Room-temperature Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to maleimides and enones in the presence of CF3-substituted MeOBIPHEP analogues

Article abstract of DOI:10.1021/jo201073y

A Rh-based catalytic system implying electron-poor MeOBIPHEP analogues has been developed for the 1,4-addition of boronic acids to maleimides and enones under mild conditions at room temperature and led to succinimide derivatives and arylated cyclic ketones in good to excellent yields and ee. We uncovered the crucial role of the electronic and steric properties of diphosphine ligand and observed a strong boronic acid/ligand dependency in the case of maleimide derivatives and substrate/ligand matching in the case of cyclic enones.

Full text of DOI:10.1021/jo201073y

NOTE
pubs.acs.org/joc
Room-Temperature Rh-Catalyzed Asymmetric 1,4-Addition
of Arylboronic Acids to Maleimides and Enones in the Presence of
CF3-Substituted MeOBIPHEP Analogues
Florent Le Boucher d’Herouville,† Anthony Millet,† Michelangelo Scalone,*,‡ and Vꢀeronique Michelet*,†
†Chimie ParisTech UMR 7223, Laboratoire Charles Friedel, 11 rue P. et M. Curie, 75231 Paris Cedex 05, France
‡Process Research & Synthesis CoE Catalysis, F. Hoffmann-La Roche AG, CH-4070 Basel, Switzerland
S Supporting Information
b
ABSTRACT: A Rh-based catalytic system implying electron-poor
MeOBIPHEP analogues has been developed for the 1,4-addition of
boronic acids to maleimides and enones under mild conditions at
room temperature and led to succinimide derivatives and arylated
cyclic ketones in good to excellent yields and ee. We uncovered the
crucial role of the electronic and steric properties of diphosphine
ligand and observed a strong boronic acid/ligand dependency in
the case of maleimide derivatives and substrate/ligand matching in
the case of cyclic enones.
he twentieth century has seen an influx of chiral atropiso-
meric ligands, the first milestone representative being
enantiomeric excess (Table 1, entry 1).25 The use of MeOBI-
PHEP A or 4-MeO-3,5-(t-Bu)2-MeOBIPHEP B, the latter being
recently a leader for Au-catalyzed CꢀC formations,34ꢀ36 led to
very disappointing results as no or very low conversions were
observed, respectively (Table 1, entries 3 and 4). No reaction
was observed without additional phosphorus ligand (Table 1,
entry 2). In contrast, the reaction proceeded cleanly in the
presence of electron-poor MeOBIPHEP analogues, bearing
alkoxycarbonyl (ligands E, F) or trifluoromethyl groups
(ligands G, H) on the aromatic ring of the phosphine (Table 1,
entries 7ꢀ11). The reactivity was nevertheless not similar for all
ligands as only traces (1ꢀ2%) of the desired product 2 were
detected by 1H NMR in the presence of (R)-4-CO2t-Bu-MeO-
BIPHEP C or (R)-3-CO2t-Bu-MeOBIPHEP D (Table 1, entries
5ꢀ6).
T
Noyori’s Binap ligand.1 The performance of Binap has been
outstanding in several transformations including CꢀH and CꢀC
bond formations. Nevertheless, the need for specificity and
stereoselectivity in asymmetric processes prompted several aca-
demic and industrial groups to design novel atropisomeric
backbones and thus novel chiral diphosphines.2ꢀ5 We6ꢀ11 and
others12ꢀ17 have been interested in the synthesis of MeOBI-
PHEP analogues. We have recently described a practical and
efficient preparation of analogues via a Pd-catalyzed PꢀC
coupling, which allowed an access to several electron-poor
diphosphine ligands.6 We turned our attention to the asymmetric
Rh-catalyzed 1,4-addition reactions of boronic acids to Michael
acceptors18ꢀ20 and decided to evaluate the unprecedented
activity of our new ligands BꢀG compared to the parent one
A.21,22 Some recent studies23,24,16,17 comforted us on the ability
to perform such Rh-catalyzed processes under mild conditions.
We wish therefore to report herein the catalytic efficiency of the
fluorinated analogues of the MeOBIPHEP ligand in 1,4-addition
reactions of arylboronic acids to maleic derivatives and R,β-
unsaturated cyclic ketones.
In the case of ligands E, F, G, and H, the enantiomeric excesses
varied from 75% to 94% (Table 1, entries 7ꢀ11).37 The best
result was obtained when the 3,5-(CF3)2-substituted ligand
H was used (Table 1, entry 10). This result is very close to the
highest enantiomeric excess (95%) achieved using a chiral
diene.29,38 The importance of the amount of base (presumably
to generate the active L*Rh-OH species)18ꢀ20,23ꢀ29 was demon-
strated by conducting the reaction in the presence of 10 mol %
KOH instead of 50 mol %. The yield and the reaction stereo-
selectivity of the reaction dropped to 54% and 88%, respectively
(Table 1, entry 11).
