Binaphthyldiamine-based diazaphospholidines as a new class of chiral monodentate P-ligands

Article abstract of DOI:10.1055/s-2003-41036

A new family of chiral diazaphospholidines is readily accessible by phosphorylating commercially available (S)-1,1′-binaphthyl-2,2′ -diamine. NMR spectroscopy, mass spectrometry and X-ray crystallographic analysis reveal their unique structures. In preliminary studies these novel monodentate P-ligands were tested in Rh-catalyzed hydrogenation and hydroformylation (31% ee) reactions. The modular nature of the ligands allows for further structural diversity.

Full text of DOI:10.1055/s-2003-41036

PAPER
1809
Binaphthyldiamine-Based Diazaphospholidines as a New Class of Chiral
Monodentate P-Ligands
B
M
inaphthyldiamine-Ba
a
sed
D
iazap
n
hospholidine
f
s as
a
N
e
r
w Class
e
P-Ligandsd T. Reetz,* Hiromasa Oka, Richard Goddard
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim/Ruhr, Germany
Fax +49(208)3062985; E-mail: reetz@mpi-muelheim.mpg.de
Received 2 July 2003
Dedicated to Professor Wolfgang Steglich on the occasion of his 70th birthday.
Abstract: A new family of chiral diazaphospholidines is readily ac-
cessible by phosphorylating commercially available (S)-1,1¢-bi-
naphthyl-2,2¢-diamine. NMR spectroscopy, mass spectrometry and
X-ray crystallographic analysis reveal their unique structures. In
preliminary studies these novel monodentate P-ligands were tested
in Rh-catalyzed hydrogenation and hydroformylation (31% ee) re-
actions. The modular nature of the ligands allows for further struc-
tural diversity.
R
P
N
N
NH2
X
NH2
R
1
2 a R = CH3; X = OCH3
b R = CH3; X = NEt2
c R = C6H5; X = OCH3
d R = C6H5; X = CH3
e R = C6H5; X = CH(CH3)2
f R = C6H5; X = c-C6H11
g R = C6H5; X = C(CH3)3
Key words: asymmetric catalysis, rhodium, phosphorus, hydroge-
nation, hydroformylation
Figure 1 Diazaphospholidines 2 derived from dinaphthyldiamine 1
Recently, we and others have shown that BINOL-based
1
2,3
monodentate
phosphites,
phosphonites
and
4
phosphoramidites are excellent ligands in a number of
transition metal catalyzed reactions. For example, in Rh-
catalyzed olefin-hydrogenation unexpectedly high enanti-
oselectivities were achieved in a number of cases (ee >
The first step in the synthesis of compounds 2 from the
starting material 1 involves the introduction of the R-sub-
stituents at nitrogen with formation of the secondary di-
amines 3 (Scheme 1). Compounds 3a,b were prepared by
procedures described in the literature.7
b,8,9
The new mesi-
9
0%), which is of significant academic and industrial in-
1
–4
terest. As a consequence of these findings the long-
standing dogma that chelating bidentate ligands are neces-
sary in order to obtain high enantioselectivity no longer
tyl-derivative was synthesized by Pd-catalyzed arylation
10
using the Buchwald–Hartwig method (94% yield).
5
pertains. Moreover, these P-ligands are cheaper than the
R
traditional chiral diphosphines by a factor of at least 50. In
recent studies we extended the value of these compounds
by demonstrating that mixtures of two different monoden-
tate P-ligands can lead to dramatically enhanced enantio-
NH
1
NH
R
6
selectivities.
In contrast to the extensive use of BINOL as a building
3 a R = CH3
b R = C6H5
c R = 2,4,6 - (CH3)3C6H2
1
–5
block in a variety of chiral catalysts, little is known con-
cerning similar ligands based on 1,1¢-binaphthyl-2,2¢-di-
amine (1), bis-ketimines derived thereof being one
Scheme 1 Synthesis of methyl- and aryl-substituted dinaphthyldia-
mines 3a (reductive amination using CH
amination of arylbromides using the Buchwald–Hartwig procedure)
7
2 4
O–NaCNBH ) and 3b,c
prominent example. This may be due to the distinctly
(
higher price of 1 relative to that of BINOL. Nevertheless,
we were interested in the synthesis of monodentate diaza-
phospholidines derived from 1. In this paper we describe
the synthesis and characterization of the first representa-
tives of this novel class of chiral P-ligands 2 (Figure 1).
