (dq, J = 5.9, 2.8 Hz, 1H), 3.07 (dd, J = 12.7,
3.5 Hz, 1H), 2.80 (dd, J = 12.7, 8.6 Hz, 1H), 2.35 (d, J = 3.6 Hz, 1H),
1.49−1.41 (m, 2H), 1.40−1.29 (m, 1H), 1.20−1.17 (m, 7H), 0.79 (t,
J = 6.6 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 132.0, 128.3,
128.2, 126.2, 68.8, 36.2, 35.6, 30.7, 28.2, 24.7, 21.6, 13.1. Spectral data
are in agreement with literature values.14
2-(Phenylselanyl)octan-1-ol (3ah′). Compound 3ah′ was
prepared according to the general procedure and isolated as an oil
(22 mg, 31% yield) after flash chromatography (petroleum ether/
ethyl acetate = 40:1). 1H NMR (400 MHz, CDCl3): δ 7.56−7.39 (m,
2H), 7.30−7.11 (m, 3H), 3.55 (d, J = 12.0 Hz, 1H), 3.45 (dd, J =
11.6, 6.8 Hz, 1H), 3.16 (dtd, J = 7.6, 6.4, 5.0 Hz, 1H), 2.17 (s, 1H),
1.64−1.44 (m, 5H), 1.42−1.14 (m, 5H), 0.79 (t, J = 6.6 Hz, 3H).
13C{1H} NMR (100 MHz, CDCl3): δ 134.4, 128.1, 126.9, 126.4, 63.2,
erythro-1-Phenyl-2-(phenylselanyl)propan-1-ol (3ab). Com-
pound 3ab was prepared according to the general procedure and
isolated as an oil (65 mg, 90% yield) after flash chromatography
(petroleum ether/ethyl acetate = 25:1). 1H NMR (400 MHz,
CDCl3): δ 7.55−7.46 (m, 2H), 7.26−7.09 (m, 8H), 4.68 (t, J = 3.0
Hz, 1H), 3.53 (qd, J = 7.2, 3.3 Hz, 1H), 2.69 (d, J = 3.0 Hz, 1H), 1.14
(d, J = 7.2 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 139.9,
133.7, 128.2 127.7, 127.1, 126.8, 126.4, 125.0, 73.3, 46.9, 13.0.
Spectral data are in agreement with literature values.42
anti-2-(Phenylselanyl)cyclohexan-1-ol (3ac). Compound 3ac
was prepared according to the general procedure and isolated as an oil
(61 mg, 96% yield) after flash chromatography (petroleum ether/
ethyl acetate = 20:1). 1H NMR (400 MHz, CDCl3): δ 7.60−7.43 (m,
2H), 7.31−7.12 (m, 3H), 3.25 (tdd, J = 10.3, 4.3, 1.4 Hz, 1H), 2.90
(s, 1H), 2.82 (ddd, J = 12.3, 10.0, 4.0 Hz, 1H), 2.23−1.96 (m, 1H),
1.67−1.62 (m, 1H), 1.58−1.52 (m, 1H), 1.44−1.02 (m, 5H).
13C{1H} NMR (100 MHz, CDCl3): δ 135.1, 128.0, 127.1, 125.5, 71.2,
52.5, 32.8, 32.3, 25.8, 23.4. Spectral data are in agreement with
literature values.22
anti-2-(Phenylselanyl)cyclooctan-1-ol (3ad). Compound 3ad
was prepared according to the general procedure and isolated as an oil
(58 mg, 82% yield) after flash chromatography (petroleum ether/
ethyl acetate = 30:1). 1H NMR (400 MHz, CDCl3): δ 7.60−7.41 (m,
2H), 7.27−7.12 (m, 3H), 3.61 (dd, J = 10.1, 4.6 Hz, 1H), 3.24 (ddd, J
= 10.4, 8.5, 2.7 Hz, 1H), 2.87 (s, 1H), 2.22−2.14 (m, 1H), 1.95−1.71
(m, 2H), 1.70−1.58 (m, 3H), 1.54−1.38 (m, 6H). 13C{1H} NMR
(100 MHz, CDCl3): δ 134.4, 128.0, 126.9, 126.8, 72.6, 54.2, 30.9,
30.6, 25.8, 25.7, 24.2, 22.6. Spectral data are in agreement with
literature values.11a
1-Methyl-2-(phenylselanyl)cyclohexan-1-ol (3ae). Com-
pound 3ae was prepared according to the general procedure and
isolated as an oil (61 mg, 90% yield) after flash chromatography
(petroleum ether/ethyl acetate = 20:1). 1H NMR (400 MHz,
CDCl3): δ 7.73−7.48 (m, 2H), 7.24−7.17 (m, 3H), 3.13 (dd, J =
12.3, 4.2 Hz, 1H), 2.58 (brs, 1H), 2.29−1.97 (m, 1H), 1.90−1.77 (m,