The addition of boronic acids to maleimides derivatives has
been pioneered by Hayashi’s group,25ꢀ28 and the best results
have been obtained in the presence of chiral dienes as ligands.29
The resulting R-substituted succinimides are of potential interest
for pharmaceutical applications.30ꢀ32 In this context, we studied
the addition of phenylboronic acid to benzylmaleimide in the
presence of a rhodium catalyst consisting of [RhCl(C2H4)]2
dimer, a chiral diphosphine, and KOH33 as a base (Table 1). A
previous report had shown that the use of (R)-BINAP allowed
the formation of the desired product 2 in a moderate
Interestingly the observed enantiomeric excesses could be
correlated with the σ-donor properties of the ligands AꢀH
(Table 2). General and simple methods have indeed been
Received: June 1, 2011
Published: July 08, 2011
r
2011 American Chemical Society
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|

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NOTE
Table 1. Screening of Ligands
Table 3. Substrate Scope of the [Rh]/(R)-3,5-(CF3)2-MeO-
BIPHEP H System
x
t
yield ee
entry
1c (R)-BINAP
L*
(%) (h) (%)a (%)b
entry
R
Ar
t (h)
yield (%)a
ee (%)b
50
50
50
3
24
24
24
24
24
24
24
12
12
24
70
nr
0
58
1
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Me
Cy
Cy
4-Me-C6H4
4-MeO-C6H4
4-Br-C6H4
4-F-C6H4
12
12
15
15
24
20
24
12
24
24
24
24
24
15
15
80
76
71
74
52
89
56
73
55
83
81
69
68
88
71
3
92
85
70
80
82
88
74
70
37
58
40
80
83
91
84
2
3
4
5
6
7
8
9
2
4
(R)-MeOBIPHEP A
3
5
(R)-4-MeO-3,5-(t-Bu)2-MeOBIPHEP B 50
0d
0d
0d
50
82
72
86
54
4
6
(R)-4-CO2t-Bu-MeOBIPHEP C
(R)-3-CO2t-Bu-MeOBIPHEP D
(R)-4-CO2Bn-MeOBIPHEP E
(R)-3,5-(CO2t-Bu)2-MeOBIPHEP F
(R)-4-CF3-MeOBIPHEP G
50
50
50
50
50
50
10
5
4-CF3-C6H4
3-MeO-C6H4
3-Cl-C6H4
3-CF3-C6H4
3,5-(CF3)2-C6H3
3,5-Me2-C6H3
2-Me-C6H4
2-naphthyl
C6H5
7
6
8
80
75
80
94
88
7
9
8
10
11
12
13
14
15
16
17
9
10 (R)-3,5-(CF3)2-MeOBIPHEP H
11 (R)-3,5-(CF3)2-MeOBIPHEP H
10
11
12
13
14
15
C6H5
4-Me-C6H4
a Isolated yield. b Determined by HPLC analysis (Chiralcel ODH; see
Supporting Information).
correlation between the strength of the electron-withdrawing
group on the phosphine ligand (resulting from the substitution
position and the nature of the group) and the reactivity of the
corresponding Rh complex toward 1,4-addition (Table 2 and
Table 1 entries 5 and 6 compared to entries 7ꢀ11) was observed.
Indeed, the 4-CF3-, 4-CO2Bn-, and 3,5-(CO2t-Bu)2-substituted
selenide derivatives present similar and g757 Hz 1J values, which
may be correlated to the observed enantiomeric excesses
(Table 1). The same trend was observed when measuring the
νCO stretching frequency by infrared spectroscopy of the com-
plexes [Rh(CO)Cl(L*)].
We then evaluated the efficiency of the [RhCl(C2H4)2]2/(R)-
3,5-(CF3)2-MeOBIPHEP H catalytic system on 1,4-addition
reactions of various boronic acids to maleimides (Table 3). In
the case of the benzyl-substituted maleimide, good enantiomeric
excesses (80ꢀ92%) were obtained when electron-donating or
electron-withdrawing groups were placed in the para position of
the boronic acid (Table 3, entries 1ꢀ5). The use of 4-bromo-
substituted boronic acid afforded surprisingly the desired pro-
duct 5 in a lower enantiomeric excess (Table 3, entry 3). The
reaction was much more sensitive to the meta substitution of the
boronic acid. Indeed, succinimides 8, 9, and 10 were obtained in
88%, 74%, and 70% enantiomeric excesses, respectively (Table 3,
entries 6ꢀ8). In order to confirm the electronic versus steric
influence on the reaction stereoselectivity, we conducted the 1,4-
addition reaction in the presence of 3,5-dimethyl- and 3,5-
ditrifluoromethyl-substituted boronic acids (Table 3, entries 9
and 10). As anticipated, when the reaction was conducted in the
presence of the 3,5-ditrifluoromethylboronic acid, a low enan-
tiomeric excess of 37% was measured (Table 3, entry 9).
