Enantioselective synthesis of optically active Bis(β-hydroxy) sulfones through asymmetric hydrogenation of corresponding ketones catalyzed by a chiral cationic ruthenium diamine catalyst

Article abstract of DOI:10.1002/cjoc.201400409

Chiral molecules containing sulfonyl and 1,5-diol moieties are useful synthetic blocks for various asymmetric transformations. A protocol has been developed for the enantioselective synthesis of optically active bis(β-hydroxy) sulfones catalyzed by a chiral cationic ruthenium diamine catalyst. A series of bis(β-hydroxy) sulfones have been obtained in excellent yields (up to 99%) with excellent enantioselectivities (up to 99%) as well as good diastereoselectivities (up to 99:1). Chiral molecules containing sulfonyl and 1,5-diol moieties are useful synthetic blocks for various asymmetric transformations. A protocol has been developed for the enantioselective synthesis of optically active bis(β-hydroxy) sulfones catalyzed by a chiral cationic ruthenium diamine catalyst. A series of bis(β-hydroxy) sulfones have been obtained in excellent yields (up to 99%) with excellent enantioselectivities (up to 99%) as well as good diastereoselectivities (up to 99:1). Copyright

Full text of DOI:10.1002/cjoc.201400409

FULL PAPER
DOI: 10.1002/cjoc.201400409
Enantioselective Synthesis of Optically Active Bis(β-hydroxy)
Sulfones through Asymmetric Hydrogenation of
Corresponding Ketones Catalyzed by a Chiral Cationic
Ruthenium Diamine Catalyst†
Xiaofei Huang,a Min Zhao,a Naikai Li,a Haiyan Li,a Jie Li,*,b and Xingwang Wang*,a
a Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry and Chemical Engineering,
Suzhou University, Suzhou, Jiangsu, 215123 China
b Shanghai Institute of Measurement and Testing Technology, Shanghai 201203, China
Chiral molecules containing sulfonyl and 1,5-diol moieties are useful synthetic blocks for various asymmetric
transformations. A protocol has been developed for the enantioselective synthesis of optically active bis(β-hydroxy)
sulfones catalyzed by a chiral cationic ruthenium diamine catalyst. A series of bis(β-hydroxy) sulfones have been
obtained in excellent yields (up to 99%) with excellent enantioselectivities (up to 99%) as well as good diastereose-
lectivities (up to 99∶1).
Keywords asymmetric catalysis, hydrogenation, ruthenium, sulfone, 1,5-diol
Introduction
Scheme 1 Biologically active thiomorpholine 1,1-dioxide-
containing compounds
Chiral diol[1] and sulfonyl group[2] are two types of
important structural motifs, whose derivatives are
prevalent not only in natural products, pharmaceutical
compounds and biologically active molecules, but also
in versatile intermediates in organic synthesis. Therefore,
bis(β-hydroxy) sulfones, which combine the important
backbones of both 1,5-diol and sulfone, are very attrac-
tive targets for synthetic studies by virtue of their syn-
thetic versatility. There are examples in literature in
which they are used as synthetic intermediates for syn-
thesis of some drugs.[3] For instance, thiomorpholine
1,1-dioxide-containing compounds are of pharmaceuti-
cal interest as shown in Scheme 1.[4] Due to biological
and synthetic importance of bis(β-hydroxy) sulfones,
the development of synthetically effective protocol for
such type of compounds is of high demand.
The non-asymmetric version synthesis of bis(β-hy-
droxy) sulfones was reported as early as in 1967, when
Charles R. Hauser and Edwin M. Kaiser found that
treatment of benzophenone with dimethyl sulfone in the
presence of an equivalent of sodium hydride or lithium
amide yielded bis(β-hydroxy) sulfones.[5] Subsequently,
Yus et al.[6] reported that the DTBB-catalyzed lithiation
of bis(chloromethyl) sulfone in the presence of different
carbonyl compounds led to the formation of corre-
sponding dihydroxy sulfones. However, to the best of
O
O
S
OH
O
S
Ref. 3
R
N
N
R
OH
O
O
NO2
O
O
S
R = CH3, CH2OPr, CH2OEt
NO2
H3C
N
N
H
N
S
N
Cl
our knowledge, the catalytic enantioselective method to
access optically active bis(β-hydroxy) sulfones remain
rarely explored so far.
On the other hand, chiral diols can be prepared by
many methods.[7] Among these different reported meth-
ods, asymmetric hydrogenation (AH) of ketones repre-
sents one of the most convenient and straightforward
approaches for attaining optically active diols.[7q] Since
2006, cationic ruthenium complexes of chiral mono-
tosylated diamines have been found to be very efficient
catalysts for the AH of ketones[8] and imines.[9] Recently,
we also reported that highly efficient AH of β-keto sul-
*
E-mail: wangxw@suda.edu.cn; lijie@simt.com.cn
Received June 24, 2014; accepted August 10, 2014; published online August 25, 2014.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201400409 or from the author.
Dedicated to Professor Chengye Yuan and Professor Li-Xin Dai on the occasion of their 90th birthdays.
†
Chin. J. Chem. 2014, 32, 803—813
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Huang et al.
FULL PAPER
fonamides, β-keto sulfones[10] and benzils[11] promoted
by this catalytic system afforded the corresponding op-
tically active products. Encouraged by these results, we
envisioned that this phosphine-free catalytic system
could also be used to catalyze the enantioselective hy-
drogenation of bis(β-keto) sulfones.
＞99% ee. The enantiomeric excess was determined by
HPLC on Daicel Chiralpak AD-H with hexane/i-PrOH
(85∶15) as the eluent. Flow: 1.0 mL/min; λ＝210 nm:
t
major＝14.244 min; tminor＝15.976 min; tmeso＝16.150
25
min. [α]D ＋159.0 (c 0.50 in CH3COCH3); 1H NMR
(400 MHz, CDCl3) δ: 7.38－7.36 (m, 4H), 7.34－7.31
(m, 4H), 5.38 (d, J＝10.8 Hz, 2H), 3.71 (dd, J＝14.4,
4.0 Hz, 2H), 3.25 (d, J＝15.6 Hz, 2H), 3.09 (d, J＝3.2
Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 139.54,
Experimental
General procedure for the asymmetric hydrogena-
tion
134.50, 129.24, 127.18, 68.71, 62.52; IR (KBr) νmax
:
3596.8, 3412.7, 1490.2, 1404.6, 1387.7, 1211.6, 1064.9,
989.2, 859.0, 811.7, 684.8 cm−1; HRMS m/z: [M＋
NH4] ＋ calcd for C16H20Cl2NO4S: 392.0485; found
392.0486.
2,2'-Sulfonylbis(1-(4-bromophenyl)ethanol) (2d)
White solid, m.p. 152－153 ℃, 99% yield, 95∶5 dr,
＞99% ee. The enantiomeric excess was determined by
HPLC on Daicel Chiralpak AD-H with hexane/i-PrOH
(85∶15) as the eluent. Flow: 1.0 mL/min; λ＝210 nm:
Compounds 1, 2 or 5 (0.2 mmol), catalyst I (0.002
mmol), and degassed MeOH (2 mL) were added to a
glass tube under nitrogen. The tube was then placed into
a stainless steel autoclave, which was purged with hy-
drogen gas for three times before being pressurized with
H2 to 40 atm. Subsequently, the mixture was stirred un-
der this H2 pressure at room temperature for 24 h. After
careful release of the hydrogen, methanol was concen-
trated to afford the crude product. Purification was per-
formed with a silica gel column eluted with DCM to
give the pure product.
t
major＝17.719 min; tminor＝23.352 min; tmeso＝19.901
25
min. [α]D ＋184.8 (c 0.50 in CH3COCH3); 1H NMR
(600 MHz, CDCl3) δ: 7.52 (d, J＝7.2 Hz, 4H), 7.25 (d,
J＝7.2 Hz, 4H), 5.35 (d, J＝9.6 Hz, 2H), 3.69 (dd, J＝
14.4, 3.6 Hz, 2H), 3.23 (d, J＝15.0 Hz, 2H), 3.12 (s,
2H); 13C NMR (151 MHz, CDCl3) δ: 140.00, 132.29,
127.52, 122.75, 68.93, 62.63; IR (KBr) νmax: 3597.3,
3416.5, 1486.5, 1277.7, 1242.2, 1164.1, 1119.7, 1064.3,
1010.5, 807.9 cm−1; HRMS m/z: [M＋NH4]＋ calcd for
C16H20Br2NO4S: 479.9474; found 374.9483.
Characterization data of bis(β-hydroxy) sulfones
2,2'-Sulfonylbis(1-phenylethanol) (2a) White
solid, m.p. 129－130 ℃, 99% yield, 98∶2 dr, ＞99%
ee. The enantiomeric excess was determined by HPLC
on Chiralcel OD-H with hexane/i-PrOH (90∶10) as the
eluent. Flow: 1.0 mL/min; λ＝210 nm: tmajor＝27.590
25
min; tminor＝23.710 min; tmeso＝34.086 min. [α]D
2,2'-Sulfonylbis(1-(4-nitrophenyl)ethanol) (2e)
White solid, m.p. 52－53 ℃, 95% yield, 90∶10 dr,
＞99% ee. The enantiomeric excess was determined by
HPLC on Daicel Chiralpak AD-H with hexane/i-PrOH
(80∶20) as the eluent. Flow: 1.0 mL/min; λ＝210 nm:
＋155.8 (c 0.50 in CH3COCH3). 1H NMR (400 MHz,
DMSO-d6) δ: 7.42－7.35 (m, 8H), 7.30－7.27 (m, 2H),
5.92 (d, J＝4.4 Hz, 2H), 5.13－5.10 (m, 2H), 3.82 (dd,
J＝14.0, 4.4 Hz, 2H), 3.27 (d, J＝14.8 Hz, 2H); 13C
NMR (101 MHz, DMSO-d6) δ: 143.55, 128.35, 127.50,
125.91, 67.92, 61.97; IR (KBr) νmax: 3453.9, 3397.6,
1520.5, 1288.0, 1260.1, 1118.9, 1091.7, 1066.6, 782.2,
748.7, 717.5 cm−1; HRMS m/z: [M＋NH4]＋ calcd for
C16H22NO4S: 324.1264; found 324.1275.
t
major＝26.017 min; tminor＝36.383 min; tmeso＝41.272
25
min. [α]D ＋152.0 (c 0.50 in CH3COCH3); 1H NMR
(400 MHz, DMSO-d6) δ: 8.24 (s, 4H), 7.37 (s, 4H), 6.33
(s, 2H), 5.28 (s, 2H), 3.85 (s, 2H), 3.45 (s, 2H); 13C
NMR (101 MHz, DMSO-d6) δ: 150.99, 146.88, 127.33,
123.54, 67.29, 61.39; IR (KBr) νmax: 3521.3, 3505.7,
1611.4, 1541.4, 1310.2, 1288.1, 1111.7, 1065.1, 989.4,
856.8, 743.9, 694.3 cm−1; HRMS m/z: [M＋NH4]＋
calcd for C16H20N3O8S: 414.0966; found 414.0982.