1H), 1.72−1.54 (m, 3H), 1.48−1.30 (m, 2H), 1.21 (s, 3H), 1.20−
1.10 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 134.3, 130.0,
129.1, 127.5, 72.7, 60.2, 39.5, 33.4, 27.0, 24.0, 23.4. Spectral data are
in agreement with literature values.18c
49.6, 30.7, 30.6, 28.0, 26.8, 21.6, 13.1. Spectral data are in agreement
with literature values.14
(8R,9S,13S,14S)-3-(1-Hydroxy-2-(phenylselanyl)ethyl)-13-
methyl-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta-
[a]phenanthren-17-one (3ai). Compound 3ai was prepared
according to the general procedure and isolated as an oil (84 mg,
74% yield) after flash chromatography (petroleum ether/ethyl acetate
1
= 5:1). H NMR (400 MHz, CDCl3): δ 7.46 (dd, J = 6.6, 2.9 Hz,
2H), 7.26−7.15 (m, 4H), 7.09−6.98 (m, 2H), 4.63 (dt, J = 9.2, 2.9
Hz, 1H), 3.22 (dd, J = 12.8, 3.8 Hz, 1H), 3.07 (dd, J = 12.7, 9.4 Hz,
1H), 2.82 (dd, J = 9.3, 4.3 Hz, 2H), 2.74 (brs, 1H), 2.43 (dd, J = 18.8,
8.7 Hz, 1H), 2.33 (dd, J = 10.0, 4.5 Hz, 1H), 2.26−2.17 (m, 1H),
2.12−1.85 (m, 4H), 1.60−1.50 (m, 2H), 1.49−1.35 (m, 4H), 0.83 (s,
3H). 13C{1H} NMR (100 MHz, CDCl3): δ 220.1, 138.9, 138.5, 138.4,
135.7, 132.0, 128.2, 126.3, 125.3, 124.5, 122.3, 71.0, 49.4, 46.9, 43.3,
37.2, 37.0, 34.8, 30.5, 28.4, 25.4, 24.7, 20.5, 12.8. HRMS (ESI): m/z
[M + H − H2O]+ calcd for C26H29OSe, 437.1378; found, 437.1370.
7-(1-Hydroxy-2-(phenylselanyl)ethyl)-2H-chromen-2-one
(3aj). Compound 3aj was prepared according to the general
procedure and isolated as a yellow solid (70 mg, 81% yield) after
flash chromatography (petroleum ether/ethyl acetate = 3:1). Mp:
77−79 °C. 1H NMR (400 MHz, CDCl3): δ 7.58 (d, J = 9.5 Hz, 1H),
7.45 (dd, J = 6.6, 3.0 Hz, 2H), 7.34 (d, J = 7.9 Hz, 1H), 7.26−7.10
(m, 5H), 6.30 (d, J = 9.5 Hz, 1H), 4.73 (d, J = 7 Hz, 1H), 3.22 (dd, J
= 12.9, 4.0 Hz, 1H), 3.17 (brs, 1H), 3.03 (dd, J = 12.9, 8.9 Hz, 1H).
13C{1H} NMR (100 MHz, CDCl3): δ 159.8, 153.0, 146.2, 142.1,
132.2, 128.3, 127.6, 126.9, 126.6, 121.0, 117.2, 115.4, 113.2, 70.4,
37.1. HRMS (ESI): m/z [M + H]+ calcd for C17H15O3Se. 347.0181;
found, 347.0176.
(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 4-(1-Hydroxy-2-
(phenylselanyl)ethyl)benzoate (3ak). Compound 3ak was
prepared according to the general procedure and isolated as an oil
(103 mg, 90% yield) after flash chromatography (petroleum ether/
ethyl acetate = 18:1). 1H NMR (400 MHz, CDCl3): δ 7.91 (d, J = 8.3
Hz, 2H), 7.56−7.37 (m, 2H), 7.31 (d, J = 8.3 Hz, 2H), 7.26−7.14 (m,
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3H), 4.84 (td, J = 10.9, 4.4 Hz, 1H), 4.70 (dt, J = 9.1, 3.3 Hz, 1H),
3.20 (dd, J = 12.8, 3.8 Hz, 1H), 3.10−2.92 (m, 2H), 2.03 (dd, J =
12.0, 4.3 Hz, 1H), 1.93−1.81 (m, 1H), 1.64 (dt, J = 11.9, 2.8 Hz, 2H),
1.52−1.41 (m, 2H), 1.12−0.96 (m, 2H), 0.85 (d, J = 4.9 Hz, 3H),
0.83 (d, J = 5.2 Hz, 3H), 0.80−0.76 (m, 1H), 0.70 (d, J = 6.9 Hz,
3H). 13C{1H} NMR (100 MHz, CDCl3): δ 164.8, 146.3, 132.2, 129.2,
128.8, 128.3, 127.8, 126.5, 124.7, 73.8, 70.7, 46.2, 39.9, 37.2, 33.3,
30.4, 25.4, 22.6, 21.0, 19.7, 15.5. HRMS (ESI): m/z [M + H]+ calcd
for C25H33O3Se, 461.1589; found, 461.1577.
