Effect of chiral diene ligands in rhodium-catalyzed asymmetric addition of arylboronic acids to α,β-unsaturated sulfonyl compounds

Article abstract of DOI:10.1021/ja303109q

Asymmetric addition of arylboronic acids to α,β-unsaturated sulfonyl compounds proceeded in the presence of a rhodium catalyst coordinated with a chiral diene ligand to give high yields of the addition products with high enantioselectivity (96->99.5% ee). The diene ligand was proved to be essential for the formation of the addition products, while the use of a bisphosphine ligand mainly gave the cine-substitution product.

Full text of DOI:10.1021/ja303109q

Communication
pubs.acs.org/JACS
Effect of Chiral Diene Ligands in Rhodium-Catalyzed Asymmetric
Addition of Arylboronic Acids to α,β-Unsaturated Sulfonyl
Compounds
Takahiro Nishimura,* Yuka Takiguchi, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
S
* Supporting Information
Scheme 1. Rhodium-Catalyzed Arylation of α,β-Unsaturated
Sulfonyl Compounds
ABSTRACT: Asymmetric addition of arylboronic acids to
α,β-unsaturated sulfonyl compounds proceeded in the
presence of a rhodium catalyst coordinated with a chiral
diene ligand to give high yields of the addition products
with high enantioselectivity (96−>99.5% ee). The diene
ligand was proved to be essential for the formation of the
addition products, while the use of a bisphosphine ligand
mainly gave the cine-substitution product.
ecent progress in the rhodium-catalyzed asymmetric
R
addition of organoboron reagents to electron-deficient
alkenes provides one of the most reliable methods available for
the synthesis of chiral carbonyl compounds, where a variety of
aryl and alkenyl groups are introduced with high enantio-
selectivity.1 Since the first report on the asymmetric addition of
arylboronic acids to conjugated enones by use of a Rh/binap
catalyst in 1998,2 this type of asymmetric catalysis has been
extended to the addition to α,β-unsaturated esters,3 amides,4
aldehydes,5 phosphonates,6 and nitro compounds.7 Boryl-
alkenes8 and electron-deficient alkenylarenes9 have also been
reported as a new class of substrates in the rhodium-catalyzed
asymmetric arylation and alkenylation.
arylrhodium species, is a key reaction step leading to the cine-
substitution product. Thus, to achieve the addition reaction,
protonation of the intermediate A needs to be faster than β-
hydrogen elimination. Here we report that the use of a chiral
diene ligand enables the rhodium-catalyzed asymmetric
addition of arylboronic acids to a wide variety of α,β-
unsaturated sulfonyl compounds with very high enantioselec-
tivity.
A significant difference in reactivity between a Rh/
bisphosphine and a Rh/diene catalyst was observed in the
addition of an arylboronic acid to an alkenylsulfonate (Scheme
2). Thus, treatment of alkenylsulfonate 1a with p-tolylboronic
acid (2m, 2 equiv) in the presence of [RhCl((R)-binap)]220 (3
mol % of Rh) and K3PO4 in 1,4-dioxane/H2O (9:1) at 60 °C
for 3 h gave the substitution product 3 in 43% yield, where the
formation of only a 9% yield of the addition product 4am was
observed (Scheme 2a). In sharp contrast, the reaction in the
presence of a rhodium catalyst coordinated with a chiral diene
Chiral sulfonyl compounds have great versatility in organic
synthesis, and they are also important as biologically active
substances in medicinal chemistry.10 Successful examples of
rhodium-catalyzed asymmetric addition of arylboronic acids to
alkenyl 2-pyridyl sulfones have been reported by Carretero and
co-workers.11 The selective addition is achieved by use of a
rhodium/chiral bisphosphine catalyst, where it is proposed that
the distinctive reactivity of the alkenyl 2-pyridyl sulfone is due
to the formation of a stable five-membered intermediate by
intramolecular coordination of the pyridyl group to rhodium.
Copper-catalyzed asymmetric alkylation of alkenyl 2-pyridyl
sulfones has also been reported by Bechara/Charette12 and
Feringa.13,14 Unfortunately, however, applicable substrates in
their reports have so far been limited to 2-pyridyl sulfones, and
thus development of a new catalytic system is desirable.15,16
One of the unique reactivities of the α,β-unsaturated sulfonyl
compounds toward nucleophiles is the cine-substitution.17 The
first catalytic cine-substitution of alkenyl sulfones with
aryltitanium reagents was reported in 2003 by use of a
rhodium/bisphosphine (binap) complex (Scheme 1).18,19 The
reaction pathway of the cine-substitution has been proposed as
shown in Scheme 1, where β-hydrogen elimination from an
alkylrhodium intermediate A, formed via syn addition of an
22
ligand21 [RhCl((S,S)-Fc-tfb*)]2 (tfb: tetrafluorobenzobarre-
lene) gave the addition product 4am in 98% yield as a sole
product with 96% ee (Scheme 2b). These results indicate that
the nature of the ligand determines the selectivity toward the
addition or substitution, despite the fact that both catalysts
promote the asymmetric addition of arylboronic acids to α,β-
unsaturated carbonyl compounds.20,23
Of the chiral diene ligands at hand, tetrafluorobenzobarre-
lenes (tfb’s)23 were found to display high catalytic activity and
enantioselectivity (Table 1). Thus, the reaction by use of a
chiral tfb ligand substituted with phenyl groups (Ph-tfb*) gave
