Organocatalytic Enantioselective Selenosulfonylation of a C-C Double Bond to Form Two Stereogenic Centers in an Aqueous Medium

Article abstract of DOI:10.1021/acs.joc.9b00973

Organocatalytic selenosulfonylation of the C-C double bond of α,β-unsaturated ketones to construct two contiguous stereogenic centers in an aqueous medium was described. A series of α-selenyl and β-sulfonyl ketones with various functional groups were synthesized in good yields and enantioselectivities with saturated NaCl solution as the solvent. In addition, this protocol had been successfully scaled up to a decagram scale via a simple workup procedure.

Full text of DOI:10.1021/acs.joc.9b00973

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Article
Organocatalytic Enantioselective Selenosulfonylation of C-C Double
Bond to Form Two Stereogenic Centers in an Aqueous Medium
Zhili Chen, Fangli Hu, Shengli Huang, Zhengxing Zhao, Hui Mao, and Wenling Qin
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 22 May 2019
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Organocatalytic Enantioselective Selenosulfonylation of C-C Double
Bond to Form Two Stereogenic Centers in an Aqueous Medium
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Zhili Chen,† Fangli Hu,† Shengli Huang,†,‡ Zhengxing Zhao,† Hui Mao*,§ and Wenling Qin*,†
†Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical
Sciences, Chongqing University, Chongqing 401331, P. R. China.
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‡School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 401331, P. R. China.
§Pharmaceutical and Material Engineering School, Jinhua Polytechnic, Jinhua, Zhejiang Province,
321000, P. R. China.
ABSTRACT
R1
OMe
O
O
O
H
O
O
S
N
D
catalyst
R1SO2SeR2
+
R3
R4
R3
R4
sat. NaCl
NH
SeR2
N
NH
Ar
 Enantioselective selenosulfonylation  Contiguous chiral centers
 Green reaction solvent  Mild conditions  Deca-gram scalable
O
D
, Ar = 3,5-(CF3)2C6H3
Organocatalytic selenosulfonylation of C-C double bond of α,β-unsaturated ketones to construct
two contiguous stereogenic centers in an aqueous medium was described. A series of α-selenyl, β-
sulfonyl ketones with various functional groups were synthesized in good yields and enantioselectivies
with saturated NaCl solution as the solvent. In addition, this protocol had been successfully scaled up to
a deca-gram scale via a simple workup procedure.
INTRODUCTION
Both selenyl1 and sulfonyl2 groups are important functional groups in some biologically active
molecules and functional organic materials. Selenium3 and sulfone4 can be readily transformed into
useful building blocks, which constitute a family of synthetically valuable synthons. Therefore, the
incorporation of selenium and sulfone into one molecular structure is of the significant synthetic value.
Selenosulfonates were first reported by Foss in 19475 and provided a straightforward avenue to install
selenium and sulfone groups in a single step through direct selenosulfonylation of an unsaturated
substrate. As showing in Scheme 1a, Back and Collins reported the selenosulfonylation reaction of a
variety of olefins to produce β-phenylseleno sulfones in the presence of boron trifluoride or elevated
temperature in its absence.6 In addition, Kice demonstrated the photodecomposition of selenosulfonates
and reported its addition to alkene to form β-phenylseleno sulfones in good yield (Scheme 1a).7 In 1988,
Backvall explored regioselective selenosulfonylation of terminal C-C double bond of 1,3-dienes and an
oxidation process to access 2-(phenylsulfonyl)-1,3-dienes.8 Recently, Sun and Zhang reported a protocol
to direct access β-seleno sulfones under mild conditions through selenosulfonylation of alkenes.9
Moreover, Billard and Tlili investigated the reactivity of fluoroalkylselenotoluenesulfonates and
developed a visible-light promoted selenosulfonylation of unsaturated compounds through radical
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intermediates (Scheme 1a).10 Despite of these investigations, the enantioselective version of
selenosulfonylation reaction was rarely addressed. Recently, we reported the organocatalytic
enantioselective addition of selenosulfonates to α,β-unsaturated ketone to realize the asymmetric
selenolation of C-C double bound (Scheme 1b). 11a In the development of green methodologies for the
enantioselective construction of C-X (X=Se, S) bonds,11 we were interested in the development of
organocatalytic selenosulfonylation of α,β-unsaturated ketones to form two contiguous stereogenic
centers.
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Scheme 1. Selenosulfonylation of C-C double bonds
a) Prior works: Symmetric selenosulfonylation of C-C double bound
R1
O
O
S
R4
catalyst or light
organic solvents
R3
R1SO2SeR2
+
R4
R3
SeR2
BF3 catalyst: by Back and Collins, ref 6
UV: by Kice, ref 7
achiral products
Visible light: by Billard and Tlili, ref 10
b) Our previous work: Asymmetric selenolation of C-C double bound
R1
O
O
O
S
O
organocatalyst
organic solvents
R1SO2SePh
+
R2
R2
SePh
chiral products
Bifunctional catalyst: ref 11a
c) Current work: Organocatalytic asymmetric selenosulfonylation of C-C
double bound in an aqueous medium
R1
O
O
O
S
O
organocatalyst
R1SO2SeR2
+
R3
R4
R3
R4
aqueous medium
SeR2
=
chiral products
CH2OH,
CH2CH2Ph
CH3,
The usage of environmentally friendly catalysts and solvents significantly increases the value of a
synthetic methodology. The highly stereoselective organocatalytic methodology in an aqueous medium
has become one of the hotspots in organic chemistry and has offered unique opportunities to develop
sustainable chemical processes.12 Herein, we report our recent results on organocatalyzed asymmetric
selenosulfonylation of α,β-unsaturated ketones to construct two contiguous chiral centers in an aqueous
environment, and the reaction can be scaled up to deca-gram without any chromatography technology to
give a desired product with high yield and enantioselectivity.
RESULTS AND DISCUSSION
The study started with para-isopropyl substituted α,β-unsaturated ketone 2a as the substrate and
selenosulfonate 1a as the selenosulfonylation agent by using saturated NaCl solution as the solvent. The
reaction proceeded at 25 oC in the presence of a small collection of organocatalysts. Catalyst A was first
evaluated and the selenosulfonylation adduct 3a was formed with 42% ee in moderate yield. Then, the
Takemoto catalyst B was tested and resulted in a better enantioselectivity (80% ee, Table 1, entry 2).
These results encouraged us to test the cinchona alkaloid-derived thiourea catalyst C. Consequently,
enantiocontrol was improved by catalyst C, but the yield was not significantly increased. Squaramides
had been successfully employed as hydrogen bond donor catalysts in a wide range of asymmetric
reactions. The distance between the two hydrogen donor atoms of squaramides was longer than that of
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Table 1. Condition screeninga
5
6
7
8
9
O
O
O
O
S
O
O
S
catalyst
solvent
Se
+
Se
1a
2a
3a
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S
OMe
N
OMe
Ar
H
H
N
N
N
N
H
H
N
NH
OH
N
Ar = 3,5-(CF3)2C6H3
S
NH
Ar
A
B
C
OMe
N
R
H
H
O
N
N
NH
NH
HN Ar
S
H
N
N
O
NH
Ar
S
O
D,
E,
F
R = OMe;
R = OH
entry
catalyst
solvent
yield (%)b
55
ee (%)c
42
drd
1
2
A
B
C
D
E
F
sat. NaCl
sat. NaCl
sat. NaCl
sat. NaCl
sat. NaCl
sat. NaCl
sat. KCl
sat. KBr
sat. NH4Cl
sat. KI
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
48
80
3
53
86
4
85
90
5
80
88
6
56
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7
D
D
D
D
D
D
D
D
D
80
87
8
80
86
9
86
86
10
11
12
13
14
15
76
84
sat. KSCN
sat. KBF4
sat. BaCl2
sat. LiCl
H2O
43
86
50
88
45
62
52
43
78
88
aUnless otherwise noted, all reactions were carried out with 1a (0.1 mmol), 2a (0.1 mmol) and catalyst (10 mol%) in solvent (1
mL) at 25 oC for 16 h. bIsolated yield. cDetermined by HPLC analysis on a chiral stationary phase. dDiastereomeric ratio (dr) was
determined by 1H NMR.
thioureas.13 Thus, we turned our attention to evaluate a series of squaramides-based
organocatalysts. Gratifyingly, catalyst D resulted in the better yield and enantioselectivity (Table
1, entry 4). The hydroxyl cinchona-derived squaramide catalyst E led to the slightly decreased
enantioselectivity and yield (Table 1, entry 5). Catalyst F significantly decreased the reaction
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yield and enantioselectivity. Subsequent evaluation of various aqueous solutions did not lead to
further improvements in yield and stereocontrol (Table 1, entries 7-15).
With the optimized reaction conditions in hand, we further investigated the substrate scope. Various
α-selenyl, β-sulfonyl ketones could be synthesized in good enantioselectivities by this straightforward
and efficient methodology (Table 2). When the R1 group of selenosulfonates bearing methyl and different
halides at para-position of phenyl were well tolerated, expected products 3a-3d were obtained in good
yields with good stereoselectivitives (up to 90% ee, dr > 20:1). Moreover, the adduct without any
substitution group at phenyl groups of selenosulfonate could be formed in good yield and
enantioselectivity (Table 2, 3e). Next, we evaluated a series of substrates with substitution groups at
different positions of R2 groups on the selenium part. A series of substitution with electron-donating and
electron-withdrawing groups on para-position of phenyl were examined under standard conditions and
the adducts were successfully formed with slight variations of enantioselectivities and yields (3f-3h).
Notably, the ortho-substituted R2 groups were also tolerated to the reaction system and gave desired
products with good chemical yields and enantioselectivities (Table 2, 3i-3k), whereas the bulkier
substituent groups such as isopropyl at ortho-position caused a decreased yield (3l). The substrates with
meta-substituted R2 groups were also tolerant to our reaction system and gave the desired products in
good yields and enantioselectivities (3m-3o). Moreover, the substrates with 2,5-disubstituted phenyl
groups on selenium part were also tolerated to this enantioselective selenosulfonylation reaction (3p-3q).
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Table 2. Substrate scopea,b
R1
O
2
O
O
O
S
3
D
R1SO2SeR2
SeR2
+
25 °C, sat. NaCl
1
2a
3
F
Cl
S
O
O
O
O
O
O
O
O
O
O
S
O
S
Se
Se
Se
3c
3a
3b
(2R,3S)-
81%, 78% ee
(2R,3S)-
(2R,3S)-
85%, 90% ee
72%, 80% ee
Br
O
O
O
O
O
O
S
O
S
O
S
Se
Se
Se
3e
(2R,3S)-
3d
(2R,3S)-
3f
(2R,3S)-
70%, 86% ee
76%, 81% ee
55%, 83% ee
2
3g
(2R,3S)- (R = 4-FC6H4): 58%, 85% ee
2
3h
(2R,3S)- (R = 4-ClC6H4): 56%, 84% ee
2
3i
(2R,3S)- (R = 2-ClC6H4): 72%, 83% ee
2
O
O
3j
(2R,3S)- (R = 2-BrC6H4): 68%, 83% ee
O
S
O
2
O
S
3k
(2R,3S)- (R = 2-MeC6H4): 55%, 82% ee
2
i
3l
(2R,3S)- (R = 2- PrC6H4): 42%, 82% ee
2
Se
F
F
3m
(2R,3S)-
(R = 3-MeC6H4): 58%, 81% ee
2
SeR2
3n
(2R,3S)- (R = 3-ClC6H4): 59%, 86% ee
2
3o
(2R,3S)- (R =3-BrC6H4): 61%, 85% ee
3q
(2R,3S)-
2
3p
(2R,3S)- (R = 2-Me-5-FC6H3): 68%, 86% ee
74%, 84% ee
aReaction conditions: 1 (0.1 mmol), D (10 mol%) and 2a (0.1 mmol) in sat. NaCl solution (1 mL) at 25oC for 16 h. bDiastereomeric
ratio (dr) was determined by 1H NMR and dr > 20:1.