2,2'-Sulfonylbis(1-(4-(trifluoromethyl)phenyl)-
ethanol) (2f) White solid, m.p. 125－126 ℃, 99%
yield, 94∶6 dr, ＞99% ee. The enantiomeric excess
was determined by HPLC on Daicel Chiralpak AD-H
with hexane/i-PrOH (90∶10) as the eluent. Flow: 1.0
mL/min; λ＝210 nm: tmajor＝14.532 min; tminor＝19.529
2,2'-Sulfonylbis(1-(4-fluorophenyl)ethanol) (2b)
White solid, m.p. 98－99 ℃, 96% yield, 94∶6 dr,
＞99% ee. The enantiomeric excess was determined by
HPLC on Daicel Chiralpak AD-H with hexane/i-PrOH
(90∶10) as the eluent. Flow: 1.0 mL/min; λ＝210 nm:
t
major＝21.789 min; tminor＝24.533 min; tmeso＝26.296
25
min. [α]D ＋107.2 (c 0.50 in CH3COCH3); 1H NMR
(400 MHz, CDCl3) δ: 7.35－7.31 (m, 4H), 7.07－7.03
(m, 4H), 5.34 (d, J＝6.4 Hz, 2H), 3.72 (dd, J＝14.8, 4.0
Hz, 2H), 3.34 (d, J＝3.2 Hz, 2H), 3.20 (d, J＝15.2 Hz,
＝
1
2H); 13C NMR (101 MHz, CDCl3) δ: 161.27 (d, JC,F
25
min; tmeso ＝ 16.827 min. [α]D ＋ 96.0 (c 0.50 in
4
3
CH3COCH3); 1H NMR (400 MHz, DMSO-d6) δ: 7.74 (d,
J＝8.4 Hz, 4H), 7.66 (d, J＝8.0 Hz, 4H), 6.20 (d, J＝
4.4 Hz, 2H), 5.25 (s, 2H), 3.84 (dd, J＝14.0, 3.6 Hz,
2H), 3.40 (d, J＝14.8 Hz, 2H); 13C NMR (101 MHz,
248 Hz), 136.82 (d, JC,F＝3 Hz), 127.48 (d, JC,F＝9
2
Hz), 115.91 (d, JC,F＝22 Hz), 68.68, 62.58; IR (KBr)
νmax: 3494.9, 3472.3, 1603.4, 1509.8, 1279.1, 1115.3,
1096.7, 1058.1, 840.2, 748.3 cm−1; HRMS m/z: [M＋
NH4] ＋ calcd for C16H20F2NO4S: 360.1076; found
360.1076.
2,2'-Sulfonylbis(1-(4-chlorophenyl)ethanol) (2c)
White solid, m.p. 117－118 ℃, 98% yield, 95∶5 dr,
2
DMSO-d63) δ: 148.13, 128.2 (q, JC,F＝31 Hz), 126.84,
125.2 (q, JC,F＝4 Hz), 124.3 (q, 1JC,F＝273 Hz), 67.45,
61.60; IR (KBr) νmax: 3473.6, 1623.6, 1424.2, 1174.5,
1081.1, 1048.7, 989.7, 842.3, 607.8 cm−1; HRMS m/z:
804
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Chin. J. Chem. 2014, 32, 803—813

Enantioselective Synthesis of Optically Active Bis(β-hydroxy) Sulfones
[M＋Na]＋ calcd for C18H16F6NaO4S: 465.0566; found
465.0563.
min; [α]D ＋128.8 (c 0.50 in CH3COCH3); H NMR
(400 MHz, DMSO-d6) δ: 7.47 (s, 2H), 7.40－7.35 (m,
6H), 6.10 (d, J＝4.4 Hz, 2H), 5.12 (s, 2H), 3.79 (dd, J＝
14.4, 4.0 Hz, 2H), 3.36 (s, 2H); 13C NMR (101 MHz,
DMSO-d6) δ: 146.03, 133.07, 130.28, 127.44, 125.88,
124.71, 67.29, 61.63; IR (KBr) νmax: 3590.3, 3471.1,
1574.8, 1478.9, 1288.8, 1117.7, 1080.9, 803.9, 784.2,
691.8 cm−1; HRMS m/z: [M ＋ NH4] ＋ calcd for
C16H20Cl2NO4S: 392.0485; found 392.0476.
25
1
2,2'-Sulfonylbis(1-(biphenyl-4-yl)ethanol)
(2g)
White solid, m.p. 192－193 ℃, 90% yield, 96∶4 dr,
＞99% ee. The enantiomeric excess was determined by
HPLC on Daicel Chiralpak IA with hexane/i-PrOH
(70∶30) as the eluent. Flow: 1.0 mL/min; λ＝210 nm:
t
major＝12.588 min; tminor＝18.485 min (major); tmeso＝
25
15.631 min. [α]D ＋114.2 (c 0.50 in CH3COCH3); 1H
NMR (400 MHz, DMSO-d6) δ: 7.66 (d, J＝8.0 Hz, 8H),
7.52－7.45 (m, 8H), 7.39－7.35 (m, 2H), 5.99 (d, J＝
4.4 Hz, 2H), 5.19－5.17 (m, 2H), 3.87 (dd, J＝14.4, 4.0
Hz, 2H), 3.37 (s, 2H); 13C NMR (101 MHz, DMSO-d6)
δ: 142.69, 139.87, 139.41, 128.94, 127.44, 126.66,
126.64, 126.59, 67.66, 61.86; IR (KBr) νmax: 3549.5,
1623.8, 1524.2, 1347.2, 1312.3, 1146.8, 1081.4, 1027.3,
827.1, 752.1 cm−1; HRMS m/z: [M＋Na]＋ calcd for
C28H26NaO4S: 481.1449; found 481.1452.
2,2'-Sulfonylbis(1-(3-bromophenyl)ethanol) (2k)
White solid, m.p. 98－99 ℃, 97% yield, 97∶3 dr,
＞99% ee. The enantiomeric excess was determined by
HPLC on Daicel Chiralpak AD-H with hexane/i-PrOH
(90∶10) as the eluent. Flow: 1.0 mL/min; λ＝210 nm:
t
major＝20.025 min; tminor＝24.195 min; tmeso＝21.170
25
min; [α]D ＋118.4 (c 0.50 in CH3COCH3); 1H NMR
(600 MHz, CDCl3) δ: 7.53 (s, 2H), 7.43 (d, J＝7.8 Hz,
2H), 7.26 (d, J＝7.2 Hz, 2H), 7.22 (t, J＝7.8 Hz, 2H),
5.29 (d, J＝10.2 Hz, 2H), 3.68 (dd, J＝15.0, 4.2 Hz,
2H), 3.47 (d, J＝3.6 Hz, 2H), 3.19 (d, J＝15.0 Hz, 2H);
13C NMR (151 MHz, CDCl3) δ: 143.32, 131.77, 130.66,
2,2'-Sulfonylbis(1-(4-methoxyphenyl)ethanol) (2h)
White solid, m.p. 131－132 ℃, 94% yield, 98∶2 dr,
＞99% ee. The enantiomeric excess was determined by
HPLC on Daicel Chiralpak AD-H with hexane/i-PrOH
(85∶15) as the eluent. Flow: 1.0 mL/min; λ＝210 nm:
128.95, 124.45, 123.13, 68.73, 62.54; IR (KBr) νmax
:
3419.2, 3336.4, 1570.7, 1475.3, 1431.2, 1116.7, 1073.0,
1050.3, 999.9, 780.1, 693.2 cm−1; HRMS m/z: [M＋
NH4] ＋ calcd for C16H20Br2NO4S: 479.9474; found
479.9481.
2,2'-Sulfonylbis(1-(3-methoxyphenyl)ethanol) (2l)
Colorless oil, 99% yield, 99∶1 dr, ＞99% ee. The en-
antiomeric excess was determined by HPLC on Chiral-
cel OD-H with hexane/i-PrOH (90∶10) as the eluent.
Flow: 1.0 mL/min; λ＝210 nm: tmajor＝22.360 min; tminor
t
major＝26.763 min; tminor＝43.107 min; tmeso＝30.540
25
min. [α]D ＋132.4 (c 0.50 in CH3COCH3); 1H NMR
(400 MHz, CDCl3) δ: 7.27 (d, J＝8.8 Hz, 4H), 6.89 (d,
J＝8.8 Hz, 4H), 5.30 (d, J＝10.4 Hz, 2H), 3.79 (s, 6H),
3.75 (dd, J＝14.8, 4.0 Hz, 2H), 3.20 (d, J＝14.8 Hz,
2H), 3.15 (d, J＝3.2 Hz, 2H); 13C NMR (101 MHz,
CDCl3) δ: 159.86, 133.33, 127.16, 114.42, 69.07, 62.63,
55.47; IR (KBr) νmax: 3549.5, 1603.9, 1509.9, 1395.6,
1346.1, 1125.5, 1050.4, 1031.4, 847.3, 771.2 cm−1;
HRMS m/z: [M ＋ Na] ＋ calcd for C18H22NaO6S:
389.1029; found 389.1021.
