Tert-butanesulfinylphosphines: Simple chiral ligands in rhodium-catalyzed asymmetric addition of arylboronic acids to electron-deficient olefins

Article abstract of DOI:10.1002/adsc.200900792

An efficient rhodium complex catalyst system was developed by using a class of simple tert-butanesulfinylphosphines as bidentate ligands, which solely bear sulfur chirality and combine the advantages of both sulfoxide and phosphine ligands. Excellent activities (in 0.5 hour, up to 99% yield) and enantioselectivities (up to 98% ee) were displayed in Rh-catalyzed asymmetric 1,4-additions under mild conditions.

Full text of DOI:10.1002/adsc.200900792

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DOI: 10.1002/adsc.200900792
tert-Butanesulfinylphosphines: Simple Chiral Ligands in
Rhodium-Catalyzed Asymmetric Addition of Arylboronic
Acids to Electron-Deficient Olefins
Feng Lang,a,b Dong Li,a,b Junmin Chen,a,b,c Jun Chen,a,b Liangchun Li,a
Linfeng Cun,a Jin Zhu,a Jingen Deng,a,b and Jian Liaoa,b,*
a
Key Laboratory of Asymmetric Synthesis and Chirotechnology of Sichuan Province, Chengdu Institute of Organic
Chemistry, Chinese Academy of Sciences, Chengdu 610041, Peopleꢀs Republic of China
Fax : (+86)-28-8522-9250; phone: (+86)-28-8522-9250; e-mail: jliao10@cioc.ac.cn
Graduate School of Chinese Academy of Science, Beijing 100049, Peopleꢀs Republic of China
College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022, Peopleꢀs Republic of
b
c
China
Received: November 12, 2009; Published online: March 5, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900792.
Abstract: An efficient rhodium complex catalyst
system was developed by using a class of simple
tert-butanesulfinylphosphines as bidentate ligands,
which solely bear sulfur chirality and combine the
advantages of both sulfoxide and phosphine ligands.
Excellent activities (in 0.5 hour, up to 99% yield)
and enantioselectivities (up to 98% ee) were dis-
played in Rh-catalyzed asymmetric 1,4-additions
under mild conditions.
metric reactions. However, up to date, no satisfactory
results were obtained from this type of ligands.[5,6]
Pioneered by Hayashi and Miyaura,[7] the asymmet-
ric 1,4-addition of arylboronic acid to a,b-unsaturated
compounds catalyzed by rhodium complexes has
À
become a useful tool for asymmetric C C bond form-
ing,[8] and variants of chiral ligands, like bis-phos-
phines,[7,9] dienes,[10] phosphine-olefins,[11] and other
phosphine ligands[12] have been devoted to this reac-
tion. Very recently, Dorta and co-workers made a
major contribution to this field, a new type of bis-sulf-
oxide ligand was developed and these ligands showed
excellent activity and enantioselectivity.[13] To the best
of our knowledge, utilizing phosphine sulfoxide as li-
gands in this reaction still remains an unexplored
area. Herein, we would like to report an efficient Rh-
catalyzed system by using a simple class of tert-
Keywords: 1,4-addition; asymmetric catalysis; rho-
dium complexes; S-chirality; tert-butanesulfinyl-
phosphine ligand
Asymmetric metal catalysis represents an effective
strategy for the construction of enantiopure chiral
compounds, and the proper design and preparation of
new chiral ligands is one of the most important sub-
jects in this area.[1]
Among the thousands of chiral ligands reported so
far, C1-symmetrical hybrid bidentate phosphine li-
gands, like the famous P,N-ligand, have demonstrated
unique properties in some reactions.[2] Our interest
was to construct another class of simple hybrid biden-
tate ligand, that is phosphine sulfoxide, which utilizes
sulfoxide as chiral source and ligating entity[3]
(Figure 1). For this type of ligand (1), the tert-butyl-
sulfinyl moiety could provide a good chiral environ-
ment[4] while the phosphine promotes the coordina-
tion ability of the ligand to transition metals. Thus,
good results could be anticipated in catalyzed asym- Figure 1. Pfaltzꢀs P,N ligands and our P,SO ligands.
Adv. Synth. Catal. 2010, 352, 843 – 846
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843