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Table 3. Substrate scopea, b
5
6
7
8
9
O
O
O
O
2
O
S
D
O
S
Se
R3
R4
+
25 °C, sat. NaCl
R3
3 R4
SePh
4
1a
2
3
c
3
4j
(2R,3S)- (R = 4-BrC6H4): 62%, 83% ee
4a
(2R,3S)- (R = Ph): 73%, 88% ee
3
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3
4k
(2R,3S)- (R = 4-NO2C6H4): 41%, 71% ee
4b
(2R,3S)- (R = 4-MeC6H4): 83%, 83% ee
3
3
t
4l
(2R,3S)- (R = 2-(OMe)C6H4): 77%, 85% ee
4c
(2R,3S)- (R = 4- BuC6H4): 74%, 89% ee
3
3
i
4m
4n
(2R,3S)-
(R = 2-FC6H4): 75%, 81% ee
(2R,3S)- (R3 = 3-FC6H4): 79%, 82% ee
(2R,3S)- (R3 = 2,4-Me2C6H3): 54%, 69% ee
(2R,3S)- (R3 = 2,4-F2C6H3): 73%, 81% ee
4d
(2R,3S)- (R = 4- BuC6H4): 68%, 86% ee
3
4e
(2R,3S)- (R = 4-CF3C6H4): 80%, 83% ee
O
O
O
S
3
4o
4f
(2R,3S)- (R = 4-(Ph)C6H4): 63%, 80% ee
3
R3
4p
4g
(2R,3S)- (R = 4-(OMe)C6H4): 66%, 87% ee
(2R,3S)- (R3 = naphthyl): 73%, 84% ee
3
4q
4h
(2R,3S)- (R = 4-FC6H4): 66%, 87% ee
SePh
3
4i
(2R,3S)- (R = 4-ClC6H4): 69%, 83% ee
O
O
O
O
O
O
O
S
O
S
O
S
Ph
2
Se
O
Se
S
Se
4r
4s
4t
(2R,3S)-
72%, 87% ee
(2R,3S)-
67%, 80% ee
(2R,3S)-
49%, 64% ee
O
O
O
O
O
S
O
S
OH
Se
Se
4u
4v
(2R,3S)-
(2R,3S)-
42%, 69% ee
CCDC 1882009
46%, 74% ee
Ph
O
Ph
O
Se
O
O
S
Se
S
O
O
4w
4x
(2S,3S)-
21%, 69% ee
(2S,3S)-
40%, 68% ee
CCDC 1914869
aReaction conditions: 1 (0.1 mmol), D (10 mol%) and 2a (0.1 mmol) in sat. NaCl solution (1 mL) at 25 oC for 16 h. bDiastereomeric
ratio (dr) was determined by 1H NMR and dr > 20:1. cAfter recrystallization from DCM, up to 96% ee.
After exploring the substrate scope of selenosulfonates, with Se-phenyl 4-
methylbenzenesulfonoselenoate (1a) as counter partner, we investigated the substrate tolerance of α,β-
unsaturated ketones. As for substitution group R3, a phenyl group bearing normal electron-donating or
electron-withdrawing substituents at the para-position allowed good yields and stereocontrol (4a-4j).
Notably, excellent enantioselectivity could be achieved through recrystallization from dichloromethane
(4j, 96% ee). Nevertheless, when the strong electron-withdrawing group existed at para-position, the
product was obtained with decreased yield (4k). As for R3 group with methoxyl group at ortho-position
of phenyl, the corresponding substrate formed the product 4l in good yield and enantioselectivity. With
interesting fluoro substituent at either ortho- or meta-position of phenyl group, adducts 4m and 4n were
formed with good yields and ee values. Moreover, the substrate with R3 bearing 2,4-difluoro substituted
phenyl was also well tolerated to reaction conditions (4p), whereas in the case of 2,4-dimethyl substituted
substrate, the reaction yield and stereoselectivity were decreased (4o). Interestingly, when R3 groups
were naphthyl or heterocyclic rings, the corresponding adducts could be formed in good yields and
enantioselectivities (4q-4s). The substrates in which R4 was replaced by other alkyl substituents were
also examined and the products were successfully generated but with lower yields and
enantioselectivities (4t and 4u). The absolute configuration of 4u was determined to be (2R,3S) by single
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crystal X-ray crystallographic analysis and others were assigned by analogue. Finally, instead of α,β-
unsaturated ketone, allyl alcohol ketone could also be used as the substrate in this enantioselective
selenosulfonylation reaction to give desired adduct 4v with the similar result of alkyl substituted substrate.
It is noteworthy that the substrate in which R4 was aryl group did not react with selenosulfonates to give
desired product, we have investigated chalcones and other β-aryl substituted substrates, there were no
reaction taken place after 72 hours under standard reaction conditions. At the end, we were interested in
using cyclic enones as substrates in our reaction system, to our delight, products 4w and 4x were
successfully formed under standard reaction conditions although lower degree of yields and selectivities
were observed. Product 4x was determined absolute configuration by single crystal X-ray
crystallographic analysis and 4w was assigned by analogue.
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Scheme 2. Gram-scale synthesis and transformation of 4j
a) Deca-Gram scale preparationa
O
O
O
O
2
O
D
(10 mol%)
S
O
S
3
+
Se
25 °C, sat. NaCl
Br
Se
Br
1a
2k
4j
(2R,3S)-
20.2 g
14.6 g
81%, 87% ee
1A
1B
1C
Product
Reaction
Workup
b) Transformation of 4j
O
2
O
O
O
O
S
3
OH
S
3
NaBH4, CeCl3•7H2O
2
1
CH3OH, 0 o
C
Se
Se
Br
Br
4j
(2R,3S)-
96% ee (after recrystallization)
5
(1S,2R,3S)-
CCDC 1886927
74%, 93% ee
aPictures of the reaction processes: (1A) Reaction mixture; (1B) Reaction workup; (1C) Product 4j.
After the exploration of reaction substrate scope, we performed some experiments to further
demonstrate the practicability of the current reaction. First, a deca-gram scale reaction of 2k with
selenosulfonate 1a under standard reaction conditions was performed (Scheme 2a). The reaction went
smoothly to give product 4j with improved yield and enantioselectivity. Notably, the workup procedures
of the scaled reaction were modified by a simple slurry of reaction mixture with acetonitrile. After phase
separation and filtration, the product 4j was obtained in good yield and ee value (81% yield, 87% ee)
without any chromatography technology.
Moreover, the chiral α-selenyl β-sulfone ketone obtained from this reaction was transformed into
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corresponding alcohol with good stereocontrol. The treatment of 4j (with 96% ee) with NaBH4 and
CeCl3∙7H2O in MeOH easily generated stereo-enriched alcohol bearing selenyl and sulfone functional
groups with 74% yield and 93% ee. The configuration of 5 was determined to be (1S,2R,3S) by X-ray
analysis.
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In order to give an insight into the reaction mechanism, a plausible reaction mechanism is depicted
in Scheme 3. We speculated that the cinchona alkaloid catalyst D might interact with selenosulfonate
and α,β-unsaturated ketones 2 to form complex TS-1. The selenium part of TS-1 was then attached to
electron-rich conjugated carbon-carbon double bond, thus forming a stereo-controlled seleniranium ion
as transition state TS-2 and releasing one molecular of sulfone anion. The stereo-fused TS-2 was then
triggered by previously generated sulfone anion to open the selenium ring from favored plane to give
product 4. Meanwhile, the catalyst was regenerated, thereby closing the catalytic cycle.
Scheme 3. Plausible mechanism
N
O
O
OMe
O
SO2Tol
R4
H
Ar
N
H
N
H
O
R3
R3
R4
N
SePh
4
2
+
D
TolSO2SePh
N
N
O
O
O
O
H
OMe
Ar
OMe
H
N
Ar
N
H
N
H
N
H
H
Ph
N
sterically
hindered
Ph
N
O
TS-3
Se
TS-1
O
Se
TolSO2
SO2Tol
R3
TolSO2
R4
R3
R4
N
favored
O
O
H
OMe
Ar
N
N
H
H
Ph
N
O
Se
TolSO2
R3
R4
TS-2
CONCLUSION
In conclusion, we developed an organocatalyzed asymmetric selenosulfonylation reaction of α,β-
unsaturated ketones in an aqueous medium. The reaction was characterized by green reaction solvent,
mild conditions and high enantioselectivities. Moreover, the reaction was scalable via a facile workup
process to give desired product in the improved yield and enantioselectivity. Furthermore, the product
could be transformed into useful synthons with excellent stereocontrol. The method provides a simple,
efficient and scalable pathway to access stereo-controlled α-selenyl, β-sulfonyl ketones in an aqueous
medium with the generation of two contiguous stereogenic centers.
EXPERIMENTAL SECTION
General information: 1H and 13C{1H} NMR spectra were recorded on Agilent 400MR DD2 (400 MHz)
spectrometer and Agilent 600MR DD2 (600 MHz) spectrometer. Chemical shifts were reported in parts
per million (ppm), and tetramethylsilane or the residual solvent peak was used as an internal reference:
CDCl3 (1H NMR δ 0.00, 13C{1H} NMR δ 77.00). Data are reported as follows: chemical shift,
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multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad), coupling constants
(Hz) and integration. Enantiomeric excesses (ee) were determined by HPLC analysis on Hitachi
Chromaster using DAICEL CHIRALCEL AD-H, 4.6mm Ф × 250 mmL and DAICEL CHIRALCEL
OD-H, 4.6mm Ф ×250 mmL. The HRMS spectra were acquired on a 7 T SolariX FT-ICR MS (Bruker
Daltonics, Bremen, Germany) with an ESI source. X-ray crystallography analysis of single crystal was
performed on an Agilent SuperNova-CCD X-Ray diffractometer. Optical Rotation was measured on a
Rudolph Autopol I polarimeter. Melting points were measured using a SGWX-4A Microscopic melting
point meter and are uncorrected. Unless otherwise stated, all reagents were purchased from commercial
suppliers and used without further purification.
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General procedure for the synthesis of selenosulfonates (GP-1): Selenosulfonates 1 are known
compounds and were prepared through a two step procedure according to literatures.
Step 1: To a stirred solution of Se0 metal (10.0 mmol, 2.0 equiv.) and halides (5.0 mmol, 1.0 equiv.) in
DMSO (10 mL) was added CuO nanoparticles (0.5 mmol, 0.1 equiv.) followed by KOH (10.0 mmol, 2.0
equiv.) under nitrogen atmosphere. The resulting reaction mixture was stirred at 90 C for 6 h. After the
reaction was complete, the reaction mixture was allowed to cool to room temperature, extraction with
CH2Cl2. The combined organic layer was washed with brine, dried over anhydrous Na2SO4, and
concentrated in vacuum. The crude product was purified by chromatograph (PE:EA = 100:1) to afford
diphenyl diselenide.
Step 2: A suspension of appropriate sodium benzenesulfinates (20.0 mmol, 4.0 equiv.) in CH2Cl2 (50
mL) containing diphenyl diselenide (5.0 mmol, 1.0 equiv.) was cooled at
0 C and
[bis(trifluoroacetoxy)iodo]benzene (5.5 mmol, 1.1 equiv.) in CH2Cl2 (20 mL) was added slowly. Then
the mixture was stirred at room temperature for 3 h. The reaction mixture was washed with H2O, dried
over anhydrous Na2SO4. The solvent CH2Cl2 was removed under reduced pressure and the residue was
purified by chromatograph (PE:EA = 6:1) to afford compounds 1.
Selenosulfonates 1a-1q were prepared according to GP-1, the spectroscopic data are in good agreement
with reported values.14
General procedure for the synthesis of substituted (E)-1-phenylbut-2-en-1-ones (GP-2): α,β-
unsaturated ketones 2 are known compounds and were prepared through a three step procedure according
to literatures.
Step 1: A solution of appropriate ketone (20.0 mmol, 1.0 equiv.) in CHCl3 (15 mL) was added in one
portion to a vigorously stirred, refluxing suspension of CuBr2 (40.0 mmol, 2.0 equiv.) in ethyl acetate
(20 mL). The reaction was practically complete after reflux for 2 h, as indicated by the conversion of
CuBr2 (black) into CuBr (white), then the solid was removed by filtration through celite. The combined
organic layer was washed with 5% Na2CO3 and brine, dried over anhydrous Na2SO4 and evaporated
under vacuum to give corresponding 2-bromo-1-phenylethan-1-one used in next step without further
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Step 2: A mixture of 2-bromo-1-phenylethan-1-one (10.0 mmol) and triphenylphosphine (10.0 mmol) in
toluene (20 mL) was stirred for 24 h at room temperature. The formed precipitate was filtered, then
dissolved in CH2Cl2 (10 mL) followed by Na2CO3 (1.5 equiv.) in water (20 mL) was added. After stirred
for 2 h, the organic layer was separated and water was extracted with CH2Cl2. The solvent was removed
under vacuum and the solid was washed with PE then filtrated to give stabilized ylide.