Moreover, preliminary results concerning their applica-
tion in several asymmetric transition metal catalyzed reac-
tions are presented. These ligands are modular in nature
because the substituents at nitrogen (R) and at phosphorus
Ring-closing reaction of 3b with PCl in the presence of
3
Et N readily provided the sensitive chloride 4 in quantita-
3
tive yield. This key compound was then used in the intro-
duction of alkoxy and amino groups, the products being
isolated and purified as the BH -adducts 5a,b, respective-
3
ly. Compound 5b can be prepared even more convenient-
ly by treating 3a with (Et N) PCl and protecting with BH
2
2
3
(
72% overall yield) (Scheme 2).
(
X) can be varied.
Unfortunately, these reactions failed to proceed smoothly
with the aryl substituted derivatives 3b,c, possibly due to
steric effects. Therefore, more forcing conditions had to
be applied, specifically double deprotonation using n-bu-
Synthesis 2003, No. 12, Print: 02 09 2003. Web: 13 08 2003.
Art Id.1437-210X,E;2003,0,12,1809,1814,ftx,en;T06203SS.pdf.
DOI: 10.1055/s-2003-41036
©
Georg Thieme Verlag Stuttgart · New York

1
810
M. T. Reetz et al.
PAPER
(
5b and 5c) suitable crystals were grown for X-ray crys-
CH3
PCl
tallographic analyses. Figures 2 and 3 show that chiral
seven-membered P-heterocycles are indeed involved,
Et3N / PCl3
00%
N
N
11
3
a
1
the degree of puckering depending on the nature of R. In
CH3
5c all the N atoms are almost planar (R = C H , max.
6
5
r.m.s. deviation 0.028 Å), whereas in 5b N1 lies 0.330 Å
out of its coordination plane.
4
1
. CH3OH
Et3N
CH3
.
N
N
OCH3
2. BH3 THF
4
P
99%
BH3
CH3
5
a
1
. Et2NH
Et3N
CH3
.
N
N
NEt2
2. BH3 THF
4
P
72%
BH3
CH3
5
b
Figure 2 Crystal structure of 5b: selected distances (Å), angles and
torsion angles (º): P–N1 1.696(2), P–N2 1.685(2), P–N3 1.655(2),
N1–P–N2 100.4(1), N1–P–N3 104.0(1), N2–P–N3 111.9(1), B–P–
N1–C21 71(1), B–P–N2–C22 –49(1), B–P–N3–C25 –2(1).
Scheme 2 Preparation of BH -protected diazaphospholidines
3
1
2
3
4
. n-C4H5Li
. PCl3
C6H5
OCH3
P
. CH3OH / Et3N
.
N
N
. BH3 THF
3
b
25%
BH3
C6H5
5
c
Scheme 3 Synthesis of 5c
tyllithium followed by phosphorylation, as in the case of
c (25% yield) (Scheme 3).
5
Along similar lines further derivatives 5d–g were pre-
pared and isolated in pure form (Scheme 4). However,
upon subjecting the mesityl-derivative 3c to the reaction
conditions, mixtures of inseparable products were ob-
tained. The synthesis of P-ligands based on 3c was there-
fore not pursued.
All compounds 5d–g were characterized by NMR spec-
troscopy and mass spectrometry (MS), and in two cases
Figure 3 Crystal structure of 5c: selected distances (Å), angles and
torsion angles (º): P–N1 1.680(1), P–N2 1.650(2), P–O 1.589(1), N1–
P–N2 102.7(1), N1–P–O1 97.8(1), N2–P–O1 107.7(1), B–P–N1–C21
87(1), B–P–N2–C27 –1(1), B–P–O1–C33 42(1).
1
. n-C4H9Li
R
2
. XPCl2
.
N
N
X
3
. BH3 THF
3
a,b
P
BH3
The final step in the synthetic sequence called for depro-
tection of the P-function, which in other cases is known to
R
12
proceed best with DABCO. However, in the present cas-
es the reaction generally failed to occur cleanly. There-
5
d R = C6H5; X = CH3
e R = C6H5; X = CH(CH3)2 (70%)
f R = C6H5; X = c-C6H11
(50%)
g R = C6H5; X = C(CH3)3 (53%)
(84%)
fore, Et NH was used, which resulted in smooth
2
deprotection and concomitant generation of the desired
ligands 2a–g in essentially pure form as shown by NMR
analyses. Since chromatography of the compounds for an-
Scheme 4 Synthesis of 5e–g
Synthesis 2003, No. 12, 1809–1814 © Thieme Stuttgart · New York

PAPER
Binaphthyldiamine-Based Diazaphospholidines as a New Class of P-Ligands
1811
alytical purposes led to excessive decomposition, the Table 1 Rh-Catalyzed Hydroformylation of Styrene (8)a
ligands were used directly in various transition metal cat-
alyzed reactions.
