Novel axially chiral phosphine ligand with a fluoro alcohol moiety for Rh-catalyzed asymmetric arylation of aromatic aldehydes

Article abstract of DOI:10.1021/ol100697a

A new chiral phosphine ligand (R)-1 possessing a fluoroalcohol moiety was prepared. The (R)-1-coordinated Rh(I) complex showed an excellent catalytic activity for asymmetric 1,2-addition of arylboronic acids to aldehydes to afford highly enantioenriched diarylmethanols. The fluoroalcohol moiety in ligand (R)-1 plays a pivotal role for the high enantioselectivity of the present Rh(I)-catalyzed transformation.

Full text of DOI:10.1021/ol100697a

ORGANIC
LETTERS
2010
Vol. 12, No. 11
2520-2523
Novel Axially Chiral Phosphine Ligand
with a Fluoro Alcohol Moiety for
Rh-Catalyzed Asymmetric Arylation of
Aromatic Aldehydes
Satoshi Morikawa, Kyosuke Michigami, and Hideki Amii*
Department of Chemistry, Graduate School of Science,
Kobe UniVersity, Kobe 657-8501, Japan
amii@kobe-u.ac.jp
Received March 27, 2010
ABSTRACT
A new chiral phosphine ligand (R)-1 possessing a fluoroalcohol moiety was prepared. The (R)-1-coordinated Rh(I) complex showed an excellent
catalytic activity for asymmetric 1,2-addition of arylboronic acids to aldehydes to afford highly enantioenriched diarylmethanols. The fluoroalcohol
moiety in ligand (R)-1 plays a pivotal role for the high enantioselectivity of the present Rh(I)-catalyzed transformation.
Enantiopure diarylmethanols are important compounds be-
cause of the biological activity of their derivatives, such as
neobenodine and orphenadrine.1 Besides asymmetric hydro-
genation of diarylketones,2 catalytic asymmetric addition of
carbon-based nucleophiles to carbonyl compounds provides
a direct route for synthesis of enantiomerically enriched
diarylmethanols.3 Arylboronic acids are among the most
convenient reagents because of their stability and easy
handling, and therefore they have been used for a wide
repertoire of organic transformations.4,5 In 1998, Miyaura
reported the first example of Rh-catalyzed asymmetric 1,2-
addition of PhB(OH)2 to 1-naphthaldehyde to give the
diarylmethanol in 41% ee.6 Despite the synthetic advantage
to use arylboronic acids, the progress in catalytic enantiose-
lective arylation reactions of aldehydes using ArB(OH)2 has
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Chem. Pharm. Bull. 2004, 52, 818–829, and references therein.
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Lett. 2000, 2, 659–662. (b) Lee, C.-T.; Lipshutz, B. H. Org. Lett. 2008, 10,
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.
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combination of ArB(OH)2 (or Ar3B) and Et2, see: (a) Bolm, C.; Rudolph,
J. J. Am. Chem. Soc. 2002, 124, 14850–14851. (b) Rudolph, J.; Schmidt,
F.; Bolm, C. AdV. Synth. Catal. 2004, 346, 867–872. (c) Ji, J.-X.; Wu, J.;
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Process Res. DeV. 2007, 11, 560–567. (g) Ruan, J.-W.; Lu, G.; Xu, L.; Li,
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10.1021/ol100697a  2010 American Chemical Society
Published on Web 05/12/2010