Step 3: To a solution of the appropriate stabilized ylide (5.0 mmol) in THF (15 mL) was added aldehyde
(15.0 mmol), and the solution was heated under reflux for 3 h. The solution was cooled and the solvent
evaporated in vacuum. The product was purified by chromatography to give 2 and was used immediately.
Substituted (E)-1-phenylbut-2-en-1-ones 2a-2v were prepared according to GP-2, the spectroscopic data
are in good agreement with reported values.15
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Procedure for the synthesis of (E)-4-hydroxy-1-phenylbut-2-en-1-one (2w): The reaction was carried
out according to a literature method.16 To a solution of the stabilized ylide (3.6 mmol) in THF (15 mL)
was added glycoaldehyde dimer (180.0 mg, 1.8 mmol), and the resulting solution was heated under reflux
for 3 h. The solution was cooled and the solvent evaporated under vacuum. The crude product was
purified by column chromatography on silica gel (hexane:EA = 3:1), the spectroscopic data are in good
agreement with reported values.
General procedure for the synthesis of compound 3 or 4 (GP-3): The selenosulfonates 1 (0.1 mmol,
1.0 equiv.), α,β-unsaturated ketones 2 (0.1 mmol, 1.0 equiv.) and catalyst D (0.01 mmol, 0.1 equiv.) were
added to a 10 mL tube with a magnetic stirring bar, sat. NaCl solution (1 mL) was injected into the tube.
After stirring at 25 C for 16 h, the reaction mixture was extracted with ethyl acetate, and concentrated
under vacuum. The crude product was purified by column chromatography on silica gel (DCM:PE = 2:1)
to afford 3 or 4.
(2R,3S)-1-(4-isopropylphenyl)-2-(phenylselanyl)-3-tosylbutan-1-one (3a): According to GP-3,
combining selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2a (0.1 mmol, 18.8 mg)
to gave compound 3a (42.4 mg, 85% yield) as a white solid with an excellent diastereomeric ratio; mp
104-106 C ; 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 6.6 Hz, 2H), 7.66 (d, J = 8.0 Hz, 2H), 7.40 (d, J
= 6.9 Hz, 2H), 7.36 – 7.29 (m, 1H), 7.28 – 7.16 (m, 6H), 4.99 (d, J = 10.1 Hz, 1H), 4.21 – 4.10 (m, 1H),
3.02 – 2.89 (m, 1H), 2.37 (s, 3H), 1.73 (d, J = 5.3 Hz, 3H), 1.27 (d, J = 6.8 Hz, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 192.6, 154.4, 144.8, 135.6, 134.9, 133.0, 129.6, 129.3, 129.1, 128.8, 128.7, 127.4, 126.5,
60.3, 46.1, 34.2, 23.7, 21.6, 15.0; HRMS (ESI-FT-ICR) m/z Calcd for [C26H28NaO3SSe, M + Na]+:
[α]2D0
523.0817, Found: 523.0816; Optical Rotation:
= -49.9 (c = 1.0, CHCl3); HPLC analysis:
Chiralcel OD-H (Hexane/i-PrOH) = 80:20, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 9.494
min (major), tR = 11.147 min (minor).
(2R,3S)-3-((4-fluorophenyl)sulfonyl)-1-(4-isopropylphenyl)-2-(phenylselanyl)butan-1-one
(3b):
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According to GP-3, combining selenosulfonate 1b (0.1 mmol, 31.5 mg) and α,β-unsaturated ketone 2a
(0.1 mmol, 18.8 mg) to gave compound 3b (36.2 mg, 72% yield) as a white solid with an excellent
diastereomeric ratio; mp 101-102 C; 1H NMR (400 MHz, CDCl3) δ 7.81 – 7.71 (m, 4H), 7.39 (d, J =
7.5 Hz, 2H), 7.33 (t, J = 7.2 Hz, 1H), 7.29 – 7.20 (m, 4H), 7.06 (t, J = 8.4 Hz, 2H), 4.98 (d, J = 10.2 Hz,
1H), 4.20 – 4.11 (m, 1H), 3.01 – 2.91 (m, 1H), 1.76 (d, J = 7.1 Hz, 3H), 1.27 (d, J = 6.9 Hz, 6H); 13C{1H}
NMR (100 MHz, CDCl3) δ 192.4, 165.7 (d, J = 255.0 Hz), 154.6, 135.6, 134.0 (d, J = 3.0 Hz), 132.8,
131.6 (d, J = 10.0 Hz), 129.2, 129.2, 128.6, 127.1, 126.5, 116.2 (d, J = 22.0 Hz), 60.5, 46.0, 34.1, 23.6,
14.8; HRMS (ESI-FT-ICR) m/z Calcd for [C25H25FNaO3SSe, M + Na]+: 527.0566, Found: 527.0565;
[α]2D0
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Optical Rotation:
= -173.2 (c = 1.0, CHCl3); HPLC analysis: Chiralcel AD-H (Hexane/i-PrOH)
= 70:30, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 10.471 min (major), tR = 14.106 min (minor).
(2R,3S)-3-((4-chlorophenyl)sulfonyl)-1-(4-isopropylphenyl)-2-(phenylselanyl)butan-1-one (3c):
According to GP-3, combining selenosulfonate 1c (0.1 mmol, 33.2 mg) and α,β-unsaturated ketone 2a
(0.1 mmol, 18.8 mg) to gave compound 3c (42.2 mg, 81% yield) as a white solid with an excellent
diastereomeric ratio; mp 121-122 C; 1H NMR (400 MHz, CDCl3) δ 7.75 – 7.65 (m, 4H), 7.40 (d, J =
7.2 Hz, 2H), 7.37 – 7.29 (m, 3H), 7.29 – 7.21 (m, 4H), 4.95 (d, J = 10.2 Hz, 1H), 4.21 – 4.10 (m, 1H),
3.02 – 2.89 (m, 1H), 1.76 (d, J = 7.1 Hz, 3H), 1.28 (d, J = 6.9 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3)
δ 192.3, 154.6, 140.5, 136.4, 135.6, 132.7, 130.3, 129.3, 129.2, 128.6, 127.10 126.5, 60.5, 46.0, 34.2,
23.6, 14.8; HRMS (ESI-FT-ICR) m/z Calcd for [C25H25ClNaO3SSe, M + Na]+: 543.0270, Found:
[α]2D0
543.0271; Optical Rotation:
= -100.3 (c = 1.0, CHCl3); HPLC analysis: Chiralcel AD-H
(Hexane/i-PrOH) = 70:30, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 11.629 min (major), tR =
15.546 min (minor).
(2R,3S)-3-((4-bromophenyl)sulfonyl)-1-(4-isopropylphenyl)-2-(phenylselanyl)butan-1-one
(3d):
According to GP-3, combining selenosulfonate 1d (0.1 mmol, 37.6 mg) and α,β-unsaturated ketone 2a
(0.1 mmol, 18.8 mg) to gave compound 3d (42.9 mg, 76% yield) as a white solid with an excellent
diastereomeric ratio; mp 109-112 C; 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.2 Hz, 2H), 7.61 (d, J
= 8.5 Hz, 2H), 7.51 (d, J = 8.5 Hz, 2H), 7.40 (d, J = 7.3 Hz, 2H), 7.35 (t, J = 7.3 Hz, 1H), 7.29 – 7.22
(m, 4H), 4.95 (d, J = 10.2 Hz, 1H), 4.16 (dq, J = 10.1, 7.1 Hz, 1H), 3.02 – 2.92 (m, 1H), 1.77 (d, J = 7.1
Hz, 3H), 1.28 (d, J = 6.9 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 192.2, 154.6, 136.9, 135.6, 132.7,
132.2, 130.3, 129.3, 129.2, 129.2, 128.6, 127.1, 126.5, 60.4, 45.9, 34.2, 23.6, 14.7; HRMS (ESI-FT-ICR)
[α]2D0
m/z Calcd for [C25H25BrNaO3SSe, M + Na]+: 586.9765, Found: 586.9764; Optical Rotation:
= -
58.3 (c = 1.0, CHCl3); HPLC analysis: Chiralcel AD-H (Hexane/i-PrOH) = 70:30, flow rate = 1.0
mL/min, wave length = 254 nm, tR = 12.307 min (major), tR = 16.350 min (minor).
(2R,3S)-1-(4-isopropylphenyl)-2-(phenylselanyl)-3-(phenylsulfonyl)butan-1-one (3e): According to
GP-3, combining selenosulfonate 1e (0.1 mmol, 29.8 mg) and α,β-unsaturated ketone 2a (0.1 mmol, 18.8
mg) to gave compound 3e (34.0 mg, 70% yield) as a white solid with an excellent diastereomeric ratio;
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mp 108-111 C; 1H NMR (400 MHz, CDCl3) δ 7.82 – 7.72 (m, 4H), 7.57 (t, J = 7.4 Hz, 1H), 7.48 – 7.38
(m, 4H), 7.33 (t, J = 7.3 Hz, 1H), 7.25 (d, J = 8.0 Hz, 4H), 5.01 (d, J = 10.1 Hz, 1H), 4.17 (dq, J = 9.8,
7.1 Hz, 1H), 3.02 – 2.91 (m, 1H), 1.73 (d, J = 7.1 Hz, 3H), 1.27 (d, J = 6.9 Hz, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 192.6, 154.4, 138.0, 135.6, 133.7, 133.0, 129.2, 129.1, 129.0, 128.7, 128.7, 127.3, 126.5,
60.3, 46.0, 34.1, 23.6, 15.0; HRMS (ESI-FT-ICR) m/z Calcd for [C25H26NaO3SSe, M + Na]+: 509.0660,
[α]2D0
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Found: 509.0662; Optical Rotation:
= -96.4 (c = 1.0, CHCl3); HPLC analysis: Chiralcel AD-H
(Hexane/i-PrOH) = 80:20, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 14.986 min (major), tR =
18.532 min (minor).
(2R,3S)-1-(4-isopropylphenyl)-2-(p-tolylselanyl)-3-tosylbutan-1-one (3f): According to GP-3,
combining selenosulfonate 1f (0.1 mmol, 32.5 mg) and α,β-unsaturated ketone 2a (0.1 mmol, 18.8 mg)
to gave compound 3f (28.2 mg, 55% yield) as a white solid with an excellent diastereomeric ratio; mp
80-82 C ; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.0 Hz, 2H), 7.64 (d, J = 7.9 Hz, 2H), 7.25 (t, J =
8.1 Hz, 4H), 7.18 (d, J = 7.9 Hz, 2H), 7.03 (d, J = 7.7 Hz, 2H), 4.93 (d, J = 10.2 Hz, 1H), 4.12 (dq, J =
14.4, 7.1 Hz, 1H), 3.00 – 2.92 (m, 1H), 2.35 (s, 3H), 2.32 (s, 3H), 1.73 (d, J = 7.1 Hz, 3H), 1.27 (d, J =
6.9 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 192.4, 154.3, 144.7, 139.4, 135.9, 135, 133.0, 130.0,
129.6, 128.8, 128.7, 126.4, 123.5, 60.3, 46.1, 34.2, 23.7, 21.5, 21.2, 15.0; HRMS (ESI-FT-ICR) m/z
[α]2D0
Calcd for [C27H30NaO3SSe, M + Na]+: 537.0973, Found: 537.0972; Optical Rotation:
= -101.5
(c = 1.0, CHCl3); HPLC analysis: Chiralcel AD-H (Hexane/i-PrOH) = 70:30, flow rate = 1.0 mL/min,
wave length = 254 nm, tR = 11.373 min (major), tR = 13.154 min (minor).
