(R)-3,5-diCF3-SYNPHOS and (R)- p -CF3-SYNPHOS, electron-poor diphosphines for efficient room temperature Rh-catalyzed asymmetric conjugate addition of arylboronic acids

Article abstract of DOI:10.1021/ol200495a

Two new atropisomeric electron-poor chiral diphosphine ligand analogues of SYNPHOS were prepared, and their electronic properties are described. These two ligands afforded high performance for the Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to α,β-unsaturated carbonyl compounds at room temperature.

Full text of DOI:10.1021/ol200495a

ORGANIC
LETTERS
2
011
Vol. 13, No. 11
806–2809
(
R)-3,5-diCF -SYNPHOS and (R)-p-CF -
3
3
2
SYNPHOS, Electron-Poor Diphosphines
for Efficient Room Temperature Rh-
Catalyzed Asymmetric Conjugate Addition
of Arylboronic Acids
Farouk Berhal, Olivier Esseiva, Charles-Henri Martin, Hitoshi Tone, Jean-Pierre
Genet, Tahar Ayad, and Virginie Ratovelomanana-Vidal*
Chimie ParisTech, Laboratoire Charles Friedel, UMR CNRS 7223
1 rue Pierre et Marie Curie, 75231 Paris Cedex 05, France
1
virginie-vidal@chimie-paristech.fr
Received February 23, 2011
ABSTRACT
Two new atropisomeric electron-poor chiral diphosphine ligand analogues of SYNPHOS were prepared, and their electronic properties are
described. These two ligands afforded high performance for the Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to R,β-unsaturated
carbonyl compounds at room temperature.
Chiral bidentate phosphine ligands play an important
role in various homogeneous transition-metal-catalyzed
been reported over the past three decades, atropisomeric
C -symmetric diphosphine ligands have proven to be
highly efficient chiral inducers in many enantioselective
2
1
reactions, thereby making the design and synthesis of
2
transformations. The great majority of axially chiral
novel chiral diphosphine ligands an attractive area of
research. Among the chiral phosphorus ligands that have
ligandsreported todate are moreelectron-rich with respect
to triphenylphosphine, despite the fact that several studies
revealed that electron-poor diphosphine ligands can often
lead to a dramatic variation of the reactivity and enantios-
electivity for some transition-metal-mediated asymmetric
(
1) (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley
&
Sons: New York, 1994; pp 342ꢀ437. (b) Ohkuma, T.; Kitamura, M.;
Noyori, R. In Catalysis Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.;
John Wiley & Sons: New York, 2000; pp 1ꢀ110.
3
4
reactions. For example, Achiwa et al. described the
synthesis of FUPMOP and BIFUP, two biphenyl-
based ligands, which proved to be very efficient in the
Ru-catalyzed asymmetric hydrogenation of methyl 3-oxo-
(2) For reviews, see: (a) McCarthy, M.; Guiry, P. J. Tetrahedron 2001,
5
7, 3809. (b) Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029.
3) (a) Farina, V.; Krishnan, B. J. Am. Chem. Soc. 1991, 113, 9585. (b)
Jendrella, H.; Li, C. H.; Paulus, E. Tetrahedron: Asymmetry 1994, 5,
297. (c) Benincori, T.; Brenna, E.; Sannicolo, F.; Trimarco, L.; Antognazza,
(
1
5
P.; Cesarotti, E. J. Chem. Soc., Chem. Commun. 1995, 685. (d) Benincori,
T.; Brenna, E.; Sannicolo, F.; Trimarco, L.; Antognazza, P.; Cesarotti,
E.; De martin, F.; Pilati, T. J. Org. Chem. 1996, 61, 6244. (e) Kojima, A.;
Boden, C. D. J.; Shibasaki, M. Tetrahedron Lett. 1997, 38, 3459. (f)
Kojima, A.; Honzawa, S.; Boden, C. D. J.; Shibasaki, M. Tetrahedron
Lett. 1997, 38, 3455. (g) Scalone, M.; Waldmeier, P. Org. Process Res.
Dev. 2003, 7, 418. (h) Driessen-Hoelscher, B.; Kralik, J.; Agel, F.;
Steffens, C.; Hu, C. Adv. Synth. Catal. 2004, 346, 979. (i) Flanagan,
P. S.; Guiry, P. J. J. Organomet. Chem. 2006, 691, 2125.
butanoate with ee values up to 99%. Keay et al. reported
the use of BINAPFu, a biheteroaryl ligand, in an asymmetric
Heck reaction between 2,3-dihydrofuran and phenyl
(4) Murata, M.; Morimoto, T.; Achiwa, K. Synlett 1991, 882.