b
En- Ligand Rh-salt
try
H /CO Temp. Conv. 9:10
(bar) (°C) (%)
ee
(%)
2
b
b,c
Thus far only a few exploratory experiments to assess the
P-compounds 2 as ligands in transition metal catalyzed re-
actions have been performed. In all cases the S-form was
used. Upon treating Rh(cod) BF (cod = 1,5-cyclooctadi-
1
2
3
4
5
6
7
2a
2a
2b
2b
2c
2c
2d
Rh(acac)(CO)2
50
50
50
50
50
50
25
60
60
60
60
60
60
25
100 80: 20 24
100 87: 13
Rh(cod) BF
5
2
4
2
4
Rh(acac)(CO)2
100 78: 22 37
93 86: 14 10
100 87: 13 18
100 84: 16 20
98 80: 20 31
ene) with two equivalents of a P-ligand 2 and using the
Rh-complexes RhL (cod)BF as catalysts in the in situ hy-
2
4
Rh(cod) BF
2
4
drogenation of itaconic acid dimethyl ester (6) under stan-
1
–5
dard conditions (6: Rh = 1000:1; 1.3 bar H ; 20 h;
Rh(acac)(CO)
Rh(cod) BF
2
2
CH Cl as solvent) (Scheme 5), it became clear that the
2
2
2
4
catalyst systems are considerably less active than the pre-
viously described Rh-catalysts using BINOL-based phos-
Rh(acac)(CO)2
1
2,3
4
phites, phosphonites or phosphoramidites. Acceptable
conversion under these conditions was only achieved with
ligands 2a (80%, 7 having an ee of 30% in favor of the R-
product 7). The other ligands led to substrate conversions
of only 2–10%. Higher catalyst to substrate ratios and
higher pressures still need to be studied in order to make
a final assessment.
a
b
c
Rh:substrate = 1:400; 20 h; H :CO = 1:1; toluene as solvent.
Determined by GC.
Determined by GC following oxidation to the acid.
2
NMR spectroscopy and mass spectrometry has been per-
formed in all cases, and two representative ligands were
analyzed by X-ray crystallography. Some of the prelimi-
nary experiments applying these ligands in asymmetric
transition metal-catalyzed reactions are promising, as for
example, in enantioselective hydroformylation. It remains
to be seen if the modular nature of these compounds can
be exploited so that further ligand tuning will lead to effi-
cient catalyst systems. Moreover, other types of transition
metal catalyzed reactions need to be tested with the
ligands described here, either in pure form or in mixtures.
1
.3 bar H2/ 20 h
CH3
CO2CH3
Rh(cod)2BF4 / 2 eq 2a
H3CO2C
H3CO2C
CO2CH3
80% (ee = 30%)
6
7
Scheme 5 Rh-catalyzed hydrogenation of 6
In the case of the Rh-catalyzed hydroformylation of sty-
rene (8) (Scheme 6), a different picture evolved. Although
not all of the ligands were tested, initial experiments using
All reactions were carried out in anhyd flasks under an atmosphere
of argon. 1,1¢-Binaphthyl-2,2¢-diamine (1) was purchased from Flu-
ka (Switzerland) in enantiomerically pure S-form. NMR spectra
were recorded on 300 and 400 MHz instruments (Bruker, Germa-
2
a–d, turned out to be promising (Table 1). Ligand 2d
seems to be the most active, leading to a nearly quantita-
tive conversion at room temperature and only 25 bar H2/ ny).