The electron-richer 3,5-dimethylboronic acid allowed the for-
mation of the corresponding derivative 12 in a higher yield and
a Isolated yield, nr: no reaction. b Determined by HPLC analysis
c
(Chiralcel ODH). 50 °C, dioxane/H2O, ref 25. d Traces (1ꢀ2%) of
the desired product were detected by 1H NMR.
Table 2. Electronic Properties of MeOBIPHEP Ligands
31
L*
1J (77Seꢀ P) (Hz) νCO (cmꢀ1
)
(R)-MeOBIPHEP A
743
737
755
747
757
757
760
782
2003
2002
2012
2009
2011
2015
2012
2040
(R)-4-MeO-3,5-(t-Bu)2-MeOBIPHEP B
(R)-4-CO2t-Bu-MeOBIPHEP C
(R)-3-CO2t-Bu-MeOBIPHEP D
(R)-4-CO2Bn-MeOBIPHEP E
(R)-3,5-(CO2t-Bu)2-MeOBIPHEP F
(R)-4-CF3-MeOBIPHEP G
(R)-3,5-(CF3)2-MeOBIPHEP H
described in the literature to quantify the σ-donor/π-acceptor
31
character of a phosphine.39,40 The magnitude of 1J (77Seꢀ P) in
phosphine selenide obtained from the reaction of a tertiary
phosphine and selenium is dependent upon the nature of the
organic groups bound to phosphorus.41ꢀ46 Electron-withdraw-
ing groups on phosphorus should cause the coupling constant to
increase, whereas electron-donating groups and bulky groups will
cause it to decrease.47 As expected, the electron-withdrawing
character of the trifluoromethyl-substituted ligands G and H
induced higher coupling constants than those observed for
parent MeOBIPHEP A and hindered 4-MeO-3,5-(t-Bu)2-
MeOBIPHEP B ligands (Table 2). It is noteworthy that a fine
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NOTE
Scheme 1. 1,4-Addition Reactions in the Presence of the
Table 4. 1,4-Addition of Boronic Acids to Cyclic Enones
[Rh]/(R)-4-CF3-MeOBIPHEP System
t
yield
(%)
ee (%)
(config)b
entry
n
Ar
L*
(h)
1
1
1
1
1
1
1
2
0
0
0
0
0
0
0
C6H5
(S)-H
(S)-H
(S)-H
(S)-H
(S)-H
(S)-H
(S)-H
(S)-H
(R)-G
2
92
96
55
58
94
82
99
89
70
82
40
69
86
96
18
19
20
21
22
23
24
25
25
26
26
27
28
29
99 (S)
98 (S)
97 (S)
97 (S)
96 (S)
97 (S)
98 (S)
72 (S)
94 (R)
84 (S)
93 (R)
96 (R)
94 (R)
92 (R)
2
4-Br-C6H4
4-Me-C6H4
4-MeO-C6H4
4-CF3-C6H4
2-naphthyl
C6H5
15
6.5
15
15
6.5
7
3
4
enantiomeric excess (58%) (Table 3, entry 10). The ortho
substitution of the boronic acid induced a drop of the stereo-
selectivity of the reaction, as the succinimide 13 was isolated in
40% ee (Table 3, entry 11). The reaction of 2-naphthylboronic
acid allowed the formation of 14 in 69% yield and 80% ee. The
catalytic system was still active when methyl or cyclohexyl
maleimides were engaged in the reaction (Table 3, entries
13ꢀ15). The addition of phenylboronic acid led to the arylated
succinimides 15 and 16 in 83% and 91% enantiomeric excesses,
respectively. The use of 4-methyl-substituted boronic acid led
this time to a slight decrease of the enantiomeric excess (Table 3,
entry 15), compared to the case implying the benzylmaleimide
(Table 3, entry 1).
5
6
7
8
4-Br-C6H4
4-Br-C6H4
6.5
6.5
6.5
6.5
2.5
6.5
6.5
9
10
11
12
13
14
4-F-3-Cl-C6H3 (S)-H
4-F-3-Cl-C6H3 (R)-G
C6H5
(R)-G
(R)-G
(R)-G
2-naphthyl
4-MeO-C6H4
a Isolated yield. b Determined by HPLC analysis (Chiralcel ADH, ASH;
see Supporting Information).
Considering that the stereoselectivity of the reaction of the
maleimides showed a higher dependence on the boronic acid’s
structure than other 1,4-addition to Michael acceptors,18ꢀ20 we
decided to employ the less hindered but still electron-poor
atropisomeric 4-CF3-MeOBIPHEP ligand G in selected exam-
ples (Scheme 1).
Whereas lower enantiomeric excesses were observed in the
case of MeO-substituted boronic acids (para and meta posi-
tions), we were pleased to observe higher enantiomeric excesses
when 3,5-dimethyl-, 2-methyl-, and 2-naphtylphenylboronic
acids were used. Gratifyingly the corresponding derivatives 12,
13, and 14 were obtained in good yields and in 75%, 70%,
and 85% ee, respectively, which correspond to a substantial
gap compared to 58%, 40%, and 80% previously observed
(Table 3, entries 10 and 12).