(m, 2H), 7.25−6.95 (m, 3H), 6.89−6.75 (m, 2H), 4.56 (dt, J = 9.4,
2.9 Hz, 1H), 3.21 (dd, J = 12.7, 3.7 Hz, 1H), 3.09 (dd, J = 12.7, 9.5
Hz, 1H), 2.82−2.49 (m, 3H), 2.07 (s, 3H), 1.69 (dt, J = 16.1, 6.7 Hz,
2H), 1.58−1.42 (m, 8H), 1.42−1.17 (m, 10H), 1.10−0.95 (m, 6H),
0.87−0.77 (m, 12H). 13C{1H} NMR (100 MHz, CDCl3): δ 150.9,
132.0, 131.4, 128.4, 128.1, 126.2, 125.4, 124.9, 123.4, 119.4, 75.1,
71.2, 39.2, 39.1, 38.3, 37.2, 36.4, 36.4, 36.3, 31.8, 31.6, 30.1, 28.7,
27.0, 23.8, 23.4, 23.3, 23.2, 21.7, 21.6, 21.3, 20.0, 18.7, 18.6, 15.1.
HRMS (ESI): m/z [M + H − H2O]+ calcd for C35H53OSe, 569.3256;
found, 569.3248.
((3aR,5R,5aS,8aS,8bR)-2,2,7,7-Tetramethyltetrahydro-5H-
bis([1,3]dioxolo)[4,5-b:4′,5′-d]pyran-5-yl)methyl 4-(1-Hy-
droxy-2-(phenylselanyl)ethyl)benzoate (3al). Compound 3al
was prepared according to the general procedure and isolated as a
white solid (84 mg, 60% yield) after flash chromatography (petroleum
4 - ( 4 - ( 1 - H y d r o x y - 2 - ( p h e n y l s e l a n y l ) e t h y l ) - 3 -
methoxyphenyl)butan-2-one (3aq). Compound 3aq was pre-
pared according to the general procedure and isolated as an oil (60
mg, 64% yield) after flash chromatography (petroleum ether/ethyl
1
1
acetate = 4:1). H NMR (400 MHz, CDCl3): δ 7.53−7.35 (m, 2H),
ether/ethyl acetate = 5:1). Mp: 35−36 °C. H NMR (400 MHz,
7.24 (d, J = 7.7 Hz, 1H), 7.21−7.10 (m, 3H), 6.70 (dd, J = 7.7, 1.5
Hz, 1H), 6.59 (d, J = 1.5 Hz, 1H), 4.92 (dt, J = 9.0, 4.5 Hz, 1H), 3.71
(s, 3H), 3.35 (dd, J = 12.6, 4.0 Hz, 1H), 3.05 (dd, J = 12.7, 8.9 Hz,
1H), 2.95 (d, J = 5.2 Hz, 1H), 2.80 (t, J = 7.8 Hz, 2H), 2.80 (t, J = 7.3
Hz, 2H), 2.07 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 206.9,
155.1, 140.9, 131.3, 128.9, 128.0, 127.2, 125.8, 125.7, 119.4, 109.6,
67.9, 54.1, 44.1, 35.0, 29.1, 28.7. HRMS (ESI): m/z [M + H − H2O]+
calcd for C19H21O2Se, 361.0701; found, 361.0694.
CDCl3): δ 7.94 (d, J = 8.3 Hz, 2H), 7.60−7.45 (m, 2H), 7.33 (d, J =
8.3 Hz, 2H), 7.27−7.14 (m, 3H), 5.49 (d, J = 5.0 Hz, 1H), 4.70 (dd, J
= 9.4, 3.6 Hz, 1H), 4.58 (dd, J = 7.9, 2.5 Hz, 1H), 4.45 (dd, J = 11.5,
4.8 Hz, 1H), 4.35 (dd, J = 11.5, 7.6 Hz, 1H), 4.28 (dd, J = 5.1, 2.6 Hz,
1H), 4.25 (dd, J = 7.9, 1.9 Hz, 1H), 4.10 (ddd, J = 7.1, 4.7, 1.8 Hz,
1H), 3.22 (dd, J = 12.9, 3.7 Hz, 1H), 3.01 (dd, J = 12.8, 9.4 Hz, 1H),
2.91 (brs, 1H), 1.44 (s, 3H), 1.41 (s, 3H), 1.28 (s, 3H), 1.26 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3): δ 165.1, 146.5, 132.3, 129.0,
2-(Methylselanyl)-1-phenylethan-1-ol (4a). Compound 4a
was prepared according to the general procedure and isolated as an
oil (47 mg, 88% yield) after flash chromatography (petroleum ether/
ethyl acetate = 20:1). 1H NMR (400 MHz, CDCl3): δ 8.01−6.80 (m,
5H), 4.67 (ddd, J = 9.1, 4.1, 2.5 Hz, 1H), 2.97 (s, 1H), 2.83 (dd, J =
12.8, 4.2 Hz, 1H), 2.72 (dd, J = 12.8, 9.0 Hz, 1H), 1.87 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3): δ 141.7, 127.5, 126.8, 124.8, 71.0,
34.9, 3.6. Spectral data are in agreement with literature values.44
2-(Ethylselanyl)-1-phenylethan-1-ol (4b). Compound 4b was
prepared according to the general procedure and isolated as an oil (44
mg, 76% yield) after flash chromatography (petroleum ether/ethyl
acetate = 30:1). 1H NMR (400 MHz, CDCl3): δ 7.49−7.23 (m, 5H),
4.77 (dt, J = 9.1, 3.2 Hz, 1H), 3.00 (dd, J = 12.9, 3.9 Hz, 1H), 2.91 (d,
J = 2.8 Hz, 1H), 2.82 (dd, J = 12.9, 9.2 Hz, 1H), 2.57 (q, J = 7.5 Hz,
2H), 1.40 (t, J = 7.5 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ
142.8, 128.5, 127.8, 125.8, 72.3, 34.2, 17.9, 15.8. HRMS (ESI): m/z
[M + H − H2O]+ calcd for C10H13Se, 213.0177; found, 213.0173.
