Palladium-catalyzed intermolecular asymmetric hydroamination with 4,4′-disubstituted BINAP and SEGPHOS

Article abstract of DOI:10.1002/adsc.200606208

A family of tunable precatalysts [Pd((S)-L*)(NCMe) ₂](OTf)₂, where L* is 4,4′-disubstituted BINAP or SEGPHOS, was synthesized and used for the asymmetric intermolecular hydroamination of aniline to vinylarenes with ee values of up to

Full text of DOI:10.1002/adsc.200606208

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DOI: 10.1002/adsc.200606208
Palladium-Catalyzed Intermolecular Asymmetric Hydroamination
with 4,4’-Disubstituted BINAP and SEGPHOS
Aiguo Hu,a Masamichi Ogasawara,b,* Takeshi Sakamoto,b Atsushi Okada,b
Kiyohiko Nakajima,c Tamotsu Takahashi,b,* and Wenbin Lina,*
a
Department of Chemistry, CB#3290, University of North Carolina, Chapel Hill, NC 27599, USA
Fax : (+1)-919-962-6320; e-mail: wlin@unc.edu
Catalysis Research Center and Graduate School of Pharmaceutical Sciences, Hokkaido University, and SORST Japan,
b
Science and Technology Agency (JST), Kita-ku, Sapporo 001-0021, Japan
Fax : (+81)-11-706-9150; e-mail: ogasawar@cat.hokudai.ac.jp or tamotsu@cat.hokudai.ac.jp
Department of Chemistry, Aichi University of Education, Igaya, Kariya, Aichi 448-8542, Japan
c
Received: May 1, 2006; Accepted: August 3, 2006
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: A family of tunable precatalysts [Pd((S)-
L*)(NCMe)2](OTf)2, where L* is 4,4’-disubstituted
actions. It is also well established that the dihedral
angle of the biaryl moiety in chiral chelating phos-
phines can have significant effects in transition metal-
catalyzed asymmetric reactions.[6] SEGPHOS (2;
Figure 1),[7] which is believed to have the narrowest
A
ACHTREUNG
BINAP or SEGPHOS, was synthesized and used
for the asymmetric intermolecular hydroamination
of aniline to vinylarenes with ee values of up to
85%, and it is believed that the bulky groups on
the 4,4’-positions and the narrower dihedral angle
of the biaryl moiety are responsible for the ee en-
hancement in these reactions.
Keywords: asymmetric catalysis; chiral amine; hy-
droamination; palladium; phosphine
Asymmetric hydroamination of olefins is one of the
simplest and the most atom-economical methods for
the synthesis of chiral secondary amines.[1] The devel-
opment of efficient asymmetric hydroamination reac-
tions is, however, slow due to the high energy barrier
Figure 1. Modified BINAPs (1) and SEGPHOS (2).
À
of the C N bond-forming process. Whereas Marks
et al. and others carried out intramolecular asymmet-
ric hydroamination using chiral organolanthanide cat- dihedral angle among these bisphosphines, indeed
alysts,[2] Hartwig et al. and others recently reported a gives better ees than others in many Ru-,[7,8] Rh-,[9]
novel Pd-catalyzed intermolecular hydroamination of Pd-,[10] and Cu-catalyzed[11] reactions. We hypothesize
anilines to vinylarenes to afford Markovnikov addi- that more enantioselective catalysts for intermolecu-
tion products.[3] Asymmetric hydroamination has been lar hydroamination reactions can be designed by com-
explored for a few substrates, but only moderate bining the potential positive effects of bulky substitu-
enantioselectivities were obtained.[3a,c] Since we have ents and narrow dihedral angles in biaryl-based bis-
recently observed significant ee enhancements of 4,4’- phosphines. We decided to combine the 4,4’-substitu-
disubstituted BINAPs over the parent BINAP in a va- ent effect with the smaller dihedral angle in a SEG-
riety of Ru-catalyzed hydrogenation[4] and Pd-cata- PHOS system. Herein, we report the synthesis and
[5]
À
lyzed C C bond-forming reactions, we have decided optical resolution of new 4,4’-disubstituted SEG-
to explore the use of modified BINAPs in Pd-cata- PHOS (t-Bu-SEGPHOS, 2b) and the applications of
lyzed asymmetric intermolecular hydroamination re- 4,4’-disubstituted BINAPs 1 and SEGPHOS 2 in Pd-
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Aiguo Hu et al.
