Rhodium-catalyzed enantioselective conjugate addition of sodium tetraarylborates to 2,3-dihydro-4-pyridones and 4-quinolones by using (R,R)-1,2-Bis(tert-butylsulfinyl)benzene as a ligand

Article abstract of DOI:10.1002/ejoc.201001613

(R,R)-1,2-Bis(tert-butylsulfinyl)benzene as an efficient and simple ligand can be applied in the rhodium-catalyzed asymmetric 1,4-addition of sodium tetraarylborate reagents to N-substituted 2,3-dihydro-4-pyridones and 4-quinolones. The reactions proceede

Full text of DOI:10.1002/ejoc.201001613

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201001613
Rhodium-Catalyzed Enantioselective Conjugate Addition of Sodium
Tetraarylborates to 2,3-Dihydro-4-pyridones and 4-Quinolones by Using
(
R,R)-1,2-Bis(tert-butylsulfinyl)benzene as a Ligand
Xiangyang Zhang,[a,b,c] Jun Chen,[a,b,c] Fuzhong Han,
Jian Liao*[
[a,b,c]
Linfeng Cun, and
[a]
a,b,c]
Keywords: Heterocycles / Borates / Michael addition / Sulfur / Rhodium
(
R,R)-1,2-Bis(tert-butylsulfinyl)benzene as an efficient and
reactions proceeded smoothly to provide the corresponding
adducts in good yields (up to 92%) and excellent enantio-
selectivities (up to 99%ee) under mild conditions.
simple ligand can be applied in the rhodium-catalyzed asym-
metric 1,4-addition of sodium tetraarylborate reagents to N-
substituted 2,3-dihydro-4-pyridones and 4-quinolones. The
chlorotrimethylsilane.[7g] Therefore, the direct asymmetric
synthesis of 2-aryl-4-piperidones, especially 2-aryl-2,3-dihy-
dro-4-quinolones, remains a challenge. To the best of our
Introduction
Since the pioneer reports of Miyaura and Hayashi re-
garding the asymmetric 1,4-addition of arylboronic acids to
α,β-unsaturated compounds catalyzed by rhodium com-
[9]
knowledge, the use of air-stable sodium tetraarylborates
as effective nucleophiles in the rhodium-catalyzed 1,4-ad-
dition to N-substituted 2,3-dihydro-4-pyridones and 4-quin-
olones has not been reported.
[
1]
plexes, this method has become a fascinating tool for or-
[
2]
ganic chemists to build many useful heterocycles. There
has been considerable interest in the development of syn-
thetic routes to substituted piperidones and 4-quinol-
Chiral bis-sulfoxides have been used as a class of ligands
[10]
in late-transition-metal-catalyzed asymmetric reactions.
[
3,4]
ones,
especially in a highly enantioselective manner, be-
An important breakthrough was achieved by Dorta’s group,
who developed a class of bis-sulfoxide ligands with an atro-
cause of their widespread occurrence in nature and their
important biological activity.[
catalytic route toward substituted piperidones and
-quinolones is based on the asymmetric conjugate addition
4a,4c,5]
A short and effective
pisomeric backbone that induced excellent outcomes in
[11]
rhodium-catalyzed asymmetric reactions.
We demon-
4
strated that simple chiral tert-butyl sulfoxide, as an element
[
6]
of organometallic reagents to Michael acceptors. In the
past decade, Hayashi et al. and Feringa et al. have per-
formed elegant work in this area.[ Very recently, Shi devel-
oped an effective axially chiral bis(NHC)–Pd-catalyzed
asymmetric conjugate addition of arylboronic acids to N-
substituted 2,3-dihydro-4-pyridones.[ Although the asym-
metric Michael addition of organometallic reagents to N-
of a ligand or an organocatalyst, can be used in many asym-
[12]
metric procedures,
especially in the rhodium-catalyzed
7]
1
,4-stereocontrolled addition of arylboronic acids to α,β-
[12d,12e]
unsaturated ketones.
Inspired by these excellent re-
sults, our research group hopes to deal with some challeng-
ing and useful substrates in this area. More recently, we
have reported the synthesis of 2-aryl-2,3-dihydrochromen-
8]
substituted 2,3-dihydro-4-pyridones has been report-
4
-one with high ee values by using the Rh/C -symmetric
2
ed,[
7a–7f,8]
there is only one example of the asymmetric syn-
chiral bis-sulfoxide-catalyzed conjugate addition of sodium
thesis of 2-aryl-2,3-dihydro-4-quinolones by rhodium-cata-
lyzed 1,4-addition of arylzinc reagents in the presence of
[12e]
tetraarylborates to chromenones (Scheme 1).
To further
explore the applications of sodium tetraarylborates and this
[
a] Key Laboratory of Asymmetric Synthesis and Chirotechnology
of Sichuan Province, Chengdu Institute of Organic Chemistry,
Chinese Academy of Sciences,
Chengdu 610041, P. R. China
[b] Natural Products Center, Chengdu Institute of Biology, Chinese
Academy of Sciences,
Chengdu 610041, P. R. China
Fax: +86-28-8522-9250
E-mail: jliao@cib.ac.cn
[c] Graduate School of Chinese Academy of Sciences,
Beijing 100049, P. R. China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001613.
Scheme 1.
Eur. J. Org. Chem. 2011, 1443–1446
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1443