The efficiency of the Rh/MeOBIPHEP analogues was finally
studied with more classical substrates such as cyclic enones,
having in mind that cyclopentenone was the most challenging
substrate.18ꢀ20 The reaction conditions were similar to those
used in the case of maleimides, except that a lower amount of
base was sufficient to perform the reaction at room tempera-
ture.18ꢀ20,23,24 As anticipated, in the presence of 3,5-(CF3)2-
MeOBIPHEP H ligand as the chiral inducer, the addition of
electron-rich and electron-poor boronic acids afforded the
corresponding arylated cyclohexanones 18ꢀ23 in good yields
and excellent enantiomeric excesses (Table 4, entries 1ꢀ6). The
lower yields obtained in the case of 4-methyl- and 4-methox-
yphenylboronic acids (Table 4, entries 3 and 4) compared
to literature16,17,24 may be due to fast protodeboronation of
boronic acid as a smaller amount of KOH (10 mol % instead of 20
or 50 mol %) was used.
obtained in the presence of the 3,5-(CF3)2-MeOBIPHEP H
(Table 3, entry 8). Suspecting a substrate/ligand mismatch, we
performed the same reaction with the less hindered 4-CF3-
MeOBIPHEP ligand G. The corresponding bromo adduct 25
was this time isolated in 94% enantiomeric excess instead of 72%
(table 4, entry 9). This superiority of the 4-CF3-MeOBIPHEP
ligand G was confirmed by reacting the 4-fluoro-3-chloroboronic
acid (Table 4, entries 10 and 11). The arylated ketone 26 was
isolated in modest to good yields but 84% and 93% ee,
respectively. Other boronic acids reacted smoothly under the
same conditions with cyclopentenone substrate and led to the
corresponding ketones with enantiomeric excesses superior to
90% (Table 4, entries 12ꢀ14).
In summary, we have extended the methodology of Rh-
catalyzed 1,4-addition of boronic acids to Michael acceptors
such as challenging maleimides and cyclic enones. We showed
that a Rh-based catalytic system imploying electron-poor MeO-
BIPHEP analogues allowed very clean reactions under mild
conditions at room temperature and led to the succinimide
derivatives and arylated cyclic ketones in good to excellent yields
and ee. We uncovered the crucial role of the electronic and steric
properties of diphosphine ligand and observed a strong boronic
acid/ligand dependency in the case of maleimide derivatives and
substrate/ligand matching in the case of cyclic enones. Further
studies will be dedicated to the study of other catalytic applica-
tions of trifluoromethyl-substituted ligands based on the MeO-
BIPHEP skeleton.
’ EXPERIMENTAL SECTION
The 1,4-addition of phenylboronic acid to cycloheptenone
afforded the ketone 24 in high enantiomeric excess also (Table 4,
entry 7). The reaction of cyclopentenone was much more
interesting as, surprisingly, a moderate enantiomeric excess was
General Information. Reactions were carried out in dried glass-
ware under argon atmosphere, with degassed solvents. Toluene was
distilled from calcium hydride. Solvents used in silica gel chromatogra-
phies were “analytical grade” and those used for extractions were
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The Journal of Organic Chemistry
NOTE
“synthesis grade”. 1H and 13C NMR data for compounds 2, 4, 6, 12, 13,
15, 16, 18ꢀ25, and 27ꢀ29 were identical to those described in the
literature.25ꢀ29,33 Flash chromatography separations were made on silica
8.4, 4JHꢀP = 2.1 Hz, 4H), 7.82 (dd, 3J = 8.1, 3JHꢀP = 12.9 Hz, 4H), 8.01
3
3
(dd, J = 8.1, JHꢀP = 13.2 Hz, 4H). NMR 31P (CHCl3, 121 MHz):
δ 31.6 (1JPꢀSe = 760 Hz). [Rh(4-CF3-MeOBIPHEP)(CO)Cl] 31P
1
2
1
gel 0.040ꢀ0.063 mm, Art. 11567. H, 13C, and 31P nuclear magnetic
NMR (CHCl3, 121 MHz): δ 24.6 (dd, JPꢀP = 47 Hz, JPꢀRh =
2 1
resonance spectra were recorded at 300 MHz (or 400 MHz), 75 MHz (or
100 MHz), and 121 MHz respectively. High pressure liquid chro-
matography analyses (HPLC) equipped with a UV detector were
performed on instruments equipped with Daicel Chiralcel OA, OB,
OD, OD-H, OJ and Chiralpak AD and AS-H. Supercritical fluid chroma-
tography analyses (SFC) were performed on instruments (equipped with
Daicel Chiralcel OD-H, OJ and Chiralpak AD and AS-H).
130 Hz), 44.5 (dd, JPꢀP = 47 Hz, JPꢀRh = 163 Hz). IR (CHCl3):
νCO = 2012 cmꢀ1
.