CO (Table 1, entry 7). The regioselectivity in favor of the
(
S)-N,N¢-Bis(2,4,6-trimethylphenyl)dinaphthyldiamine (3c)
The mixture of (S)-1,1¢-binaphthyl-2,2¢-diamine [(S)-1] (284 mg,
.0 mmol), 2-bromomesitylene (0.33 mL, 436 mg, 2.2 mmol),
Pd (dba) (22 mg, 0.04 mmol Pd), (±)-BINAP (25 mg, 0.04 mmol)
branched isomer (9:10 = 80:20) and the ee-value of 31%
in favor of (S)-9] are remarkable for a monodentate
[
1
ligand in asymmetric hydroformylation, but certainly far
below the standard set by Takaya and Nozaki using their
2
3
and sodium tert-butoxide (270 mg, 2.8 mmol) was suspended in an-
hyd o-xylene (8 mL) and stirred at 150 °C for 24 h. To the dark
ture of the diazaphospholidines described in the present brown reaction mixture was added H O (20 mL) and the mixture
1
3
bidentate MOP-ligand. However, due to the modular na-
2
paper, further ligand tuning can be expected to be straight- was extracted with tert-butyl methyl ether (3 × 30 mL). The com-
bined organic phases were washed with H O, then with brine and
forward. Moreover, the concept of using mixtures of two
different P-ligands recently introduced by us can now be
extended to include the new chiral monodentate ligands
prepared in the present study.
2
6
dried (MgSO ). Evaporation of the solvents gave an orange oil (ca.
4
7
00 mg), which was purified by chromatography (SiO ; hexane–
2
EtOAc, 20:1).
Yield: 490 mg (94%); colorless solid.
1
H NMR (CDCl ): d = 2.1 (s, 12 H, 4 CH ), 2.27 (s, 6 H, 2 CH )
3 ,
3
3
5
7
.18 (br, s, 2 H, NH), 6.72 (d, J = 8.9 Hz, 2 H, Ar), 6.88 (s, 4 H, Ar),
.16–7.32 (m, 4 H, Ar), 7.67–7.83 (m, 4 H, Ar).
1
3
C NMR: d = 18.6, 20.9, 111.3, 114.3, 122.0, 124.2, 126.6, 128.0,
1
28.1, 129.1, 129.5, 134.0, 134.9, 135.7, 136.6, 143.3.
Scheme 6 Rh-catalyzed hydroformylation of 8
+
MS (EI): m/z = 520 [M ], 386.
Thus, starting from commercially available 1,1¢-binaph-
(
S)-5a
thyl-2,2¢-diamine (1), we have prepared a number of nov- A stirred mixture of diamine (S)-3a (146 mg, 0.467 mmol) and Et N
3
el diazaphospholidines 2a–g. They constitute a new class (0.5 mL, 360 mg, 3.6 mmol) in CH Cl (7 mL) in a Schlenk flask
of chiral monodentate P-ligands. Characterization by
2
2
was treated with an Et O solution of PCl (0.5 M; 1.05 mL, 0.525
2
3
Synthesis 2003, No. 12, 1809–1814 © Thieme Stuttgart · New York

1
812
M. T. Reetz et al.
PAPER
mmol) dropwise at 0 °C. After stirring for 16 h, anhyd MeOH (25
mL, 20 mg, 0.6 mmol) was added and the mixture was stirred for 2
h. All volatiles were removed under reduced pressure and the result-
ant solid was suspended in toluene. A portion did not dissolve, and
purified by chromatography (SiO ; hexane–EtOAc, 15:1) to pro-
vide (S)-5c. Crystallization for an X-ray structural analysis was per-
formed in toluene–pentane.
2
Yield: 126 mg (25%); colorless solid.
®
was filtered off by a pad of Celite under argon. The yellowish or-
1
H NMR (CDCl ): d = 0.0–1.5 (br, 3 H, BH ), 3.48 (d, J = 11.1 Hz,
ange filtrate was treated with a THF solution of BH ·THF (1 M; 1
3
3
3
3
H, OCH ), 6.8–8.1 (m, 22 H, Ar).
3
mL, 1 mmol) and the mixture stirred at r.t. for 2 h. All volatiles were
removed and the resultant colorless solid was purified by chroma-
tography (5 g neutral alumina; EtOAc).
13
C NMR: d = 54.2 (d, J = 9.0 Hz), 123–132 (Ar), 141.0 (d), 144.3
(
d).
Yield: 184 mg (99%); colorless solid.
31
P NMR: d = 120.3 (m).
1
H NMR (CDCl ): d = –0.2–1.4 (br, 3 H, BH ), 2.9–3.1 (m, 6 H,
+
3
3
MS (EI): m/z = = 496 [M – BH ], 343.
3
2
NCH ), 3.62 (d, J = 11.5 Hz, 3 H, OCH ), 7.0–8.1 (m, 12 H, Ar).
