Dynamic kinetic resolution of β-keto sulfones via asymmetric transfer hydrogenation

Article abstract of DOI:10.1039/b818257d

The dynamic kinetic resolution of β-keto sulfones was achieved via asymmetric transfer hydrogenation using (S,S)-RuCl[N-(tosyl)-1,2- diphenylethylenediamine](p-cymene) in the presence of formic acid and triethylamine afforded the desired products in good

Full text of DOI:10.1039/b818257d

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
Dynamic kinetic resolution of b-keto sulfones via asymmetric transfer
hydrogenationw
Zhenhua Ding, Jin Yang, Ting Wang, Zongxuan Shen and Yawen Zhang*
Received (in Cambridge, UK) 20th October 2008, Accepted 26th November 2008
First published as an Advance Article on the web 19th December 2008
DOI: 10.1039/b818257d
The dynamic kinetic resolution of b-keto sulfones was achieved via
asymmetric transfer hydrogenation using (S,S)-RuCl[N-(tosyl)-
1,2-diphenylethylenediamine](p-cymene) in the presence of formic
acid and triethylamine afforded the desired products in good yield
with up to 499 : 1 dr and high ee up to 499%.
Dynamic kinetic resolution (DKR) is an efficient method to
obtain optically pure compounds from racemic substrates,
which combines the resolution step of kinetic resolution with
an in situ equilibration or racemisation of the configurationally
labile substrate.1 Recently, increasing attention has been given
to the discovery of DKR reactions, which can, theoretically,
result in quantitative yield with enantiomeric excess (ee)
approaching 100%.2
Scheme 1 Dynamic kinetic resolution of 1-phenyl-2-(phenylsulfonyl)-
propan-1-one 1a.
While the reaction conducted at room temperature in DMF
using (S,S)-RuCl[N-(tosyl)-1,2-diphenylenediamine](p-cymene)
(0.6%) as the catalyst and formic acid (5 equiv.)–triethylamine
(2 equiv.) as the hydrogen source, the reaction was very slow and
no product could be detected by TLC after 24 h. Considerable
rate acceleration was observed by performing the reaction at
50 1C compared to room temperature, it gave a combined yield
of 95% with 93 : 7 diastereomeric ratio (dr). The enantiomeric
excess (ee) of the major and the minor diastereomers, deter-
mined by HPLC analysis, was 98 and 85%, respectively. The
influence of reaction solvent on the DKR was then investigated.
The results are shown in Table 1.
Hydrogen transfer reactions are mild methodologies for
reduction of ketones or imines and oxidation of alcohols or
amines in which a substrate-selective catalyst transfers hydro-
gen between the substrate and hydrogen donor or acceptor,
respectively.3 In recent years, hydrogen transfer reduction has
gained a prominent position as to be rated second in order of
importance immediately behind asymmetric hydrogenation
with molecular hydrogen.4
To our knowledge, a few examples about DKRs have been
reported via asymmetric transfer hydrogenation. Excellent
examples include Noyori’s reduction of benzils,5 Cossy’s
reduction of 1,3-diketones6 and reduction of cyclic b-keto
esters, cycloalkylamines, b-keto-a-amino esters and cyclic
ketones.7
Table 1 1 Solvent effects on the DKR of 1a
Optically active b-hydroxy aryl sulfones are useful chiral
synthons in organic synthesis.8 Many methods have been
developed for the enantioselective synthesis of optically active
b-hydroxy sulfones, such as kinetic and dynamic kinetic resolu-
tion of racemic b-hydroxy sulfones9 and asymmetric reduction
of b-keto sulfones.10 As these compounds are very useful, we
designed the DKR of b-keto sulfones via asymmetric hydrogen
transfer reaction to obtain enantiomerically enriched b-hydroxy
sulfones.