2-(Benzylselanyl)-1-phenylethan-1-ol (4c). Compound 4c was
prepared according to the general procedure and isolated as a white
solid (55 mg, 75% yield) after flash chromatography (petroleum
128.5, 128.3, 127.7, 126.6, 124.7, 108.7, 107.8, 95.3, 70.6, 70.1, 69.7,
69.5, 65.1, 62.9, 37.4, 25.0, 24.9, 24.0, 23.5. HRMS (ESI): m/z [M +
H]+ calcd for C27H33O8Se, 565.1335; found, 565.1327.
4-(1-Hydroxy-2-(phenylselanyl)ethyl)phenyl (2S)-2-(6-Me-
thoxynaphthalen-2-yl)propanoate (3am). Compound 3am was
prepared according to the general procedure and isolated as an oil (90
mg, 71% yield) after flash chromatography (petroleum ether/ethyl
1
acetate = 5:1). H NMR (400 MHz, CDCl3): δ 7.77−7.58 (m, 3H),
7.51−7.34 (m, 3H), 7.26−7.14 (m, 5H), 7.16−7.05 (m, 2H), 6.87 (d,
J = 8.6 Hz, 2H), 4.62 (dd, J = 9.4, 3.5 Hz, 1H), 4.01 (q, J = 7.1 Hz,
1H), 3.85 (s, 3H), 3.17 (dd, J = 12.8, 3.7 Hz, 1H), 2.99 (dd, J = 12.8,
9.4 Hz, 1H), 2.74 (brs, 1H), 1.61 (d, J = 7.1 Hz, 3H). 13C{1H} NMR
(100 MHz, CDCl3): δ 172.1, 156.7, 149.3, 138.9, 134.0, 132.8, 132.1,
128.28, 128.25, 127.92, 127.88, 126.4, 126.3, 125.8, 125.10, 125.05,
120.4, 118.1, 104.5, 70.6, 54.3, 44.5, 37.4, 17.5. HRMS (ESI): m/z [M
+ H − H2O]+ calcd for C28H25O3Se, 489.0963; found, 489.0953.
7-(1-Hydroxy-2-(phenylselanyl)ethyl)-3-(4-methoxyphen-
yl)-4H-chromen-4-one (3an). Compound 3an was prepared
according to the general procedure and isolated as a white solid
(104 mg, 92% yield) after flash chromatography (petroleum ether/
ethyl acetate = 3:1). Mp: 114−116 °C. 1H NMR (400 MHz, CDCl3):
δ 8.08 (d, J = 8.2 Hz, 1H), 7.86 (s, 1H), 7.54−7.29 (m, 5H), 7.22−
7.08 (m, 4H), 6.87 (d, J = 8.8 Hz, 2H), 4.74 (dd, J = 8.9, 3.9 Hz, 1H),
3.74 (s, 3H), 3.40 (d, J = 3.6 Hz, 1H), 3.22 (dd, J = 12.8, 4.0 Hz, 1H),
3.03 (dd, J = 12.8, 8.9 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ
175.2, 158.6, 155.1, 151.6, 148.1, 132.2, 129.0, 128.3, 127.7, 126.5,
125.5, 123.9, 122.9, 122.6, 121.8, 114.1, 112.9, 70.4, 54.3, 36.9.
HRMS (ESI): m/z [M + H]+ calcd for C24H21O4Se, 453.0600; found,
453.0593.
1
ether/ethyl acetate = 20:1). Mp: 38−40 °C. H NMR (400 MHz,
CDCl3): δ 7.45−7.02 (m, 10H), 4.55 (dt, J = 8.7, 3.4 Hz, 1H), 3.65
(s, 2H), 2.79−2.72 (m, 2H), 2.67 (dd, J = 13.1, 8.8 Hz, 1H). 13C{1H}
NMR (100 MHz, CDCl3): δ 141.8, 137.8, 127.9, 127.6, 127.4, 126.8,
125.9, 124.7, 71.3, 33.1, 26.4. Spectral data are in agreement with
literature values.26
2-(Cyclohexylselanyl)-1-phenylethan-1-ol (4d). Compound
4d was prepared according to the general procedure and isolated as
an oil (45 mg, 63% yield) after flash chromatography (petroleum
1
ether/ethyl acetate = 20:1). H NMR (400 MHz, CDCl3): δ 7.64−
4-(1-Hydroxy-2-(phenylselanyl)ethyl)phenyl (tert-butoxy-
carbonyl)-L-valinate (3ao). Compound 3ao was prepared accord-
ing to the general procedure and isolated as an oil (98 mg, 80% yield)
after flash chromatography (petroleum ether/ethyl acetate = 5:1). 1H
NMR (400 MHz, CDCl3): δ 7.50−7.38 (m, 2H), 7.27 (d, J = 8.7 Hz,
2H), 7.23−7.14 (m, 3H), 6.97 (d, J = 8.6 Hz, 2H), 5.04 (d, J = 9.1
Hz, 1H), 4.66 (dd, J = 9.5, 3.6 Hz, 1H), 4.37 (dd, J = 9.1, 4.7 Hz,
1H), 3.19 (dd, J = 12.8, 3.8 Hz, 1H), 3.02 (dd, J = 12.8, 9.3 Hz, 1H),
2.94 (brs, 1H), 2.39−2.17 (m, 1H), 1.39 (s, 9H), 0.99 (d, J = 6.8 Hz,
3H), 0.93 (d, J = 7.0 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ
170.1, 154.7, 148.9, 139.4, 132.1, 128.3 128.0, 126.4, 126.0, 120.4,
79.0, 70.6, 57.6, 37.3, 30.3, 27.3, 18.1, 16.6. HRMS (ESI): m/z [M +
H]+ calcd for C24H32NO5Se, 494.1440; found, 494.1429.