25
＝21.528 min; tmeso＝26.113 min. [α]D ＋122.2 (c
0.50 in CH3COCH3); 1H NMR (400 MHz, CDCl3) δ:
7.30－7.28 (m, 2H), 6.94－6.92 (m, 4H), 6.86－6.84
(m, 2H), 5.31 (d, J＝10.8 Hz, 2H), 3.79 (s, 6H), 3.75
(dd, J＝14.8, 4.0 Hz, 2H), 3.44 (d, J＝3.6 Hz, 2H), 3.24
(d, J＝15.2 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ:
159.96, 142.74, 130.03, 117.85, 113.90, 111.31, 69.21,
62.50, 55.31; IR (film) νmax: 3449.9, 1602.0, 1490.5,
1288.3, 1262.8, 1120.0, 1044.4, 698.1 cm−1; HRMS m/z:
[M＋NH4]＋ calcd for C18H26NO4S: 384.1475; found
384.1458.
2,2'-Sulfonylbis(1-(3-fluorophenyl)ethanol)
(2i)
White solid, m.p. 115－116 ℃, 98% yield, 97∶3 dr,
96% ee. The enantiomeric excess was determined by
HPLC on Daicel Chiralpak IA with hexane/i-PrOH
(90∶10) as the eluent. Flow: 1.0 mL/min; λ＝210 nm:
t
major＝15.272 min; tminor＝19.417 min; tmeso＝17.901
25
min; [α]D ＋131.2 (c 0.50 in CH3COCH3); 1H NMR
(400 MHz, CDCl3) δ: 7.36－7.31 (m, 2H), 7.13－7.09
(m, 4H), 7.03－6.99 (m, 2H), 5.36 (d, J＝10.0 Hz, 2H),
3.71 (dd, J＝14.4, 4.0 Hz, 2H), 3.33 (d, J＝3.6 Hz, 2H),
3.23 (d, J＝14.8 Hz, 2H); 13C NMR (101 MHz, CDCl3)
2,2'-Sulfonylbis(1-(2-chlorophenyl)ethanol) (2m)
White solid, m.p. 167－168 ℃, 96% yield, 93∶7 dr,
＞99% ee. The enantiomeric excess was determined by
HPLC on Daicel Chiralpak IA with hexane/i-PrOH
(90∶10) as the eluent. Flow: 1.0 mL/min; λ＝210 nm:
1
3
δ: 163.18 (d, JC,F＝248 Hz), 143.63 (d, JC,F＝6 Hz),
130.75 (d, 3JC,F＝8 Hz), 121.38 (d, 4JC,F＝3 Hz), 115.65
(d, 2JC,F＝21 Hz), 112.91 (d, 2JC,F＝26 Hz), 68.85, 62.61;
IR (KBr) νmax: 3607.5, 3470.6, 1611.8, 1590.7, 1483.8,
1450.2, 1290.7, 1113.5, 1079.2, 1052.2, 881.1, 796.4,
695.0 cm−1; HRMS m/z: [M ＋ NH4] ＋ calcd for
C16H20F2NO4S: 360.1076; found 360.1080.
2,2'-Sulfonylbis(1-(3-chlorophenyl)ethanol) (2j)
White solid, m.p. 87－88 ℃, 98% yield, 95∶5 dr,
＞99% ee. The enantiomeric excess was determined by
HPLC on Daicel Chiralpak AD-H with hexane/i-PrOH
(90∶10) as the eluent. Flow: 1.0 mL/min; λ＝210 nm:
t
major＝14.343 min; tminor＝107.091 min; tmeso＝18.060
25
1
min. [α]D ＋158.4 (c 0.50 in CH3COCH3); H NMR
(400 MHz, CDCl3) δ: 7.66 (dd, J＝8.0, 2.0 Hz, 2H),
7.39－7.35 (m, 4H), 7.32－7.28 (m, 2H), 5.80－5.77
(m, 2H), 3.60 (dd, J＝14.4, 4.4 Hz, 2H), 3.51 (dd, J＝
14.4, 4.4 Hz, 2H), 3.44 (d, J＝3.6 Hz, 2H); 13C NMR
(101 MHz, CDCl3) δ: 138.05, 131.25, 129.71, 129.55,
127.52, 127.18, 66.08, 60.45; IR (KBr) νmax: 3441.1,
1475.2, 1314.7, 1280.9, 1134.6, 1114.8, 1076.9, 1049.6,
1033.9, 753.1 cm−1; HRMS m/z: [M＋NH4]＋ calcd for
C16H20Cl2NO4S: 392.0485; found 392.0495.
t
major＝10.385 min; tminor＝11.570 min; tmeso＝12.377
Chin. J. Chem. 2014, 32, 803—813
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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805

Huang et al.
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25
1
2,2'-Sulfonylbis(1-o-tolylethanol) (2n) White
solid, m.p. 128－1 29 ℃, 98% yield, 92∶8 dr, 98% ee.
The enantiomeric excess was determined by HPLC on
Daicel Chiralpak AD-H with hexane/i-PrOH (80∶20)
(minor). [α]D ＋135.6 (c 0.50 in CH3COCH3); H
NMR (400 MHz, CDCl3) δ: 7.38－7.29 (m, 9H), 5.34 (d,
J＝10.4 Hz, 2H), 3.78－3.75 (m, 1H), 3.71－3.67 (m,
1H), 3.36 (d, J＝4.8 Hz, 1H), 3.22 (d, J＝14.4 Hz, 2H),
3.13 (d, J＝2.8 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ:
140.89, 139.53, 134.35, 129.12, 129.04, 128.73, 127.10,
as the eluent. Flow: 1.0 mL/min; λ＝210 nm: tmajor
＝
25
9.015 min; tminor＝12.012 min; tmeso＝9.770 min. [α]D
＋247.4 (c 0.50 in CH3COCH3); 1H NMR (400 MHz,
CDCl3) δ: 7.51 (d, J＝6.4 Hz, 2H), 7.26－7.20 (m, 6H),
5.63 (d, J＝10.0 Hz, 2H), 3.74 (dd, J＝14.4, 3.6 Hz,
2H), 3.22 (d, J＝14.4 Hz, 2H), 3.09 (s, 2H), 2.39 (s, 6H);
13C NMR (101 MHz, CDCl3) δ: 139.10, 134.21, 130.88,
128.33, 126.70, 125.26, 66.08, 61.44, 18.90; IR (KBr)
νmax: 3542.7, 3456.6, 1491.2, 1421.5, 1300.1, 1278.3,
125.69, 69.45, 68.60, 62.59, 62.49; IR (KBr) νmax
:
3442.0, 1502.9, 1490.1, 1455.6, 1119.3, 1063.4, 1044.4,
997.9, 862.9, 812.7, 702.7 cm−1; HRMS m/z: [M＋Na]＋
calcd for C16H17ClNaO4S: 363.0434; found 363.0440.
1-(4-Bromophenyl)-2-(2-hydroxy-2-phenylethyl-
sulfonyl)ethanol (4c) White solid, m.p. 127－128 ℃,
97% yield, 98∶2 dr, ＞99% ee. The enantiomeric ex-
cess was determined by HPLC on Chiralcel OD-H with
hexane/i-PrOH (80 ∶ 20) as the eluent. Flow: 1.0
mL/min; λ＝210 nm: tmajor＝21.103 min; tminor＝11.200
min (major). tmajor＝15.714 min; tminor＝23.279 min
1123.8, 1053.7, 766.5, 749.6 cm−1; HRMS m/z: [M＋
＋
Na]
357.1117.
2,2'-Sulfonylbis(1-(thiophen-2-yl)ethanol) (2o)
calcd for C18H22NaO4S: 357.1131; found
25
1
White solid, m.p. 105－1 06 ℃, 96% yield, 98∶2 dr,
＞99% ee. The enantiomeric excess was determined by
HPLC on Daicel Chiralpak AD-H with hexane/i-PrOH
(90∶10) as the eluent. Flow: 1.0 mL/min; λ＝210 nm:
(minor). [α]D ＋118.6 (c 0.50 in CH3COCH3); H
NMR (400 MHz, CDCl3) δ: 7.50 (d, J＝8.0 Hz, 2H),
7.40－7.31 (m, 5H), 7.25 (d, J＝8.8 Hz, 2H), 5.35－
5.34 (m, 2H), 3.71－3.67 (m, 1H), 3.34 (s, 1H), 3.23
(dd, J＝14.8, 4.8 Hz, 2H), 3.08 (s, 2H); 13C NMR (101
MHz, CDCl3) δ: 140.87, 140.04, 132.08, 129.05, 128.74,
127.41, 125.69, 122.47, 69.47, 68.65, 62.59, 62.45; IR
(KBr) νmax: 3483.9, 3401.5, 1498.2, 1400.1, 1307.6,
1299.1, 1120.2, 1064.6, 1010.8, 817.5, 753.7, 706.8
cm−1; HRMS m/z: [M＋Na]＋ calcd for C16H17BrNaO4S:
406.9929; found 406.9923.
t
major＝10.708 min; tminor＝17.412 min; tmeso＝14.738
25
1
min. [α]D ＋83.8 (c 0.50 in CH3COCH3); H NMR
(400 MHz, CDCl3) δ: 7.43 (d, J＝0.8 Hz, 1H), 7.42 (d,
J＝1.2 Hz, 1H), 7.04 (d, J＝3.2 Hz, 2H), 6.96 (dd, J＝
4.8, 1.2 Hz, 2H), 6.37 (d, J＝4.8 Hz, 2H), 5.35－5.31
(m, 2H), 3.84 (dd, J＝14.4, 4.0 Hz, 2H), 3.38 (d, J＝
14.0 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 144.48,
127.10, 125.84, 124.57, 65.62, 62.50; IR (KBr) νmax
:
2-(-2-Hydroxy-2-(4-nitrophenyl)ethylsulfonyl)-1-
phenylethanol (4d) Colorless oil, 98% yield, 96∶4
dr, ＞99% ee. The enantiomeric excess was determined
by HPLC on Daicel Chiralpak OJ-H with hexane/
i-PrOH (85∶15) as the eluent. Flow: 1.0 mL/min; λ＝
3376.5, 1434.3, 1382.5, 1288.6, 1264.6, 1210.9, 1059.9,
974.0, 856.6, 717.6, 704.8 cm−1; HRMS m/z: [M＋Na]＋
calcd for C12H14NaO4S3: 340.9946; found 340.9960.