(5) Andersen, N. G.; Parvez, M.; Keay, B. A. Org. Lett. 2000, 2, 2817.
1
0.1021/ol200495a r 2011 American Chemical Society
Published on Web 05/03/2011

6
triflate. Recently, Sakai et al. demonstrated that the
enantioselective conjugate addition of arylboronic acids to
1
2
catalytic activity for Rh-catalyzed 1,4-addition of aryl-
boronic acids at room temperature could be significantly
improved by using an MeO-F -BIPHEP ligand. Another
R,β-unsaturated carbonyl compounds under very mild
reaction conditions.
Our synthetic approach to enantiopure ligands 6a and
6b is outlined in Scheme 1.
1
2
representative example of an electron-poor atropisomeric
diphosphine, which displays better activity and enantios-
electivity compared to electron-rich diphosphines for
7
8
several transition-metal-catalyzed CꢀC and CꢀH bond
9
formations, is the DIFLUORPHOS ligand bearing a
Scheme 1. Synthesis of Electron-Poor Ligands 6a and 6b
bi(difluorobenzodioxole)backbone that has been devel-
oped in our group. These results, in conjunction with our
9
,10
continued interest in ligand design,
two new electron-poor chelating diphosphines derived
led us to develop
1
1
from SYNPHOS containing one or two trifluoromethyl
functional groups on each of the phosphorus phenyl
rings: (R)-3,5-diCF -SYNPHOS 6a and (R)-p-CF -SYN-
3
3
PHOS 6b. We report herein a concise synthesis of the title
compounds, the evaluation of their electronic properties,
and their applications in HayashiꢀMiyaura Rh-catalyzed
(
6) (a) Korenaga, T.; Osaki, K.; Maenishi, R.; Sakai, T. Org. Lett.
009, 11, 2325. (b) Korenaga, T.; Maenishi, R.; Hayashi, K.; Sakai, T.
Adv. Synth. Catal. 2010, 352, 3247.
7) For representative examples, see: (a) Sibi, M. P.; Tatamidani, H.;
2
(
Patil, K. Org. Lett. 2005, 7, 2571. (b) Yamamoto, Y.; Yamamoto, H.
Angew. Chem., Int. Ed. 2005, 44, 7082. (c) Wadamoto, M.; Yamamoto,
H. J. Am. Chem. Soc. 2005, 127, 14556. (d) Oisaki, K.; Zhao, D.; Kanai,
M.; Shibasaki, M. J. Am. Chem. Soc. 2007, 129, 7439. (e) Pinto, A.; Jia,
Y.; Neuville, L.; Zhu, J. Chem.;Eur. J. 2007, 13, 961. (f) Du, L.; Xu, L.-
W.; Shimizu, Y.; Oisaki, K.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc.
In the first step, commercially available bromobenzo-
1,4-dioxane 1 was readily phosphorylated using an Arbu-
zov type reaction inthe presenceof triethyl phosphiteand a
catalytic amount of nickel dichloride at a constant tem-
perature of 160 °C for 2 h to give diethyl phosphonate 2 in
2
(
1
008, 130, 16146. (g) Umeda, R.; Studer, A. Org. Lett. 2007, 9, 2175.
h) Liao, X.; Weng, Z.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130,
95. (i) Navarre, L.; Martinez, R.; Genet, J.-P.; Darses, S. J. Am. Chem.
Soc. 2008, 130, 6159.
8) (a) Jeulin, S.; Duprat de Paule, S.; Ratovelomanana-Vidal, V.; Genet,
J.-P.; Champion, N.; Dellis, P. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5799.
b) Deport, C.; Buchotte, M.; Abecassis, K.; Tadaoka, H.; Ayad, T.;
Ohshima, T.; Genet, J.-P.; Mashima, K.; Ratovelomanana-Vidal, V. Synlett
007, 2743. (c) Tadaoka, H.; Cartigny, D.; Nagano, T.; Gosavi, T.; Ayad, T.;
(
9
5% yield. Ortho-lithiation of 2 by LDA at ꢀ78 °C in THF
(
and further oxidative coupling with anhydrous ferric chlor-
ide furnished the racemic bis(diethyl) phosphonate 3 in a
50% unoptimized yield. The optical resolution of racemic
2
Genet, J.-P.; Ohshima, T.; Ratovelomanana-Vidal, V.; Mashima, K.