3
3
1
3
Crystal data for 5c
C NMR: d = 35.3 (d, J = 8.4 Hz), 37.7 (d, J = 16.1 Hz), 53.1 (d,
J = 4.2 Hz), 122–133 (Ar).
[
C H BN OP], from toluene–pentane, M = 510.35, crystal size:
33 28
2
r
0
.04
×
0.15
×
0.16 mm; a = 9.1778(1), b = 10.1788(1),
3
1
P NMR: d = 134.9 (m).
3
c = 28.8611(3) Å, V = 2696.17(5) Å , T = 100 K, orthorhombic,
+
–3
MS (EI): m/z = 372 [M – BH ], 281.
space group P 2 2 2 (No. 19), Z = 4, r
= 1.257 g cm , Nonius
3
1
1
1
calcd
–
1
KappaCCD diffractometer, l(MoKa) = 0.71073 Å, m = 0.13 mm ,
49894 measured and 10319 independent reflections (Rint = 0.089),
8392 with I > 2s(I), qmax = 33.20°, Tmin = 0.981, Tmax = 0.995, direct
(
S)-5b
A 20 mL Schlenk flask equipped with a bubbler was charged with
S)-3a (152 mg, 0.487 mmol) in toluene (5 mL). After the addition
of ClP(NEt ) (0.11 mL, 110 mg, 0.523 mmol) the mixture was
(
methods (SHELXS-97) and least-squares refinement (SHELXL-97)
2
on F , both programs from G. Sheldrick, University of Göttingen,
2
2
o
stirred for 20 h at 90 °C. The light-yellow suspension was filtered
through a pad of Celite and the filtrate was treated with a THF so-
H atoms riding, Flack parameter -0.11(7), Chebychev weights,
®
R = 0.055 [I > 2s(I)], wR = 0.122 (all data), Dr
= 0.386/–
1
2
max/min
–
3
lution of BH ·THF (1 M; 1 mL, 1 mmol). After stirring for 3 h, all
0.391 eÅ . CCDC 213917.
3
volatiles were removed and the resultant solid was purified by chro-
matography (25 g SiO ; hexane–EtOAc, 20: 1) to provide 5b. Crys-
Compounds (S)-5d–g; General Procedure
2
tallization for an X-ray structural analysis was performed in EtOAc.
In a Schlenk flask a solution of (S)-3a or (S)-3b (0.6 mmol) in Et O
2
(
1
7 mL) was treated with a hexane solution of BuLi (1.6 M; 0.9 mL,
.44 mmol) at –78 °C. After stirring at r.t. for 20 min, the solution
Yield: 155 mg (72%); colorless solid.
1
H NMR (CDCl ): d = –0.2–1.3 (br, 3 H, BH ), 1.05 (t, J = 7.0 Hz,
3
3
was cooled once more to –78 °C and then treated with the appropri-
ate RPCl (0.72 mmol). The suspension was stirred at r.t. for 24 h
and then treated with a THF solution of BH ·THF (1 M; 1 mL, 1
mmol) at r.t. After 2 h all volatiles were removed and the solid ma-
6
H, 2 CH ), 2.8–3.1 (br, m, 4 H, 2 NCH ), 3.00 (s, 3 H, NCH ), 3.04
3
2
3
2
(
s, 3 H, NCH ), 6.95–8.00 (m, 12 H, Ar).
3
3
1
3
C NMR: d = 13.9, 35.8 (d, J = 9.0 Hz), 36.2 (d, J = 14.2 Hz), 38.3,
terial was purified by chromatography (SiO ; hexane–EtOAc, 3:1).
1
22–133 (Ar).
2
3
1
P NMR: d = 121.5 (m).
(
S)-5d
+
MS (EI): m/z = 413 [M – BH ], 386, 281.
Yield: 160 mg (84%).
3
1
H NMR (CDCl ): d = –0.1–1.6 (br, 3 H, BH ), 1.65 (d, J = 7.3 Hz,
3
3
Crystal data for 5b
3
H, CH ), 6.7–8.1 (m, 22 H, Ar).
3
[
×
C H BN P], from EtOAc, M = 427.32, crystal size: 0.07 × 0.10
26 31 3 r
1
3
C NMR: d = 16.2 (d, J = 39.0 Hz), 125–133 (Ar), 140–145 (Ar).