(3,5-(CF3)2-MeOBIPHEP)Se2. 1H NMR (CDCl3, 300 MHz): δ 3.44 (s,
6H), 6.66 (d, J = 9 Hz, 2H), 6.94 (d, J = 9 Hz, 2H), 7.41 (t, J = 9 Hz, 2H),
7.57 (d, J = 36 Hz, 8H), 7.81 (d, J = 30 Hz, 4H).31P NMR (CHCl3, 121
MHz, d ppm): 32.1 (1JPꢀSe = 782 Hz). [Rh(3,5-(CF3)2-MeOBIPHEP)-
(CO)Cl] 31P NMR (CHCl3, 121 MHz): δ 25.3 (dd, JPꢀP = 49 Hz,
2
1JPꢀRh = 132 Hz) IR (CHCl3): νCO = 2040 cmꢀ1
.
Experimental Details for selected (PꢀP)Se2 and Rh
Complexes
General Procedure for the 1,4-Addition Reactions. In a
Schlenk tube, a solution of 2.9 mg of [RhCl(C2H4)2]2 (0.0075 mmol,
1.5 mol %, M = 388.93) and diphosphine6 (3 mol %) in a mixture of
toluene (1 mL) and KOH (0.10 mL, 0.25 mmol; 2.5 M aqueous) or
KOH (0.10 mL, 0.05 mmol; 0.5 M aqueous) was stirred 20 min at room
temperature. This mixture was transferred to a vessel containing
maleimide (0.50 mmol) or R,β-unsaturated ketone (0.50 mmol) and
arylboronic acid (2.5 equiv or 5 equiv) and stirred at room temperature.
After completion of the reaction, dichloromethane was added, and the
solution was washed twice with an aqueous saturated solution of
NaHCO3, dried over MgSO4, filtered, and concentrated. Crude product
was purified by flash chromatography (PE/EtOAc 98/2). Proton and
carbon nuclear magnetic resonance spectra were recorded at 300 MHz
(or 400 MHz) and 75 MHz (or 100 MHz), respectively.
Diphosphine Diselenide Formation. A solution of diphosphine
(1 equiv) and 50 mg of selenium powder (excess) in degassed CHCl3
(or MeOH) (0.015 M) under argon was stirred during 15 h at reflux
temperature. The reaction mixture was brought to room temperature,
and the black suspension was filtered through a short pad of Celite
(CH2Cl2). The filtrate was concentrated under reduced pressure, and
the solid obtained was used for NMR spectroscopy without further
purification.
Synthesis of [RhCl(CO)(P*P)] Complexes. A solution of
[Rh(CO)2Cl]2 (0.5 equiv, M = 388.80) and diphosphine (1 equiv) in
dry and degassed CH2Cl2 (0.1 M) was degassed and stirred at room
temperature under argon during 3 h. The reaction mixture was then
concentrated, and the solid obtained was dried under vacuo and directly
used for IR νCO determination without purification.
Compound 3. White solid, 112 mg, 80% yield. Mp 98 °C. 1H NMR
(CDCl3): δ 7.43ꢀ7.40 (m, 2H), 7.34ꢀ7.26 (m, 3H), 7.15 (d, J = 9 Hz,
2H), 7.05 (d, J = 9 Hz), 4.76 (d, J = 13.8 Hz, 1H), 4.69 (d, J = 13.8 Hz,
1H), 3.96 (dd, J = 9 Hz, 6 Hz, 1H), 3.16 (dd, J = 19 Hz, J = 9 Hz, 1H),
2.79 (dd, J = 19 Hz, J = 5 Hz, 1H), 2.34 (s, 3H). 13C NMR (CDCl3): δ
176.6, 174.9, 136.6, 134.8, 133.1, 128.8, 127.8, 127.6, 126.9, 126.1, 44.5,
41.6, 36.1, 20.0. The ee was determined on a Daicel Chiralcel OD-H
column with hexane/isopyl alcohol = 90:10, flow = 1.0 mL/min, 92% ee.
[R]25D = +29.4 (c 1, CHCl3) (R). HRMS calculated for C18H17O2NNa
302.01001, found 302.01024.
(4-CO2t-Bu-MeOBIPHEP)Se2. 1H NMR (CDCl3, 300 MHz): δ 1.55
(s, 18H), 1.60 (s, 18H), 2.90 (s, 6H), 6.70 (d, 3J = 8.0 Hz, 2H), 6.87 (dd,
3J = 7.9, 3JHꢀP = 13.9 Hz, 2H), 7.19 (app td, 3J = 8.0, 4JHꢀP = 3.1 Hz,
2H), 7.71 (dd, 3J = 8.4, 3JHꢀP = 12.9 Hz, 4H), 7.88ꢀ8.02 (m, 12H). 31
P
NMR (CHCl3, 121 MHz): δ 31.7 (1JPꢀSe = 755 Hz). [Rh(pCO2t-Bu-
MeOBIPHEP)(CO)Cl] 31P NMR (CHCl3, 121 MHz): δ 22.7 (dd,
1
2
1
2JPꢀP = 46 Hz, JPꢀRh = 129 Hz), 43.4 (dd, JPꢀP = 46 Hz, JPꢀRh
=
162 Hz). IR (CHCl3): νCO = 2012 cmꢀ1
.