1-(4-Fluorophenyl)-2-(2-hydroxy-2-phenylethyl-
sulfonyl)ethanol (4a) White solid, m.p. 102－103 ℃,
97% yield, 99∶1 dr, ＞99% ee. The enantiomeric ex-
cess was determined by HPLC on Chiralcel OD-H with
hexane/i-PrOH (90∶10) as the eluent. Flow: 1.0
mL/min; λ＝210 nm: tmajor＝25.821 min; tminor＝22.933
min (major). tmajor＝30.166 min; tminor＝31.776 min
210 nm: tmajor＝74.666 min; tminor＝72.232 min (major).
25
t
major＝84.742 min; tminor＝97.170 min (minor). [α]D
＋128.4 (c 0.50 in CH3COCH3); 1H NMR (400 MHz,
CDCl3) δ: 8.20 (d, J＝8.4 Hz, 2H), 7.55 (d, J＝8.8 Hz,
2H), 7.39－7.32 (m, 5H), 5.49 (d, J＝10.0 Hz, 1H),
5.35 (d, J＝10.4 Hz, 1H), 3.78 (s, 1H), 3.76－3.73 (m,
1H), 3.71－3.67 (m, 1H), 3.32 (d, J＝14.8, 2H), 3.24－
3.17 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 13C NMR
(101 MHz, CDCl3) δ: 148.19, 147.76, 140.74, 129.10,
128.87, 126.64, 125.68, 124.10, 69.56, 68.23, 62.67,
62.31; IR (film) νmax: 3454.8, 1602.1, 1520.6, 1348.9,
1291.2, 1122.0, 1059.1, 991.7, 856.8, 749.9, 699.4 cm−1;
HRMS m/z: [M ＋ Na] ＋ calcd for C16H17NNaO6S:
374.0674; found 374.0669.
25
1
(minor). [α]D ＋127.6 (c 0.50 in CH3COCH3); H
NMR (400 MHz, CDCl3) δ: 7.34－7.28 (m, 7H), 7.02 (t,
J＝8.4 Hz, 2H), 5.29 (d, J＝10.4 Hz, 2H), 3.76－3.67
(m, 2H), 3.58 (d, J＝3.6 Hz, 1H), 3.47 (d, J＝3.6 Hz,
1H), 3.16 (d, J＝14.8 Hz, 2H); 13C NMR (101 MHz,
CDCl3) δ: 162.67 (d, 1JC,F＝248 Hz), 141.09, 137.02 (d,
2
3JC,F＝3 Hz), 129.05, 128.70, 127.56 (d, JC,F＝9 Hz),
125.78, 116.80 (d, 4JC,F＝2 Hz), 65.62, 62.50.; IR (KBr)
νmax: 3488.0, 1602.6, 1508.7, 1492.5, 1453.7, 1292.5,
1052.9, 985.9, 840.2, 752.3, 701.5 cm−1; HRMS m/z:
[M＋Na]＋ calcd for C16H17FNaO4S: 347.0729; found
347.0732.
1-(Biphenyl-4-yl)-2-(-2-hydroxy-2-phenyleth-
ylsulfonyl)ethanol (4e) White solid, m.p. 182－183
℃, 92% yield, 98∶2 dr, ＞99% ee. The enantiomeric
excess was determined by HPLC on Daicel Chiralpak
IA with hexane/i-PrOH (90∶10) as the eluent. Flow:
1-(4-Chlorophenyl)-2-(2-hydroxy-2-phenylethyl-
sulfonyl)ethanol (4b) White solid, m.p. 130－131 ℃,
98% yield, 98∶2 dr, ＞99% ee. The enantiomeric ex-
cess was determined by HPLC on Chiralcel OD-H with
hexane/i-PrOH (90 ∶ 10) as the eluent. Flow: 1.0
mL/min; λ＝210 nm: tmajor＝37.754 min; tminor＝45.326
min (major). tmajor＝35.202 min; tminor＝24.463 min
1.0 mL/min; λ＝210 nm: tmajor＝33.453 min; tminor
＝
45.629 min (major). tmajor＝38.876 min; tminor＝35.628
25
min (minor). [α]D ＋143.2 (c 0.50 in CH3COCH3); 1H
NMR (400 MHz, DMSO-d6) δ: 7.67 (d, J＝8.0 Hz, 4H),
7.52－7.36 (m, 9H), 7.29 (t, J＝7.2 Hz, 1H), 5.97 (dd,
J＝14.8, 4.4 Hz, 2H), 5.19－5.13 (m, 2H), 3.90－3.81
806
www.cjc.wiley-vch.de
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2014, 32, 803—813

Enantioselective Synthesis of Optically Active Bis(β-hydroxy) Sulfones
(m, 2H), 3.32－3.28 (m, 2H); 13C NMR (101 MHz,
DMSO-d6) δ: 144.01, 143.16, 140.34, 139.88, 129.42,
128.82, 127.97, 127.91, 127.13, 127.11, 127.05, 126.39,
68.40, 68.15, 62.47, 62.31; IR (KBr) νmax: 3458.4,
3393.3, 1497.8, 1404.2, 1311.2, 1273.6, 1254.7, 1066.7,
780.6, 769.7, 707.7 cm−1; HRMS m/z: [M＋Na]＋ calcd
for C22H22NaO4S: 405.1136; found 405.1118.
3480.2, 1591.2, 1492.4, 1452.1, 1290.6, 1114.3, 1049.2,
793.4, 699.6 cm−1; HRMS m/z: [M＋Na]＋ calcd for
C16H17FNaO4S: 347.0729; found 347.0719.
1-(3-Chlorophenyl)-2-(2-hydroxy-2-phenylethyl-
sulfonyl)ethanol (4i) White solid, m.p. 82－83 ℃,
98% yield, 99∶1 dr, ＞99% ee. The enantiomeric ex-
cess was determined by HPLC on Daicel Chiralpak
OJ-H with hexane/i-PrOH (90∶10) as the eluent. Flow:
2-(-2-Hydroxy-2-p-tolylethylsulfonyl)-1-phenyle-
thanol (4f) White solid, m.p. 72－73 ℃, 99% yield,
98∶2 dr, ＞99% ee. The enantiomeric excess was de-
termined by HPLC on Chiralcel OD-H with hexane/
i-PrOH (90∶10) as the eluent. Flow: 1.0 mL/min;
λ＝210 nm: tmajor＝30.359 min; tminor＝47.124 min (ma-
jor). tmajor＝26.166 min; tminor＝36.456 min (minor).
1.0 mL/min; λ＝210 nm: tmajor＝58.064 min; tminor
＝
47.330 min (major). tmajor＝51.975 min; tminor＝72.727
25
min (minor). [α]D ＋145.6 (c 0.50 in CH3COCH3); 1H
NMR (400 MHz, DMSO-d6) δ: 7.48 (s, 1H), 7.42－7.35
(m, 7H), 7.29 (t, J＝7.2 Hz, 1H), 6.09 (d, J＝4.4 Hz,
1H), 5.95 (d, J＝4.4 Hz, 1H), 5.14－5.11 (m, 2H), 3.81
(dd, J＝14.4, 4.4 Hz, 2H), 3.34－3.27 (m, 2H); 13C
NMR (101 MHz, DMSO-d6) δ: 146.52, 143.94, 133.50,
130.72, 128.80, 127.96, 127.86, 126.37, 126.31, 125.14,
68.36, 67.75, 62.49, 62.00; IR (KBr) νmax: 3471.9,
25
[α]D ＋142.4 (c 0.50 in CH3COCH3); 1H NMR (400
MHz, CDCl3) δ: 7.41－7.31 (m, 5H), 7.25 (d, J＝4.2 Hz,
2H), 7.18 (d, J＝8.0 Hz, 2H), 5.39－5.33 (m, 2H), 3.79
－3.24 (m, 2H), 3.28－3.24 (m, 2H), 3.16 (d, J＝3.2 Hz,
1H), 3.03 (d, J＝3.2 Hz, 1H), 2.35 (s, 3H); 13C NMR
(101 MHz, CDCl3) δ: 141.15, 138.41, 138.16, 129.59,
128.92, 128.51, 125.72, 125.68, 69.23, 69.16, 62.46,
62.45, 21.15; IR (KBr) νmax: 3455.9, 3409.7, 1522.8,
1465.3, 1311.1, 1288.7, 1121.3, 1065.2, 821.7, 750.7,
706.9 cm−1; HRMS m/z: [M ＋ NH4] ＋ calcd for
C17H24NO4S: 338.1421; found 338.1431.
2-(-2-Hydroxy-2-(4-methoxyphenyl)ethylsulfon-
yl)-1-phenylethanol (4g) White solid, m.p. 103－104
℃, 98% yield, 98∶2 dr, ＞99% ee. The enantiomeric
excess was determined by HPLC on Daicel Chiralpak
OJ-H with hexane/i-PrOH (75∶25) as the eluent. Flow:
1558.2, 1455.4, 1289.4, 1118.7, 995.9, 850.7, 762.7,
＋
697.6 cm−1; HRMS m/z: [M ＋ Na]
calcd for
C16H17ClNaO4S: 363.0434; found 363.0430.
1-(2-Hydroxy-2-phenylethylsulfonyl)propan-2-ol
(4j) White solid, m.p. 68－69 ℃, 97% yield, 2∶1 dr,
＞99% (major), 93 (minor) ee. The enantiomeric excess
was determined by HPLC on Daicel Chiralpak AS-H
and AD-H with hexane/i-PrOH (80∶20) as the eluent.