6.57 (m, 5H), 4.68 (dt, J = 9.2, 3.3 Hz, 1H), 2.95 (dd, J = 12.8, 3.9
Hz, 1H), 2.92 (d, J = 3.0 Hz, 1H), 2.84−2.79 (m, 1H), 2.75 (dd, J =
12.8, 9.1 Hz, 1H), 1.98−1.89 (m, 2H), 1.72−1.63 (m, 2H), 1.50−
1.34 (m, 2H), 1.28−1.11 (m, 4H). 13C{1H} NMR (100 MHz,
CDCl3): δ 141.9, 127.4, 126.7, 124.79, 71.3, 38.4, 33.6, 33.6, 32.3,
25.78, 25.77, 24.7. HRMS (ESI): m/z [M + H − H2O]+ calcd for
C14H19Se, 267.0646; found, 267.0643.
2-((4-Methoxyphenyl)selanyl)-1-phenylethan-1-ol (4e).
Compound 4e was prepared according to the general procedure
and isolated as an oil (54 mg, 70% yield) after flash chromatography
(petroleum ether/ethyl acetate = 10:1). 1H NMR (400 MHz,
CDCl3): δ 7.41 (d, J = 8.7 Hz, 2H), 7.28−7.15 (m, 5H), 6.74 (d, J =
8.7 Hz, 2H), 4.58 (dd, J = 9.5, 3.6 Hz, 1H), 3.71 (s, 3H), 3.10 (dd, J =
12.7, 3.6 Hz, 1H), 2.94 (dd, J = 12.7, 9.6 Hz, 1H), 2.88 (s, 1H).
13C{1H} NMR (100 MHz, CDCl3): δ 158.5, 141.4, 134.9, 127.4,
126.8, 124.8, 117.7, 113.9, 70.9, 54.3, 38.5. HRMS (ESI): m/z [M +
H − H2O]+ calcd for C15H15OSe 291.0283; found, 291.0278.
1-((R)-2,8-Dimethyl-2-((4R,8R)-4,8,12-trimethyltridecyl)-
chroman-6-yl)-2-(phenylselanyl)ethan-1-ol (3ap). Compound
3ap was prepared according to the general procedure and isolated
as an oil (92 mg, 63% yield) after flash chromatography (petroleum
ether/ethyl acetate = 5:1). 1H NMR (400 MHz, CDCl3): δ 7.55−7.44
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2-((4-(tert-Butyl)phenyl)selanyl)-1-phenylethan-1-ol (4f).
Compound 4f was prepared according to the general procedure and
isolated as an oil (67 mg, 81% yield) after flash chromatography
(petroleum ether/ethyl acetate = 40:1). 1H NMR (400 MHz,
CDCl3): δ 7.41 (d, J = 8.4 Hz, 2H), 7.31−7.16 (m, 7H), 4.67 (dd, J =
9.5, 3.6 Hz, 1H), 3.21 (dd, J = 12.8, 3.7 Hz, 1H), 3.03 (dd, J = 12.8,
9.5 Hz, 1H), 2.30 (s, 1H), 1.24 (s, 9H). 13C{1H} NMR (100 MHz,
CDCl3): δ 149.7, 141.5, 132.1, 127.5, 126.8, 125.4, 124.8, 124.3, 71.1,
37.6, 33.5, 30.2. HRMS (ESI): m/z [M + H − H2O]+ calcd for
C18H21Se, 317.0803; found, 317.0797.
2-(Benzo[d][1,3]dioxol-5-ylselanyl)-1-phenylethan-1-ol
(4g). Compound 4g was prepared according to the general procedure
and isolated as an oil (67 mg, 84% yield) after flash chromatography
(petroleum ether/ethyl acetate = 10:1). 1H NMR (400 MHz,
CDCl3): δ 7.35−7.14 (m, 5H), 7.01 (dd, J = 7.9, 1.7 Hz, 1H), 6.98
(d, J = 1.6 Hz, 1H), 6.67 (d, J = 7.9 Hz, 1H), 5.91 (s, 2H), 4.64 (dd, J
= 9.4, 3.6 Hz, 1H), 3.15 (dd, J = 12.7, 3.6 Hz, 1H), 2.99 (dd, J = 12.8,
9.5 Hz, 1H), 2.74 (d, J = 2.7 Hz, 1H). 13C{1H} NMR (100 MHz,
CDCl3): δ 147.1, 146.8, 141.4, 127.5, 127.2, 126.9, 124.8, 118.8,
113.6, 108.2, 100.3, 71.0, 38.7. HRMS (ESI): m/z [M + H − H2O]+
calcd for C15H13O2Se, 305.0075; found, 305.0070.