(3-CO2t-Bu-MeOBIPHEP)Se2. 1H NMR (CDCl3, 300 MHz): δ 1.50
(s, 18H), 1.51 (s, 18H), 3.07 (s, 6H), 6.55 (d, 3J = 8.3 Hz, 2H), 6.99 (dd,
3J = 8.1, 3JHꢀP = 14.3 Hz, 2H), 7.13 (app td, 3J = 8.3, 4JHꢀP = 3.4 Hz,
2H), 7.44 (app dtd, 3J = 8.2, 4JHꢀP = 2.6 Hz, 4H), 7.96ꢀ8.17 (m, 10H),
8.45 (m, 2H). 31P NMR (CHCl3, 121 MHz): δ 33.3 (1JPꢀSe = 747 Hz).
[Rh(3-CO2t-Bu-MeOBIPHEP)(CO)Cl] 31P NMR (CHCl3, 121 MHz):
δ 23.8 (dd, 2JPꢀP = 44 Hz, 1JPꢀRh = 132 Hz), 43.9 (dd, 2JPꢀP = 44 Hz,
1
Compound 5. Yellow oil, 99 mg, 71% yield. H NMR (CDCl3): δ
7.43ꢀ7.17 (m, 7H), 6.94 (d, J = 12 Hz, 2H), 4.64 (d, J = 13.8 Hz, 1H),
4.58 (d, J = 13.8 Hz, 1H), 3.87 (dd, J = 9.2, 5.1 Hz, 1H), 3.09 (dd, J =
18 Hz, J = 9.6 Hz, 1H), 2.66 (dd, J = 18 Hz, J = 4.8 Hz, 1H). 13C NMR
(CDCl3): δ 176.9, 175.4, 136.0, 135.6, 132.3, 129.1, 128.8, 128.7, 128.1,
122.0, 45.3, 42.8, 36.8. The ee was determined on a Daicel Chiralcel OJ-
H column with hexane/2-propanol = 90:10, flow = 1.0 mL/min, 70% ee.
[R]25D = +39.4 (c 1, CHCl3) (R). HRMS calculated for C17H14O2N-
BrNa 366.01022, found 366.01024.
1JPꢀRh = 159 Hz). IR (CHCl3): νCO = 2007 cmꢀ1
.
(4-CO2Bn-MeOBIPHEP)Se2. 1H NMR (CDCl3, 300 MHz): δ 2.87 (s,
6H), 5.34 (s, 4H), 5.39 (s, 4H), 6.68 (d, 3J = 8.4 Hz, 2H), 6.85 (dd, 3J =
8.2, 3JHꢀP = 14.0 Hz, 2H), 7.19 (app td, 3J = 8.3, 4JHꢀP = 2.9 Hz, 2H),
Compound 7. Colorless oil, 87 mg, 52% yield. 1H NMR (CDCl3): δ
7.60 (d, J = 9 Hz, 2H), 7.42ꢀ7.26 (m, 7H), 4.77 (d, J = 14.1 Hz, 1H),
4.06 (d, J = 14.1 Hz, 1H), 4.07 (dd, J = 9.3, 5.1 Hz, 1H), 3.22 (dd, J = 18.1
Hz, J = 9.6 Hz, 1H), 2.80 (dd, J = 18.1 Hz, J = 5.1 Hz, 1H). 13C NMR
(CDCl3): δ 177.3, 175.2, 135.6, 128.8, 128.7, 128.1, 127.8, 126.1, 126.0,
64.2, 45.6, 42.8, 36.7, 31.6, 25.2, 22.6, 14.0. The ee was determined on a
Daicel Chiralcel OJ-H column with hexane/2-propanol = 90:10, flow =
3
3
7.34ꢀ7.44 (m, 20H, Har), 7.74 (dd, J = 8.4, JHꢀP = 13.4 Hz, 4H),
7.91ꢀ8.02 (m, 8H), 8.11 (dd, 3J = 8.7, 4JHꢀP = 2.7 Hz, 4H). 31P NMR
(CHCl3, 121 MHz): δ 31.6 (1JPꢀSe = 757 Hz). [Rh(4-CO2Bn-
MeOBIPHEP)(CO)Cl] 31P NMR (CHCl3, 121 MHz): δ 23.1 (dd,
1
2
1
2JPꢀP = 46 Hz, JPꢀRh = 128 Hz), 43.4 (dd, JPꢀP = 46 Hz, JPꢀRh
=
159 Hz). IR (CHCl3): νCO = 2011 cmꢀ1
.