(2R,3S)-2-((4-fluorophenyl)selanyl)-1-(4-isopropylphenyl)-3-tosylbutan-1-one (3g): According to
GP-3, combining selenosulfonate 1g (0.1 mmol, 32.9 mg) and α,β-unsaturated ketone 2a (0.1 mmol,
18.8 mg) to gave compound 3g (29.9 mg, 58% yield) as a white solid with an excellent diastereomeric
ratio; mp 118-119 C ; 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.1 Hz, 2H), 7.65 (d, J = 8.1 Hz, 2H),
7.38 – 7.31 (m, 2H), 7.24 (d, J = 8.1 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 6.90 (t, J = 8.5 Hz, 2H), 4.98 (d,
J = 9.9 Hz, 1H), 4.08 (dq, J = 14.3, 7.1 Hz, 1H), 3.00 – 2.89 (m, 1H), 2.35 (s, 3H), 1.72 (d, J = 7.1 Hz,
3H), 1.27 (d, J = 6.9 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.3, 163.4 (d, J = 249.0 Hz), 154.5,
144.8, 138.3 (d, J = 8.0 Hz), 134.8, 133.0, 129.6, 128.8, 128.6, 126.4, 121.5 (d, J = 4.0 Hz), 116.41 (d, J
= 22.0 Hz), 60.0, 45.9, 34.1, 23.6, 21.5, 14.9; HRMS (ESI-FT-ICR) m/z Calcd for [C26H27FNaO3SSe, M
+ Na]+: 541.0722, Found: 541.0723; HPLC analysis: Chiralcel AD-H (Hexane/i-PrOH) = 70:30, flow
rate = 1.0 mL/min, wave length = 254 nm, tR = 11.312 min (major), tR = 13.970 min (minor).
(2R,3S)-2-((4-chlorophenyl)selanyl)-1-(4-isopropylphenyl)-3-tosylbutan-1-one (3h): According to
GP-3, combining selenosulfonate 1h (0.1 mmol, 34.6 mg) and α,β-unsaturated ketone 2a (0.1 mmol,
18.8 mg) to gave compound 3h (30.0 mg, 56% yield) as a white solid with an excellent diastereomeric
ratio; mp 113-115 C; 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 7.9 Hz, 2H), 7.65 (d, J = 7.9 Hz, 2H),
7.32 – 7.21 (m, 4H), 7.18 (t, J = 8.9 Hz, 4H), 5.01 (d, J = 9.8 Hz, 1H), 4.14 – 4.05 (m, 1H), 2.99 – 2.90
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(m, 1H), 2.34 (s, 3H), 1.70 (d, J = 7.0 Hz, 3H), 1.26 (d, J = 6.8 Hz, 6H); 13C{1H} NMR (100 MHz,
CDCl3) δ 192.3, 154.5, 144.7, 137.1, 135.6, 134.6, 132.8, 129.5, 129.3, 128.7, 128.6, 126.4, 125.0, 59.9,
45.8, 34.0, 23.5, 21.4, 14.8; HRMS (ESI-FT-ICR) m/z Calcd for [C26H27ClO3SSe, M + Na]+: 557.0427,
[α]2D0
Found: 557.0425; Optical Rotation:
= -78.1 (c = 1.0, CHCl3); HPLC analysis: Chiralcel AD-H
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(Hexane/i-PrOH) = 70:30, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 11.062 min (major), tR =
12.770 min (minor).
(2R,3S)-2-((2-chlorophenyl)selanyl)-1-(4-isopropylphenyl)-3-tosylbutan-1-one (3i): According to
GP-3, combining selenosulfonate 1i (0.1 mmol, 34.6 mg) and α,β-unsaturated ketone 2a (0.1 mmol, 18.8
mg) to gave compound 3i (38.6 mg, 72% yield) as a white solid with an excellent diastereomeric ratio;
mp 108-110 C; 1H NMR (400 MHz, CDCl3) δ 7.72 – 7.66 (m, 4H), 7.46 (d, J = 7.7 Hz, 1H), 7.34 (d, J
= 7.9 Hz, 1H), 7.26 – 7.16 (m, 5H), 7.11 (t, J = 7.5 Hz, 1H), 5.27 (d, J = 10.1 Hz, 1H), 4.37 – 4.26 (m,
1H), 2.98 – 2.87 (m, 1H), 2.38 (s, 3H), 1.67 (d, J = 7.1 Hz, 3H), 1.25 (d, J = 6.8 Hz, 6H); 13C{1H} NMR
(100 MHz, CDCl3) δ 193.4, 154.5, 144.8, 137.0, 134.7, 134.5, 132.9, 129.7, 129.6, 129.5, 128.8, 128.6,
127.4, 126.3, 60.5, 44.8, 34.1, 23.6, 21.5, 14.4; HRMS (ESI-FT-ICR) m/z Calcd for [C26H27ClNaO3SSe,
[α]2D0
M + Na]+: 557.0427, Found: 557.0425; Optical Rotation:
= -194.2 (c = 1.0, CHCl3); HPLC
analysis: Chiralcel AD-H (Hexane/i-PrOH) = 70:30, flow rate = 1.0 mL/min, wave length = 254 nm, tR
= 18.369 min (minor), tR = 23.586 min (major).
(2R,3S)-2-((2-bromophenyl)selanyl)-1-(4-isopropylphenyl)-3-tosylbutan-1-one (3j): According to
GP-3, combining selenosulfonate 1j (0.1 mmol, 39.0 mg) and α,β-unsaturated ketone 2a (0.1 mmol, 18.8
mg) to gave compound 3j (39.3 mg, 68% yield) as a white solid with an excellent diastereomeric ratio;
mp 109-110 C; 1H NMR (400 MHz, CDCl3) δ 7.70 (t, J = 6.9 Hz, 4H), 7.53 – 7.44 (m, 2H), 7.28 – 7.14
(m, 5H), 7.10 (t, J = 7.5 Hz, 1H), 5.29 (d, J = 10.1 Hz, 1H), 4.40 – 4.29 (m, 1H), 2.98 – 2.87 (m, 1H),
2.38 (s, 3H), 1.66 (d, J = 7.2 Hz, 3H), 1.24 (d, J = 6.8 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ
193.5, 154.6, 144.9, 134.6, 133.9, 133.0, 132.9, 131.5, 129.6, 129.3, 128.8, 128.6, 128.1, 127.2, 126.4,
60.5, 45.2, 34.1, 23.6, 21.5, 14.4; HRMS (ESI-FT-ICR) m/z Calcd for [C26H27BrNaO3SSe, M + Na]+:
[α]2D0
600.9922, Found: 600.9924; Optical Rotation:
= -143.8 (c = 1.0, CHCl3); HPLC analysis:
Chiralcel AD-H (Hexane/i-PrOH) = 70:30, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 21.059
min (minor), tR = 27.951 min (major).
(2R,3S)-1-(4-isopropylphenyl)-2-(o-tolylselanyl)-3-tosylbutan-1-one (3k): According to GP-3,
combining selenosulfonate 1k (0.1 mmol, 32.5 mg) and α,β-unsaturated ketone 2a (0.1 mmol, 18.8 mg)
to gave compound 3k (28.0 mg, 55% yield) as a white solid with an excellent diastereomeric ratio; mp
82-84 C ; 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 8.1 Hz, 2H), 7.61 (d, J = 8.1 Hz, 2H), 7.45 (d, J =
7.7 Hz, 1H), 7.25 – 7.12 (m, 5H), 7.09 (d, J = 7.3 Hz, 1H), 7.04 (t, J = 7.4 Hz, 1H), 5.08 (d, J = 9.9 Hz,
1H), 4.31 – 4.22 (m, 1H), 2.96 – 2.86 (m, 1H), 2.37 (s, 3H), 2.15 (s, 3H), 1.71 (d, J = 7.1 Hz, 3H), 1.24
(d, J = 6.9 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 193.6, 154.4, 144.7, 141.4, 135.2, 134.7, 133.0,
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130.2, 129.6, 129.4, 128.9, 128.8, 128.6, 126.8, 126.2, 60.4, 45.4, 34.1, 23.6, 22.5, 21.5, 14.8; HRMS
(ESI-FT-ICR) m/z Calcd for [C27H30NaO3SSe, M + Na]+: 537.0973, Found: 537.0972; Optical Rotation:
[α]2D0
= -169.1 (c = 1.0, CHCl3); HPLC analysis: Chiralcel OD-H (Hexane/i-PrOH) = 80:20, flow rate
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= 1.0 mL/min, wave length = 254 nm, tR = 9.915 min (major), tR = 10.812 min (minor).
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(2R,3S)-1-(4-isopropylphenyl)-2-((2-isopropylphenyl)selanyl)-3-tosylbutan-1-one (3l): According to
GP-3, combining selenosulfonate 1l (0.1 mmol, 35.3 mg) and α,β-unsaturated ketone 2a (0.1 mmol, 18.8
mg) to gave compound 3l (22.8 mg, 42% yield) as a white solid with an excellent diastereomeric ratio;
mp 62-64 C; 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 8.0 Hz, 2H), 7.59 (d, J = 8.0 Hz, 2H), 7.53 (d,
J = 7.7 Hz, 1H), 7.26 (t, J = 7.5 Hz, 1H), 7.21 (d, J = 8.0 Hz, 2H), 7.18 – 7.11 (m, 3H), 7.07 (t, J = 7.4
Hz, 1H), 5.06 (d, J = 9.9 Hz, 1H), 4.32 – 4.23 (m, 1H), 3.15 – 3.06 (m, 1H), 2.94 – 2.85 (m, 1H), 2.36
(s, 3H), 1.73 (d, J = 7.1 Hz, 3H), 1.22 (d, J = 6.9 Hz, 6H), 1.01 (d, J = 6.8 Hz, 3H), 0.90 (d, J = 6.8 Hz,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 193.4, 154.3, 151.6, 144.8, 135.4, 134.7, 132.9, 129.6, 129.2,
129.1, 128.8, 128.6, 126.8, 126.2, 125.7, 60.4, 46.4, 34.1, 32.7, 24.1, 23.6, 23.1, 21.5, 14.9; HRMS (ESI-
FT-ICR) m/z Calcd for [C29H34NaO3SSe, M + Na]+: 565.1286, Found: 565.1288; Optical Rotation:
[α]2D0
= -155.2 (c = 1.0, CHCl3); HPLC analysis: Chiralcel AD-H (Hexane/i-PrOH) = 70:30, flow rate
= 1.0 mL/min, wave length = 254 nm, tR = 8.355 min (major), tR = 10.548 min (minor).
(2R,3S)-1-(4-isopropylphenyl)-2-(m-tolylselanyl)-3-tosylbutan-1-one (3m): According to GP-3,
combining selenosulfonate 1m (0.1 mmol, 32.5 mg) and α,β-unsaturated ketone 2a (0.1 mmol, 18.8 mg)
to gave compound 3m (30.0 mg, 58% yield) as a white solid with an excellent diastereomeric ratio; mp
84-86 C ; 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.1 Hz, 2H), 7.66 (d, J = 8.0 Hz, 2H), 7.28 – 7.17
(m, 6H), 7.12 (d, J = 4.7 Hz, 2H), 4.97 (d, J = 10.1 Hz, 1H), 4.22 – 4.13 (m, 1H), 3.00 – 2.91 (m, 1H),
2.38 (s, 3H), 2.26 (s, 3H), 1.72 (d, J = 7.1 Hz, 3H), 1.27 (d, J = 6.9 Hz, 6H); 13C{1H} NMR (100 MHz,
CDCl3) δ 192.9, 154.4, 144.8, 139.1, 136.2, 135.0, 133.1, 132.5, 129.9, 129.6, 129.1, 128.9, 128.8, 127.4,
126.4, 60.4, 46.2, 34.2, 23.7, 21.6, 21.2, 15.0; HRMS (ESI-FT-ICR) m/z Calcd for [C27H30NaO3SSe, M
[α]2D0
+ Na]+: 537.0973, Found: 537.0972; Optical Rotation:
= -67.3 (c = 1.0, CHCl3); HPLC analysis:
Chiralcel AD-H (Hexane/i-PrOH) = 70:30, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 10.486
min (major), tR = 11.392 min (minor).