Chem.;Eur. J. 2009, 15, 9990. (d) Cartigny, D.; Nagano, T.; Ayad, T.;
Genet, J.-P.; Ohshima, T.; Mashima, K.; Ratovelomanana-Vidal, V. Adv.
Synth. Catal. 2010, 352, 1886. (e) Prevost, S.; Gauthier, S.; Cano de Andrade,
M. C.; Mordant, C.; Touati, A. R.; Lesot, P.; Savignac, P.; Ayad, T.;
Phansavath, P.; Ratovelomanana-Vidal, V.; Genet, J.-P. Tetrahedron:
Asymmetry 2010, 21, 1436.
3
was carried out in a mixture of CHCl /AcOEt (1:3) at room
3
temperature. Both enantiomers 3a and 3b can be obtained
on a multigram scale with enantiomeric excesses up to 99%
by using 2,3-dibenzoyltartaric acid ((þ)- or (ꢀ)-DBTA) as
the resolving reagents. The bis(phosphine oxide) 5 was
then obtained in 87% yield using a one-pot two-step pro-
cedure involving conversion of 3 into the corresponding
bis(phosphonic dichloride) derivative 4 followed by treat-
ment with an excess of the required aryl Grignard reagents.
(
9) Jeulin, S.; Duprat de Paule, S.; Ratovelomanana-Vidal, V.;
Genet, J.-P.; Champion, N.; Dellis, P. Angew. Chem., Int. Ed. 2004,
3, 320.
10) (a) Guerreiro, P.; Ratovelomanana-Vidal, V.; Genet, J.-P.;
4
(
Dellis, P. Tetrahedron Lett. 2001, 42, 3423. (b) Duprat de Paule, S.;
Champion, N.; Ratovelomanana-Vidal, V.; Genet, J.-P.; Dellis, P.
French Patent 2830254, 2001. (c) Duprat de Paule, S.; Champion, N.;
Ratovelomanana-Vidal, V.; Genet, J.-P.; Dellis, P. WO Patent 03029259,
2
003. (d) Duprat de Paule, S.; Jeulin, S.; Ratovelomanana-Vidal, V.; Genet,
J.-P.; Champion, N.; Deschaux, G.; Dellis, P. Org. Process Res. Dev. 2003, 7,
99.
11) (a) Duprat de Paule, S.; Jeulin, S.; Ratovelomanana-Vidal, V.;
Genet, J.-P.; Champion, N.; Dellis, P. Eur. J. Org. Chem. 2003, 1931.
b) Labeeuw, O.; Blanc, D.; Phansavath, P.; Ratovelomanana-Vidal, V.;
Finally, HSiCl reduction of compound 5 in the presence
3
1
3
of PPh as an oxygen acceptor afforded the enantiomeri-
3
3
cally pure ligands 6a and 6b, respectively, in 79% and 78%
yields. The configuration of (R)-6 was assigned as R by
comparison of its hydrogenation products with those
(
(
Genet, J.-P. Eur. J. Org. Chem. 2004, 2352. (c) Touati, R.; Ratoveloma-
nana-Vidal, V.; Ben Hassine, B.; Genet, J.-P. Tetrahedron: Asymmetry
1
1
obtained with its parent compound, (R)-SYNPHOS.
2006, 17, 3400. (d) Blanc, D.; Madec, J.; Popowyck, F.; Ayad, T.;
Phansavath, P.; Ratovelomanana-Vidal, V.; Genet, J.-P. Adv. Synth.
Catal. 2007, 349, 1592. (e) Mordant, C.; Reymond, S.; Tone, H.;
Lavergne, D.; Touati, R.; Ben Hassine, B.; Ratovelomanana-Vidal,
V.; Genet, J.-P. Tetrahedron 2007, 63, 6115. (f) Pautigny, C.; Jeulin, S.;
Ayad, T.; Genet, J.-P.; Ratovelomanana-Vidal, V. Adv. Synth. Catal.
(12) (a) Takaya, Y.; Ogasawara, M.; Hayashi, T.; Sakai, M.;
Miyaura, N. J. Am. Chem. Soc. 1998, 120, 5579. (b) Hayashi, T.;
Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem. Soc. 2002,
124, 5052. For reviews, see:(c) Hayashi, T. Synlett 2001, 879.