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catalyzed asymmetric intermolecular hydroamination propriate DBTA complex. For example, rac-6 and
reactions.
0.5 equivs. of (À)-DBTA were dissolved in EtOAc/
As shown in Scheme 1, t-Bu-SEGPHOS (2b) was CHCl3 and addition of the above needle crystals pre-
synthesized from 5-bromo-3-tert-butylcatechol (3).[12] cipitated diastereomerically pure (À)-6/(À)-DBTA
complex in 42% yield. Seeding of the solution of the
mother liquor and additional (À)-DBTA (0.42 equivs.
with respect to the initial amount of rac-6) with the
above prism crystals precipitated diastereomerically
pure (+)-6/(À)-DBTA in 44% yield. Second and
third crops were collected in the same way. Decom-
plexation of (À)-DBTA from the diastereomeric pairs
by treating with aqueous NaOH afforded (+)- and
(À)-6 in 48% and 45% yield, respectively.
Reduction of (À)-6 with HSiCl3/NEt3 in xylenes at
1308C afforded (À)-2b in 91% yield. The absolute
configuration of (+)-6 was determined by single-crys-
tal X-ray diffraction studies of the [(+)-6/(À)-
DBTA]·EtOAc complex. [(+)-6/(À)-DBTA]·EtOAc
crystallizes in the C2 space group. The co-crystallized
EtOAc molecules are highly disordered in the lattice.
As unambiguously shown in Figure 2, (+)-6 has the
(R)-configuration.
Scheme 1. Synthesis and resolution of t-Bu-SEGPHOS (2b).
Treatment of 3 with CH2Br2 and K2CO3 in DMF at
908C afforded benzo
ACHTREUNG
After conversion of
4
Grignard reagent, a reaction with Ph2P(O)Cl gave
phosphine oxide 5 in 90% yield. Oxidative homocou-
pling of 5 using FeCl3 furnished racemic t-Bu-SEG-
PHOS dioxide 6 in 82% yield.
Optical resolution of rac-6 was accomplished using
dibenzoyltartaric acid (DBTA) as a resolving re-
agent.[13] Both (R)- and (S)-6 can be isolated in enan-
tiomerically pure forms using (À)-DBTA (natural
form). When an equimolar mixture of rac-6 and (À)-
DBTA was dissolved in ethyl acetate/chloroform, col-
orless precipitates formed in several hours. The pre-
cipitates contain prism- and needle-shaped crystals.
Small portions of each crystalline form were manually
Figure 2. Ball-and-stick drawing of the single-crystal X-ray
structure of (R)-(+)-6/(À)-DBTA. Purple, red, grey, and
cyan colors represent P, O, C, and H atoms, respectively.
The dotted line indicates H-bonding.
1
separated and analyzed by H NMR and chiral HPLC
(Daicel Chiralpak AD-H; eluent: hexane/EtOH=50/
50). The prisms and needles were shown to be a dia-
stereomeric pair of 1:1 molecular complexes between
(À)-DBTA and (+)- or (À)-6, respectively. The phos-
The asymmetric hydroamination of aniline to p-flu-
phine oxide 6 recovered from the mother liquor was orostyrene was chosen for ligand screening experi-
nearly racemic (<5% ee), indicating similar solubility ments. As summarized in Table 1, the substituents on
of the two diastereomeric 6/(À)-DBTA complexes. In- the phenyl rings of BINAP (e.g., 1b and 1c; entries 2
terestingly, by taking advantage of the slow complexa- and 3) lowered the ee, while the bulky substituents on
tion of 6/(À)-DBTA, selective crystallization of either the 4,4’-positions of BINAP have positive effects on
enantiomer of 6 was achieved by seeding with an ap- the ee values (entries 4–7). About 10% ee enhance-
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Palladium-Catalyzed Intermolecular Asymmetric Hydroamination
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Table 1. Asymmetric addition of aniline to p-fluorostyrene.[a]
Table 2. Asymmetric addition of aniline to vinylarenes.[a]
Entry
Ar
% ee[b] (yield [%][c])
Entry
L*
Yield [%][b]
% ee[c]
1a
1g
2b
1
2
3
4
5
6
7
8
4-F-C6H4-
Ph
69 (80)
71 (75)
73 (87)
64 (92)
70 (85)
27 (89)
32 (97)
43 (86)
78 (53)
79 (51)
75 (70)
70 (92)
74 (85)
41 (85)
36 (82)
59 (79)
84 (65)
81 (71)
85 (72)
85 (67)
84 (70)
31 (89)
42 (81)
50 (72)
1
2
3
4
5
6
7
8
9
BINAP (1a)
tol-BINAP (1b)
xyl-BINAP (1c)
1d
1e
1 f
tms-BINAP (1g)
SEGPHOS (2a)
t-Bu-SEGPHOS (2b)
80
45
15
20
80
50
85
77
65
69
59
46
66
73
74
79
76
84
4-Cl-C6H4-
4-CF3-C6H4-
4-MeOCO-C6H4-
1-naphthyl
2-naphthyl
6-MeO-2-naphthyl
[a]
With 2 mol% catalyst loading.