(2R,3S)-2-((3-chlorophenyl)selanyl)-1-(4-isopropylphenyl)-3-tosylbutan-1-one (3n): According to
GP-3, combining selenosulfonate 1n (0.1 mmol, 34.6 mg) and α,β-unsaturated ketone 2a (0.1 mmol,
18.8 mg) to gave compound 3n (31.5 mg, 59% yield) as a white solid with an excellent diastereomeric
1
ratio; mp 64-66 C; H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.2 Hz, 2H), 7.66 (d, J = 8.1 Hz, 2H),
7.36 – 7.17 (m, 7H), 7.14 (t, J = 7.8 Hz, 1H), 5.05 (d, J = 9.8 Hz, 1H), 4.15 (dq, J = 14.3, 7.1 Hz, 1H),
2.99 – 2.89 (m, 1H), 2.33 (s, 3H), 1.69 (d, J = 7.1 Hz, 3H), 1.25 (d, J = 6.9 Hz, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 192.4, 154.4, 144.7, 135.1, 134.5, 134.2, 133.5, 132.8, 130.12 129.5, 129.1, 128.6, 128.5,
128.5, 126.0, 59.9, 46.0, 34.0, 23.4, 21.4, 14.8; HRMS (ESI-FT-ICR) m/z Calcd for [C26H27ClNaO3SSe,
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[α]2D0
M + Na]+: 557.0427, Found: 557.0425; Optical Rotation:
= -105.8 (c = 1.0, CHCl3); HPLC
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analysis: Chiralcel AD-H (Hexane/i-PrOH) = 70:30, flow rate = 1.0 mL/min, wave length = 254 nm, tR
= 11.319 min (major), tR = 13.137 min (minor).
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(2R,3S)-2-((3-bromophenyl)selanyl)-1-(4-isopropylphenyl)-3-tosylbutan-1-one (3o): According to
GP-3, combining selenosulfonate 1o (0.1 mmol, 39.0 mg) and α,β-unsaturated ketone 2a (0.1 mmol,
18.8 mg) to gave compound 3o (35.4 mg, 61% yield) as a white solid with an excellent diastereomeric
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ratio; mp 64-67 C; H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.2 Hz, 2H), 7.67 (d, J = 8.1 Hz, 2H),
7.47 (s, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 7.6 Hz, 1H), 7.28 – 7.19 (m, 4H), 7.10 (t, J = 7.8 Hz,
1H), 5.04 (d, J = 9.8 Hz, 1H), 4.19 – 4.08 (m, 1H), 3.01 – 2.89 (m, 1H), 2.36 (s, 3H), 1.69 (d, J = 7.1 Hz,
3H), 1.27 (d, J = 6.9 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 192.6, 154.6, 144.8, 138.1, 134.6,
134.1, 132.8, 132.1, 130.5, 129.6, 128.9, 128.8, 128.6, 126.5, 122.5, 60.1, 46.1, 34.1, 23.6, 21.5, 14.9;
HRMS (ESI-FT-ICR) m/z Calcd for [C26H27BrNaO3SSe, M + Na]+: 600.9922, Found: 600.9924;
Chiralcel AD-H (Hexane/i-PrOH) = 70:30, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 11.188
min (major), tR = 14.017 min (minor).
(2R,3S)-2-((5-fluoro-2-methylphenyl)selanyl)-1-(4-isopropylphenyl)-3-tosylbutan-1-one
(3p):
According to GP-3, combining selenosulfonate 1p (0.1 mmol, 34.3 mg) and α,β-unsaturated ketone 2a
(0.1 mmol, 18.8 mg) to gave compound 3p (36.2 mg, 68% yield) as a white solid with an excellent
diastereomeric ratio; mp 53-55 C; 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.1 Hz, 2H), 7.63 (d, J =
8.2 Hz, 2H), 7.27 – 7.22 (m, 2H), 7.17 (d, J = 8.1 Hz, 2H), 7.12 – 7.03 (m, 2H), 6.86 (t, J = 8.3 Hz, 1H),
5.09 (d, J = 9.8 Hz, 1H), 4.31 – 4.21 (m, 1H), 2.97 – 2.87 (m, 1H), 2.38 (s, 3H), 2.15 (s, 3H), 1.68 (d, J
= 7.2 Hz, 3H), 1.24 (d, J = 6.9 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 193.5, 160.4 (d, J = 247.0
Hz), 154.6, 144.9, 136.9 (d, J = 3.0 Hz), 134.5, 133.0, 131.5 (d, J = 8.0 Hz), 130.1 (d, J = 6.0 Hz), 129.7,
128.8, 128.6, 126.3, 121.6 (d, J = 22.0 Hz), 115.7 (d, J = 21.0 Hz), 60.2, 45.4, 34.1, 23.6, 21.6, 21.5,
14.7; HRMS (ESI-FT-ICR) m/z Calcd for [C27H29FNaO3SSe, M + Na]+: 555.0879, Found: 555.0881;
[α]2D0
Optical Rotation:
= -129.0 (c = 1.0, CHCl3); HPLC analysis: Chiralcel AD-H (Hexane/i-PrOH)
= 80:20, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 17.497 min (major), tR = 18.425 min (minor).
(2R,3S)-2-((2,5-difluorophenyl)selanyl)-1-(4-isopropylphenyl)-3-tosylbutan-1-one (3q): According
to GP-3, combining selenosulfonate 1q (0.1 mmol, 34.7 mg) and α,β-unsaturated ketone 2a (0.1 mmol,
18.8 mg) to gave compound 3q (39.6 mg, 74% yield) as a white solid with an excellent diastereomeric
1
ratio; mp 89-92 C; H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 7.9 Hz, 2H), 7.67 (d, J = 7.8 Hz, 2H),
7.29 – 7.19 (m, 4H), 7.00 (t, J = 5.8 Hz, 3H), 5.14 (d, J = 10.2 Hz, 1H), 4.19 (dq, J = 14.7, 7.1 Hz, 1H),
3.01 – 2.91 (m, 1H), 2.38 (s, 3H), 1.70 (d, J = 7.1 Hz, 3H), 1.27 (d, J = 6.9 Hz, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 192.6, 158.9 (dd, J = 240.0, 2.0 Hz), 157.9 (dd, J = 246.0, 2.0 Hz), 157.7, 156.7, 156.7,
154.8 144.9, 134.7, 132.8, 129.7, 128.9, 128.7, 126.5, 123.6 (dd, J = 24.5, 1.0 Hz), 118.1 (dd, J = 24.0,
8.0 Hz), 116.4 (dd, J = 27.0, 9.0 Hz), 115.1 (dd, J = 26.0, 7.0 Hz), 60.5, 45.6, 34.2, 23.6, 21.6, 14.8;
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HRMS (ESI-FT-ICR) m/z Calcd for [C26H26F2NaO3SSe, M + Na]+: 559.0628, Found: 559.0627; Optical
[α]2D0
Rotation:
= -67.7 (c = 1.0, CHCl3); HPLC analysis: Chiralcel AD-H (Hexane/i-PrOH) = 70:30,
flow rate = 1.0 mL/min, wave length = 254 nm, tR = 13.753 min (minor), tR = 17.220 min (major).
(2R,3S)-1-phenyl-2-(phenylselanyl)-3-tosylbutan-1-one (4a): According to GP-3, combining
selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2b (0.1 mmol, 14.6 mg) to gave
compound 4a (33.4 mg, 73% yield) as a white solid with an excellent diastereomeric ratio; mp 90-91 C;
1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 7.7 Hz, 2H), 7.66 (d, J = 7.9 Hz, 2H), 7.53 (t, J = 7.2 Hz, 1H),
7.44 – 7.36 (m, 4H), 7.36 – 7.30 (m, 1H), 7.26 – 7.19 (m, 4H), 4.99 (d, J = 10.1 Hz, 1H), 4.20 – 4.10 (m,
1H), 2.37 (s, 3H), 1.73 (d, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 192.8, 144.8, 135.6,
135.3, 134.8, 132.8, 129.6, 129.3, 129.2, 128.8, 128.4, 128.3, 127.2, 60.2, 46.3, 21.5, 15.0; HRMS (ESI-
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[α]2D0
FT-ICR) m/z Calcd for [C23H22NaO3SSe, M + Na]+: 481.0347, Found: 481.0346; Optical Rotation:
= -126.5 (c = 1.0, CHCl3); HPLC analysis: Chiralcel OD-H (Hexane/i-PrOH) = 85:15, flow rate = 1.0
mL/min, wave length = 254 nm, tR = 11.870 min (major), tR = 14.112 min (minor).
(2R,3S)-2-(phenylselanyl)-1-(p-tolyl)-3-tosylbutan-1-one (4b): According to GP-3, combining
selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2c (0.1 mmol, 16.0 mg) to gave
compound 4b(39.3 mg, 83% yield) as a white solid with an excellent diastereomeric ratio; mp 120-121
C; 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.1 Hz, 2H), 7.66 (d, J = 8.1 Hz, 2H), 7.40 (d, J = 7.4 Hz,
2H), 7.34 (t, J = 7.4 Hz, 1H), 7.25 (d, J = 7.2 Hz, 2H), 7.23 – 7.16 (m, 4H), 4.98 (d, J = 10.1 Hz, 1H),
4.20 – 4.08 (m, 1H), 2.42 (s, 3H), 2.38 (s, 3H), 1.72 (d, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 192.5, 144.8, 143.8, 135. 6, 134.9, 132.6, 129.6, 129.2, 129.1, 129.1, 128.8, 128.6, 127.4, 60.3,
46.2, 21.6, 21.5, 15.0; HRMS (ESI-FT-ICR) m/z Calcd for [C24H24NaO3SSe, M + Na]+: 495.0504, Found:
[α]2D0
495.0501; Optical Rotation:
= -122.9 (c = 1.0, CHCl3); HPLC analysis: Chiralcel OD-H
(Hexane/i-PrOH) = 85:15, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 15.658 min (major), tR =
21.293 min (minor).
(2R,3S)-1-(4-(tert-butyl)phenyl)-2-(phenylselanyl)-3-tosylbutan-1-one (4c): According to GP-3,
combining selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2d (0.1 mmol, 20.2 mg)
to gave compound 4c (37.9 mg, 74% yield) as a white solid with an excellent diastereomeric ratio; mp
119-120 C; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.4 Hz, 2H), 7.65 (d, J = 8.1 Hz, 2H), 7.39 (d, J
= 8.1 Hz, 4H), 7.30 (t, J = 7.3 Hz, 1H), 7.24 – 7.14 (m, 4H), 5.01 (d, J = 10.1 Hz, 1H), 4.20 – 4.11 (m,
1H), 2.32 (s, 3H), 1.72 (d, J = 7.1 Hz, 3H), 1.33 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 192.4,
156.4, 144.6, 135.4, 134.7, 132.4, 129.5, 129.1, 129.0, 128.7, 128.3, 127.3, 125.2, 60.2, 45.9, 34.9, 30.9,
21.4, 14.9; HRMS (ESI-FT-ICR) m/z Calcd for [C27H30NaO3SSe, M + Na]+: 537.0973, Found: 537.0972;
[α]2D0
Optical Rotation:
= -124.5 (c = 1.0, CHCl3); HPLC analysis: Chiralcel AD-H (Hexane/i-PrOH)
= 80:20, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 16.763 min (minor), tR = 17.608 min (major).
(2R,3S)-1-(4-isobutylphenyl)-2-(phenylselanyl)-3-tosylbutan-1-one (4d): According to GP-3,
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combining selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2e (0.1 mmol, 20.2 mg)to
gave compound 4d (34.9 mg, 68% yield) as a white solid with an excellent diastereomeric ratio; mp
94-95 C; 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.0 Hz, 2H), 7.66 (d, J = 8.0 Hz, 2H), 7.40 (d, J =
7.3 Hz, 2H), 7.33 (t, J = 7.3 Hz, 1H), 7.26 (d, J = 4.0 Hz, 1H), 7.24 – 7.18 (m, 3H), 7.16 (d, J = 8.0 Hz,
2H), 4.99 (d, J = 10.0 Hz, 1H), 4.15 (dq, J = 14.4, 7.1 Hz, 1H), 2.53 (d, J = 7.1 Hz, 2H), 2.37 (s, 3H),
1.96 – 1.85 (m, 1H), 1.73 (d, J = 7.1 Hz, 3H), 0.93 (d, J = 6.5 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3)
δ 192.7, 147.4, 144.8, 135.6, 134.9, 132.9, 129.6, 129.3, 129.1, 129.1, 128.8, 128.5, 127.4, 60.2, 46.2,
45.3, 30.1, 22.3, 21.5, 15.0; HRMS (ESI-FT-ICR) m/z Calcd for [C27H30NaO3SSe, M + Na]+: 537.0973,
[α]2D0
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Found: 537.0972; Optical Rotation:
= -97.0 (c = 1.0, CHCl3); HPLC analysis: Chiralcel OD-H
(Hexane/i-PrOH) = 80:20, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 8.496 min (major), tR =
11.212 min (minor).
