CL-180260
Received: March 26, 2018 | Accepted: April 16, 2018 | Web Released: April 27, 2018
A Diastereomeric Pair of Sulfoxide-containing Chiral MOP-type Ligands:
Preparation and Application to Rhodium-catalyzed Asymmetric 1,4-Addition Reactions
Takashi Hoshi,* Masataka Fujita, Shouta Matsushima, Hisahiro Hagiwara, and Toshio Suzuki
Department of Applied Chemistry and Chemical Engineering, Niigata University, Nishi-ku, Niigata 950-2181, Japan
E-mail: hoshi@gs.niigata-u.ac.jp
(
R,S )-Sulfoxide-MOP (L2) and (R,R )-sulfoxide-MOP (L3)
type ligands,5,6 (R,S )-sulfoxide-MOP (L2) and (R,R )-sulfox-
S S
S
S
were developed as a diastereomeric pair of sulfoxide-containing
chiral MOP-type ligands. These two ligands also represent the
first monosulfoxide analogues of BINAP. The chiral ligand L2
was successfully applied to the highly enantioselective rhodium-
catalyzed 1,4-addition between α,β-unsaturated ketones or esters
and arylboronic acids, and exhibited a broad substrate scope
when the reaction was performed using 1.5 mol% Rh in
cyclohexane/H2O (10:1) at 40 °C under mild basic conditions.
ide-MOP (L3), as a pair of diastereomeric sulfoxide-containing
chiral P,S-ligands (Figure 1, center and right). These two non-
C -symmetric bidentate ligands also represent the first mono-
2
7
sulfoxide analogues of BINAP. In the presence of L2, the
rhodium-catalyzed asymmetric 1,4-addition of α,β-unsaturated
ketones and esters with arylboronic acids proceeded smoothly in
generally high yields and excellent enantioselectivities under
8
,9
mild conditions.
R,SS)-Sulfoxide-MOP (L2) and (R,RS)-sulfoxide-MOP
(
Keywords: Sulfoxide ligand
|
Rhodium catalyst
|
1,4-Addition
(L3) were prepared in enantiomerically and diastereomerically
pure form via the route depicted in Scheme 1. The mCPBA
oxidation of BH3-protected (R)-sulfide-MOP (L1¢BH3) gener-
2
The use of chiral non-C2-symmetric bidentate ligands
containing strong and weak donor heteroatom pairs in tran-
sition-metal-catalyzed enantioselective processes has proven to
be a powerful strategy for controlling the stereochemistry-
determining step through the different trans influence of the two
ligating heteroatoms. Among such ligands, P,S-ligands are
especially attractive, because the extra chirality on sulfur
generated by coordination to the metal center (sulfur chirality)
ated the corresponding sulfoxides L2¢BH and L3¢BH as a
3
3
mixture of diastereomers, which were readily separated by
simple column chromatography to afford 34% and 45% isolated
yields of L2¢BH3 and L3¢BH3, respectively. Deprotection of
each diastereomer using morpholine as a BH3 scavenger
furnished the corresponding sulfoxide-MOP ligands L2 and
L3 in almost quantitative yields. The relative stereochemistry of
L2 and L3 was determined via the single-crystal XRD analysis
of the L2¢PtCl2 and L3¢PtCl2 complexes (Figure 2). The sulfur-
bound phenyl groups of L2¢PtCl2 and L3¢PtCl2, which would
be expected to possess geometries similar to those of the
rhodium complexes generated in the catalytic cycle, were found
to occupy the quasi-axial and quasi-equatorial positions,
respectively.
1
can be utilized as an additional stereocontrol element. Con-
sequently, the labile metal-bound substrate is positioned trans to
the stronger phosphorus donor and adjacent to the stereogenic
sulfur center. We have previously reported the development of
sulfide-containing MOP-type ligands, such as (R)-sulfide-MOP
(
L1) and its various analogues (Figure 1, left), and their
application to the highly enantioselective palladium-catalyzed
allylic alkylation of indoles with 1,3-diphenylpropenyl acetate.
However, because the stereogenic sulfur center generated at the
metal-bound sulfide donor has the potential to undergo inversion
owing to its low energy barrier, the erosion of enantioselectivity
must be considered when using sulfides as donor ligands in
metal-catalyzed asymmetric processes. Sulfoxides, which pos-
sess many potentially attractive features as chiral ligands,
2
The rhodium-catalyzed asymmetric arylation of electron-
deficient alkenes, such as α,β-unsaturated carbonyl compounds,
with arylboronic acids, has emerged as one of the most
convenient and reliable carboncarbon bond-forming processes
3
8
,9
for creating benzylic stereocenters. Therefore, we selected this
important transformation as a test reaction for evaluating L2 and
1
c,4
resist sulfur inversion owing to their inherent central chirality
with a high inversion barrier. Furthermore, when the chiral
sulfoxide also contains additional chirality in the ligand back-
bone, a pair of diastereomers is generated, and their different
stereochemistry can be used as a control element to influence the
reactivity and enantioselectivity of catalytic asymmetric process-
es. Herein, we report the development of a new class of MOP-
Figure 1. (R)-Sulfide-MOP (L1), (R,SS)-sulfoxide-MOP (L2),
and (R,RS)-sulfoxide-MOP (L3).
Scheme 1. Synthesis of sulfoxide-MOP ligands L2 and L3.
© 2018 The Chemical Society of Japan