been slow as a result of their difficulty;7-10 the lack of
suitable catalyst systems has limited their further develop-
ment during the past decade. Recently, excellent results on
enantioselective carbonyl addition of arylboron reagents
have been reported by several groups.11-17 In particular,
Yamamoto and Miyaura demonstrated highly enantioselec-
tive addition of arylboronic acids to aldehydes catalyzed by
Ru(II)-bipam complexes.17 For the investigation of a novel
catalyst system,the design of a new chiral ligand is a key
challenge to achieve highly stereocontrolled reactions. Using
bifunctional molecular catalysts containing transition metals
and ancillary ligands with hydrogen bond donor groups (so-
called “concerto catalysis”) is one of the most elegant and
efficient methods for catalytic asymmetric transforma-
tion.18-22 Herein, we report a preparation of a new chiral
phosphine ligand (R)-1 endowed with a fluoroalcohol moiety
and its application to rhodium-catalyzed asymmetric 1,2-
addition of arylboronic acids to aldehydes to give diaryl-
methanols with high enantioselectivities (Scheme 1).
Scheme 1
(7) Focken, T.; Rudolph, J.; Bolm, C. Synthesis 2005, 429–436
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(c) Arao, T.; Suzuki, K.; Kondo, K.; Aoyama, T. Synthesis 2006, 3809–
Enantiopure binaphthyl ligand (R)-1 tethered to a fluoro-
alcohol moiety was synthesized via nucleophilic transforma-
tions of ester (R)-2,23 which was readily prepared from (R)-
BINOL (Scheme 2). Sequential introduction of trifluoromethyl
3814
(9) Duan, H.-F.; Xie, J.-H.; Shi, W.-J.; Zhang, Q.; Zhou, Q.-L. Org.
Lett. 2006, 8, 1479–1481
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Commun. 2009, 5713–5715
.
.
.
.
Scheme 2
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Chem., Int. Ed. 2006, 45, 3353–3356. (b) Toullec, P. Y.; Jagt, R. B. C.; de
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K.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2009, 131, 6946–6948
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.
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.
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48, 4115–4117. (b) Yamamoto, K.; Tsurumi, K.; Sakurai, F.; Kondo, K.;
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24
ronic acids, see: Yamamoto, Y.; Kurihara, K.; Miyaura, N. Angew. Chem.,
groups to (R)-2 by the use of CF3SiMe3 provided bis(tri-
Int. Ed. 2009, 48, 4414–4416
.
fluoromethyl)methanol (R)-4. Reduction of phosphine oxide
(R)-4 by HSiCl3 afforded phosphine (R)-1 without loss of
enantiopurity.
Next, the new rhodium complex with chiral ligand (R)-1
was used for the asymmetric arylation of aldehydes with
arylboronic acids. A mixture of p-tolylaldehyde (5a) and
phenylboronic acid (6a) in xylene/H2O was heated at 60 °C
for 24 h in the presence of t-BuONa (2 equiv) and a catalytic
amount of Rh(I) complex prepared in situ by mixing
dinuclear complex [Rh(CH2dCH2)2Cl]2 (1.5 mol %) with
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Org. Lett., Vol. 12, No. 11, 2010
2521

(R)-1 (3 mol %) to afford diarylmethanol 7aa in 83% yield
arylboronic acids 6 to various aldehydes 5 were examined.
with 69% ee (Table 1, entry 1). Enhancement of the
Representative results are summarized in Table 2. To achieve
Table 1. Rh-Catalyzed Addition of Phenylboronic Acid to
p-Tolylaldehyde: Screening of Ligands and Solvents
Table 2. Rh-Catalyzed 1,2-Addition of Arylboronic Acids to
Aromatic Aldehydes
entry
Ar1
Ar2
Ph (6a)
Ph (6a)
Ph (6a)
Ph (6a)
Ph (6a)
Ph (6a)
yield, %a ee, %b
1
2
4-MeC6H4 (5a)
2,4-Me2C6H3 (5b)
4-iPrC6H4 (5c)
4-iPrC6H4 (5c)
4-MeOC6H4 (5d)
4-MeOC6H4 (5d)
78 (7aa) 82 (R)
75 (7ba) 82 (R)
96 (7ca) 80 (R)
68 (7ca) 86 (R)
99 (7da) 81 (R)
56 (7da) 90 (R)
96 (7ea) 81 (R)
7aa
3
entry chiral ligand
solvent
xylene
ClCH2CH2Cl
xylene
ClCH2CH2Cl
xylene
ClCH2CH2Cl
xylene
yield, %a ee, %b (config)
4c
5
1
2
3
4
5
6
7
8
(R)-1
(R)-1
(R)-8
(R)-8
(R)-9
(R)-9
(R)-10
(R)-10
83
78
9
69 (R)
82 (R)
0
6c
7
3,4-(OCH2O)C6H3 (5e) Ph (6a)
0
c
8
4-MeC6H4 (5a)
Ph (5f)
4-MeC6H4 (5a)
4-AcC6H4 (6b) 57 (7ab) 80 (+)
4-ClC6H4 (6c) 99 (7 fc) 87 (S)
4-ClC6H4 (6c) 99 (7ac) 80 (S)
4-ClC6H4 (6c) 64 (7ac) 88 (S)
3-ClC6H4 (6d) 99 (7ad) 84 (S)
4-ClC6H4 (6c) 84 (7dc) 89 (S)
3-ClC6H4 (6d) 73 (7dd) 92 (S)
4-ClC6H4 (6c) 93 (7gc) 90 (S)
3-ClC6H4 (6d) 74 (7gd) 91 (S)
9c
10
41
<3
0
16 (S)
c
c
c
11c 4-MeC6H4 (5a)
12
ClCH2CH2Cl
0
4-MeC6H4 (5a)
13c 4-MeOC6H4 (5d)
14c 4-MeOC6H4 (5d)
15c 2-thienyl (5g)
16c 2-thienyl (5g)
a Isolated yield. b Enantiomeric excesses were determined by HPLC
analyses (Daicel Chiralcel OD-H). c Enantiomeric excesses were not
determined.
a Isolated yield. b Enantiomeric excesses were determined by HPLC
analyses (Daicel Chiralcel OD-H, OB, Chiralpak AD-H, or AS). c These
reactions were carried out at 30 °C for 24 h.
high enantioselectivities, several recent examples of catalytic
arylation of aldehydes require the presence of ortho substit-
uents on the benzene ring of aromatic aldehydes9,16 or that
of arylboronic acids.11 In our case, the position of substituents
of aldehydes 5 and arylboronic acids 6 is not restrictive for
obtaining good enantioselectivities (entries 1-16). When the
reactions were carried out at 30 °C, enantioselectivities were
improved (entries 4, 6, 9, 11, 13, and 15). Furthermore, the
present transformation is tolerant of functional groups of
arylboronic acids 6 (entries 8-16). The combination of
aromatic aldehydes 5a-g bearing electron-donating groups
on the aryl rings and arylboronic acids 6 possessing electron-
withdrawing substituents on the aryl rings provided 7 with
high enantioselectivities. In particular, the reactions of
p-anisaldehyde (5d) and 2-thiophenecarboxaldehyde (5g)
with 3-chlorophenylboronic acid (6d) afforded the adducts
7dd and 7gd in 73% isolated yield with 92% ee and in 74%
isolated yield with 91% ee, respectively (entries 14 and 16).
A plausible mechanism for the present Rh(I)-catalyzed
arylation is pictured in Scheme 3A. In the first step,
transmetalation of arylboronic acids 4 with hydroxy
rhodium(I) complex 11, which is generated from
[Rh(CH2dCH2)2Cl]2 and phosphine ligand (R)-1 upon treat-
ment with aqueous base, gives arylrhodium(I) species 12.
Next, coordination of 12 with aldehydes 5 provides the
intermediates 13, which undergo insertion of the C-O double
enantioselectivity (82% ee) in arylation of aldehyde 5a was
observed employing a dichloroethane-H2O solvent system
(entry 2). On the other hand, phosphine ligands (R)-8 and
(R)-9 with (nonfluorinated) alcohol moieties displayed lower
catalytic activitities and enantioselectivities (entries 3-6).
Furthermore, the use of a ligand possessing a carboxy group
was not effective for the present Rh-catalyzed arylation
(entries 7 and 8). Therefore, the presence of a weakly acidic
fluoroalcohol moiety25,26 in the ligand (R)-1 leads to a
significant increase of the product yield and enantioselectivity
in 1,2-addition.
With the optimized reaction conditions (at 60 °C, in
ClCH2CH2Cl/H2O) asymmetric 1,2-addition reactions of
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Tetrahedron: Asymmetry 2006, 17, 2654–2658. (b) Sokeirik, Y. S.; Mori,
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Hoshina, A.; Omote, M.; Sato, K.; Tarui, A.; Kumadaki, I.; Ando, A. Chem.
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.
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tion using fluorinated alcohol solvents, see: (a) Abe, H.; Amii, H.; Uneyama,
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2522
Org. Lett., Vol. 12, No. 11, 2010