Determined by chiral GC or chiral HPLC.
Isolated yield.
[b]
[c]
[a]
With 2 mol% catalyst loading.
Isolated yield.
Determined by chiral GC.
[b]
[c]
termined X-ray single crystal structure of Pd[(S)-
2b]Cl2 (Figure 3). Yellow crystals of Pd[(S)-2b]Cl2
ment was observed for 4,4’-(Me3Si)2-BINAP (tms- were obtained by slow diffusion of hexane into a di-
BINAP, 1g) over BINAP (entry 7 vs. entry 1). In addi- chloromethane solution of Pd[(S)-2b]Cl2. The X-ray
tion to the introduction of bulky substituents on the single crystal structural analysis shows that the dihe-
4,4’-positions of BINAP, the dihedral angle of the dral angle of 62.98 for the biaryl moiety in Pd[(S)-
biaryl moiety can also have a positive effect on the 2b]Cl2 is comparable to that of Pd[(S)-2a]Cl2
enantioselectivity of BINAP analogues[6–11]. We thus (60.18),[10c] and both of them are significantly narrow-
tested SEGPHOS[7] in the hydroamination of aniline er than that of Pd[(S)-1a]Cl2 (70.18)[10c,14] and that of
to p-fluorostyrene, and it indeed shows ~7% ee en-
hancement over BINAP (entry 8 vs. entry 1). Encour-
aged by this promising result, we examined the new
ligand t-Bu-SEGPHOS (2b) in the hydroamination
reaction. Gratifyingly, a much higher ee of 84% was
obtained with 2b under identical conditions (entry 9).
The 15 % ee enhancement seen for 2b is probably a
result of both the bulky 4,4’-substituents and narrow
dihedral angle of the biaryl moiety. This level of ee
value is the highest observed for asymmetric intermo-
lecular hydroamination reactions.
Based on these ligand screening results, we have
further examined the utility of 1g and 2b in the hydro-
amination of aniline to a series of vinylarene. As
shown in Table 2, for all the styrene derivatives exam-
ined (entries 1–5), both 1g and 2b have significantly
outperformed the parent BINAP 1a. With 2b, higher
than 80% ee was obtained for all the styrene deriva-
tives. The substrates with electron-withdrawing
groups all gave higher ees than styrene. For vinyl-
naphthalenes, however, much lower ees were obtained
for all the three bisphosphines (entries 6–8). Earlier
work suggested that the hydroamination of vinylnaph-
thalenes probably went through a different pathway
than the vinylstyrenes owing to the stabilization of
the Pd-p-allyl type intermediate for vinylnaphtha-
Figure 3. ORTEP drawing of the single-crystal X-ray struc-
lenes.[3b]
À
À
ture of Pd[(S)-2b]Cl2. Pd1 Cl1: 2.337 Š, Pd1 P2: 2.254 Š;
1
To gain insight on the origin of the ee enhancement
of 2b over BINAPs 1 and SEGPHOS 2a, we have de- Cl1: 89.008, Cl1 Pd1 Cl A: 91.188.
À
À
À
À
À
À
P2 Pd1 P2A: 92.198, P2 Pd1 Cl A: 171.14(1)8, P2 Pd1
1
À
À
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Aiguo Hu et al.
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the analogous Pd-allyl complex of tms-BINAP (1g).[5]
Thus, the significant ee enhancement observed for 2b
can be attributed to both the bulky 4,4’-substituents
and narrow dihedral angle of the biaryl moiety.
(10 mL) solution of Ph2POCl (4.35 g, 18.4 mmol) dropwise,
then the mixture was stirred for 6 h. The reaction mixture
was quenched with water and extracted with chloroform.