Flow: 1.0 mL/min; λ＝210 nm: major isomer, tmajor
＝
26.931 min; tminor＝17.350 min (AS-H ); minor isomer,
25
t
major＝9.807 min; tminor＝7.847 min (AD-H). [α]D
1
＋68.8 (c 0.50 in CH3COCH3); H NMR (400 MHz,
CDCl3) δ: 7.37－7.32 (m, 5H), 7.34－7.30 (m, 1H),
4.49－4.45 (m, 1H), 3.68 (dd, J＝14.8, 4.4 Hz, 1H
(major)), 3.51 (dd, J＝14.8, 4.4 Hz, 1H (minor)), 3.45－
3.07 (m, 5H), 1.30 (d, J＝6.4 Hz, 3H); 13C NMR (101
MHz, CDCl3) δ: 141.06, 128.98, 128.97, 125.70, 69.26,
63.05, 62.36, 62.21, 23.30; IR (KBr) νmax: 3423.2,
1523.4, 1452.8, 1391.8, 1326.9, 1294.7, 1130.9, 1116.4,
1058.5, 1002.7, 836.4, 771.3, 745.5, 701.1 cm−1; HRMS
m/z: [M＋Na]＋ calcd for C11H16NaO4S: 267.0667;
found 267.0659.
1.0 mL/min; λ＝210 nm: tmajor＝24.227 min; tminor
＝
23.318 min (major). tmajor＝27.618 min; tminor＝42.585
25
min (minor). [α]D ＋132.8 (c 0.50 in CH3COCH3); 1H
NMR (400 MHz, DMSO-d6) δ: 7.39－7.31 (m, 7H),
6.92 (s, 2H), 5.91 (s, 1H), 5.81 (s, 1H), 5.08 (s, 2H),
3.82－3.74 (m, 2H), 3.74 (s, 3H), 3.27－3.20 (m, 2H);
13C NMR (101 MHz, DMSO-d6) δ: 159.11, 144.00,
135.99, 128.79, 127.94, 127.61, 126.36, 114.14, 68.36,
67.96, 62.49, 62.37, 55.56; IR (KBr) νmax: 3502.3,
1620.4, 1514.4, 1453.9, 1277.1, 1176.4, 1116.7, 1063.1,
996.2, 833.9, 704.4, 546.0 cm−1; HRMS m/z: [M＋Na]＋
calcd for C17H20NaO5S: 359.0929; found 359.0920.
1-(3-Fluorophenyl)-2-(2-hydroxy-2-phenylethyl-
sulfonyl)ethanol (4h) White solid, m.p. 106－107 ℃,
96% yield, 98∶2 dr, ＞99% ee. The enantiomeric ex-
cess was determined by HPLC on Daicel Chiralpak
AD-H with hexane/i-PrOH (90∶10) as the eluent. Flow:
Ethyl 2-(2-hydroxy-2-phenylethylsulfonyl)acetate
(6a) White solid, m.p. 76－77 ℃, 99% yield, 97% ee.
The enantiomeric excess was determined by HPLC on
Daicel Chiralpak AD-H with hexane/i-PrOH (80∶20)
as the eluent. Flow: 1.0 mL/min; λ＝210 nm: tmajor
＝
25
10.375 min; tminor＝8.819 min. [α]D ＋44.0 (c 0.50 in
CH3COCH3); 1H NMR (400 MHz, CDCl3) δ: 7.41 (d,
J＝4.4 Hz, 4H), 7.39－7.35 (m, 1H), 5.39－5.35 (m,
1H), 4.41 (d, J＝14.8 Hz, 1H), 4.30 (q, J＝7.2 Hz, 2H),
4.04－3.99 (m, 1H), 3.95 (dd, J＝15.2, 4.4 Hz, 1H),
3.31 (d, J＝15.2 Hz, 1H), 3.02 (d, J＝2.8 Hz, 1H), 1.35
(t, J＝6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ:
163.40, 140.77, 129.02, 128.73, 125.73, 69.35, 62.70,
60.67, 58.98, 13.99; IR (KBr) νmax: 3517.4, 3036.2,
2973.8, 1741.1, 1511.2, 1452.4, 1390.8, 1304.4, 1285.3,
1235.2, 1125.0, 1048.3, 1027.7, 1003.9, 752.7, 701.3
cm−1; HRMS m/z: [M＋Na]＋ calcd for C12H16NaO5S:
295.0616; found 295.0614.
1.0 mL/min; λ＝210 nm: tmajor＝19.621 min; tminor
＝
25.248 min (major). tmajor＝22.858 min; tminor＝21.776
25
min (minor). [α]D ＋130.2 (c 0.50 in CH3COCH3); 1H
NMR (400 MHz, CDCl3) δ: 7.39－7.30 (m, 6H), 7.13－
7.09 (m, 2H), 7.00 (t, J＝8.4 Hz, 1H), 5.37－5.34 (m,
2H), 3.78－3.74 (m, 1H), 3.72－3.67 (m, 1H), 3.45－
3.38 (m, 1H), 3.26－3.19 (m, 3H); 13C NMR (101 MHz,
1
CDCl3) δ: 163.06 (d, JC,F＝248 Hz), 143.60, 140.89,
130.55 (d, 3JC,F＝8 Hz), 129.02, 128.71, 125.69, 121.25
4
2
(d, JC,F＝3 Hz), 115.4 (d, JC,F＝21 Hz), 112.74 (d,
2JC,F＝22 Hz), 69.44, 68.62, 62.57, 62.46; IR (KBr) νmax
:
Chin. J. Chem. 2014, 32, 803—813
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
807

Huang et al.
FULL PAPER
Ethyl 2-(2-(4-fluorophenyl)-2-hydroxyethyl-
sulfonyl)acetate (6b) White solid, m.p. 86－87 ℃,
96% yield, 92% ee. The enantiomeric excess was de-
termined by HPLC on Daicel Chiralpak AD-H with
hexane/i-PrOH (80 ∶ 20) as the eluent. Flow: 1.0
mL/min; λ＝210 nm: tmajor＝14.310 min; tminor＝8.828
by HPLC on Daicel Chiralpak AD-H with hex-
ane/i-PrOH (80∶20) as the eluent. Flow: 1.0 mL/min;
λ＝210 nm: tmajor＝13.785 min; tminor＝11.634 min.
25
1
[α]D ＋34.4 (c 0.50 in CH3COCH3); H NMR (400
MHz, CDCl3) δ: 7.73 (d, J＝8.0 Hz 2H), 7.16 (d, J＝8.4
Hz, 2H), 5.31 (d, J＝10.4 Hz, 1H), 4.38 (d, J＝15.2 Hz,
1H), 4.28 (q, J＝7.2 Hz, 2H), 4.02 (d, J＝14.8 Hz, 1H),
3.86 (dd, J＝14.8, 4.4 Hz, 1H), 3.29－3.26 (m, 2H),
1.34 (t, J＝7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ:
163.36, 140.50, 138.06, 127.64, 94.23, 68.71, 62.80,
60.49, 58.99, 14.00; IR (KBr) νmax: 3505.2, 3024.7,
2985.1, 1717.2, 1489.2, 1405.6, 1368.3, 1310.9, 1291.1,
1228.9, 1124.4, 1059.3, 1002.6, 842.2, 811.4, 717.4
cm−1; HRMS m/z: [M＋NH4]＋ calcd for C12H15INaO5S:
420.9583; found 420.9523.
25
1
min. [α]D ＋37.2 (c 0.50 in CH3COCH3); H NMR
(400 MHz, CDCl3) δ: 7.37 (t, J＝7.6 Hz, 2H), 7.07 (d,
J＝7.6 Hz, 2H), 5.34 (d, J＝9.6 Hz, 1H), 4.38 (d, J＝
14.8 Hz, 1H), 4.27 (q, J＝6.8 Hz, 2H), 4.01 (d, J＝14.8
Hz, 1H), 3.91－3.85 (m, 1H), 3.27 (d, J＝14.8 Hz, 1H),
3.12 (s, 1H), 1.32 (t, J＝6.4 Hz, 3H); 13C NMR (101
1
MHz, CDCl3) δ: 163.37, 162.71 (d, JC,F＝248 Hz),
3
2
136.61, 127.53 (d, JC,F＝9 Hz), 115.91 (d, JC,F＝21
Hz), 68.63, 62.76, 60.67, 58.95, 13.97; IR (KBr) νmax
:
3518.3, 3029.7, 2988.0, 1745.3, 1610.8, 1515.0, 1393.0,
Ethyl 2-(2-hydroxy-2-(4-nitrophenyl)ethylsul-
fonyl) acetate (6f) White solid, m.p. 121－122 ℃,
96% yield, 88% ee. The enantiomeric excess was de-
termined by HPLC on Daicel Chiralpak AD-H with hex-
ane/i-PrOH (80∶20) as the eluent. Flow: 1.0 mL/min;
λ＝210 nm: tmajor＝27.663 min; tminor＝16.912 min.
[α]D ＋37.6 (c 0.50 in CH3COCH3); H NMR (400
MHz, CDCl3) δ: 8.23 (d, J＝8.8 Hz 2H), 7.61 (d, J＝8.4
Hz, 2H), 5.50 (d, J＝10.0 Hz, 1H), 4.34 (d, J＝14.8 Hz,
1H), 4.28 (q, J＝7.2 Hz, 2H), 4.07 (d, J＝15.2 Hz, 1H),
3.84 (dd, J＝14.8, 4.4 Hz, 1H), 3.49 (s, 1H), 3.39 (d,
J＝14.8 Hz, 1H) 1.33 (t, J＝7.2 Hz, 3H); 13C NMR (101
MHz, CDCl3) δ: 163.30, 147.89, 147.69, 126.66, 124.16,
68.24, 62.98, 60.48, 59.06, 13.97; IR (KBr) νmax: 3491.6,
3036.1, 2962.4, 1715.8, 1592.7, 1518.8, 1357.0, 1288.1,
1223.9, 1125.4, 1059.4, 857.9, 830.1, 749.8 cm−1;
HRMS m/z: [M ＋ Na] ＋ calcd for C12H15NNaO7S:
340.0461; found 340.0463.
1312.0, 1283.1, 1229.6, 1173.1, 1125.8, 1050.4, 837.1,
＋
488.5 cm−1; HRMS m/z: [M ＋ Na]
calcd for
C12H15FNaO5S: 313.0522; found 313.0527.