Entry Solvent
t/h Yielda (%) drb
eeb(%) major
1
2
3
4
5
6
7
DMF
THF
Toluene
12 95
20 85
20 88
93 : 7 98
90 : 10 93
90 : 10 92
86 : 14 97
89 : 11 98
89 : 11 98
89 : 11 98
Diisopropyl ether 12 80
DMSO
CH3CN
CH3OH
12 92
12 85
12 82
a
b
Isolated yield. Determined by chiral HPLC analysis using a Chiralpak
AD–H column.
We first chose the reduction of 1-phenyl-2-(phenylsulfonyl)-
propan-1-one 1a as our research model (Scheme 1).
Table 2 Influence of the catalyst/substrate ratio on the DKR of 1a
Entry
S/C
t/h
Yielda (%)
drb
eeb(%) major
Key Laboratory of Organic Synthesis of Jiangsu Province, College of
Chemistry and Chemical Engineering, Soochow University, Suzhou,
215123, China. E-mail: zhangyw@suda.edu.cn;
1
2
3
4
40
80
120
160
12
12
24
24
92
95
85
70
88 : 12
93 : 7
89 : 11
90 : 10
97
98
98
99
Fax: +86-0512-65880305; Tel: +86-0512-65880340
w Electronic supplementary information (ESI) available: General
experimental procedure for the transfer hydrogenative DKR of the
b-ketosulfones, 1H and 13C NMR spectra, HRMS spectra and HPLC
data. CCDC 696276. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/b818257d
a
b
Isolated yields. Determined by chiral HPLC analysis using a
Chiralpak AD–H column.
ꢀc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 571–573 | 571

View Article Online
Table 3 Results of DKR of 1a–1p at 50 1C in DMF
Fig. 1 X-Ray crystal structure of the major diastereomer of 2a.
DMF as the solvent to investigate the influence of the catalyst/
substrate ratio on the DKR of 1a. The results are listed in Table 2.
The diastereo- and enantioselectivity of the transformation
was only marginally influenced by the catalyst/substrate ratio.
However, longer reaction time was necessary at lower catalyst
loading.
DKR reactions of many other b-keto sulfones11 were then
investigated at 50 1C using DMF as the solvent.12 The results
are summarized in Table 3.
Data showed that substitution in benzene ring did significantly
affect the reaction, the substrates with electron-withdrawing
group such as p-chloro gave faster reaction, while the electron-
donating such as p-methoxy group deactivated the reaction
(entries 1–5). With the o-chloro substrates, the dr and ee dropped
sharply (entries 6 and 7). The reduction of cyclic b-keto sulfones
gave excellent dr.
For the absolute configuration assignment, single crystals of
the major diastereomer of 2a, were prepared and the structure
established by X-ray crystallography. According to the results
of the major diastereomer of 2a,13 there are two independent
molecules in the asymmetric unit. They have the same absolute
configurations of (1R,2S) (Fig. 1).
In summary, a convenient and highly stereoselective app-
roach to chiral b-hydroxy sulfones has been developed. The
asymmetric transfer hydrogenation of the corresponding
sulfones by using Noyori’s Ru(cymene)-TsDPEN catalyst and
HCOOH–Et3N as the hydrogen source proceeds via dynamic
kinetic resolution to selectively afford (1R,2S)-compounds for a
variety of substrates. Remarkable results concerning the reac-
tivity and enantioselectivities (499 : 1 dr, 499% ee) were
achieved for rigid cyclic a-tetralone and a-indanone derivatives.
a
b
Isolated yield.
Chiralpak AD–H column or Chiralcel OD–H column. The product
was 1-phenyl-2-(phenylsulfonyl)ethanol.
Determined by chiral HPLC analysis using a
c
Notes and references
1 H. Pellissier, Tetrahedron, 2008, 64, 1563.
2 (a) Y. Wang, Z. Shen, B. Li, Y. Zhang and Y.-W. Zhang, Chem.