The chloroform solution was dried over MgSO4 and evapo-
rated. The residue was purified by silica gel chromatography
(with EtOAc) to give a very viscous pale yellow oil. Recrys-
tallization from hot toluene to give colorless crystals, which
contain co-crystallized toluene. Prolonged evacuation of the
crystals at 1008C gave the toluene-free compound as a col-
orless oil; yield: 6.05 g (16.0 mmol, 90%). 1H NMR
(CDCl3): d=1.30 (s, 9H), 5.99 (s, 2H), 6.84 (dd, J=1.4 and
11.5 Hz, 1H), 7.26 (dd, J=1.4 and 13.5 Hz, 1H), 7.43–7.47
(m, 4H), 7.50–7.55 (m, 2H), 7.65–7.70 (m, 4H); 13C NMR
In summary, we have designed a novel chiral bis-
phosphine based on the SEGPHOS framework which
can combine the positive effects of both the bulky
4,4’-substituents and narrow dihedral angle of the
biaryl moiety. We have used Pd complexes of this
series of tunable chiral biaryl diphosphines in the in-
termolecular hydroamination of aniline to vinylarenes
and observed up to 15% ee enhancement over the
BINAP-derived catalyst. We believe that these tuna-
ble chiral biaryldiphosphines should prove useful for
other transition metal-catalyzed asymmetric reactions.
(CDCl3): d=29.1 (s), 34.0 (s), 100.9 (s), 109.6 (d, JPH
=
13.5 Hz), 124.5 (d, JPH =108.4 Hz), 124.8 (d, JPH =11.0 Hz),
128.3 (d, JPH =11.8 Hz), 131.7 (d, JPH =2.5 Hz), 131.9 (d,
J
PH =9.7 Hz), 132.8 (d, JPH =104.3 Hz), 133.1 (d, JPH =
13.5 Hz), 147.7 (d, JPH =19.0 Hz), 148.2 (d, JPH =2.9 Hz);
31P NMR (CDCl3): d=30.4 (s); anal. calcd for C23H23O3P: C
73.00, H 6.13; found: C 72.18, H 5.99; EI-HR-MS: m/z=
378.1380 (calcd. for C23H23O3P: 378.1383).
Experimental Section
General Remarks
All anaerobic and/or moisture-sensitive manipulations were
carried out with standard Schlenk techniques or with glove
box techniques under prepurified argon. 1H NMR (at
400 MHz) and 13C NMR (at 101 MHz) chemical shifts are
reported in ppm downfield of internal tetramethylsilane.
31P{1H} NMR (at 162 MHz) chemical shifts are reported in
ppm relative to external 85% H3PO4. Solvents used for
anaerobic reactions were purified by standard procedures. 5-
rac-5,5’-Bis(diphenylphosphinyl)-7,7’-di-tert-butyl-4,4’-
bibenzo[1,3]dioxole (rac-6, rac-t-Bu-SEGPHOS
Dioxide)
G
To a solution of 5 (5.00 g, 13.2 mmol) in THF (20 mL) was
added an LDA solution, which was prepared from i-Pr2NH
(2.07 g, 20.5 mmol) and n-BuLi (1.58M hexane solution,
13.0 mL, 20.5 mmol) in THF (15 mL), at À158C and the
mixture was stirred at this temperature for 2 h. The mixture
was added to a suspension of FeCl3 (3.33 g, 20.5 mmol) in a
THF (20 mL)/toluene (20 mL) mixture at 08C, then stirred
overnight at room temperature. After evaporation of the
solvent, the residue was dissolved in CH2Cl2 and washed
with dilute HCl and water successively, and then dried over
MgSO4. The crude product was recrystallized from hot
EtOAc to give the title compound in pure form; yield:
4.10 g (5.43 mmol, 82%). 1H NMR (CDCl3): d=1.15 (s,
18H), 5.31 (d, J=1.4 Hz, 2H), 5.69 (d, J=1.4 Hz, 2H), 6.81
(d, J=15.4 Hz, 2H), 7.21–7.32 (m, 6H), 7.39–7.49 (m, 6H),
7.63–7.68 (m, 4H), 7.72–7.77 (m, 4H); 13C NMR (CDCl3):
d=29.1 (s), 33.8 (s), 100.7 (s), 117.1 (dd, JPH =3.3 and
11.0 Hz), 123.6 (d, JPH =108.4 Hz), 126.9 (d, JPH =13.7 Hz),
127.6 (d, JPH =12.3 Hz), 127.8 (d, JPH =12.3 Hz), 130.9 (d,
Bromo-3-tert-butylcatechol (3),[12] 4,4’-disubstituted BINAPs
[15]
(1b–g),[4] (S)-SEGPHOS (2a),[7] and PdCl2
(NCMe)2 were
R
prepared according to the reported methods. All the other
chemicals were obtained from commercial sources and used
without further purification.