(d) Hayashi, T.; Yamasaki, K. Chem. Rev. 2003, 103, 2829. (e) Fagnou,
K.; Lautens, M. Chem. Rev. 2003, 103, 169. (f) Yoshida, K.; Hayashi, T.
In Modern Rhodium-Catalyzed Organic Reactions; Evans, P. A., Ed.;
Wiley-VCH: Weinheim, 2005; Chapter 3. (g) Edwards, H. J.; Hargrave, J. D.;
Penrose, S. D.; Frost, C. G. Chem. Soc. Rev. 2010, 39, 2093.
2008, 350, 2525. (g) Roche, C.; Labeeuw, O.; Haddad, M.; Ayad, T.;
Genet, J.-P.; Ratovelomanana-Vidal, V.; Phansavath, P. Eur. J. Org.
Chem. 2009, 23, 3977. (h) Tone, H.; Buchotte, M.; Mordant, C.; Guittet,
E.; Ayad, T.; Ratovelomanana-Vidal, V. Org. Lett. 2009, 11, 1995. (i)
Pautigny, C.; Debouit, C.; Vayron, P.; Ayad, T.; Ratovelomanana-
Vidal, V. Tetrahedron: Asymmetry 2010, 21, 1382.
(13) Wu, H.-C.; Yu, J.-Q.; Spencer, J. B. Org. Lett. 2004, 6, 4675.
Org. Lett., Vol. 13, No. 11, 2011
2807

Having ligands 6a and 6b in hand, attention was then
focused on the evaluation of their electronic properties,
since subtle changes in the electronic properties of the
chiral ligand can often lead to a dramatic variation of the
catalytic activity in metal-catalyzed asymmetric reactions.
The electronic coordination mode of diphosphine ligands
to a transition metal involves σ-donation from the ligand
to the metal and π-retrodonation from the ligand to
the metal. A valuable method for the evaluation of the
diphosphines (R)-3,5-diCF -SYNPHOS 6a and (R)-p-CF -
3 3
SYNPHOS 6b containing one or two trifluoromethyl func-
tional groups, respectively, on each phosphorus phenyl
ring are the best π-acceptors compared to nonfluorinated
SYNPHOS ligands (compare entries 1ꢀ2 vs 3ꢀ5).
To evaluate the potential of our ligands 6a and 6b, the
Rh-catalyzed asymmetric 1,4-addition of arylboronic
1
2
acids to R,β-unsaturated carbonyl compounds was cho-
sen as a model reaction since it has been demonstrated that
electron-poor ligands would accelerate both transmetala-
σ-donation ability of a phosphine group is to measure the
coupling constant of the corre-
1
magnitude of the J
16
17
12
tion and insertion steps in the catalytic cycle. In the
first set of experiments, we studied the addition of aryl-
boronic acids 8 to 2-cyclohexenone 7a using 1.5 mol % of
[RhCl(C H ) ] and 3 mol % of the moreelectron-deficient
P,Se
1
sponding diphosphine(V) selenide. Indeed, Allen and
4
1
4a
Taylor have reported
that phosphorus(V) selenides
incorporating electron-withdrawing groups exhibit larger
coupling constants than those for phosphorus(V) selenides
bearing electron-donating groups, which indicates an in-
creasein the scharacterofthephosphoruslone-pairorbital
2
4 2 2
ligand (R)-6a in the presence of KOH in toluene/H O (9/1)
2
at 20 °C. The results are summarized in Table 2.
(
i.e., a less basic phosphine). To estimate the donor ability
of phosphorus centers in ligands 6a and 6b, we therefore
prepared the diselenide derivatives by the oxidation of the
corresponding diphosphines with elemental selenium in
refluxing chloroform and compared it with other SYN-
PHOS-derived ligands. The results depicted in Table 1
Table 2. Rhodium Catalyzed 1,4-Addition of Arylboronic
Acids to Cyclohexenone
clearly show that (R)-3,5-diCF -SYNPHOS 6a (Table 1,
3
entry 1, 773.9 Hz) and (R)-p-CF -SYNPHOS 6b (Table 1,
3
1
entry 2, 758.1 Hz) have significantly higher J
coupling
constant values among all the SYNPHOS ligand family
P,Se
a
b
entry
Ar of boronic acid 8
C H (8a)
product
yield (%)
ee (%)
c
1
(Table 1, entries 3ꢀ5), including the electron-poor DI-
FLUORPHOS (Table 1, entry 6, 749 Hz), which indicates
a lower σ-donor ability.