Commun., 2007, 1284; (b) F. Eustache, P. I. Dalko and J. Cossy,
J. Org. Chem., 2003, 68, 9994; (c) A. Ros, A. Magriz, H. Dietrich,
The data demonstrate that excellent results could be obtained
in many solvents explored, such as DMF, CH3OH, CH3CN and
DMSO. In THF and in toluene, the reaction was slower. When
DMF was employed as the solvent, it gave the highest yield,
diastereomer ratio and ee for the major isomer. So we chose
R. Ferna
´
127; (d) K. Boga
ndez, E. Alvarez and J. M. Lassaletta, Org. Lett., 2006, 8,
r, P. H. Vidal, A. R. A. Leon and J.-E. Backval,
´
´
¨
Org. Lett., 2007, 9, 3401; (e) X. Cheng, R. Goddard, G. Buth and
B. List, Angew. Chem., Int. Ed., 2008, 47, 5079; (f) M.-J. Kim,
ꢀc
This journal is The Royal Society of Chemistry 2009
572 | Chem. Commun., 2009, 571–573

View Article Online
W.-H. Kim, K. Han, Y. K. Choi and J. Park, Org. Lett., 2007, 9,
1157; (g) J. Wang, H.-X. Xie, H. Li, L. Zu and W. Wang, Angew.
Chem., Int. Ed., 2008, 47, 4177; (h) P. Vongvilai, R. Larsson and
O. Ramstrom, Adv. Synth. Catal., 2008, 350, 448; (i) J.-H. Xie,
¨
Z.-T. Zhou, W.-L. Kong and Q.-L. Zhou, J. Am. Chem. Soc., 2007,
V. Ratovelomanana-Vidal and J.-P. Genet, Tetrahedron Lett.,
1999, 40, 3175.
11 L. Field and J. W. McFarland, J. Am. Chem. Soc., 1953, 75, 5582.
12 Dynamic kinetic resolutions (DKR) of 1-phenyl-2-(phenylsulfonyl)-
propan-1-one (1a)—A general procedure:
A
suspension of
129, 1868; (j) K. Bogar and J.-E. Backvall, Tetrahedron Lett., 2007,
´
¨
[RuCl2(p-cymene)]2 (3.75 mg, 0.00625 mmol) and (S,S)-TsDPEN
(4.58 mg, 0.0125 mmol) in DMF (0.5 mL) was degassed three times,
and then stirred at 80 1C for 1 h. After cooling to room temperature,
5 : 2 HCOOH–Et3N (0.2 mL) was added, and then 1a (0.5 mmol) was
added. The reaction was stirred at 50 1C until completion according to
TLC detection. 5.0 mL water was added to the reaction, the mixture
was then extracted three times with EtOAc (10 mL), dried over
anhydrous sodium sulfate and concentrated. After removal of the
solvent, the residue was purified by flash column chromatography
(silica gel H, EtOAc–petroleum = 1 : 2) to give the pure product, 95%
yield, which was determined by HRMS, IR, 1H and 13C NMR
spectroscopy. 1-phenyl-2-(phenylsulfonyl)propan-1-ol (2a): white
48, 5471; (k) S. Hoffmann, M. Nicoletti and B. List, J. Am. Chem.
Soc., 2006, 128, 13074; (l) S.-B. Ko, B. Baburaj, M.-J. Kim and
J. Park, J. Org. Chem., 2007, 72, 6860.
3 J. S. M. Samec, J.-E. Backvall, P. G. Andersson and P. Brandt,
¨
Chem. Soc. Rev., 2006, 35, 237.
4 S. Gladiali and E. Alberico, Chem. Soc. Rev., 2006, 35, 226.
5 K. Murata, K. Okano, M. Miyagi, H. Iwane, R. Noyori and
T. Ikariya, Org. Lett., 1999, 1, 1119.
6 F. Eustache, P. Dalko and J. Cossy, Org. Lett., 2002, 4, 1263.
7 (a) A. Ros, A. Magriz, H. Dietrich, J. M. Lassaletta and
R. Ferna
´
H. Dietrich, M. Ford, R. Ferna
ndez, Tetrahedron, 2007, 63, 7532; (b) A. Ros, A. Magriz,
ndez and J. M. Lassaletta, Adv.