0.19 mm; a = 7.7547(1), b = 8.0805(1), c = 35.8042(4) Å,
3
V = 2243.56(5) Å , T = 100 K, orthorhombic, space group P 2 2 2
(
meter, l(Mo ) = 0.71073 Å, m = 0.14 mm , 23107 measured and
8
q
9
grams from G. Sheldrick, University of Göttingen, H atoms riding,
Flack parameter 0.10(9), Chebychev weights, R = 0.058 [I >
2
31
1
1
1
P NMR: d = 120.4 (m).
–
3
No. 19), Z = 4, rcalcd = 1.265 g cm , Nonius KappaCCD diffracto-
+
–
1
MS (EI): m/z = 480 [M – BH
3
], 465.
Ka
043 independent reflections (Rint = 0.053), 6683 with I > 2s(I),
(
S)-5e
= 33.06°, Tmin = 0.973, Tmax = 0.989, direct methods (SHELXS-
max
2
Yield: 184 mg (70%).
1
7) and least-squares refinement (SHELXL-97) on F , both pro-
o
H NMR (CDCl ): d = 0.1–1.4 (br, 3 H, BH ), 0.53 (dd, J = 7.2,
3 3
12.6 Hz, 3 H, CH ), 1.48 (dd, J = 7.2, 18.7 Hz, 3 H, CH ), 2.51 (m,
1 H, PCH), 6.7–8.0 (m, 22 H, Ar).
1
3
3
–
3
s(I)], wR = 0.126 (all data), Dr
= 0.462/–0.335 eÅ .
2
max/min
CCDC 213916.
13
C NMR: d = 16.1 (d, J = 6.6 Hz), 17.1 (d, J = 4.0 Hz), 29.8 (d,
J = 36.6 Hz), 125–133 (Ar), 141–146 (Ar).
(
S)-5c
3
1
P NMR: d = 131.1 (m).
In a Schlenk flask an Et O solution of (S)-3b (10 mL; 436 mg, 1.0
mmol) was treated with a BuLi solution in hexane (1.6 M; 1.5 mL,
2
+
MS (EI): m/z = 508 [M – BH ], 465.
3
2
.4 mmol) at –78 °C. The orange solution was stirred at r.t. for 20
min, cooled once again to –78 °C and then treated dropwise with a
solution of PCl in Et O (0.5 M; 2.5 mL, 1.25 mmol). The yellow
(
S)-5f
3
2
Yield: 142 mg (50%).
1
solution was warmed to r.t., stirred for 16 h and then treated with an-
hyd MeOH (0.05 mL, 40 mg, 1.2 mmol). After 2 h all volatiles were
removed under reduced pressure and the solid suspended in toluene
H NMR (CDCl ): d = 0.1–1.5 (br, 3 H, BH ), 0.5–2.45 (m, 11 H, c-
3
3
C H ), 6.7–8.0 (m, 22 H, Ar).
31
6
11
®
(
50 mL). The remaining solid was filtered off by a pad of Celite
P NMR: d = 128.3 (m).
under argon. The yellow–orange filtrate was treated with a THF so-
+
MS (EI): m/z = 548 [M – BH ], 465.
3
lution of BH ·THF (1 M; 2 mL, 2 mmol) and stirred at r.t. for 2 h.
3
All volatiles were removed and the resultant colorless solid was
Synthesis 2003, No. 12, 1809–1814 © Thieme Stuttgart · New York

PAPER
S)-5g
Binaphthyldiamine-Based Diazaphospholidines as a New Class of P-Ligands
1813
(
Hydrogenation of 6; General Procedure
Yield: 141 mg (53%).
A 25 mL Schlenk flask was charged with a CH Cl stock solution
2 2
1
of Rh(cod)
2
BF
(2 mM; 0.5 mL, 0.001 mmol), additional CH Cl
4 2 2
H NMR (CDCl ): d = 0.3–1.5 (br, 3 H, BH ), 1.07 (d, J = 14.3 Hz,
3
3
(7.3 mL), a CH Cl solution of a chiral P-ligand 2 (10 mM; 0.2 mL,
2
2
9
1
H, 3 CH ), 6.7–8.0 (m, 22 H, Ar).
3
0
.002 mmol) and a CH Cl solution of 6 (0.5 M; 2 mL, 1.0 mmol)
2 2
3
C NMR: d = 27.8, 38.0 (d, J = 31.5 Hz), 122–135 (Ar), 142–145
at r.t. The argon gas was evacuated until bubbles could be observed
in the solution, then H gas was introduced until 1 bar was reached.
The evacuation/introduction cycle was carried out three times, then
(
3
Ar).