1.0 mL/min, 82% ee. [R]25 = +11.1 (c 1, CHCl3) (R). HRMS
1
(3,5-(CO2t-Bu)2-MeOBIPHEP)Se2. H NMR (CDCl3, 300 MHz): δ
1.55 (s, 36H), 1.57 (s, 36H), 3.24 (s, 6H), 6.70 (d, 3J = 8.3 Hz, 2H), 7.07
(dd, 3J = 8.1 Hz, 3JHꢀP = 14.0 Hz, 2H), 7.31 (m, 2H), 7.76 (d, 3J = 1.6 Hz,
2H), 7.78 (d, 3J = 1.6 Hz, 2H), 7.95 (dd, 3J = 1.6 Hz, 4JHꢀP = 13.7 Hz,
D
calculated for C18H14O2NF3Na 356.08688, found 356.08705.
Compound 8. Pale yellow oil, 127 mg, 86% yield. 1H NMR (CDCl3):
δ 7.43ꢀ7.23 (m, 6H), 6.73 (d, J = 7.2 Hz, 1H), 6.68 (m, 2H), 4.75 (d, J =
13.8 Hz, 1H), 4.69 (d, J = 13.8 Hz, 1H), 3.95 (dd, J = 10.5 Hz, 4.5 Hz,
1H), 3.73 (s, 3H), 3.17 (dd, J = 18.4 Hz, J = 9.5 Hz, 1H), 2.88 (dd, J =
18.4 Hz, J = 4.7 Hz, 1H). 13C NMR (CDCl3): δ 177.3, 175.8, 160.1,
138.8, 135.8, 130.2, 129.5, 128.8, 128.7, 128.0, 120.7, 119.5, 113.9, 113.4,
113.1, 55.2, 55.1, 45.9, 42.7, 37.2. The ee was determined on a Daicel
Chiralcel OD-H column with hexane/2-propanol = 90:10, flow =
4H, H5), 8.75 (dd, J = 1.6 Hz, J5-P = 13.5 Hz, 4H, H5 ). 31P NMR
(CHCl3, 121 MHz): δ 33.0 (1JPꢀSe = 757 Hz). [Rh(3,5-(CO2t-Bu)2-
MeOBIPHEP)(CO)Cl] 31P NMR (CHCl3, 121 MHz): δ 22.9 (dd,
3
4
0
1
2
1
2JPꢀP = 46 Hz, JPꢀRh = 129 Hz), 43.9 (dd, JPꢀP = 46 Hz, JPꢀRh
=
161 Hz). IR (CHCl3): νCO = 2015 cmꢀ1
.
1
(4-CF3-MeOBIPHEP)Se2. H NMR (CDCl3, 300 MHz): δ 2.94 (s,
1.0 mL/min, 78% ee. [R]25 = +38.4 (c 1, CHCl3) (R). HRMS
6H), 6.69 (d, 3J = 8.4 Hz, 2H), 6.85 (dd, 3J = 7.2, 3JHꢀP = 14.0 Hz, 2H),
D
3
4
3
7.26 (m, 2H), 7.62 (dd, J = 8.5, JHꢀP = 2.2 Hz, 4H), 7.67 (dd, J =
calculated for C18H17O3NNa 318.11006, found 318.10998.
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The Journal of Organic Chemistry
NOTE
Compound 9. Pale yellow oil, 84 mg, 56% yield. 1H NMR (CDCl3): δ
7.33ꢀ7.15 (m, 6H), 7.08ꢀ6.92 (m, 3H), 4.63 (d, J = 14.1 Hz, 1H), 4.60
(d, J = 14.1 Hz, 1H), 3.88 (dd, J = 12 Hz, 4.8 Hz, 1H), 3.11 (dd, J =
16.5 Hz, J = 9.6 Hz, 1H), 2.78 (dd, J = 16.5 Hz, J = 4.8 Hz, 1H). 13C NMR
(CDCl3): δ 176.8, 175.3, 139.0, 135.6, 135.0, 130.4, 128.8, 128.7, 128.2,
128.1, 127.7, 125.6, 45.4, 42.8, 36.9. The ee was determined on a
Daicel Chiralcel OD-H column with hexane/2-propanol = 90:10, flow =
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: michelangelo.scalone@roche.com; veronique-michelet@
chimie-paristech.fr.
1.0 mL/min, 74% ee. [R]25 = +26.2 (c 1, CHCl3) (R). HRMS
’ ACKNOWLEDGMENT
D
calculated for C17H14O2NClNa 322.06053, found 322.06056.
F.L.B.H. is grateful to the CNRS and F. Hoffmann-La Roche
AG for financial support. Helpful discussions with K. P€untener
(F. Hoffmann-La Roche AG, Basel) are kindly acknowledged.