´
1
solid; mp 108–110 1C; H NMR (400 MHz, CDCl3) d: 1.22 (d, J =
Synth. Catal., 2005, 347, 1917; (c) B. Mohar, A. Valleix,
J. R. Desmurs, M. Felemez, A. Wagner and C. Mioskowski, Chem.
Commun., 2001, 2572; (d) N. J. Alcock, I. Mann, P. Peach and
´
M. Wills, Tetrahedron: Asymmetry, 2002, 13, 2485; (e) R. Fernandez,
A. Ros, A. Magriz, H. Dietrich and J. M. Lassaletta, Tetrahedron,
2007, 63, 6755.
8 X.-B. Wan, Q.-H. Meng, H.-W. Zhang, Y.-H. Sun, W.-Z. Fan and
Z.-G. Zhang, Org. Lett., 2007, 9, 5613.
9 P. Kie"basinski, M. Rachwalski, M. Miko"ajczyk, M.A.
´
7.1 Hz, 3H, CHCH3), 3.21–3.26 (q, J = 7.2 Hz, 1H, CHCHCH3), 3.28
(s, 1H, OH), 5.54 (s, 1H, CHOH), 7.26–7.36, (m, 5H, Ar–H), 7.65
(t, J = 7.3 Hz, 2H, Ar–H), 7.74 (t, J = 7.5 Hz, 1H, Ar–H), 7.99
(d, J = 8.3 Hz, 2H, Ar–H); 13C NMR (100 MHz, CDCl3) d: 6.21,
66.09, 69.68, 125.98, 128.20, 128.90, 129.17, 129.86, 134.57, 137.75,
140.24; IR (film) nmax/cmÀ1 3480.1, 1591.5, 1448.5, 1295.1, 1189.0,
1143.8, 1080.9, 761.6, 725.7, 697.3; HRMS (EI): m/z = 276.0820 (calc.
for C15H16O3S = 276.0820); HPLC: Chiralpak AD-H (i-PrOH–
hexane, 10 : 90, flow rate 1 mL minÀ1, l = 210.5 nm): t1
=
13.814 min, t2 = 18.318 min, t3 = 22.008 min, t4 = 23.733 min;
H. Moelands, B. Zwanenburg and F. P. J. T. Rutjes, Tetrahedron:
Asymmetry, 2005, 16, 2157.
24
[a]D = À12.86 (c = 1.0, acetone), dr = 97 : 3, ee = 98%.
10 (a) P. Bertus, P. Phansavath, V. Ratovelomanana-Vidal, J.-P. Genet,
A. R. Touati, T. Homri and B. B. Hassine, Tetrahedron: Asymmetry,
1999, 10, 1369; (b) H.-L. Zhang, X.-L. Hou, L.-X. Dai and
Z.-B. Luo, Tetrahedron: Asymmetry, 2007, 18, 224; (c) G. Zhao,
J.-B. Hu, Z.-S. Qian and W.-X. Yin, Tetrahedron: Asymmetry, 2002,
13, 2095; (d) V. Gotor, F. Rebolledo and R. Liz, Tetrahedron:
Asymmetry, 2001, 12, 513; (e) P. Bertus, P. Phansavath,
13 Careful evaporation of a solution of 2a in AcOEt–petroleum (1 : 4)
gave single crystals which were suitable for crystallographic ana-
lysis. Selected crystal structure data: C15H16O3S, space group P21,
a = 10.4899(19), b = 11.433(2), c = 11.813(2) A, b = 100.702(4)1,
V = 1392.0(4) A3, Z = 2, T = 293 K, R (reflections) = 0.0510,
wR2 (reflections) = 0.1081.
ꢀc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 571–573 | 573