2-(Naphthalen-2-ylselanyl)-1-phenylethan-1-ol (4h). Com-
pound 4h was prepared according to the general procedure and
isolated as an oil (61 mg, 75% yield) after flash chromatography
(petroleum ether/ethyl acetate = 20:1). 1H NMR (400 MHz,
CDCl3): δ 8.33 (d, J = 8.4 Hz, 1H), 7.85−7.65 (m, 3H), 7.47 (ddd, J
= 19.3, 8.1, 6.8 Hz, 2H), 7.30 (dd, J = 8.2, 7.1 Hz, 1H), 7.27−7.08 (m,
5H), 4.73 (dt, J = 9.1, 3.2 Hz, 1H), 3.23 (dd, J = 12.6, 3.7 Hz, 1H),
3.11 (dd, J = 12.6, 9.4 Hz, 1H), 2.73 (d, J = 2.7 Hz, 1H). 13C{1H}
NMR (100 MHz, CDCl3): δ 141.4, 133.2, 133.0, 132.2, 127.9, 127.7,
127.5, 127.2, 126.9, 126.6, 125.9, 125.3, 124.8, 124.7, 71.3, 37.4.
Spectral data are in agreement with literature values.45
125.47, 77.7, 68.7, 35.0, 22.3, 20.3. Spectral data are in agreement
with literature values.21b
(2-(Methoxy-d3)-2-phenylethyl)(phenyl)selane (5d). Com-
pound 5d was prepared according to the general procedure and
isolated as an oil (65 mg, 88% yield) after flash chromatography
(petroleum ether/ethyl acetate = 100:1). 1H NMR (400 MHz,
CDCl3): δ 7.43−7.35 (m, 2H), 7.29−7.18 (m, 5H), 7.18−7.09 (m,
3H), 4.26 (dd, J = 8.5, 5.0 Hz, 1H), 3.24 (dd, J = 12.2, 8.4 Hz, 1H),
3.01 (dd, J = 12.2, 5.0 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ
139.9, 131.5, 129.6, 128.0, 127.5, 127.0, 125.7, 125.6, 82.0, 55.5−54.7
(m), 34.3. HRMS (ESI): m/z [M + H]+ calcd for C15H14D3OSe,
296.0627; found, 296.0624.
Phenyl(2-phenyl-2-(2,2,2-trifluoroethoxy)ethyl)selane (5e).
Compound 5e was prepared according to the general procedure and
isolated as an oil (52 mg, 58% yield) after flash chromatography
(petroleum ether/ethyl acetate = 100:1). 1H NMR (400 MHz,
CDCl3): δ 7.41−7.39 (m, 2H), 7.32−7.21 (m, 5H), 7.20−7.14 (m,
3H), 4.52 (dd, J = 8.0, 5.4 Hz, 1H), 3.82−3.47 (m, 2H), 3.30 (dd, J =
12.7, 7.9 Hz, 1H), 3.05 (dd, J = 12.6, 5.4 Hz, 1H). 13C{1H} NMR
(100 MHz, CDCl3): δ 138.2, 131.7, 129.2, 128.0, 127.8, 127.7, 126.0
(q, C−F,1JC−F = 232.0 Hz), 126.0, 125.7, 82.0, 65.1 (q, C−F, 2JC−F
=
34.3 Hz), 33.7. 19F NMR(376 MHz, CDCl3): δ −73.9. HRMS (ESI):
m/z [M + H]+ calcd for C16H16F3OSe, 361.0313; found, 361.0324.