X. Zhang, J. Chen, F. Han, L. Cun, J. Liao
SHORT COMMUNICATION
catalyst, which is stable to air and moisture and easily pre- (Table 1, Entry 2). We next attempted to optimize further
pared, here we report an interesting example of the asym- the reaction conditions. Unfortunately, decreasing the cata-
metric conjugate addition of sodium tetraarylborates to N- lyst loading to 2.0 mol-% was harmful to the conversion
substituted 2,3-dihydro-4-pyridones and 4-quinolones cata- (Table 1, Entry 3). In addition, CH Cl was found to be the
2
2
lyzed by a (R,R)-1,2-bis(tert-butylsulfinyl)benzene–Rh com- best solvent for this catalyst (Table 1, Entries 4–9). Decreas-
plex.
ing the amount of the tetraphenylborate to 2.0 equiv. and
increasing the reaction time did not afford a satisfactory
yield (Table 1, Entry 10). Furthermore, after 12 h, the reac-
tion did not perform very well, and a decrease in yield was
observed when the reaction was carried out at room tem-
perature (Table 1, Entry 11). This suggests a moderate tem-
perature (40 °C) is necessary for high activity.
The substrate scope was then investigated under the opti-
mized conditions, and the results are summarized in
Table 2. Under these conditions with (R,R)-L1 as a ligand,
various sodium tetraarylborates were treated with substi-
tuted 4-pyridones, and the phenylation reactions proceeded
effectively (87–92% yield, 97–99%ee; Table 2, Entries 1–3).
Results and Discussion
Our initial investigation began with a reaction of benzyl
4-oxo-3,4-dihydropyridine-1(2H)-carboxylate with PhB-
(
(
OH) (3.0 equiv.) in the presence of rhodium/(R,R)-1,2-bis-
tert-butylsulfinyl)benzene (5.0 mol-%) in CH Cl . Unfortu-
2
2
2
nately, the reaction failed to give the desired product. Then,
we decided to explore our chiral tert-butanesulfinylphos-
phane ligands
however, the use of this ligand was also unsuccessful, as no
product was obtained. Very recently, we reported the first
example of an asymmetric 1,4-addition of sodium tetraaryl-
borates to chromenones by using a rhodium/(R,R)-1,2-bis-
[
12d]
under the above reaction conditions;
Table 2. Asymmetric addition of sodium tetraarylborates to 2,3-
(
tert-butylsulfinyl)benzene chiral catalyst, which afforded dihydro-4-pyridones and 4-quinolones catalyzed by Rh/(R,R)-1,2-
the products in moderate yield with excellent enantio- bis(tert-butylsulfinyl)benzene.[
selectivity. We found that the use of sodium tetraarylbor-
a]
ates, which are known to be effective nucleophiles to many
[9]
substrates under rhodium catalysis, instead of arylboronic
acids could improve the conversion. To our delight, such a
transformation was highly promoted when sodium tet-
raphenylborate was utilized in place of PhB(OH) , as the
2
product was obtained in high yield (92% yield; Table 1, En-
try 1) with excellent enantioselectivity (99%ee). Moreover,
the reaction can be brought to completion at 40 °C in 5 h
Table 1. Screening of the reaction conditions for the 1,4-addition
of sodium tetraphenylborate to benzyl 4-oxo-3,4-dihydropyridine-
[
a]
1(2H)-carboxylate.
Entry
Rh
2a
Solvent
t
[h]
Yield
[%]
ee
[%]
[
b]
[c]
[
mol-%] [equiv.]
1
2
3
4
5
6
7
8
9
5.0
5.0
2.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
2.0
3.0
CH
CH
CH
toluene
dioxane
2
2
2
Cl
Cl
Cl
2
2
2
8
5
5
5
5
5
5
5
5
92
92
trace
trace
15
trace
trace
trace
trace
82
99 (R)
99
n.d.
n.d.
99
n.d.
n.d.
n.d.
n.d.
99
THF
cyclohexane
ClCH
CH
2
CH
OH
2
Cl
3
1
0
CH
CH
2
Cl
Cl
2
8
12
[d]
11
2
2
70
98
[
[
a] Reaction conditions: 4a (0.2-mmol), Rh/ligand = 1:1.2, 40 °C.
b] Isolated yield. [c] Determined by HPLC analysis with chiral col-
umns, and the absolute configuration of 5a was determined by
comparison of the specific rotation to the literature value. [d] Reac-
tion was carried out at 25 °C.
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Eur. J. Org. Chem. 2011, 1443–1446