Feng Lang et al.
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butane
in 1,4-additions of arylboronic acid to a,b-electron-de- except in THF and DMF, satisfactory yields (93–99%)
ficient olefins. and high enantioselectivities (89–96%, Table 1, en-
ACHTUNGTRENNUNGsulfinylphosphines as ligand and applying them tolerance was observed for this catalytic system,
The synthesis of ligands 1d, e followed the proce- tries 6–11) were obtained when the reactions were
dure for ligands 1a–c through two concise steps with conducted in dioxane, dichloromethane, cyclohexane
satisifactory yields.[6]
and methanol. Decreasing the catalyst loading to
Our initial investigation began with a reaction of 2- 1.0 mol% led a slight decrease in yield and enantiose-
cyclohexen-1-one 2a with PhB(OH)2 (3n, 1.5 equiv.) lectivity, but further decreases (to 0.1 mol%) were
in the presence of 2.0 mol% of rhodium/ligand 1a in harmful to both yield and ee (Table 1, entries 12 and
toluene, unfortunately, the reaction did not proceed 13). A moderate temperature (408C) was necessary
at all (Table 1, entry 1). To our delight, we found that for high activity, and a prolonged reaction time was
ligands 1b–e, which possess an electron-donating needed when the reaction was carried at room tem-
group on the phenyl ring, generated excellent catalyt- perature (Table 1, entries 14 and 15). Furthermore,
ic activities (93–99% yield, Table 1, entries 2–5) and the reaction still worked very well albeit with a slight
enantioselectivities (94–97% ee), all reactions can be loss on yield (93%) and ee (95%), when phenylboron-
finished in half an hour at 408C. The electron-donat- ic acid was decreased to 1.1 equiv. (Table 1 entry 16).
ing group might be a prerequisite to high activity and The best result (99% yield and 98% ee, Table 1, en-
its steric hindrance influence on the ee is slight tries 17 and 18) was achieved by ligand 1e when
(Table 1, entries 3 and 4). In addition, good solvent 2.0 equiv. of phenylboronic acid was used.
The substrate scope was then investigated under
the optimized conditions and the results are summar-
ized in Table 2. Excellent enantioselectivities (94–
Table 1. Catalytic asymmetric 1,4-addition of phenylboronic
acid 3n to 2-cyclohexen-1-one 2a.[a]
98% ee) and good to high yields (67–99%) were ob-
tained in half an hour when various arylboronic acids
were reacted with 6-membered cyclic enone 2a
(Table 2, entries 1–9 and 11–13). One exception was
ortho-methoxyphenylboronic acid 3w, where a lower
enantioselectivity was observed (86% ee, Table 2,
entry 10). Excellent yields and modestly decreased
Entry Solvent
Rh
L
Time Yield[b] ee[c] [%]
enantioselectivities were achieved when phenylboron-
ic acid was reacted with 5- and 7-membered cyclic
enones 2b and c and unsaturated cycloester 2d, re-
spectively (74%, 80% and 88% ee, respectively,
Table 2, entries 14–16). The catalyst system did not
work very well with the linear enone 2e, the selectivi-
ty dramatically dropped to 28% ee, although a high
yield was obtained (Table 2, entry 17).
The stereochemical outcome of these Rh-complex-
catalyzed 1,4-additions can be rationalized as depicted
in Figure 2. The Rh-complex recognizes the cyclohex-
enone by steric repulsion between the tert-butyl group
and the carbonyl moiety. Thus, the coordination with
the re-face is favorable for the cyclic enones in this re-
action, which leads to the R isomer as is consistent
with the observed stereochemitry.
In conclusion, for the first time, we have developed
an efficient Rh-catalyzed system, by using a class of
simple chiral tert-butanesulfinylphosphines, which
solely bear sulfur chirality, as ligands. And this Rh-
phosphine sulfoxide system has demonstrated excel-
lent activities (up to 99%) and enantioselectivities (up
to 98% ee) in the 1,4-addition of arylboronic acids to
electron-deficient olefins. Further studies focused on
new sulfoxide ligands and their applications to cata-
lytic asymmetric reactions are underway and will be
reported in due course.
[mol%]
[h]
[%]
(R)
1
2
3
4
5
6
7
8
toluene
toluene
toluene
toluene
toluene
dioxane
DCM
2
2
2
2
2
2
2
1a 5
nr
97
93
99
97
94
99
94
nd
97
94
96
97
91
94
96
89
nd
nd
96
83
96
95
95
97
98
1b 0.5
1c 0.5
1d 0.5
1e 0.5
1b 0.5
1b 0.5
1b 0.5
1b 0.5
1b 5
cyclohexane 2
9
CH3OH
THF
DMF
toluene
toluene
2
2
2
1
0.1
2
2
2
2
93
10
11
12
13
trace
trace
94
29
99
99
93
99
99
1b 5
1b 0.5
1b 0.5
1b 2
1b 0.2
1b 0.5
1b 0.5
1e 0.5
14[d] toluene
15[e] toluene
16[f]
toluene
17[g] toluene
18[g] toluene
2
[a]
Reaction conditions: 0.5 mmol of 2a, 1.5 equiv. of 3n,
Rh:ligand=1:1.2, 408C, 1.0 mL solvent.
Isolated yield.
Determined by HPLC analysis with chiral columns, and
the absolute configuration of 4an (R) was determined by
comparison of the specific rotation to literature value.[7]
Reaction was carried out at 258C.
Reaction was carried out at 608C.
1.1 equiv. of 3n were used.
2.0 equiv. of 3n were used.
[b]
[c]
[d]
[e]
[f]
[g]
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Adv. Synth. Catal. 2010, 352, 843 – 846