2
1
P NMR: d = 139.0 (m).
the H pressure was adjusted to 1.3 bar. The mixture was stirred at
+
2
MS (EI): m/z = 522 [M – BH ], 465.
3
r.t. for 20 h. Conversion and the ee were determined by GC.
Deprotection of Ligands; General Procedure
Hydroformylation of 8; General Procedure
A 4 mL reaction vessel equipped with a rubber septum was charged
with a toluene solution of a rhodium precursor [Rh(acac)(CO) or
Removal of BH from the P-ligands is best performed by treatment
3
with a large excess (> 10 equiv) of diethylamine at 75 °C overnight
without a solvent. Excess diethylamine and amine–borane adduct
were removed under reduced pressure (< 0.02 bar) at 45 °C for 3–4
h. Since the resulting P-ligands cannot be chromatographed without
extensive degradation, they were used as such in catalysis. Charac-
teristic NMR data could be obtained routinely.
2
Rh(cod) BF ] (2 mM; 1.25 mL, 0.025 mmol) and a toluene solution
2
4
of a monodentate P-ligand 2 (10 mM; 0.75 mL, 0.0075 mmol) under
argon. After stirring for 1 h at r.t., styrene (6) (0.115 mL, 104 mg,
1
.0 mmol) was added together with a few drops of dodecane as an
internal standard for GC analysis following hydroformylation. The
rubber septum was pierced with a short needle and the flask was
placed in a stainless steel autoclave under argon. Syngas (H /CO, 1:
(
S)-2a
1
2
H NMR (CDCl ): d = 2.85 (d, J = 9.7 Hz, 3 H, NCH ), 3.00 (d,
3
3
1
) was then introduced at the desired pressure, and the reaction car-
J = 13.8 Hz, 3 H, NCH ), 3.25 (d, J = 9.5 Hz, 3 H, OCH ), 6.9–7.9
3
3
ried out with stirring at the desired temperature for 20 h (Table 1).
Conversion and regioselectivity were determined by GC. In order to
(
m, 12 H, Ar).
1
3
C NMR: d = 33.9 (d, J = 26.2 Hz), 36.8 (d, J = 44.5 Hz), 49.5,
determine the ee-value, oxidation by CrO to the corresponding acid
3
1
3
1
20–144 (Ar).
according to a literature procedure was performed followed by GC
analysis.
3
1
P NMR: d = 165.9 (m).
(
S)-2b
Acknowledgment
3
1
P NMR: d = 149.0 (m).
Support by the Fonds der Chemischen Industrie is gratefully ack-
nowledged. H. O. thanks the Japan Society for the Promotion of
Science (JSPS) for a postdoctoral fellowship.
(
S)-2c
1
H NMR (CDCl ): d = 3.14 (d, J = 10.0 Hz, 3 H, OCH ), 6.7–7.9
(
3
3
m, 22 H, Ar).
1
3
C NMR: d = 51.6 (d, J = 2.7 Hz), 123–147 (Ar).
P NMR: d = 147.9 (m).
References
3
1
(
1) Reetz, M. T.; Mehler, G. Angew. Chem. Int. Ed. 2000, 39,
889; Angew. Chem. 2000, 112, 4047.
(2) Reetz, M. T.; Sell, T. Tetrahedron Lett. 2000, 41, 6333.
3
(
S)-2d
1
H NMR (CDCl ): d = 1.22 (d, J = 9.2 Hz, 3 H, CH ), 6.5–8.0 (m,
3
3
(
3) Claver, C.; Fernandez, E.; Gillon, A.; Heslop, K.; Hyett, D.
J.; Martorell, A.; Orpen, A. G.; Pringle, P. G. Chem.
Commun. 2000, 961.
2
1
2 H, Ar).
3
C NMR: d = 16.5 (d, J = 24.8 Hz), 116–147 (Ar).
P NMR: d = 135.0 (m).
3
1
(4) (a) van den Berg, M.; Minnaard, A. J.; Schudde, E. P.; van
Esch, J.; de Vries, A. H. M.; de Vries, J. G.; Feringa, B. L. J.
Am. Chem. Soc. 2000, 122, 11539. (b) Minnaard, A. J.; van
den Berg, M.; Schudde, E. P.; van Esch, J.; de Vries, A. H.
M.; de Vries, J. G.; Feringa, B. L. Chim. Oggi 2001, 19, 12.