high enantioface selection of the Rh-catalyzed arylation of
aldehydes is achieved. As shown in Scheme 3B, addition of
the aryl groups in 13 to the coordinated aldehydes from the
re face leads to the formation of adduct 14 in a stereoselective
manner. The chirality recognition ability is substantially high;
the chiral coordination environment in the intermediate 13
would be created by the bulky trifluoromethyl groups of
phosphine ligand (R)-1.
Scheme 3
In summary, we have developed a new enantioselective
transformation involving C-C bond formation. The axially
chiral phosphine compound (R)-1 tethered to a fluoroalcohol
moiety was found to be an effective ligand for Rh(I)-
catalyzed asymmetric arylation of aromatic aldehydes with
arylboronic acids affording enantiomerically enriched diaryl
methanols. Further investigation to expand the scope of the
present protocol for the synthesis of bioactive diaryl metha-
nols is in progress.
Acknowledgment. Funding from the Ministry of Educa-
tion, Culture, Sports, Science and Technology of Japan
(Grant-in-Aid for Scientific Research on Priority Areas
“Chemistry of Concerto Catalysis”, No. 20037050, Grant-
in-Aid for Scientific Research (B), No. 18350054) and the
Hyogo Science and Technology Association is gratefully
acknowledged. We would like to thank Prof. Masahiko
Hayashi (Kobe University) for his useful suggestions. We
are grateful to Central Glass Co., Ltd. for a gift of Tf2O.
bonds of aldehyde ligands into the C-Rh bonds in 13 to
form alkoxyrhodium(I) complexes 14.27 The subsequent
hydrolysis of 14 results in the liberation of diarylmethanols
7 and the regeneration of the active Rh(I) species 11 to make
possible the reactions catalytic in rhodium. The enantiose-
lectivity observed with the chiral ligand (R)-1 suggests that
Supporting Information Available: Details of experi-
mental procedures and characterization data (1H, 13C and 19
F
NMR, IR, and mass spectrometry) for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(27) For directly observed transmetalation from boron to rhodium, see:
Zhao, P.; Incarvito, D. C.; Hartwig, J. F. J. Am. Chem. Soc. 2007, 129,
1876–1877.
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