Ethyl 2-(2-(4-chlorophenyl)-2-hydroxyethyl-sul-
fonyl) acetate (6c) White solid, m.p. 95－96 ℃, 98%
yield, 93% ee. The enantiomeric excess was determined
by HPLC on Daicel Chiralpak AD-H with hexane/
i-PrOH (80∶20) as the eluent. Flow: 1.0 mL/min; λ＝
25
1
25
210 nm: tmajor＝13.257 min; tminor＝9.373 min. [α]D
1
＋43.6 (c 0.50 in CH3COCH3); H NMR (400 MHz,
CDCl3) δ: 7.37－7.31 (m, 4H), 5.36－5.30 (m, 1H),
4.36 (d, J＝14.8 Hz, 1H), 4.26 (q, J＝7.2 Hz, 2H), 4.01
(d, J＝14.8 Hz, 1H), 3.85 (dd, J＝15.2, 4.4 Hz, 1H),
3.26 (d, J＝14.8 Hz, 1H), 3.19 (d, J＝3.2 Hz, 1H), 1.32
(t, J＝7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ:
163.35, 139.28, 134.44, 129.14, 127.13, 68.58, 62.79,
60.56, 58.97, 13.97; IR (KBr) νmax: 3506.6, 3024.7,
2963.8, 1717.6, 1534.3, 1407.9, 1368.1, 1310.1, 1291.2,
1124.8, 1058.6, 843.2, 819.8, 777.5 cm−1; HRMS m/z:
[M＋Na]＋ calcd for C12H15ClNaO5S: 329.0226; found
329.0232.
Ethyl 2-(2-hydroxy-2-(4-(trifluoromethyl)phe-
nyl)ethylsulfonyl) acetate (6g) White solid, m.p. 144
－145 ℃, 97% yield, 97% ee. The enantiomeric excess
was determined by HPLC on Daicel Chiralpak AD-H
with hexane/i-PrOH (80∶20) as the eluent. Flow: 1.0
mL/min; λ＝210 nm: tmajor＝9.363 min; tminor＝8.158
Ethyl 2-(2-(4-bromophenyl)-2-hydroxyethylsul-
fonyl) acetate (6d) White solid, m.p. 102－103 ℃,
99% yield, 95% ee. The enantiomeric excess was de-
termined by HPLC on Daicel Chiralpak AD-H with hex-
ane/i-PrOH (80∶20) as the eluent. Flow: 1.0 mL/min;
λ＝210 nm: tmajor＝14.482 min; tminor＝10.469 min.
25
1
min. [α]D ＋34.8 (c 0.50 in CH3COCH3); H NMR
(400 MHz, CDCl3) δ: 7.68 (d, J＝8.4 Hz, 2H), 7.57 (d,
J＝8.0 Hz, 2H), 5.48 (d, J＝10.4 Hz, 1H), 4.38 (d, J＝
14.8 Hz, 1H), 4.32 (q, J＝7.2 Hz, 2H), 4.08 (d, J＝14.8
Hz, 1H), 3.90 (dd, J＝14.8, 4.0 Hz, 1H), 3.39 (d, J＝
14.8 Hz, 1H), 3.23 (d, J＝3.2 Hz, 1H), 1.33 (t, J＝7.2
Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 163.33,
144.56, 130.71, 127.9 (q, 1JC,F ＝ 273 Hz), 126.09,
25
1
[α]D ＋42.6 (c 0.50 in CH3COCH3); H NMR (400
MHz, CDCl3) δ: 7.51 (d, J＝8.4 Hz 2H), 7.28 (d, J＝8.8
Hz, 2H), 5.41－5.31 (m, 1H), 4.36 (d, J＝15.2 Hz, 1H),
4.27 (q, J＝7.2 Hz, 2H), 4.01 (d, J＝14.8 Hz, 1H), 3.86
(dd, J＝15.2, 4.4 Hz, 1H), 3.28 (d, J＝14.8 Hz, 1H),
3.19 (d, J＝3.6 Hz, 1H), 1.33 (t, J＝7.2 Hz, 3H); 13C
NMR (101 MHz, CDCl3) δ: 163.34, 139.78, 132.11,
127.43, 122.58, 68.64, 62.80, 60.52, 58.98, 13.98.; IR
(KBr) νmax: 3505.5, 3024.9, 2964.0, 1718.6, 1483.7,
1463.4, 1310.5, 1291.9, 1098.6, 1003.8, 852.6, 606.9,
503.8 cm−1; HRMS m/z: [M＋Na]＋ calcd for C12H15Br-
NaO5S: 372.9721; found 372.9734.
4
125.97 (q, JC,F＝3.8 Hz), 68.62, 62.89, 60.62, 59.04,
13.96; IR (KBr) νmax: 3504.0, 2963.5, 1718.4, 1612.1,
1509.1, 1337.9, 1289.7, 1127.3, 1059.9, 633.2 cm−1;
HRMS m/z: [M ＋ Na] ＋ calcd for C13H15F3NaO5S:
363.0484; found 363.0476.
Ethyl 2-(2-(biphenyl-4-yl)-2-hydroxyethylsul-
fonyl) acetate (6h) White solid, m.p. 143－144 ℃,
92% yield, 96% ee. The enantiomeric excess was de-
termined by HPLC on Daicel Chiralpak AD-H with hex-
ane/i-PrOH (90∶10) as the eluent. Flow: 1.0 mL/min;
λ＝210 nm: tmajor＝32.084 min; tminor＝36.021 min.
Ethyl 2-(2-hydroxy-2-(4-iodophenyl)ethylsulfonyl)
acetate (6e) White solid, m.p. 116－117 ℃, 93%
yield, 95% ee. The enantiomeric excess was determined
808
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© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2014, 32, 803—813

Enantioselective Synthesis of Optically Active Bis(β-hydroxy) Sulfones
25
1
[α]D ＋45.2 (c 0.50 in CH3COCH3); H NMR (400
MHz, CDCl3) δ: 7.67 (d, J＝8.0 Hz, 4H), 7.52－7.46 (m,
4H), 7.37 (t, J＝7.2 Hz, 1H), 6.14 (d, J＝4.4 Hz, 1H),
5.19－5.15 (m, 1H) 4.57 (d, J＝14.8 Hz, 1H), 4.41 (d,
J＝14.8 Hz, 1H), 4.20 (q, J＝7.2 Hz, 2H), 3.82 (dd, J＝
14.8, 4.4 Hz, 1H), 3.46 (d, J＝14.4 Hz, 1H), 1.24 (t, J＝
7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 163.77,
142.64, 140.27, 140.01, 129.41, 127.92, 127.14, 127.10,
J＝14.8 Hz, 1H), 3.92－3.85 (m, 1H), 3.30 (t, J＝2.4
Hz, 2H), 1.34 (t, J＝7.2 Hz, 3H); 13C NMR (101 MHz,
1
CDCl3) δ: 163.35, 163.06 (d, JC,F＝248 Hz), 143.37,
130.62 (d, 3JC,F＝8 Hz), 121.28 (d, 4JC,F＝3 Hz), 115.55
2
2
(d, JC,F＝21 Hz), 112.81 (d, JC,F＝22 Hz); IR (KBr)
νmax: 3505.2, 3024.0, 2963.4, 1716.6, 1591.2, 1447.1,
1308.5, 1285.1, 1163.2, 1052.5, 817.7, 708.4 cm−1;
HRMS m/z: [M ＋ NH4] ＋ calcd for C12H19FNO5S:
308.0962; found 308.0974.
127.03, 67.91, 62.04, 60.93, 59.42, 14.37; IR (KBr) νmax
3514.4, 3023.3, 2962.9, 1719.4, 1596.6, 1487.6, 1443.7,
1367.9, 1313.4, 1172.6, 1097.9, 784.6, 530.5 cm−1;
HRMS m/z: [M ＋ Na] ＋ calcd for C18H20NaO5S:
371.0924; found 371.0934.
Ethyl 2-(2-hydroxy-2-p-tolylethylsulfonyl)acetate
(6i) Colorless oil, 95% yield, 92% ee. The enanti-
omeric excess was determined by HPLC on Daicel
Chiralpak AD-H with hexane/i-PrOH (80∶20) as the
eluent. Flow: 1.0 mL/min; λ＝210 nm: tmajor＝11.060
:
Ethyl 2-(2-(3-chlorophenyl)-2-hydroxyethylsul-
fonyl) acetate (6l) White solid, m.p. 78－79 ℃, 97%
yield, 95% ee. The enantiomeric excess was determined
by HPLC on Daicel Chiralpak OJ-H with hexane/
i-PrOH (80∶20) as the eluent. Flow: 1.0 mL/min;
λ＝210 nm: tmajor＝20.293 min; tminor＝16.163 min.
25
1
[α]D ＋31.2 (c 0.50 in CH3COCH3); H NMR (400
MHz, CDCl3) δ: 7.44 (s, 1H), 7.34－7.27 (m, 3H), 5.35
(d, J＝10.8 Hz, 1H) 4.39 (d, J＝14.8 Hz, 1H), 4.30 (q,
J＝7.2 Hz, 2H), 4.04 (d, J＝14.8 Hz, 1H), 3.88 (dd, J＝
14.8, 4.0 Hz, 1H), 3.33－3.27 (m, 2H), 1.35 (t, J＝7.2
Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 163.35,
142.82, 134.93, 130.29, 128.79, 125.96, 123.87, 68.62,
62.82, 60.58, 59.01, 13.98; IR (KBr) νmax: 3507.9,
3021.6, 2960.5, 1717.2, 1594.8, 1573.9, 1462.8, 1404.4,
1308.8, 1226.7, 1077.6, 918.4, 895.1, 780.8, 710.2 cm−1;
HRMS m/z: [M ＋ Na] ＋ calcd for C12H15ClNaO5S:
329.0221; found 329.0208.