(2-Phenoxy-2-phenylethyl)(phenyl)selane (5f). Compound 5f
was prepared according to the general procedure and isolated as an oil
(58 mg, 66% yield) after flash chromatography (petroleum ether/
1
ethyl acetate = 100:1). H NMR (400 MHz, CDCl3): δ 7.56−7.43
(m, 2H), 7.37−7.22 (m, 4H), 7.21−7.14 (m, 4H), 7.09 (dd, J = 8.7,
7.3 Hz, 2H), 6.80 (tt, J = 7.3, 1.1 Hz, 1H), 6.76−6.66 (m, 2H), 5.23
(dd, J = 8.3, 4.9 Hz, 1H), 3.43 (dd, J = 12.6, 8.2 Hz, 1H), 3.18 (dd, J
= 12.6, 4.9 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 156.8,
139.6, 131.9, 129.3, 128.3, 128.0, 127.6, 127.0, 126.0, 125.1, 120.0,
115.0, 78.8, 34.6. Spectral data are in agreement with literature
values.46
1-Phenyl-2-(thiophen-2-ylselanyl)ethan-1-ol (4i). Compound
4i was prepared according to the general procedure and isolated as an
oil (54 mg, 76% yield) after flash chromatography (petroleum ether/
1-Phenyl-2-(phenylselanyl)ethyl Benzoate (5g). Compound
5g was prepared according to the general procedure and isolated as an
oil (65 mg, 68% yield) after flash chromatography (petroleum ether/
1
ethyl acetate = 15:1). H NMR (400 MHz, CDCl3): δ 7.32 (dd, J =
5.3, 1.2 Hz, 1H), 7.28−7.17 (m, 5H), 7.15 (dd, J = 3.5, 1.2 Hz, 1H),
6.91 (dd, J = 5.3, 3.5 Hz, 1H), 4.69 (dd, J = 9.5, 3.7 Hz, 1H), 3.09
(dd, J = 12.6, 3.7 Hz, 1H), 2.95 (dd, J = 12.7, 9.4 Hz, 1H), 2.71 (s,
1H). 13C{1H} NMR (100 MHz, CDCl3): δ 141.2, 134.9, 130.1, 127.5,
127.2, 126.9, 124.8, 121.6, 71.2, 40.4. HRMS (ESI): m/z [M + H −
H2O]+ calcd for C12H11SSe, 266.9741; found, 266.9737.
1
ethyl acetate = 100:1). H NMR (400 MHz, CDCl3): δ 8.02−7.81
(m, 2H), 7.55−7.39 (m, 3H), 7.35−7.30 (m, 4H), 7.31−7.21 (m,
3H), 7.17−7.10 (m, 3H), 6.09 (dd, J = 8.0, 5.7 Hz, 1H), 3.46 (dd, J =
12.9, 7.9 Hz, 1H), 3.29 (dd, J = 12.8, 5.7 Hz, 1H). 13C{1H} NMR
(100 MHz, CDCl3): δ 164.5, 138.5, 132.1, 132.0, 128.9, 128.72,
128.70, 128.1, 127.5, 127.4, 127.3, 126.2, 125.5, 74.8, 32.6. Spectral
data are in agreement with literature values.21a
(2-Methoxy-2-phenylethyl)(phenyl)selane (5a). Compound
5a was prepared according to the general procedure and isolated as
an oil (49 mg, 68% yield) after flash chromatography (petroleum
4-Chloro-N-(1-phenyl-2-(phenylselanyl)ethyl)aniline (5h).
Compound 5h was prepared according to the general procedure
and isolated as an oil (70 mg, 73% yield) after flash chromatography
(petroleum ether/ethyl acetate = 150:1). 1H NMR (400 MHz,
CDCl3): δ 7.54−7.33 (m, 2H), 7.29−7.10 (m, 8H), 6.90 (d, J = 8.8
Hz, 2H), 6.25 (d, J = 8.8 Hz, 2H), 4.39 (d, J = 3.8 Hz, 1H), 4.27 (dt, J
= 8.6, 4.2 Hz, 1H), 3.25 (dd, J = 12.7, 4.4 Hz, 1H), 3.06 (dd, J = 12.7,
9.1 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 144.5, 141.1,
132.6, 128.3, 127.9, 127.83, 127.82, 126.26, 126.60, 125.2, 121.3,
113.7, 56.8, 35.3. Spectral data are in agreement with literature
values.47
Phenyl(2-phenyl-2-(2,4,6-trimethoxyphenyl)ethyl)selane
(9). Compound 9 was prepared according to the general procedure
and isolated as an oil (28 mg, 26% yield) after flash chromatography
(petroleum ether/ethyl acetate = 30:1). 1H NMR (400 MHz,
CDCl3): δ 7.42−7.33 (m, 2H), 7.28−7.22 (m, 2H), 7.17−7.10 (m,
5H), 7.09−6.99 (m, 1H), 6.02 (s, 2H), 4.85 (dd, J = 9.7, 7.0 Hz, 1H),
3.81 (dd, J = 3.9, 1.8 Hz, 1H), 3.71 (s, 3H), 3.68−3.63 (m, 7H).
13C{1H} NMR (100 MHz, CDCl3): δ 158.8, 158.2, 143.2, 131.5,
1
ether/ethyl acetate = 100:1). H NMR (400 MHz, CDCl3): δ 7.45−
7.37 (m, 2H), 7.32−7.18 (m, 5H), 7.19−7.12 (m, 3H), 4.27 (dd, J =
8.5, 5.1 Hz, 1H), 3.25 (dd, J = 12.3, 8.5 Hz, 1H), 3.17 (s, 3H), 3.02
(dd, J = 12.3, 5.0 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ
139.8, 131.5, 129.6, 128.0, 127.5, 127.1, 125.8, 125.6, 82.1, 56.0, 34.3.