(2R,3S)-2-(phenylselanyl)-3-tosyl-1-(4-(trifluoromethyl)phenyl)butan-1-one (4e): According to GP-
3, combining selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2f (0.1 mmol, 21.4
mg) to gave compound 4e (41.8 mg, 80% yield) as a white solid with an excellent diastereomeric ratio;
mp 120-123 C; 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.1 Hz, 2H), 7.67 (t, J = 7.7 Hz, 4H), 7.35 (t,
J = 6.8 Hz, 3H), 7.29 – 7.22 (m, 4H), 4.95 (d, J = 10.4 Hz, 1H), 4.13 (dq, J = 10.2, 7.1 Hz, 1H), 2.40 (s,
3H), 1.72 (d, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 191.9, 145.0, 138.5, 135.7, 134.8,
134.0 (q, J = 33.0 Hz), 129.8, 129.5, 129.4, 128.8, 128.7, 126.9, 125.4 (q, J = 3.0 Hz), 123.6 (q, J = 271.0
Hz), 60.2, 46.5, 21.6, 15.1; HRMS (ESI-FT-ICR) m/z Calcd for [C24H21F3NaO3SSe, M + Na]+: 549.0221,
[α]2D0
Found: 549.0220; Optical Rotation:
= -124.0 (c = 1.0, CHCl3); HPLC analysis: Chiralcel OD-H
(Hexane/i-PrOH) = 70:30, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 7.713 min (minor), tR =
14.412 min (major).
(2R,3S)-1-([1,1'-biphenyl]-4-yl)-2-(phenylselanyl)-3-tosylbutan-1-one (4f): According to GP-3,
combining selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2g (0.1 mmol, 22.2 mg)
to gave compound 4f (33.6 mg, 63% yield) as a white solid with an excellent diastereomeric ratio; mp
1
142-143 C; H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.2 Hz, 2H), 7.68 (d, J = 7.9 Hz, 2H), 7.65 –
7.58 (m, 4H), 7.48 (t, J = 7.5 Hz, 2H), 7.44 – 7.38 (m, 3H), 7.34 (t, J = 7.4 Hz, 1H), 7.28 – 7.20 (m, 4H),
5.03 (d, J = 10.0 Hz, 1H), 4.18 (dq, J = 10.3, 7.1 Hz, 1H), 2.38 (s, 3H), 1.75 (d, J = 7.1 Hz, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 192.5, 146.0, 144.8, 139.9, 135.7, 134.9, 134.0, 129.7, 129.3, 129.2, 129.1,
128.9, 128.8, 128.2, 127.4, 127.2, 127.0, 60.3, 46.4, 21.6, 15.1; HRMS (ESI-FT-ICR) m/z Calcd for
[α]2D0
[C29H26NaO3SSe, M + Na]+: 557.0660, Found: 557.0661; Optical Rotation:
= -41.8 (c = 1.0,
CHCl3); HPLC analysis: Chiralcel OD-H (Hexane/i-PrOH) = 85:15, flow rate = 1.0 mL/min, wave length
= 254 nm, tR = 28.330min (minor), tR = 31.040 min (major).
(2R,3S)-1-(4-methoxyphenyl)-2-(phenylselanyl)-3-tosylbutan-1-one (4g): According to GP-3,
combining selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2h (0.1 mmol, 17.6 mg)
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to gave compound 4g (32.0mg, 66% yield) as a white solid with an excellent diastereomeric ratio; mp
108-109 C; 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.2 Hz, 2H), 7.65 (d, J = 7.6 Hz, 2H), 7.41 (d, J
= 7.2 Hz, 2H), 7.36 – 7.30 (m, 1H), 7.28 – 7.16 (m, 4H), 6.87 (d, J = 8.2 Hz, 2H), 4.97 (d, J = 9.8 Hz,
1H), 4.21 – 4.09 (m, 1H), 3.86 (s, 3H), 2.37 (s, 3H), 1.72 (d, J = 6.8 Hz, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 191.8, 163.4, 144.8, 135.6, 134.9, 130.8, 129.6, 129.3, 129.1, 128.8, 128.1, 127.6, 113.6, 60.4,
55.4, 46.0, 21.5, 15.0; HRMS (ESI-FT-ICR) m/z Calcd for [C24H24NaO4SSe, M + Na]+: 511.0453, Found:
[α]2D0
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511.0452; Optical Rotation:
= -113.6 (c = 1.0, CHCl3); HPLC analysis: Chiralcel AD-H
(Hexane/i-PrOH) = 70:30, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 20.260 min (minor), tR =
27.463 min (major).
(2R,3S)-1-(4-fluorophenyl)-2-(phenylselanyl)-3-tosylbutan-1-one (4h): According to GP-3,
combining selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2i (0.1 mmol, 16.4 mg)
to gave compound 4h (31.4mg, 66% yield) as a white solid with an excellent diastereomeric ratio; mp
104-105 C; 1H NMR (400 MHz, CDCl3) δ 7.87 – 7.79 (m, 2H), 7.67 (d, J = 8.2 Hz, 2H), 7.38 (d, J =
7.1 Hz, 2H), 7.34 (d, J = 7.3 Hz, 1H), 7.29 – 7.21 (m, 4H), 7.07 (t, J = 8.6 Hz, 2H), 4.94 (d, J = 10.2 Hz,
1H), 4.14 (dq, J = 10.2, 7.1 Hz, 1H), 2.39 (s, 3H), 1.72 (d, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 191.6, 165.6 (d, J = 253.0 Hz), 144.9, 135.6, 134.8, 131.8 (d, J = 3.0 Hz), 131.1 (d, J = 9.0
Hz), 129.7, 129.4, 129.3, 128.8, 127.2, 115.5 (d, J = 22.0 Hz), 60.3, 46.2, 21.5, 15.1; HRMS (ESI-FT-
[α]2D0
ICR) m/z Calcd for [C23H21FNaO3SSe, M + Na]+: 499.0253, Found: 499.0250; Optical Rotation:
= -126.9 (c = 1.0, CHCl3); HPLC analysis: Chiralcel OD-H (Hexane/i-PrOH) = 70:30, flow rate = 1.0
mL/min, wave length = 254 nm, tR = 8.246 min (minor), tR = 9.714 min (major).
(2R,3S)-1-(4-chlorophenyl)-2-(phenylselanyl)-3-tosylbutan-1-one (4i): According to GP-3,
combining selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2j (0.1 mmol, 18.0 mg)
to gave compound 4i (34.0 mg, 69% yield) as a white solid with an excellent diastereomeric ratio; mp
1
125-126 C; H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.5 Hz, 2H), 7.66 (d, J = 8.2 Hz, 2H), 7.51 –
7.30 (m, 5H), 7.30 – 7.19 (m, 4H), 4.92 (d, J = 10.3 Hz, 1H), 4.13 (dq, J = 10.2, 7.1 Hz, 1H), 2.39 (s,
3H), 1.71 (d, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 191.4, 144.7, 138.9, 135.5, 134.6,
133.6, 129.7, 129.5, 129.2, 129.2, 128.5, 128.4, 126.8, 60.1, 46.0, 21.3, 14.9; HRMS (ESI-FT-ICR) m/z
[α]2D0
Calcd for [C23H21ClNaO3SSe, M + Na]+: 514.9957, Found: 514.9954; Optical Rotation:
= -118.0
(c = 1.0, CHCl3); HPLC analysis: Chiralcel AD-H (Hexane/i-PrOH) = 75:25, flow rate = 1.0 mL/min,
wave length = 254 nm, tR = 24.652 min (minor), tR = 32.588 min (major).
(2R,3S)-1-(4-bromophenyl)-2-(phenylselanyl)-3-tosylbutan-1-one (4j): According to GP-3,
combining selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2k (0.1 mmol, 22.5 mg)
to gave compound 4j (33.0mg, 62% yield) as a white solid with an excellent diastereomeric ratio; mp
146-148 C; 1H NMR (400 MHz, CDCl3) δ 7.71 – 7.62 (m, 4H), 7.54 (d, J = 8.3 Hz, 2H), 7.40 – 7.32
(m, 3H), 7.26 (t, J = 6.4 Hz, 4H), 4.91 (d, J = 10.2 Hz, 1H), 4.12 (dq, J = 14.4, 7.1 Hz, 1H), 2.40 (s, 3H),
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1.71 (d, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 192.0, 145.0, 135.7, 134.8, 134.2, 131.6,
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130.0, 129.7, 129.4, 129.4, 128.8, 128.0, 127.1, 60.2, 46.2, 21.6, 15.1; HRMS (ESI-FT-ICR) m/z Calcd
[α]2D0
for [C23H21BrNaO3SSe, M + Na]+: 558.9452, Found: 558.9451; Optical Rotation:
= -101.7 (c =
8
9
1.0, CHCl3); HPLC analysis: Chiralcel OD-H (Hexane/i-PrOH) = 70:30, flow rate = 1.0 mL/min, wave
length = 254 nm, tR = 9.244 min (minor), tR = 13.824 min (major).
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(2R,3S)-1-(4-nitrophenyl)-2-(phenylselanyl)-3-tosylbutan-1-one (4k): According to GP-3,
combining selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2l (0.1 mmol, 19.1 mg)
to gave compound 4k (20.6 mg, 41% yield) as a white solid with an excellent diastereomeric ratio; mp
130-131 C; 1H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 8.7 Hz, 2H), 7.99 (d, J = 8.7 Hz, 2H), 7.69 (d, J
= 8.1 Hz, 2H), 7.36 (d, J = 7.5 Hz, 3H), 7.32 – 7.23 (m, 4H), 4.94 (d, J = 10.5 Hz, 1H), 4.12 (dq, J =
10.4, 7.1 Hz, 1H), 2.42 (s, 3H), 1.72 (d, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 191.3,
150.0, 145.2, 140.7, 135.7, 134.7, 129.9, 129.7, 129.6, 129.5, 128.7, 126.7, 123.6, 60.3, 46.8, 21.6, 15.2;
HRMS (ESI-FT-ICR) m/z Calcd for [C23H21NNaO5SSe, M + Na]+: 526.0198, Found: 526.0195; Optical
[α]2D0
Rotation:
= -20.7 (c = 1.0, CHCl3); HPLC analysis: Chiralcel OD-H (Hexane/i-PrOH) = 60:40,
flow rate = 1.0 mL/min, wave length = 254 nm, tR = 16.600 min (minor), tR = 32.458 min (major).
(2R,3S)-1-(2-methoxyphenyl)-2-(phenylselanyl)-3-tosylbutan-1-one (4l): According to GP-3,
combining selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2m (0.1 mmol, 17.6 mg)
to gave compound 4l (37.7 mg, 77% yield) as a white solid with an excellent diastereomeric ratio; mp
93-95 C; 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 7.5 Hz, 1H), 7.70 (d, J = 7.9 Hz, 2H), 7.40 (t, J =
7.5 Hz, 1H), 7.34 (d, J = 7.3 Hz, 2H), 7.28 – 7.13 (m, 5H), 6.97 (t, J = 7.4 Hz, 1H), 6.81 (d, J = 8.3 Hz,
1H), 5.51 (d, J = 8.9 Hz, 1H), 4.19 – 4.08 (m, 1H), 3.63 (s, 3H), 2.33 (s, 3H), 1.68 (d, J = 7.0 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 192.6, 158.0, 144.5, 134.8, 134.8, 133.6, 132.0, 129.4, 128.8, 128.7,
128.4, 127.8, 125.1, 120.4, 111.4, 59.6, 55.2, 50.4, 21.4, 14.6; HRMS (ESI-FT-ICR) m/z Calcd for
[α]2D0
[C24H24NaO4SSe, M + Na]+: 511.0453, Found: 511.0452; Optical Rotation:
= -96.6 (c = 1.0,
CHCl3); HPLC analysis: Chiralcel OD-H (Hexane/i-PrOH) = 80:20, flow rate = 1.0 mL/min, wave length
= 254 nm, tR = 11.794 min (major), tR = 16.552 min (minor).