25
min; tminor＝9.415 min. [α]D ＋22.8 (c 0.50 in
CH3COCH3); 1H NMR (400 MHz, CDCl3) δ: 7.30 (d,
J＝8.0 Hz, 2H), 7.22 (d, J＝7.6 Hz, 2H), 5.34 (d, J＝
10.4 Hz, 1H) 4.41 (d, J＝14.8 Hz, 1H), 4.31 (q, J＝7.2
Hz, 2H), 4.03－3.93 (m, 2H), 3.30 (d, J＝15.2 Hz, 1H),
2.86 (d, J＝4.2 Hz, 1H), 2.38 (s, 3H), 1.35 (t, J＝7.2 Hz,
3H); 13C NMR (101 MHz, CDCl3) δ: 163.40, 138.64,
137.80, 129.66, 125.67, 69.25, 62.66, 60.65, 58.96,
21.16, 13.99; IR (film) νmax: 3517.1, 3022.7, 1720.5,
1520.4, 1447.2, 1312.8, 1288.7, 1124.8, 1057.4, 789.4
cm−1; HRMS m/z: [M＋Na]＋ calcd for C13H18NaO5S:
309.0767; found 309.0771.
Ethyl 2-(2-hydroxy-2-(3-methoxyphenyl)ethylsul-
fonyl)acetate (6m) White solid, m.p. 67－68 ℃,
95% yield, 94% ee. The enantiomeric excess was de-
termined by HPLC on Daicel Chiralpak AD-H with hex-
ane/i-PrOH (90∶10) as the eluent. Flow: 1.0 mL/min;
λ＝210 nm: tmajor＝24.204 min; tminor＝25.898 min.
Ethyl 2-(2-hydroxy-2-(4-methoxyphenyl)ethyl-
sulfonyl)acetate (6j) White solid, m.p. 54－55 ℃,
98% yield, 97% ee. The enantiomeric excess was de-
termined by HPLC on Daicel Chiralpak OJ-H with hex-
ane/i-PrOH (70∶30) as the eluent. Flow: 1.0 mL/min;
λ＝210 nm: tmajor＝27.159 min; tminor＝18.050 min.
25
1
[α]D ＋31.8 (c 0.50 in CH3COCH3); H NMR (400
MHz, CDCl3) δ: 7.32－7.28 (m, 1H), 6.97－6.95 (m,
2H), 6.88－6.85 (m, 1H), 5.31 (d, J＝10.4 Hz, 1H) 4.40
(d, J＝15.2 Hz, 1H), 4.28 (q, J＝6.8 Hz, 2H), 4.02－
3.98 (m, 1H), 3.91 (dd, J＝15.2, 4.4 Hz, 1H), 3.81 (m,
3H), 3.28 (d, J＝15.2 Hz, 1H), 3.20 (d, J＝2.8 Hz, 1H),
1.33 (t, J＝6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ:
163.39, 160.02, 142.52, 130.08, 117.87, 114.12, 111.25,
25
1
[α]D ＋44.0 (c 0.50 in CH3COCH3); H NMR (400
MHz, CDCl3) δ: 7.32 (d, J＝8.4 Hz, 2H), 6.92 (d, J＝
8.8 Hz, 2H), 5.32－5.28 (m, 1H) 4.41 (d, J＝14.8 Hz,
1H), 4.29 (q, J＝6.8 Hz, 2H), 3.99 (dd, J＝14.8, 1.6 Hz,
1H), 3.95－3.91 (m, 1H), 3.82 (s, 3H), 3.27 (d, J＝14.8
Hz, 1H), 2.99 (d, J＝4.2 Hz, 1H), 1.34 (t, J＝7.2 Hz,
3H); 13C NMR (101 MHz, CDCl3) δ: 163.44, 159.84,
132.94, 127.10, 114.34, 68.97, 62.65, 60.62, 58.92,
55.36, 13.98; IR (KBr) νmax: 3520.08, 3022.5, 2963.3,
1719.9, 1613.3, 1515.2, 1463.5, 1367.6, 1227.2, 1124.1,
1054.3, 1001.05, 751.2 cm−1; HRMS m/z: [M＋Na]＋
calcd for C13H18NaO6S: 325.0716; found 325.0726.
Ethyl 2-(2-(3-fluorophenyl)-2-hydroxyethyl-
sulfonyl) acetate (6k) White solid, m.p. 80－81 ℃,
98% yield, 95% ee. The enantiomeric excess was de-
termined by HPLC on Daicel Chiralpak OJ-H with hex-
ane/i-PrOH (80∶20) as the eluent. Flow: 1.0 mL/min;
λ＝210 nm: tmajor＝17.817 min; tminor＝14.955 min.
69.21, 62.66, 60.65, 58.95, 55.32, 13.98; IR (KBr) νmax
:
3522.5, 1719.2, 1601.2, 1488.5, 1367.7, 1305.9, 1286.2,
1122.7, 1058.8, 1034.0, 821.1, 781.2 cm−1; HRMS m/z:
[M＋Na]＋ calcd for C13H18NaO6S: 325.0716; found
325.0704.
2-(2-Hydroxyethylsulfonyl)-1-phenylethanol (7a)
White solid, m.p. 113－114 ℃, 93% yield, ＞99% ee.
The enantiomeric excess was determined by HPLC on
Daicel Chiralpak OJ-H with hexane/i-PrOH (80∶20) as
the eluent. Flow: 1.0 mL/min; λ＝210 nm: tmajor
＝
25
15.772 min; tminor＝14.816 min. [α]D ＋30.8 (c 0.50 in
1
CH3COCH3); H NMR (400 MHz, CDCl3) δ: 7.38－
7.31 (m, 5H), 5.37 (d, J＝10.4 Hz, 1H), 4.15 (t, J＝4.4
Hz, 2H), 3.63 (dd, J＝14.8, 4.4 Hz, 1H), 3.51－3.46 (m,
1H), 3.38－3.32 (m, 1H), 3.27－3.23 (m, 2H), 2.70 (s,
1H); 13C NMR (101 MHz, CDCl3) δ: 140.89, 129.01,
128.67, 125.66, 69.22, 62.32, 56.95, 56.61; IR (KBr)
25
1
[α]D ＋37.2 (c 0.50 in CH3COCH3); H NMR (400
MHz, CDCl3) δ: 7.39－7.34 (m, 1H), 7.17 (t, J＝6.8 Hz,
2H), 7.06－7.02 (m, 1H), 5.37 (d, J＝10.0 Hz, 1H) 4.39
(d, J＝15.2 Hz, 1H), 4.29 (q, J＝7.2 Hz, 2H), 4.04 (d,
Chin. J. Chem. 2014, 32, 803—813
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
809

Huang et al.
FULL PAPER
νmax: 3492.2, 3376.6, 1532.1, 1470.5, 1384.4, 1324.5,
1264.5, 1083.8, 1061.6, 1003.7, 744.1, 701.6 cm−1;
HRMS m/z: [M ＋ Na] ＋ calcd for C10H14NaO4S:
253.0505; found 253.0496.
were first examined in this transformation, and the re-
sults are summarized in Table 2. All reactions proceeded
smoothly to afford corresponding optically active
bis(β-hydroxy) sulfones 2 in excellent yields (up to 99%)
with excellent stereoselectivities (up to ＞99% ee,
＞99∶1 dr) (Entries 2－14). Apparently, substrates
bearing electron-withdrawing or electron-donating sub-
stituents at o-, m-, or p-position of the phenyl rings had
a marginal influence on the diastereoselectivities of the
corresponding reactions. For substrates 1e and 1f bear-
ing strong electron-withdrawing (4-NO2 and 4-CF3)
groups at the phenyl rings, the diastereoselectivities of
the desired products 2e and 2f decreased to 90∶10 and
94∶6, respectively (Entries 5 and 6). By comparison,
reactions involving substrates 1h and 1l bearing elec-
tron-donating substituents (－OMe) at p- or m- position
of the phenyl ring afford the corresponding products 2h
and 2l in 98∶2 and 99∶1 diastereoselectivities, re-
spectively (Entries 8 and 12). In addition, heteroatoms
are also tolerated in this catalytic system, as 1o bearing
a thienyl group was transformed to the corresponding
product 2o in 96% yield with ＞99% ee and 98∶2 dr
(Entry 15). To our delight, X-ray diffraction analysis
(Figure 1) of single crystals of 2i obtained by recrystal-
lization from dichloromethane and n-hexane solution
allowed for an unambiguous assignment of the relative
and absolute configuration.[12]
Results and Discussion
In our initial study, hydrogenation of 2,2'-sulfonyl-
bis(1-phenylethanone) (1a) was tested with 1.0 mol%
chiral (R,R)-Ru(OTf)(cymene)-(TsDPEN) catalyst I in
CH3OH under 40 atm of H2. As expected, the desired
product 2a was obtained in 99% yield with ＞99% en-
antiomeric excess (ee) as well as 98∶2 diastereoselec-
tivity (dr) (Table 1, Entry 1). Encouraged by the prom-
ising results, the effect of other reaction conditions were
investigated (Table 1, Entries 2－8). After a survey of a
variety of solvents in the hydrogenation of 1a, methanol
was found to be the best solvent for this transformation
in terms of both yield and enantioselectivity (Table 1,
Entries 1 vs. 2－6). The hydrogenation of 1a was also
carried out in the presence of 30 and 20 atm of hydro-
gen gas, respectively, which gave products in slightly
lower yields albeit with maintained ee values (Table 1,
Entries 7 and 8). Thus, the optimal reaction conditions
have been identified as carrying out the reaction by the
use of 1.0 mol% of catalyst I in methanol (0.1 mol/L for
1a) under 40 atm H2 at room temperature.