(5) Komarov, I. V.; Börner, A. Angew. Chem. Int. Ed. 2001, 40,
1197; Angew. Chem. 2001, 113, 1237.
(
S)-2e
1
H NMR (CDCl ): d = 0.59 (dd, J = 7.2 Hz, 11.6 Hz, 3 H, CH ),
3
3
0
6
.82 (dd, J = 7.2, 14.5 Hz, 3 H, CH ), 1.92–2.08 (m, 1 H, PCH),
.5–8.0 (m, 22 H, Ar).
3
1
3
C NMR: d = 15.6 (d, J = 10.7 Hz), 16.4 (d, J = 15.4 Hz), 30.3 (d,
(6) (a) Reetz, M. T.; Sell, T.; Meiswinkel, A.; Mehler, G.
J = 26.0 Hz), 125–133 (Ar), 141–146 (Ar).
Angew. Chem. Int. Ed. 2003, 42, 790; Angew. Chem. 2003,
3
1
P NMR: d = 150.5 (m).
115, 814. (b) Reetz, M. T.; Mehler, G. Tetrahedron Lett.
2
003, 44, 4593. (c) See also: Peña, D.; Minnaard, A. J.;
(
S)-2f
Boogers, J. A. F.; de Vries, A. H. M.; de Vries, J. G.;
Feringa, B. L. Org. Biomol. Chem. 2003, 1, 1087.
1
H NMR (CDCl ): d = 0.7–1.9 (m, 11 H, c-C H ), 6.5–8.0 (m, 22
H, Ar).
3
6
11
(
7) (a) Reetz, M. T.; Haderlein, G.; Angermund, K. J. Am.
Chem. Soc. 2000, 122, 996. (b) Chelating bidentate P-
ligands based on 1: Miyano, S.; Nawa, M.; Mori, A.;
Hashimoto, H. Bull. Chem. Soc. Jpn. 1984, 57, 2171.
(c) Guo, R.; Li, X.; Wu, J.; Kwok, W. H.; Chen, J.; Choi, M.
C. K.; Chan, A. S. C. Tetrahedron Lett. 2002, 43, 6803.
3
1
P NMR: d = 148.8 (m).
(
S)-2g
1
H NMR (CDCl ): d = 0.65 (d, J = 11.9 Hz, 9 H, 3 CH ), 6.6–8.0
3
3
(
m, 22 H, Ar).
(d) Zhang, F.-Y.; Kwok, W. H.; Chan, A. S. C. Tetrahedron:
1
3
C NMR: d = 27.8, 36.9 (d, J = 32.2 Hz), 118–150 (Ar).
P NMR: d = 160.4 (m).
Asymmetry 2001, 12, 2337. (e) Zhang, F.-Y.; Pai, C.-C.;
Chan, A. S. C. J. Am. Chem. Soc. 1998, 120, 5808. (f) See
also: Ansell, J.; Wills, M. Chem. Soc. Rev. 2002, 31, 259.
3
1
Synthesis 2003, No. 12, 1809–1814 © Thieme Stuttgart · New York

1
814
M. T. Reetz et al.
PAPER
(
8) (a) Benson, S. C.; Cai, P.; Colon, M.; Haiza, M. A.; Tokles,
(11) See experimental section.
M.; Snyder, J. K. J. Org. Chem. 1988, 53, 5335.
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T.; Kusumoto, T.; Suzuki, N.; Sato, K. J. Am. Chem. Soc.
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(13) (a) Horiuchi, T.; Shirakawa, E.; Nozaki, K.; Takaya, H.
Organometallics 1997, 16, 2981. (b) Nozaki, K.; Sakai, N.;
Nanno, T.; Higashijima, T.; Mano, S.; Horiuchi, T.; Takaya,
H. J. Am. Chem. Soc. 1997, 119, 4413.
(b) Vyskočil, S.; Jaracz, S.; Smrčina, M.; Štícha, M.; Hanuš,
V.; Polášek, M.; Kočovský, P. J. Org. Chem. 1998, 63, 7727.
9) Naberfeld, G. Dissertation; Ruhr-Universität Bochum:
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10) (a) Wolfe, J. P.; Wagaw, S.; Buchwald, S. L. J. Am. Chem.
Soc. 1996, 118, 7215. (b) Driver, M. S.; Hartwig, J. F. J. Am.
Chem. Soc. 1996, 118, 7217.
(
(
Synthesis 2003, No. 12, 1809–1814 © Thieme Stuttgart · New York