Compound 10. Pale yellow oil, 87 mg, 52% yield. 1H NMR (CDCl3):
δ 7.33ꢀ7.15 (m, 6H), 7.08ꢀ6.92 (m, 3H), 4.63 (d, J = 14.1 Hz, 1H),
4.60 (d, J = 14.1 Hz, 1H), 3.88 (dd, J = 12 Hz, 4.8 Hz, 1H), 3.11 (dd, J =
16.5 Hz, J = 9.6 Hz, 1H), 2.78 (dd, J = 16.5 Hz, J = 4.8 Hz, 1H). 13C NMR
(CDCl3): δ 176.6, 175.1, 138.0, 135.6, 131.7, 131.3, 130.8, 129.7, 128.8,
128.2, 124.9, 124.8, 124.4, 124.3, 45.6, 42.9, 36.8, 25.3. The ee was
determined on a Daicel Chiralcel OD-H column with hexane/2-
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propanol = 90:10, flow = 1.0 mL/min, 82% ee. [R]25 = +3.2 (c 1,
D
CHCl3) (R). HRMS calculated for C18H14O2NF3Na 356.08688, found
356.08705.
Compound 11. Yellow oil, 111 mg, 55% yield. 1H NMR (CDCl3): δ
7.75 (s, 1H), 7.56 (s, 2H), 7.33ꢀ7.18 (m, 5H), 4.79 (d, J = 14.1 Hz, 1H),
4.63 (d, J = 14.1 Hz, 1H), 4.05 (dd, J = 9, 6 Hz, 1H), 3.19 (dd, J = 18 Hz,
J = 9.6 Hz, 1H), 2.74 (dd, J = 18 Hz, J = 5.1 Hz, 1H). 13C NMR (CDCl3):
δ 175.8, 174.4, 139.3, 135.3, 133.2, 132.7, 132.3, 132.1, 128.8, 128.7,
128.3, 127.8,124.7, 122.1, 121.1, 45.2, 43.0, 36.4. The ee was determined
on a Daicel Chiralcel OJ-H column with hexane/2-propanol = 90:10,
flow = 1.0 mL/min, 37% ee. [R]25D = +4.8 (c 1, CHCl3) (R). HRMS
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1
Compound 14. Brown solid, 130 mg, 82% yield. mp 130 °C, H
NMR (CDCl3): δ 7.63ꢀ7.50 (m, 3H), 7.63 (s, 1H), 7.50ꢀ7.32 (m,
7H), 7.23 (dd, J = 6.9 Hz, J = 9 Hz, 2H), 4.77 (d, J = 14.1 Hz, 1H), 4.73
(d, J = 14.1 Hz, 1H), 4.18 (dd, J = 11.7 Hz, 4.5 Hz, 1H), 3.26 (dd, J =
18.5 Hz, J = 9.3 Hz, 1H), 2.91 (dd, J = 18.5 Hz, J = 4.8 Hz, 1H). 13C NMR
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128.0, 120.7, 119.5, 113.9, 113.4, 113.1, 55.2, 55.1, 45.9, 42.7, 37.2. The
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isoprpyl alcohol = 90:10, flow = 1.0 mL/min, 85% ee. [R]25D = +31.2
(c 1, CHCl3) (R). HRMS calculated for C21H17O2NNa 338.11515,
found 338.11512.
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(CDCl3): δ 7.16 (d, J = 7.8 Hz, 2H), 7.07 (d, J = 8.4 Hz, 2H), 4.05 (tt, J =
12.7 Hz, 3.7 Hz, 1H), 3.93 (dd, J = 9.7 Hz, 4.5 Hz, 1H), 3.11 (dd, J =
18.1 Hz, J = 9.6 Hz, 1H), 2.72 (dd, J = 18.1 Hz, J = 4.5 Hz, 1H),
2.24ꢀ2.13 (m, 2H), 1.88ꢀ1.79 (m, 2H), 1.70ꢀ1.58 (m, 3H),
1.41ꢀ1.15 (m, 3H). 13C NMR (CDCl3): δ 177.8, 176.3, 138.0, 129.1,
127.8, 127.2, 52.0, 48.3, 45.6, 37.1, 28.9, 28.7, 25.84, 25.82, 25.0. The ee
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isoprpyl alcohol = 90:10, flow = 1.0 mL/min, 84% ee. [R]25D = +22.9
(c 1, CHCl3) (R).
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1
Compound 26. Brown oil, 45 mg, 40% yield. H NMR (CDCl3,
300 MHz): δ 7.32ꢀ7.40 (m, 2H), 7.22ꢀ7.30 (m, 3H), 3.40ꢀ3.50 (m,
1H), 2.70 (dd, J = 18 Hz, 7.8 Hz, 1H), 2.25ꢀ2.55 (m, 4H), 1.95ꢀ2.10
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flow = 0.8 mL/min, 93% ee. [R]25D = +0.33 (c 0,33 CHCl3) (R). HRMS
calculated for C11H9OFClNa 234.01241, found 234.01249.
’ ASSOCIATED CONTENT
Supporting Information. Copies of 1H, 13C NMR,
S
b
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Internet at http://pubs.acs.org.
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The Journal of Organic Chemistry
NOTE
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6930
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