(2R,3S)-1-(2-fluorophenyl)-2-(phenylselanyl)-3-tosylbutan-1-one (4m): According to GP-3,
combining selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2n (0.1 mmol, 16.4 mg)
to gave compound 4m (35.7 mg, 75% yield) as a white solid with an excellent diastereomeric ratio; mp
82-84 C; 1H NMR (400 MHz, CDCl3) δ 7.84 (t, J = 7.0 Hz, 1H), 7.70 (d, J = 8.1 Hz, 2H), 7.50 (q, J =
6.7, 6.3 Hz, 1H), 7.39 – 7.29 (m, 3H), 7.28 – 7.17 (m, 5H), 7.13 – 7.05 (m, 1H), 5.00 (d, J = 10.2 Hz,
1H), 4.12 (dq, J = 15.2, 7.1 Hz, 1H), 2.37 (s, 3H), 1.68 (d, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 189.2, 161.2 (d, J = 253.0 Hz), 144.8, 135.7, 134.9, 134.5 (d, J = 9.0 Hz), 131.7 (d, J = 2.0
Hz), 129.7, 129.2, 128.9, 126.4, 124.4 (d, J = 3.0 Hz), 123.94 (d, J = 11.0 Hz), 116.6 (d, J = 25.0 Hz),
60.0, 50.2, 21.6, 15.0; HRMS (ESI-FT-ICR) m/z Calcd for [C23H21FNaO3SSe, M + Na]+: 499.0253,
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[α]2D0
Found: 499.0250; Optical Rotation:
= -56.3 (c = 1.0, CHCl3); HPLC analysis: Chiralcel OD-H
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(Hexane/i-PrOH) = 70:30, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 7.558 min (major), tR =
8.444 min (minor).
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(2R,3S)-1-(3-fluorophenyl)-2-(phenylselanyl)-3-tosylbutan-1-one (4n): According to GP-3,
combining selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2o (0.1 mmol, 16.4 mg)
to gave compound 4n (37.7 mg, 79% yield) as a white solid with an excellent diastereomeric ratio; mp
110-111 C; 1H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 8.1 Hz, 2H), 7.59 (d, J = 7.7 Hz, 1H), 7.49 (d, J
= 9.5 Hz, 1H), 7.42 – 7.32 (m, 4H), 7.26 (t, J = 7.8 Hz, 5H), 4.90 (d, J = 10.3 Hz, 1H), 4.12 (dq, J = 10.2,
7.1 Hz, 1H), 2.40 (s, 3H), 1.73 (d, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 191.6, 162.7 (d,
J = 246.0 Hz), 145.0, 137.6 (d, J = 6.0 Hz), 135.8, 134.8, 130.0 (d, J = 8.0 Hz), 129.8, 129.4, 129.4,
128.8, 127.0, 124.1 (d, J = 3.0 Hz), 119.9 (d, J = 21.0 Hz), 115.4 (d, J = 23.0 Hz), 60.2, 46.4, 21.6, 15.1;
HRMS (ESI-FT-ICR) m/z Calcd for [C23H21FNaO3SSe, M + Na]+: 499.0253, Found: 499.0250; Optical
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Rotation:
= -111.1 (c = 1.0, CHCl3); HPLC analysis: Chiralcel AD-H (Hexane/i-PrOH) = 70:30,
flow rate = 1.0 mL/min, wave length = 254 nm, tR = 16.600 min (major), tR = 17.495 min (minor).
(2R,3S)-1-(2,4-dimethylphenyl)-2-(phenylselanyl)-3-tosylbutan-1-one (4o): According to GP-3,
combining selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2p (0.1 mmol, 17.4 mg)
to gave compound 4o (26.2 mg, 54% yield) as a white solid with an excellent diastereomeric ratio; mp
84-86 C; 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.1 Hz, 2H), 7.55 (d, J = 7.9 Hz, 1H), 7.34 – 7.23
(m, 5H), 7.16 (t, J = 7.5 Hz, 2H), 7.06 (s, 1H), 6.95 (d, J = 7.8 Hz, 1H), 4.89 (d, J = 9.7 Hz, 1H), 4.16
(dq, J = 9.5, 7.1 Hz, 1H), 2.46 (s, 3H), 2.42 (s, 3H), 2.35 (s, 3H), 1.63 (d, J = 7.2 Hz, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 195.5, 144.8, 141.9, 139.8, 135.2, 134.9, 133.4, 132.4, 129.8, 129.2, 128.7, 128.7,
128.3, 126.0, 60.0, 50.2, 21.6, 21.4, 21.0, 15.1; HRMS (ESI-FT-ICR) m/z Calcd for [C25H26NaO3SSe,
[α]2D0
M + Na]+: 509.0660, Found: 509.0661; Optical Rotation:
= -137.4 (c = 1.0, CHCl3); HPLC
analysis: Chiralcel AD-H (Hexane/i-PrOH) = 80:20, flow rate = 1.0 mL/min, wave length = 254 nm, tR
= 12.135 min (minor), tR = 21.687 min (major).
(2R,3S)-1-(2,4-difluorophenyl)-2-(phenylselanyl)-3-tosylbutan-1-one (4p): According to GP-3,
combining selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2q (0.1 mmol, 18.2 mg)
to gave compound 4p (36.0 mg, 73% yield) as a white solid with an excellent diastereomeric ratio; mp
119-120 C; 1H NMR (400 MHz, CDCl3) δ 7.94 – 7.85 (m, 1H), 7.69 (d, J = 8.0 Hz, 2H), 7.40 – 7.29
(m, 3H), 7.28 – 7.17 (m, 4H), 6.94 (t, J = 7.3 Hz, 1H), 6.83 (t, J = 10.0 Hz, 1H), 4.94 (d, J = 10.4 Hz,
1H), 4.16 – 4.06 (m, 1H), 2.37 (s, 3H), 1.66 (d, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
187.9, 165.6 (dd, J = 255.0, 12.0 Hz), 161.7 (dd, J = 256.0, 13.0 Hz), 144.8, 135.6, 134.7, 133.5 (dd, J =
10.0, 3.0 Hz), 129.6, 129.2, 129.2, 128.7, 126.1, 120.5 (dd, J = 11.0, 3.0 Hz), 112.0 (dd, J = 21.0, 3.0
Hz), 104.6 (dd, J = 28.0, 26.0Hz), 59.90, 49.8, 21.5, 14.9; HRMS (ESI-FT-ICR) m/z Calcd for
[α]2D0
[C23H20F2NaO3SSe, M + Na]+: 517.0159, Found: 517.0158; Optical Rotation:
= -24.9 (c = 1.0,
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CHCl3); HPLC analysis: Chiralcel OD-H (Hexane/i-PrOH) = 80:20, flow rate = 1.0 mL/min, wave length
= 254 nm, tR = 10.115 min (minor), tR = 12.163 min (major).
(2R,3S)-1-(naphthalen-2-yl)-2-(phenylselanyl)-3-tosylbutan-1-one (4q): According to GP-3,
combining selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2r (0.1 mmol, 19.6 mg)
to gave compound 4q (37.2 mg, 73% yield) as a white solid with an excellent diastereomeric ratio; mp
138-140 C; 1H NMR (400 MHz, CDCl3) δ 8.20 (s, 1H), 7.91 (d, J = 8.6 Hz, 1H), 7.87 – 7.82 (m, 2H),
7.78 (d, J = 8.0 Hz, 1H), 7.67 (d, J = 8.2 Hz, 2H), 7.57 (t, J = 7.0 Hz, 1H), 7.51 (t, J = 7.2 Hz, 1H), 7.40
(d, J = 7.2 Hz, 2H), 7.32 (t, J = 7.4 Hz, 1H), 7.24 – 7.11 (m, 4H), 5.15 (d, J = 10.0 Hz, 1H), 4.22 (dq, J
= 9.7, 7.1 Hz, 1H), 2.31 (s, 3H), 1.80 (d, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 192.7,
144.8, 135.8, 135.4, 134.8, 132.4, 132.2, 130.0, 129.6, 129.5, 129.3, 129.2, 128.8, 128.4, 128.2, 127.6,
126.6, 124.4, 60.2, 46.6, 21.5, 15.1; HRMS (ESI-FT-ICR) m/z Calcd for [C27H24NaO3SSe, M + Na]+:
[α]2D0
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531.0504, Found: 531.0500; Optical Rotation:
= -42.6 (c = 1.0, CHCl3); HPLC analysis:
Chiralcel OD-H (Hexane/i-PrOH) = 85:15, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 15.898
min (minor), tR = 21.068 min (major).
(2R,3S)-1-(furan-2-yl)-2-(phenylselanyl)-3-tosylbutan-1-one (4r): According to GP-3, combining
selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2s (0.1 mmol, 13.6 mg) to gave
compound 4r (32.0 mg, 72% yield) as a white solid with an excellent diastereomeric ratio; mp 111-113C;
1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.1 Hz, 2H), 7.53 – 7.45 (m, 3H), 7.34 (t, J = 7.3 Hz, 1H),
7.30 – 7.20 (m, 4H), 7.05 (d, J = 3.5 Hz, 1H), 6.50 (d, J = 3.3 Hz, 1H), 4.83 (d, J = 10.6 Hz, 1H), 4.08
(dq, J = 10.5, 7.1 Hz, 1H), 2.38 (s, 3H), 1.68 (d, J = 7.0 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
182.1, 150.8, 146.0, 144.9, 135.7, 134.6, 129.6, 129.3, 129.1, 128.9, 127.2, 117.6, 112.5, 59.6, 46.4, 21.6,
14.8; HRMS (ESI-FT-ICR) m/z Calcd for [C21H20NaO4SSe, M + Na]+: 471.0140, Found: 471.0142;
[α]2D0
Optical Rotation:
= -87.4 (c = 1.0, CHCl3); HPLC analysis: Chiralcel OD-H (Hexane/i-PrOH) =
70:30, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 9.682 min (minor), tR = 17.633 min (major).
(2R,3S)-2-(phenylselanyl)-1-(thiophen-2-yl)-3-tosylbutan-1-one (4s): According to GP-3, combining
selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2t (0.1 mmol, 15.2 mg) to gave
compound 4s (31.0 mg, 67% yield) as a yellow solid with an excellent diastereomeric ratio; mp 124-125
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C; H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 8.0 Hz, 2H), 7.58 (d, J = 4.8 Hz, 1H), 7.47 – 7.41 (m,
3H), 7.32 (t, J = 7.2 Hz, 1H), 7.23 (dt, J = 21.8, 6.0 Hz, 4H), 7.01 (t, J = 4.3 Hz, 1H), 4.79 (d, J = 10.0
Hz, 1H), 4.14 – 4.05 (m, 1H), 2.35 (s, 3H), 1.72 (d, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3)
δ 186.0, 144.8, 142.1, 135.6, 134.4, 133.9, 131.7, 129.5, 129.2, 129.1, 128.7, 127.8, 127.3, 59.9, 47.4,
21.4, 14.7; HRMS (ESI-FT-ICR) m/z Calcd for [C21H20NaO3S2Se, M + Na]+: 486.9911, Found: 486.9913;
[α]2D0
Optical Rotation:
= -120.9 (c = 1.0, CHCl3); HPLC analysis: Chiralcel AD-H (Hexane/i-PrOH)
= 80:20, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 19.253 min (major), tR = 32.079 min (minor).
(2R,3S)-1,5-diphenyl-2-(phenylselanyl)-3-tosylpentan-1-one (4t): According to GP-3, combining
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selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2u (0.1 mmol, 23.6 mg) to gave
compound 4t (26.8 mg, 49% yield) as a white solid with an excellent diastereomeric ratio; mp 87-88 C;
1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 7.6 Hz, 2H), 7.64 (d, J = 7.7 Hz, 2H), 7.52 (t, J = 7.3 Hz, 1H),
7.37 (t, J = 7.5 Hz, 2H), 7.31 (t, J = 6.7 Hz, 3H), 7.26 (d, J = 7.7 Hz, 2H), 7.24 – 7.08 (m, 7H), 5.14 (d,
J = 10.0 Hz, 1H), 4.20 – 4.11 (m, 1H), 2.97 – 2.79 (m, 2H), 2.75 – 2.65 (m, 1H), 2.60 – 2.49 (m, 1H),
2.37 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 193.0, 144.8, 140.8, 136.1, 135.6, 135.5, 132.9, 129.7,
129.3, 129.2, 128.6, 128.6, 128.5, 128.4, 127.5, 126.1, 63.8, 46.5, 33.4, 31.2, 21.6; HRMS (ESI-FT-ICR)
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[α]2D0
m/z Calcd for [C30H28NaO3SSe, M + Na]+: 571.0817, Found: 571.0814; Optical Rotation:
= -
42.7 (c = 1.0, CHCl3); HPLC analysis: Chiralcel AD-H (Hexane/i-PrOH) = 75:25, flow rate = 1.0
mL/min, wave length = 254 nm, tR = 11.787 min (major), tR = 26.571 min (minor).