6-Bromo-4-tert-butylbenzo[1,3]dioxole (4)
N
A
mixture of 5-bromo-3-tert-butylcatechol (3, 32.0 g,
131 mmol), CH2Br2 (38 g, 219 mmol), and K2CO3 (30 g,
217 mmol) was suspended in DMF (ca. 100 mL) and vigo-
rously stirred at 908C for 3 h. After cooling, hexane and
water (ca. 500 mL each) were added to the flask. The organ-
ic layer was separated, washed with saturated NaCl, dried
over MgSO4, and evaporated. The residue was purified by
silica gel chromatography (with hexane) and subsequent
vacuum-transfer gave the title compound as a colorless
solid; yield: 24.0 g (93.3 mmol, 71%). 1H NMR (CDCl3):
d=1.32 (s, 9H), 5.95 (s, 2H), 6.85 (d, J=2.0 Hz, 1H), 6.89
(d, J=2.0 Hz, 1H); 13C NMR (CDCl3): d=29.2, 34.1, 100.8,
110.2, 112.9, 122.0, 134.4, 144.4, 148.5; anal. calcd. for
C11H13O2Br: C 51.38, H 5.10; found: C 51.22, H 5.01; EI-
HR-MS: m/z=256.0084 (calcd. for C11H13O2Br: 256.0098).
J
PH =2.1 Hz), 131.0 (d, JPH =2.1 Hz), 131.1 (d, JPH =14.5 Hz),
132.1 (d, JPH =9.4 Hz), 132.2 (d, JPH =9.4 Hz), 134.2 (d, JPH
=
103.3 Hz), 134.9 (d, JPH =104.1 Hz), 146.8 (d, JPH =16.6 Hz),
147.0 (d, JPH =2.2 Hz); 31P NMR (CDCl3): d=28.8 (s); FAB-
HR-MS: m/z=755.2691 (calcd. for C46H45O6P2 [M+1]:
755.2689).
Optical Resolution of rac-6
The racemic 6 (3.10 g, 4.11 mmol) was dissolved in chloro-
form (45 mL) and to this was added a solution of (À)-
DBTA (735 mg, 2.05 mmol) in EtOAc (50 mL) at room tem-
perature. With addition of a small amount of seed crystals,
colorless needles of [(S)-(À)-6/(À)-DBTA]·EtOAc precipi-
tated in several hours. The crystals were filtered, washed
with EtOAc, and dried (2.07 g, 1.72 mmol, 42%). The com-
bined mother liquor was evaporated to dryness and dis-
4-tert-Butyl-6-(diphenylphosphinyl)benzo[1,3]dioxole
(5)
A
To a stirred suspension of magnesium turnings (437 mg,
18.0 mmol) in THF (3 mL) was added a THF (20 mL) solu-
tion of 4 (4.57 g, 17.8 mmol) dropwise via a cannula and the
mixture was stirred for 4 h at room temperature. The flask
was cooled with ice-water and to this was added a THF
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Palladium-Catalyzed Intermolecular Asymmetric Hydroamination
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solved in CHCl3 (30 mL). To this was added a solution of
(À)-DBTA (617 mg, 1.72 mmol) in EtOAc (35 mL) and
seeding precipitated colorless prisms of [(R)-(+)-6/(À)-
DBTA]·EtOAc (2.17 g, 1.81 mmol, 44%). The resolution se-
quence was repeated for two more cycles. Total yield of
[(S)-(À)-6/(À)-DBTA]·EtOAc: 2.23 g (1.86 mmol, 45%).
Total yield of [(R)-(+)-6/(À)-DBTA]·EtOAc: 2.40 g
(2.00 mmol, 48%).
column chromatography, and the ee value was determined
on chiral GC or chiral HPLC (see Supporting Information).
Crystallographic data (excluding structure factors) for the
structure(s) reported in this paper have been deposited with
the Cambridge Crystallographic Data Centre as supplemen-
tary publication no. CCDC-289834 and 289835. Copies of
the data can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [Fax: int.