Having established the optimal reaction conditions
(Table 1, Entry 1), we further explored the substrate
scope of the Ru-catalyzed asymmetric hydrogenation of
bis(β-keto) sulfones. Symmetrical bis(β-keto) sulfones
Table 2 Scope of asymmetric hydrogenation of symmetrical
bis(β-keto) sulfones 1a－1oa
O
O
S
O
OH
O
S
O
2
OH
R1
I
Cat. (1.0 mol%)
40 atm H2,
r.t., MeOH
R1
R1
R1
O
1
Table 1 Condition optimization for asymmetric hydrogenation
of 1aa
Sub-
strate
Prouct/
(Yieldb/%)
Entry
R1
eec/% drd
Ts
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
R1＝Ph
R1＝4-FC6H4
2a/99
＞99 98∶2
N
Ru
2b/96
2c/98
＞99
＞99
＞99
＞99
＞99
94∶6
95∶5
95∶5
90∶10
94∶6
OTf
N
H2
R1＝4-ClC6H4
R1＝4-BrC6H4
R1＝4-NO2C6H4
R1＝4-CF3C6H4
R1＝4-PhC6H4
cat. I
2d/99
2e/95
OH
O
S
OH
O
O
S
O
Cat. I (1.0 mol%)
H2, solvent
O
O
2f/99
1a
2a
1g
1h
1i
2g/90
＞99 96∶4
R1＝4-OCH3C6H4 2h/94
＞99
98∶2
97∶3
Entry Solvent
H2/atm Yieldb/%
eec/% drd
R1＝3-FC6H4
R1＝3-ClC6H4
R1＝3-BrC6H4
2i/98
2j/98
2k/97
96
1
2
3
4
5
6
7
8
MeOH
EtOH
40
40
40
40
40
40
30
20
99
＞99
＞99
－
98∶2
10 1j
11 1k
12 1l
＞99 95∶5
58
90∶10
－
＞99
＞99
97∶3
99∶1
CF3CH2OH
i-PrOH
DCM
＜10
＜10
＜5
＜5
92
R1＝3-OCH3C6H4 2l/99
―
―
13 1m R1＝2-ClC6H4
2m/96
2n/98
2o/96
＞99 93∶7
98 92∶8
＞99 98∶2
―
―
14 1n
R1＝2-CH3C6H4
R1＝2-thienyl
―
―
Toluene
MeOH
＞99
＞99
98∶2
98∶2
15 1o
a Unless otherwise noted, reactions were carried out with 1 (0.2
mmol), catalyst I (1.0 mol%), in MeOH (2.0 mL) at room tem-
perature under 40 atm of H2. b Isolated yield. c,d Determined by
chiral HPLC.
MeOH
88
a Unless otherwise noted, reactions were carried out with 1a (0.2
mmol), catalyst I (1.0 mol%), in solvent (2.0 mL) at room tem-
perature. b Isolated yield. c,d Determined by chiral HPLC.
810
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© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2014, 32, 803—813

Enantioselective Synthesis of Optically Active Bis(β-hydroxy) Sulfones
Single crystals of 4f were obtained from the solution of
dichloromethane and n-hexane, and the configuration of
the two stereo centers was unambiguously determined
by X-ray diffraction analysis[13] (Figure 2).
Figure 2 Solid state structure of 4f.
To further explore the substrate scope, the substrate
ethyl 2-(2-oxo-2-phenylethylsulfonyl)acetate (5a) was
investigated under the aforementioned optimal reaction
conditions, and the desired product 6a was isolated in
99% yield with 97% ee. And the bis(β-hydroxy) sulfone
(7a) was converted from 6a through NaBH4/LiCl reduc-
tion in 93% yield with ＞99% ee (Scheme 2).
Figure 1 X-ray crystal structure of 2i.
Table 3 The scope of asymmetric hydrogenation of unsymmet-
rical bis(β-keto) sulfones 3a－3ja
Cat. I (1.0 mol%)
OH
O
S
O
4
OH
R1
O
O
O
S
O
3
40 atm H2,
r.t., MeOH
R1
Scheme 2 Synthesis of the 2-(2-hydroxyethylsulfonyl)-1-phe-
nylethanol
Sub-
strate
Prouct/
Entry
R1
eec/%
drd
(Yieldb/%)
4a/97
4b/98
4c/97
4d/98
4e/92
4f/99
1
2
3
4
5
6
7
8
9
3a R1＝4-FC6H4
3b R1＝4-ClC6H4
3c R1＝4-BrC6H4
3d R1＝4-NO2C6H4
3e R1＝4-PhC6H4
3f R1＝4-CH3C6H4
3g R1＝4-OCH3C6H4
3h R1＝3-FC6H4
3i R1＝3-ClC6H4
＞99 99∶1
＞99 98∶2
＞99 98∶2
＞99 96∶4
＞99 98∶2
＞99 98∶2
＞99 98∶2
＞99 98∶2
＞99 ＞99∶1
OH
O
S
O
O
O
S
O
Cat. I (1 mol%)
OEt
OEt
40 atm H2,
r.t., MeOH
O
O
5a
6a
99% yield
97% ee
OH
O
S
NaBH4/LiCl
EtOH
OH
O
7a
4g/98
4h/96
4i/98
93% yield
>99% ee
＞99
Further studies on expansion of the substrate scope
revealed that substrates 5 were also amenable to the es-
tablished AH protocol. As shown in Table 4, for sub-
strates 5a－5m bearing either electron-donating or elec-
tron-withdrawing groups of the phenyl ring, the corre-
sponding products 6a－6m were obtained in excellent
yields (92%－99%) with excellent ees (88%－97%)
(Entries 1－1 3).
The AH of 1a was performed on a gram-scale with-
out any difficulty at a catalyst loading of 1.0 mol%,
leading to 1.2 g of the targeted product 2a in 98% yield
with 99% ee and 98∶2 dr (Table 5, Entry 1). In consid-
eration of the interest from a practical point of view, the
hydrogenation of 1a on a gram-scale was further tested
at lowered catalyst loading. The results showed that the
reaction still proceeded smoothly in the presence of a
relatively low catalyst loading (0.17 mol%), to give the
AH product 2a in 92% yield with ＞99% ee and 97∶3
dr (Table 5, Entry 4), thus attesting the practical utility
of the catalytic protocol.
10 3j R1＝CH3
4j/97
67∶33
(93e)
a Unless otherwise noted, reactions were carried out with 3 (0.2
mmol), catalyst I (1.0 mol%), in MeOH (2.0 mL) at room tem-
perature under 40 atm of H2. b Isolated yield.c,d Determined by
chiral HPLC. e The ee for the minor isomer.
Encouraged by these results, unsymmetrical bis(β-
keto) sulfones were also explored. As illustrated in Ta-
ble 3, excellent enantioselectivities (＞99%), excellent
diastereoselectivities (96∶4－99∶1) and high yields
(92%－98%) were obtained for unsymmetrical bis(β-
keto) sulfones 3a－3j, bearing either electron-with-
drawing groups or electron-donating substituents (En-
tries 1－9). In addition, the bis(β-keto) sulfones 3j with
an aliphatic ketone moiety (Me) was also investigated
for this transformation, which furnished the desired
product 4j in 97% yield with over 99% ee for major
isomer and 93% ee for minor isomer, but with a some-
what declined diastereoselectivities (67∶33) (Entry 10).
Chin. J. Chem. 2014, 32, 803—813
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
811

Huang et al.
FULL PAPER
Table 4 The scope of asymmetric hydrogenation of 5a
lectivity as well as diastereoselectivity.
OH
O
S
O
6
O
O
O
S
O
Cat. I (1.0 mol%)
Acknowledgement
R1
R1
OEt
40 atm H2,
OEt
O
5
r.t., MeOH
We are grateful for financial support of the National
Natural Science Foundation of China (No. 21272166),
the Major Basic Research Project of the Natural Science
Foundation of the Jiangsu Higher Education Institutions
(No. 13KJA150004) and the Program for New Century
Excellent Talents in University (No. NCET-12-0743).
The authors also thank Professor Hongchao Guo for
providing several chiral materials (synthesized in the
National Key Technologies R&D Program of China, No.
2012BAK25B03, CAU) for catalyst synthesis.
Prouct/
Entry Substrate R1
eec/%
(Yieldb/%)
1
5a
5b
5c
5d
5e
5f
R1＝Ph
R1＝4-FC6H4
6a/99
6b/96
6c/98
6d/99
6e/93
6f/96
6g/97
6h/92
6i/95
6j/98
6k/98
6l/97
6m/95
97
92
93
95
95
88
97
96
92
97
95
95
94
2
3
R1＝4-ClC6H4
R1＝4-BrC6H4
R1＝4-IC6H4
R1＝4-NO2C6H4
R1＝4-CF3C6H4
R1＝4-PhC6H4
R1＝4-CH3C6H4
R1＝4-OCH3C6H4
R1＝3-FC6H4
4
5
6
References
7
5g
5h
5i
8
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O
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O
OH
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Conclusions
In summary, we have developed an efficient asym-
metric hydrogenation methodology for the synthesis of
bis(β-hydroxy) sulfones catalyzed by a chiral cationic
ruthenium diamine catalyst. A series of bis(β-hydroxy)
sulfones have been obtained in excellent yields (up to
99%) with excellent enantioselectivities (up to 99%) as
well as good diastereoselectivities (up to 99∶1). The
AH of bis(β-keto) sulfones was performed on a gram-
scale without any difficulty at a low catalyst loading
(0.17 mol%), leading to gram scale of bis(β-hydroxy)
sulfones (1.2 g) in high yield with excellent enantiose-
812
www.cjc.wiley-vch.de
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2014, 32, 803—813

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[12] Crystal structure determination of compound 2i CCDC 1005896:
C16H16F2O4S, Mr＝342.35; a block crystal (0.4 mm×0.4 mm×0.2
mm), T＝293(2), λ(Mo Kα)＝0.71073 Å, Monoclinic, space group:
P 21, a＝8.9107(6) Å, b＝9.4405(4) Å, c＝10.0078(6) Å, V＝
776.23(7) Å3, 3655 total reflections, 2309 unique, Rint＝0.0236, R1＝
0.0414 (I ＞ 2σ), wR2 ＝ 0.1021, Absolute structure parameter:
0.02(10).
[13] Crystal structure determination of compound 4f CCDC 1005895:
C16H17ClO4S, Mr＝340.81; a block crystal (0.6 mm×0.2 mm×0.2
mm), T＝293(2), λ(Mo Kα)＝0.71073 Å, Monoclinic, space group:
P21, a＝11.4195(8) Å, b＝5.8351(4) Å, c＝12.0919(6) Å, V＝
799.35(9) Å3, 3866 total reflections, 2582 unique, Rint＝0.0244, R1＝
0.0465 (I ＞ 2σ), wR2 ＝ 0.1072, Absolute structure parameter:
−0.13(10).
(Lu, Y.)
Chin. J. Chem. 2014, 32, 803—813
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
813