Received: March 30, 2012
Published: May 22, 2012
© 2012 American Chemical Society
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Journal of the American Chemical Society
Communication
Scheme 2. Arylation of Sulfonate 1a
Scheme 3. Rhodium-Catalyzed Asymmetric Addition of p-
Tolylboronic Acid (2m) to 1
a
Table 1. Rhodium-Catalyzed Asymmetric Addition of p-
a
Tolylboronic Acid (2m) to Sulfonate 1a
a
Reaction conditions: 1 (0.20 mmol), 2m (0.40 mmol), [RhCl((S,S)-
Fc-tfb*)]2 (3 mol % of Rh), K3PO4 (0.20 mmol), 1,4-dioxane (0.72
mL), H2O (0.08 mL) at 60 °C for 3 h. The yields are isolated yields,
and the ee’s were determined by chiral HPLC analysis. Performed
b
b
c
entry
ligand
yield (%)
ee (%)
with 0.50 mmol of 2m at 80 °C for 15 h.
d
1
2
3
4
5
(S,S)-Fc-tfb*
(R,R)-Ph-tfb*
(R)-L1
98
96
95
83
91
94
d
86
The results obtained for the addition of several arylboronic
acids 2 to alkenylsulfonate 1b are summarized in Table 2. The
addition of p-tolylboroxine 2m′ to 1b was catalyzed by 0.3 mol
% of rhodium, and the reaction for 24 h gave 4am in 99% yield
with 99% ee (entry 2). A variety of aryl groups substituted with
both electron-donating and -withdrawing functionalities were
introduced into 1b to give the corresponding addition products
in high yields with over 97% ee (entries 3−12).
39
38
33
(R)-L2
(R)-L3
a
Reaction conditions: 1a (0.20 mmol), 2m (0.40 mmol), [RhCl(L*)]2
(3 mol % of Rh), K3PO4 (0.20 mmol), 1,4-dioxane (0.72 mL), H2O
(0.08 mL) at 60 °C for 3 h. Determined by H NMR. Determined
b
c
1
d
by chiral HPLC analysis. Isolated yield.
The asymmetric addition of phenylboronic acid (2x) to
cyclic sulfonate 1l catalyzed by the Rh/Fc-tfb* complex
proceeded to give the addition product 4lx in 92% yield with
>99.5% ee (eq 1). The same reaction was also catalyzed by the
the addition product 4am in 86% yield with 95% ee (entry 2).
Although high enantioselectivity was observed by using chiral
diene ligands L1−L39,24 derived from a natural product (R)-
phellandrene, the catalytic activities of their rhodium complexes
were lower than those of tfb-based ligands (entries 3−5).25
The Rh/Fc-tfb* catalyst displayed high catalytic activity and
enantioselectivity in the addition of p-tolylboronic acid (2m) to
diverse alkenyl sulfonyl compounds (Scheme 3). The addition
to (E)-2,6-dimethylphenyl styrylsulfonate (1b) gave the
addition product 4bm in 97% yield with 99% ee. In the
reaction of ethyl sulfonate 1c, a slightly lower yield (84%) of
the addition product 4cm with 97% ee than those obtained
with aryl sulfonates 1a and 1b was observed in spite of the
complete conversion of 1c, probably due to the decomposition
of 1c or 4cm to the sulfonic acid salts. A very high
enantioselectivity (>99.5% ee) was observed in the reaction
of alkenylsulfonamide 1d giving the addition product 4dm in
95% yield. Alkenyl sulfones 1e−1k are also good substrates in
the present reaction. Thus, the reaction of 2-benzothiazolyl
sulfone 1e gave the addition product 4em, which would be
employed in the modified Julia olefination,26 in 95% yield with
over 99.5% ee. The addition to alkenyl sulfones substituted at
the β-position with phenyl (1f), 2-furyl (1g), 2-thienyl (1h), 3-
pyridyl (1i), alkenyl (1j), and butyl (1k) gave the
corresponding addition products 4fm−4km in high yields
with over 99% ee.
Rh/binap complex, which favors the substitution in the reaction
of the linear sulfonate 1a, to give 4lx in 97% yield with 99% ee.
This is probably because the alkylrhodium intermediate formed
via the syn phenylrhodation has no β-hydrogens to be
eliminated in syn fashion.
The absolute configurations of the sulfonate (R)-4bv and
(R)-4lx produced by use of (S,S)-Fc-tfb* were determined by
X-ray crystallographic analysis.27 The absolute configurations
are in good agreement with the stereochemical model
previously proposed for the addition to α,β-unsaturated
carbonyl compounds by use of C2-symmetric chiral diene
ligands.28
A deuterium-labeling experiment provided mechanistic
insight into the protonation step (Scheme 4). Treatment of
alkenyl sulfone 1g with p-tolylboroxine 2m′ and D2O, where p-
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= >97:3). It was also confirmed that the deuterium on 4gm-d
was syn to the p-tolyl group.29 The result indicates that the
alkylrhodium intermediate A directly undergoes protonation
with retention of stereochemistry at the rhodium to give the
addition product without an extra step such as β-hydrogen
elimination or migration of rhodium onto the aryl group by 1,4-
Rh shift.30 In the present reaction, faster protonation of the
alkylrhodium intermediate A than β-hydrogen elimination
enabled the selective formation of the addition product,
which was realized by using the diene ligand.
Table 2. Rhodium-Catalyzed Asymmetric Addition of
Arylboronic Acids 2 to 1b
a
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and compound characterization data.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
tnishi@kuchem.kyoto-u.ac.jp; thayashi@kuchem.kyoto-u.ac.jp
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work has been supported by a Grant-in-Aid for Scientific
Research from the MEXT, Japan.
■
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