Treatment of
a
CH2Cl2 solution of [(S)-(À)-6/(À)-
code + 44(1223)336–033; E-mail: deposit@ccdc.cam.ac.uk].
A
DBTA]·EtOAc with aqueous NaOH afforded (S)-(À)-6
quantitatively. [a]2D0: À154.4 [c 1.00, CHCl3 for (S)-isomer].
(S)-(À)-5,5’-Bis(diphenylphosphino)-7,7’-di-tert-butyl-
Acknowledgements
4,4’-bibenzo
[1,3]dioxole [(S)-(À)-2b, (S)-(À)-t-Bu-
W.L. thanks NSF(CHE-0512495) and ACS-PRFfor finan-
cial support. M.O. thanks the Ministry of Education, Culture,
Sports, Science and Technology, Japan for partial financial
support of this work with a Grant-in-Aid for Scientific Re-
search on Priority Areas (No. 15036202, “Reaction Control
of Dynamic Complexes“).
SEGPHOS)
To a mixture of (S)-(À)-6 (1.40 g, 1.85 mmol) and NEt3
(4.0 mL, 28.7 mmol) in xylene (30 mL) was added HSiCl3
(1.5 mL, 14.8 mmol) under nitrogen at 08C. The mixture
was stirred at 1308C for 15 h. With external cooling with
ice-water, the mixture was quenched with a small amount of
saturated NaHCO3 (ca. 2 mL). The resulting suspension was
filtered and the solid was washed with hot toluene. The
combined organic layer was dried over MgSO4 and concen-
trated under reduced pressure. The residue was purified by
silica gel chromatography (with benzene) and treatment
with a small amount of cold MeOH gave the title compound
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as white powder. Yield: 1.22 g (1.69 mmol, 91%). H NMR
(CDCl3): d=1.15 (s, 18H), 5.08 (d, J=1.6 Hz, 2H), 5.71 (d,
J=1.6 Hz, 2H), 6.53 (vt, J=2.0 Hz, 2H), 7.24–7.27 (m,
20H); 13C NMR (CDCl3): d=29.3 (s), 34.0 (s), 100.3 (s),
119.5 (vt, JPH =21.0 Hz), 125.7 (s), 127.9 (vt, JPH =3.5 Hz),
127.96 (s), 128.04 (vt, JPH =3.2 Hz), 128.2 (s), 129.9 (dd,
J
PH =3.3 and 4.3 Hz), 132.3 (s), 133.5 (vt, JPH =10.2 Hz),
134.2 (vt, JPH =10.8 Hz), 137.9 (dd, JPH =5.3 and 6.2 Hz),
138.3 (dd, JPH =5.8 and 6.7 Hz), 145.3 (s), 146.3 (vt, JPH
=
6.7 Hz); 31P NMR (CDCl3): d=À10.6 (s); [a]2D0: À10.7 [c
1.02, CHCl3 for (S)-isomer]; anal. calcd for C46H44O4P2: C
76.44, H 6.14; found: C 76.23, H 6.07; FAB-HR-MS: m/z=
723.2802 (calcd. for C46H45O4P2 [M+1]: 723.2791).
Typical Procedure for Preparing Palladium Catalysts
A mixture of PdCl2(NCMe)2 (26 mg, 0.1 mmol) and (S)-
G
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BINAP (63 mg, 0.1 mmol) in anhydrous toluene (2 mL) was
stirred under argon for 2 h and then evaporated to dryness
under reduced pressure. The yellow solid was dissolved in
CH2Cl2 (6 mL) and AgOTf (51 mg, 0.2 mmol) in CH3CN
(3 mL) was added. The solution turned cloudy immediately,
after being stirred for 5 min, the mixture was filtered
through Celite and washed with CH2Cl2, the filtrate was
concentrated and dried under high vacuum to afford a yel-
lowish solid product. This solid was used for asymmetric hy-
droaminations without purification.
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Typical Procedure for Hydroamination
To
a
Teflon-sealed flask, palladium catalyst (11 mg,
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0.01 mmol) was added, and then freshly distilled aniline
(45 mL, 0.5 mmol), styrene (85 mL, 0.75 mmol), and anhy-
drous degassed toluene (1 mL) were added. The flask was
sealed and the reaction mixture was stirred at 758C (oil
bath) for 40 h. The pure product was obtained by silica gel
Adv. Synth. Catal. 2006, 348, 2051 – 2056
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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