tert-Butanesulfinylphosphines: Simple Chiral Ligands
Table 2. Catalytic asymmetric 1,4-addition of arylboronic acids 2 to electron-deficient olefins 3.[a]
Entry
2
3
4
Yield[b] [%]
99
ee[c] [%]
1
2a
3n
98
2
3
4
5
6
2a
2a
2a
2a
2a
R=F 3o
98
99
89
93
99
96
96
95
94
96
R=Cl 3p
R=Me 3q
R=MeO 3r
R=t-Bu 3s
7
8
2a
2a
R=Cl 3t
R=Me 3u
67
97
96
96
9
10
2a
2a
R=Me 3v
R=MeO 3w
92
79
95
86
11
12
2a
3x
99
96
2a
2a
3y
3z
93
83
98
96
13
14
2b
2c
3n
3n
99
98
74
80
15
16
2d
2e
3n
3n
94
92
88
28
17
[a]
The reactions were carried out with 2 (0.5 mmol), 3 (2.0 equiv.), KOH (2.5M, 0.1 mL), [RhCl
Rh) and 1e (2.4 mmol%) in toluene (1.0 mL) under argon at 408C for 30 min.
Isolated yield.
ACHTUNGNERT(UNGN C2H4)2]2 (2.0 mmol% of
[b]
[c]
Determined by HPLC analysis with chiral columns.
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Feng Lang et al.
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Procedure for the 1,4-Addition
Under an argon atmosphere and at room temperature, to a
10-mL Schlenk tube with a teflon cap was added ligand 1e
(5.1 mg. 2.4 mol%) and [RhACHTNUTGRNE(UNG C2H4)2Cl]2 (1.9 mg, 1.0 mol%)
followed by 1.0 mL toluene. The mixture was stirred for half
hour and arylboronic acid (1.0 mmol) was added. The tem-
perature was increased to 408C and enone (0.5 mmol) was
then added via syringe followed by degassed KOH (2.5M in
H2O, 1.0 mL, 0.25 mmol). The reaction mixture was stirred
at 408C for half hour (monitored by TLC). The reaction
mixture was then directly charged onto a column (silica gel)
for flash chromatography with a mixture of petroleum
ether/EtOAc to afford the product.
Acknowledgements
We are grateful to the support of NSFC (No. 20872139), the
West Light Foundation of Chinese Academy of Sciences and
973 program (2010CB833301).
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