(2R,3S)-1-phenyl-2-(phenylselanyl)-3-tosylpentan-1-one (4u): According to GP-3, combining
selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2v (0.1 mmol, 16.0 mg) to gave
compound 4u (21.5 mg, 46% yield) as a white solid with an excellent diastereomeric ratio; mp 107-108
C; 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 7.7 Hz, 2H), 7.64 (d, J = 8.1 Hz, 2H), 7.52 (t, J = 7.3 Hz,
1H), 7.38 (t, J = 7.9 Hz, 4H), 7.32 (d, J = 7.2 Hz, 1H), 7.22 (dd, J = 12.8, 7.7 Hz, 4H), 5.09 (d, J = 10.1
Hz, 1H), 4.05 – 3.98 (m, 1H), 2.51 – 2.43 (m, 1H), 2.37 (s, 3H), 2.34 – 2.27 (m, 1H), 1.59 (s, 3H), 1.14
(t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 193.0, 144.6, 136.4, 135.6, 135.5, 132.8, 129.6,
129.2, 129.2, 128.5, 128.4, 128.3, 127.4, 65.7, 46.2, 22.6, 21.5, 12.0; HRMS (ESI-FT-ICR) m/z Calcd
[α]2D0
for [C24H24NaO3SSe, M + Na]+: 495.0504, Found: 495.0500; Optical Rotation:
= -110.6 (c = 1.0,
CHCl3); HPLC analysis: Chiralcel AD-H (Hexane/i-PrOH) = 90:10, flow rate = 1.0 mL/min, wave length
= 254 nm, tR = 29.349 min (major), tR = 31.315 min (minor).
(2R,3S)-4-hydroxy-1-phenyl-2-(phenylselanyl)-3-tosylbutan-1-one (4v): According to GP-3,
combining selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2w (0.1 mmol, 16.2 mg)
to gave compound 4v (19.9 mg, 42% yield) as a yellow solid with an excellent diastereomeric ratio; mp
81-82 C; 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 7.6 Hz, 2H), 7.69 (d, J = 8.1 Hz, 2H), 7.51 (t, J =
7.4 Hz, 1H), 7.38 (t, J = 7.4 Hz, 4H), 7.31 (d, J = 7.1 Hz, 1H), 7.25 – 7.17 (m, 4H), 5.24 (d, J = 11.2 Hz,
1H), 4.63 – 4.49 (m, 2H), 4.15 – 4.08 (m, 1H), 3.42 (s, 1H), 2.34 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 192.2, 145.1, 136.2, 135.7, 135.2, 132.9, 129.8, 129.4, 129.1, 128.5, 128.3, 126.7, 66.2, 60.3,
42.9, 21.5; HRMS (ESI-FT-ICR) m/z Calcd for [C23H22NaO4SSe, M + Na]+: 497.0296, Found: 497.0295;
[α]2D0
Optical Rotation:
= -107.6 (c = 1.0, CHCl3); HPLC analysis: Chiralcel OD-H (Hexane/i-PrOH)
= 80:20, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 10.587 min (major), tR = 14.650 min (minor).
(2S,3S)-2-(phenylselanyl)-3-tosylcyclopentan-1-one (4w): According to GP-3, combining
selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2x (0.1 mmol, 9.6 mg) to gave
compound 4w (8.6 mg, 21% yield) as a yellow solid with an excellent diastereomeric ratio; mp 77-80 C
; 1H NMR (400 MHz, CDCl3) δ 7.64 (d, J = 8.1 Hz, 2H), 7.27 (dd, J = 15.8, 7.8 Hz, 5H), 7.16 (t, J = 7.6
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Hz, 2H), 3.97 – 3.91 (m, 1H), 3.59 – 3.55 (m, 1H), 2.86 – 2.75 (m, 1H), 2.52 – 2.41 (m, 5H), 2.40 – 2.24
(m, 2H), 2.02 – 1.93 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 202.9, 145.0, 134.4, 133.9, 129.9,
129.4, 128.8, 128.5, 127.4, 66.5, 45.8, 36.5, 21.5, 21.2, 19.8; HRMS (ESI-FT-ICR) m/z Calcd for
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[α]2D0
[C18H18NaO3SSe, M + Na]+: 417.0034, Found: 417.0030; Optical Rotation:
= -64.0 (c = 1.0,
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CHCl3); HPLC analysis: Chiralcel OD-H (Hexane/i-PrOH) = 85:15, flow rate = 1.0 mL/min, wave length
= 254 nm, tR = 14.295 min (minor), tR = 15.084 min (major).
(2S,3S)-2-(phenylselanyl)-3-tosylcycloheptan-1-one (4x): According to GP-3, combining
selenosulfonate 1a (0.1 mmol, 31.1 mg) and α,β-unsaturated ketone 2y (0.1 mmol, 11.0 mg) to gave
compound 4x (16.9 mg, 40% yield) as a white solid with an excellent diastereomeric ratio; mp 130-131
C; 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.1 Hz, 2H), 7.39 (d, J = 7.1 Hz, 2H), 7.34 (d, J = 8.1 Hz,
2H), 7.30 (d, J = 7.1 Hz, 1H), 7.27 – 7.18 (m, 2H), 3.95 (d, J = 7.2 Hz, 1H), 3.40 (td, J = 7.4, 2.4 Hz,
1H), 2.94 – 2.85 (m, 1H), 2.55 – 2.36 (m, 5H), 2.12 – 2.02 (m, 1H), 1.99 – 1.88 (m, 2H), 1.76 – 1.64 (m,
2H); 13C{1H} NMR (100 MHz, CDCl3) δ 203.8, 145.3, 134.7, 134.3, 130.0, 129.3, 129.0, 128.8, 128.0,
66.2, 51.8, 40.8, 27.7, 27.3, 24.8, 21.7; HRMS (ESI-FT-ICR) m/z Calcd for [C20H22NaO3SSe, M + Na]+:
[α]2D0
445.0347, Found: 445.0344; Optical Rotation:
= -44.4 (c = 1.0, CHCl3); HPLC analysis:
Chiralcel AD-H (Hexane/i-PrOH) = 80:20, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 17.662
min (major), tR = 19.320 min (minor).
Procedure for scale-up experiment (P-1): In a 500 mL jacket reactor was added 300 mL sat. NaCl
solution with vigorous agitating by machinery stirring. And then a mixture of selenosulfonate 1a (20.2
g, 65.0 mmol, 1.0 equiv.), substrate 2k (14.6 g, 65.0 mmol, 1.0 equiv.) and catalyst D (10 mmol%) were
added into reaction mixture in portion. After stirring vigorously at 25 C for 2 h, 200 mL CH3CN was
added and stirred for 20 min. The reaction mixture was standing for 15 min. The aqueous layer was
separated, and the organic layer was filtered to give 4j (28.2 g, 81% yield) as white solid with 87% ee.
Procedure for the synthesis of 5 (P-2): 4j (53.6mg, 96% ee, 0.1 mmol, 1.0 equiv.) and CeCl3∙7H2O
(74.5 mg, 0.2 mmol, 2.0 equiv.) were added into a 10 mL tube followed by CH3OH (1 mL) was
introduced, then the mixture was cooled down to 0 °C. NaBH4 (0.2 mmol, 2.0 equiv.) was added in
portion. The reaction mixture was stirred for 2 h at 0 °C, then quenched by H2O, extracted with ethyl
acetate, washed with brine, dried over Na2SO4 and filtered, concentrated under reduced pressure and
purified by column chromatography (SiO2, PE:EA = 6:1) to afford 5 as white solid (74% yield, 93% ee).
(1S,2R,3S)-1-(4-bromophenyl)-2-(phenylselanyl)-3-tosylbutan-1-ol (5): This product was prepared
according to P-2, 5 (39.8 mg, 74% yield) was afforded as a white solid; mp 151-152 °C; 1H NMR (600
MHz, CDCl3) δ 7.51 (d, J = 8.1 Hz, 2H), 7.35 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 7.3 Hz, 2H), 7.23 (d, J =
8.1 Hz, 3H), 7.16 (dd, J = 12.7, 7.9 Hz, 4H), 5.15 (t, J = 4.5 Hz, 1H), 3.71 (t, J = 5.0 Hz, 1H), 3.42 – 3.37
(m, 1H), 3.36 (d, J = 4.2 Hz, 1H), 2.42 (s, 3H), 1.40 (d, J = 7.0 Hz, 3H); 13C{1H} NMR (150 MHz,
CDCl3) δ 144.8, 140.0 134.5, 134.2, 131.2, 129.7, 129.5, 129.0, 128.6, 128.1, 127.7, 121.7, 74.1, 61.7,
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56.8, 21.6, 14.3; HRMS (ESI-FT-ICR) m/z Calcd for [C23H23NaBrO3SSe, M + Na]+: 560.9609, Found:
[α]2D0
560.9608; Optical Rotation:
= 15.6 (c = 1.0, CHCl3); HPLC analysis: Chiralcel AD-H (Hexane/i-
PrOH) = 70:30, flow rate = 1.0 mL/min, wave length = 254 nm, tR = 10.820 min (minor), tR = 16.343
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ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
1H NMR and 13C NMR spectra of new compounds and crystallographic data of 4u, 4x and 5 (PDF)
Crystal data for 4u (CIF)
Crystal data for 4x (CIF)
Crystal data for 5 (CIF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: wenling.qin@cqu.edu.cn
*E-mail: maohui1988@126.com
ORCID
Wenling Qin: 0000-0002-5654-5785
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This study was supported by Fundamental Research Funds for the Central Universities
(2018CDYXYX0027), Chongqing Science and Technology Commission (Grant No.:
cstc2017zdcyadyfX0022), Zhejiang Provincial Natural Science Foundation of China (LQ19B020003).
H. Mao thanks the support from Jinhua Science and Technology Bureau (2018-4-105).
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(14) Selenosulfonates 1 are known compounds and were prepared according to literature procedures, see
reference 11b and: (a) Chen. D. W.; Chen Z. C. Hypervalent Iodine in Synthesis X V III: Synthesis
of Selenosulfonates Using a One Pot Reaction of Diaryl Diselenides, Sodium Sulfinates and
[Bis(trifluoroacetoxy)iodo]benzene. Tetrahedron Letters. 1994, 35, 7637-7638. (b) Billard T.;
Langlois B. R. A New Synthesis of Thioesters and Selenoesters of Triflic Acid under Oxidative
Conditions. Journal of Fluorine Chemistry. 1997, 84, 63-64. (c) Singh D.; Deobald A. M.; Camargo
L. R. S.; Tabarelli G.; Rodrigues O. E. D.; Braga A. L. An Efficient One-Pot Synthesis of
Symmetrical Diselenides or Ditellurides from Halides with CuO Nanopowder/Se0 or Te0/Base. Org.
Lett. 2010, 12, 3288-3291.
(15) α,β-unsaturated ketones 2 are known compounds and were prepared according to literature
procedures, see: (a) Kajigaeshi S.; Kakinami T.; Okamoto T.; Fujisaki S. Synthesis of Bromoacetyl
Derivatives by Use of Tetrabutylammonium Tribromide. Bull. Chem. Soc. Jpn. 1987, 60, 1159-
1160. (b) Kumar K.; More S. S.; Goyal S.; Ganger M.; Khatik G. L.; Rawal R. K.; Nair V. A. A
convenient synthesis of 4-alkyl-3-benzoylpyrroles from α,β-unsaturated and tosylmethyl
isocyanide. Tetrahedron Letters. 2016, 57, 2315-2319.
(16) Liu, Y.; Ao, J.; Paladhi, S.; Song, C. E.; Yan, H. Organocatalytic Asymmetric Synthesis of Chiral
Dioxazinanes and Dioxazepanes with in Situ Generated Nitrones via a Tandem Reaction Pathway
Using a Cooperative Cation Binding Catalyst. J. Am. Chem. Soc. 2016, 138, 16486–16492.
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