Rhodium-Catalyzed Enantioselective Conjugate Addition Reactions
Table 2. (continued)
Experimental Section
General Procedure for the Enantioselective Rhodium-Catalyzed Ad-
dition of Sodium Tetraarylborate to 2,3-Dihydro-4-pyridones and 4-
Quinolones: Under an argon atmosphere and at room temperature,
to a 10-mL Schlenk tube with a Teflon cap was added ligand (R,R)-
L1 (3.4 mg, 6.0 mol-%), [RhCl(C
CH Cl (1.0 mL). The mixture was stirred at 25 °C for 40 min, and
then, sodium tetraarylborate (0.6 mmol, 3.0 equiv.), the substrate
0.2 mmol), and degassed H O (0.1 mL, 6.0 mmol) were added se-
quentially. The mixture was stirred for the appropriate time at
0 °C and directly charged onto a column (silica gel) for flash
2 4 2 2
H ) ] (1.9 mg, 5.0 mol-%), and
2
2
(
2
4
chromatography (petroleum ether/EtOAc) to afford product 5.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, characterization of the prepared
compounds, and copies of the NMR spectra and chiral HPLC
traces of the Michael addition products.
Acknowledgments
We are grateful for support from the National Sciences Foundation
of China (20872139 and 21072186), West Light Foundation of Chi-
nese Academy of Sciences, National Basic Research Program of
China (973 Program, 2010CB833300), and Chengdu Institute of
Biology, Chinese Academy of Sciences (Y0B1051100).
[
[
1] a) For the first example of a rhodium-catalyzed 1,4-addition,
see: M. Sakai, T. Hayashi, N. Miyaura, Organometallics 1997,
[
(
a] Reaction conditions: 4 (0.2 mmol), sodium tetraarylborate
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CH Cl /H O (10:1, 1.1 mL), 40 °C. [b] Isolated yield. [c] Deter-
16, 4229–4231; b) Y. Takaya, M. Ogasawara, T. Hayashi, M.
2
H
4
)
2
2
Sakai, N. Miyaura, J. Am. Chem. Soc. 1998, 120, 5579–5580.
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2
2
2
mined by chiral HPLC analysis. [d] The absolute configurations
were determined by comparison to literature data.
2105.
[
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dium tetraphenylborate to 4-quinolones, a prolonged reac-
tion time was needed (12 h; Table 2, Entry 4). It is worth
noting that this type of substrate is less reactive towards
8
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[
[
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enantioselectivity of the reaction remained high.
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In summary, we have developed (R,R)-1,2-bis(tert-butyl-
sulfinyl)benzene as an efficient and simple ligand for the
rhodium-catalyzed asymmetric 1,4-addition of sodium tet-
raarylborates to N-substituted 2,3-dihydro-4-pyridones and
4-quinolones; the corresponding adducts are obtained in
[
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selectivities. Investigation to further expand this methodol-
ogy to build more useful heterocycles is underway in our
laboratory.
Eur. J. Org. Chem. 2011, 1443–1446
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1445

X. Zhang, J. Chen, F. Han, L. Cun, J. Liao
SHORT COMMUNICATION
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Received: November 30, 2010
Published Online: February 4, 2011
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