Spectral data are in agreement with literature values.22
(2-Ethoxy-2-phenylethyl)(phenyl)selane (5b). Compound 5b
was prepared according to the general procedure and isolated as an oil
(55 mg, 72% yield) after flash chromatography (petroleum ether/
1
ethyl acetate = 120:1). H NMR (400 MHz, CDCl3): δ 7.45−7.38
(m, 2H), 7.32−7.08 (m, 8H), 4.39 (dd, J = 8.5, 5.1 Hz, 1H), 3.50−
3.18 (m, 3H), 3.02 (dd, J = 12.2, 5.1 Hz, 1H), 1.11 (t, J = 7.0 Hz,
3H). 13C{1H} NMR (100 MHz, CDCl3): δ 140.6, 131.5, 129.8, 127.9,
127.4, 126.9, 125.7, 125.5, 80.4, 63.6, 34.5, 14.2. Spectral data are in
agreement with literature values.22
(2-Isopropoxy-2-phenylethyl)(phenyl)selane (5c). Com-
pound 5c was prepared according to the general procedure and
isolated as a white solid (55 mg, 69% yield) after flash
chromatography (petroleum ether/ethyl acetate = 100:1). Mp: 44−
130.3, 127.7, 126.84, 126.75, 125.3, 124.6, 111.3, 90.0, 54.6, 54.2,
39.1, 30.5. Spectral data are in agreement with literature values.48
Phenyl(2,4,6-trimethoxyphenyl)selane (10). Compound 10
was prepared according to the general procedure and isolated as a
white solid (11 mg, 13% yield) after flash chromatography (petroleum
1
46 °C. H NMR (400 MHz, CDCl3): δ 7.46−7.33 (m, 2H), 7.26−
7.05 (m, 8H), 4.50 (dd, J = 8.8, 4.8 Hz, 1H), 3.42 (p, J = 6.1 Hz, 1H),
3.21 (dd, J = 12.1, 8.8 Hz, 1H), 2.98 (dd, J = 12.1, 4.7 Hz, 1H), 1.08
(d, J = 6.0 Hz, 3H), 0.99 (d, J = 6.2 Hz, 3H). 13C{1H} NMR (100
MHz, CDCl3): δ 141.4, 131.2, 130.0, 127.9, 127.4, 126.8, 125.53,
1
ether/ethyl acetate = 25:1). Mp: 103−105 °C. H NMR (400 MHz,
CDCl3): δ 7.41−6.70 (m, 5H), 6.14 (s, 2H), 3.79 (s, 3H), 3.72 (s,
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6H). 13C{1H} NMR (100 MHz, CDCl3): δ 161.9, 160.9, 132.5, 127.7,
127.6, 124.2, 96.0, 90.1, 55.3, 54.4. Spectral data are in agreement
with literature values.32
Technology Plan Projects of Nantong (JC2020072 and
JC2019102).
Gram-Scale Reaction for the Synthesis of β-Hydroxy
Selenide 3a. To a 50 mL round-bottomed flask with a magnetic
stir bar were added styrene (0.52 g, 5.00 mmol, 1.00 equiv), Ph2Se2
(1.56 g, 5.00 mmol, 1.00 equiv), PhIO (1.10 g, 5.00 mmol, 1.00
equiv), and 20 mL of CH3CN/water (3:1). The reaction mixture was
stirred overnight. The reaction was monitored by TLC. After
completion of reaction, the mixture was added to 10 mL of H2O
and extracted with ethyl acetate (20 mL) three times. The combined
organic layer was dried (Na2SO4) and concentrated to give a crude
residue, which was purified by flash column chromatography (silica
gel, petroleum ether/ethyl acetate = 15:1) to give 3a in 82% yield
(1.14 g).
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00257.
■
sı
Mechanistic studies, copies of NMR spectra for the
obtained compounds, and X-ray crystallographic data of
compounds 3s (PDF)
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Accession Codes
CCDC 2057938 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
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data_request@ccdc.cam.ac.uk, or by contacting The Cam-
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AUTHOR INFORMATION
■
Corresponding Authors
Gong-Qing Liu − School of Pharmacy and Analysis & Testing
Center, Nantong University, Nantong 226019, People′s
Republic of China; orcid.org/0000-0002-8162-707X;
Email: gqliu@ntu.edu.cn
Yong Ling − School of Pharmacy and Analysis & Testing
Center, Nantong University, Nantong 226019, People′s
Republic of China; Email: Lyyyy111@sina.com
Authors
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Temperini, A.; Bagnoli, L.; Marini, F.; Santi, C. Ring-closure reactions
through intramolecular displacement of the phenylselenonyl group by
nitrogen nucleophiles: a new stereospecific synthesis of N-tosyl and
N-benzoyl-1,3-oxazolidin-2-ones from β-hydroxyalkyl phenyl sele-
nides. Chem. - Eur. J. 2004, 10, 1752−1764. (c) Tiecco, M.; Testaferri,
L.; Marini, F.; Sternativo, S.; Santi, C.; Bagnoli, L.; Temperini, A.
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Zhi-Peng Liang − School of Pharmacy and Analysis & Testing
Center, Nantong University, Nantong 226019, People′s
Republic of China
Wei Yi − School of Pharmacy and Analysis & Testing Center,
Nantong University, Nantong 226019, People′s Republic of
China
Peng-Fei Wang − School of Pharmacy and Analysis & Testing
Center, Nantong University, Nantong 226019, People′s
Republic of China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00257
Author Contributions
†W.Y. and P.-F.W. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This study was supported by the Natural Science Foundation
of Jiangsu Province (BK20170439) and Science and
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nolate. A useful reagent for the preparation of selenoesters. A new
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