9aa
9aa
9ab
9ac
9ad
9ae
9af
20
95
90
90
84
50
81
82
86
81
98
99
99
99
99
96
99
99
93
90
6
6
5
5
2
C
H
(8a)
3
4-MeC (8b)
H
6 4
4
6 3
3,5-diMeC H (8c)
5
4-MeOC
3-MeOC
6
H
H
4
(8d)
(8e)
6
6
4
7
4-BrC
3-ClC
6
H
4
(8f)
Table 1. Electronic Properties of Ligands 6a and 6b
8
6
H
4
(8g)
9ag
9ah
9ai
νCO of
9
6 4
2-MeC H (8h)
1
31
77
J( Pꢀ Se) [RhCl(L*)(CO)]
10
1-Naphthyl (8i)
ꢀ
1
entry
diphosphine (L*)
in (Hz)
(cm )
a
b
Isolated yield. Determined by stationary phase chiral HPLC
c
analysis. (R)-SYNPHOS was used instead of (R)-6a.
1
2
3
4
5
6
(R)-3,5-diCF
3
-SYNPHOS 6a
773.9
758.1
740
2032
2015
2001
2000
1997
2015
(R)-p-CF
3
-SYNPHOS 6b
(R)-SYNPHOS
(R)-3,5-CH -SYNPHOS
(R)-p-CH -SYNPHOS
(R)-DIFLUORPHOS
734
A high chemical yield and excellent enantioselectivity up
to 99% for the 1,4-adduct 9aa was obtained in the reaction
between phenylboronic acid 8a and 2-cyclohexenone 7a.
This excellent result suggests that the strong electron-
withdrawing effect of the trifluoromethyl groups probably
plays a crucial role in the reactivity of the reaction since,
under similar reaction conditions, only a 20% yield was
obtained when the parent (R)-SYNPHOS ligand was used
(Table 2, entry1 vs2). The dataofTable 2 clearlyshow that
the electron-donating substituents onthe phenylring of the
boronic acids did not affect the selectivity of the reaction,
providing the expected products 9abꢀ9ae in high enantios-
electivity (Table 2, entries 3ꢀ6). A similarly high selectivity
was obtained when arylboronic acids bearing electron-with-
drawing groups were employed (Table 2, entries 7 and 8).
In contrast, the use of sterically more hindered arylboronic
3
3
733
749
Electronic donorꢀacceptor properties of new dipho-
sphines 6a and 6b have also been estimated by studying
the carbonyl stretching frequencies of the corresponding
[RhCl(diphosphine)(CO)] complexes, which were prepared
by the reaction of [RhCl(CO) ] with diphosphine ligands
2
2
15
(
(
Table 1). The higher the carbonyl stretching frequency
νCO), the lower the electronic density on the rhodium center,
and the higher the π-acidic character of the ligand. From this
electronic comparative study, we can conclude that the new
(
14) (a) Allen, D. W.; Taylor, B. F. J. Chem. Soc., Dalton Trans. 1982,
1. (b) Mashima, K.; Kusano, K. H.; Sato, N.; Matsumura, Y. I.; Nozaki,
5
K.; Kumobayashi, H.; Sayo, N.; Hori, Y.; Ishizaki, T.; Akutagawa, S.;
Takaya, H. J. Org. Chem. 1994, 59, 3064. (c) Suarez, A.; Mendes-Rojas,
M. A.; Pizzano, A. Organometallics 2002, 21, 4611.
(16) Clarke, M. L.; Heydt, M. Organometallics 2005, 24, 6475.
(17) Chen, Q.; Lin, B.-L.; Fu, Y.; Liu, L.; Guo, Q.-X. Res. Chem.
Intermed. 2005, 31, 759.
(15) (a) Vallarino, L. J. Chem. Soc. 1957, 2287. (b) Sanger, A.
J. Chem. Soc., Dalton Trans. 1977, 120.
2
808
Org. Lett., Vol. 13, No. 11, 2011

acids, such as 2-tolylboronic acid and 1-naphthylboronic
acid, gave 9ah and 9ai, respectively, in good yields but with
slightly lower enantioselectivity, probably due to steric
hindrance (Table 2, entries 9 and 10).
In the next stage, the substrate scope of this Rh-catalyzed
asymmetric 1,4-addition reaction was examined. Several
cyclic and acyclic R,β-unsaturated carbonyl compounds were
allowed to react with phenylboronic acid, using 1.5 mol %
of a rhodium catalyst bearing (R)-6a or (R)-6b as ligands in
From the results listed in Table 3, we can see that better
catalytic activity in terms of both yield and enantioselec-
tivity was obtained in the reaction between phenylboronic
acid 8a and cyclic R,β-unsaturated ketones 7aꢀc when
ligand (R)-6a was employed (Table 3, entries 1ꢀ6). In
contrast, (R)-6b proves to be a much more efficient ligand
for this reaction when cyclic R,β-unsaturated lactones
7dꢀe were used as substrates (Table 3, entries 7ꢀ10). In
the cases of acyclic R,β-unsaturated ketones 7f and 7g, no
significant difference between the two ligands was ob-
served regarding the enantioselectivity, although the 1,4-
adducts 9fa and 9ga were isolated in higher yields when the
reaction was run in the presence of (R)-6a (Table 3, entries
the presence of KOH in toluene/H O (9/1) at 20 °C.
2
Table 3. Rhodium Catalyzed 1,4-Addition of Phenylboronic
Acid to R,β-Unsaturated Carbonyl Compounds
1
with a 93% yield was obtained with (R)-3,5-diCF -
1ꢀ14). Remarkably, enantioselectivity up to 88%
3
SYNPHOS 6a for the reaction of phenylboronic acid
8
a with N-methylmaleimide 7h, which is one of the
trickiest substrates of particular interest because the 1,
-adducts are synthetically and biologically important
4
1
8
R-substituted succinimides. It should be noted that
this result represents by far the best selectivity obtained
for these types of compounds compared to other atro-
1
9
pisomeric diphosphine ligands.
In summary, we have synthesized new electron-poor
atropisomeric diphosphines containing one or two tri-
fluoromethyl functional groups on each diphenylpho-
sphine substituent. A comparative study of their electronic
a
b
properties showed that (R)-3,5-diCF -SYNPHOS and
3
entry
substrate
ligand
product
yield (%)
ee (%)
(
R)-p-CF -SYNPHOS possess a lower σ-donor ability
3
1
2
(R)-6a
(R)-6b
9aa
9aa
95
92
99
99
and the best π-acceptor ability compared to nonfluori-
nated SYNPHOS ligands. These ligands proved to be
highly effective in the Rh-catalyzed asymmetric 1,4-addi-
tion of arylboronic acids to a variety of R,β-unsaturated
carbonyl compounds at room temperature. Studies on the
applications of these new diphosphines to various transi-
tion-metal-catalyzed asymmetric processes are ongoing.
7
7
7
7
7
a
b
c
3
4
(R)-6a
(R)-6b
9ba
9ba
84
69
96
88
5
6
(R)-6a
(R)-6b
9ca
9ca
84
80
99
96
7
8
(R)-6a
(R)-6b
9da
9da
70
80
90
97
d
e
Acknowledgment. We thank the Centre National de la
Recherche Scientifique (CNRS) and the Minist ꢀe re de
l’Education et de la Recherche for financial support.
9
(R)-6a
(R)-6b
9ea
9ea
48
77
77
97
1
0
c
1
1
(R)-6a
(R)-6b
9fa
9fa
92
57
93
93
c
2
7f
1
Supporting Information Available. Experimental pro-
cedures and compound characterization data. This ma-
terial is available free of charge via Internet at http://pubs.
acs.org.
1
1
3
4
(R)-6a
(R)-6b
9ga
9ga
76
65
97
99
7
g
d
1
5
7h
(R)-6a
9ha
93
88
(18) Curtin, M. L.; Garland, R. B.; Heyman, H. R.; Frey, R. R.;
Michaelides, M. R.; Li, J.; Pease, L. J.; Glaser, K. B.; Marcotte, P. A.;
Davidsen, S.; K. Bioorg. Med. Chem. Lett. 2002, 12, 2919.
a
b
Isolated yield. Determined by stationary phase chiral HPLC
c
analysis. Reaction run for 60 h using 3 mol % of [Rh(C
mol % of ligand. Reaction run in dioxane/H O (9/1) at 50 °C.
2
H
4
)
2
Cl] and
2
d
6
2
(
19) Shintani, R.; Ueyama, K.; Yamada, I.; Hayashi, T. Org. Lett.
2
004, 6, 3425.
Org. Lett., Vol. 13, No. 11, 2011
2809