Synthesis and application of atropisomeric dihydrobenzofuran-based bisphosphine (BICMAP)

Article abstract of DOI:10.1016/j.tetlet.2009.02.182

A new atropisomeric dihydrobenzofuran-based bisphosphine ligand 1 was easily prepared from 1,4-dibromo-2-fluorobenzene. This racemic bisphosphine (±)-1 was used as a ligand for the palladium-catalyzed Suzuki-Miyaura reaction of aryl chloride with arylboronic acids and Hartwig-Buchwald amination of aryl bromides with aniline derivatives. The optical resolution of (±)-1 was also carried out by HPLC with a chiral stationary phase column.

Full text of DOI:10.1016/j.tetlet.2009.02.182

Tetrahedron Letters 50 (2009) 2239–2241
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Tetrahedron Letters
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Synthesis and application of atropisomeric dihydrobenzofuran-based
bisphosphine (BICMAP)
*
Takashi Mino , Yoshiaki Naruse, Shohei Kobayashi, Shunsuke Oishi, Masami Sakamoto, Tsutomu Fujita
Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, Chiba University, 1-33, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A new atropisomeric dihydrobenzofuran-based bisphosphine ligand 1 was easily prepared from 1,4-
dibromo-2-fluorobenzene. This racemic bisphosphine ( )-1 was used as a ligand for the palladium-cata-
lyzed Suzuki–Miyaura reaction of aryl chloride with arylboronic acids and Hartwig–Buchwald amination
of aryl bromides with aniline derivatives. The optical resolution of ( )-1 was also carried out by HPLC
with a chiral stationary phase column.
Received 23 January 2009
Revised 23 February 2009
Accepted 24 February 2009
Available online 27 February 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Chiral phosphines are important molecules that affect asym-
metric inductions as ligands for transition metal catalysts.1 Atrop-
isomeric biaryls are also well established as one important class of
ligands for asymmetric metal-catalyzed reactions by the discovery
and the application of BINAP.2 Recently many new chiral biaryl-
phosphines have been reported, such as MeO-BIPHEP,3 BIBFUP,4 BI-
FAP,5 BICAP,6 SEGPHOS,7 and SYNPHOS.8 We herein report the
synthesis of a new atropisomeric bisphosphine ligand bearing a
dihydrobenzofuran (coumaran) core, hereafter named BICMAP
(( )-1), and its use in the palladium-catalyzed Suzuki–Miyaura
reaction9 and Hartwig–Buchwald amination.10,11 The optical reso-
lution of ( )-1 was also carried out by use of HPLC with a chiral sta-
tionary phase column.
shown in Figure 1. The optical resolution of ( )-1 was efficiently
carried out by HPLC with a chiral stationary phase column (Chir-
OH
Br
F
Br
HO
t-BuOK
66%
HO
Br
O
Br
2
3
Br
CBr4, PPh3
92%
1) n-BuLi (2 eq.)
Br
2) ClPPh2 (1.1 eq.)
66%
O
Br
4
Dihydrobenzofuran-based bisphosphine ligand 1 was easily
prepared from inexpensive reagent 1,4-dibromo-2-fluorobenzene
(2) (ꢀ$1/g)12 via 6-diphenylphosphino-2,3-dihydrobenzofuran (5)
(Scheme 1). A nucleophilic aromatic substitution (SNAr) reaction
of 1,4-dibromo-2-fluorobenzene (2) and ethylene glycol with
potassium tert-butoxide gave corresponding alcohol 313 that was
converted into bromide 4 using CBr4–PPh3 in good yield.14 6-
Diphenylphosphino-2,3-dihydrobenzofuran (5) was prepared by
intramolecular alkylation and phosphination with chlorodiphenyl-
phosphine via double lithium–bromide exchange of 4 with two
equivalents of n-butyllithium.15 After oxidation of the phosphine
atom by hydrogen peroxide in chloroform, ortholithiation of phos-
phine oxides 616 and further oxidative coupling with anhydrous
ferric chloride furnished bisphosphine oxide ( )-7 in good yield.17
This bisphosphine oxide ( )-7 was converted into racemic bisphos-
phine ligand ( )-1 using trichlorosilane-triethylamine in
good yield.18 We successfully conducted single-crystal X-ray
diffraction analysis of ( )-1, and the ORTEP diagram of ( )-1 is
H2O2
99%
O
O
PPh2
P(O)Ph2
5
6
HSiCl3 (30 eq.)
Et3N (36 eq.)
1) t-BuLi (1.1 eq.)
O
P(O)Ph2
P(O)Ph2
2) FeCl3 (1.2 eq.)
57%
O
53%
( )-7
resolution
O
O
PPh2
PPh2
(+)-1 + (–)-1
by chiral HPLC
(Chiralpak IA)
( )-1
Scheme 1. Preparation of diphosphine ligand 1.
* Corresponding author. Tel.: +81 43 290 3385; fax: +81 43 290 3401.
E-mail address: tmino@faculty.chiba-u.jp (T. Mino).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.02.182

2240
T. Mino et al. / Tetrahedron Letters 50 (2009) 2239–2241
Table 2
Palladium-catalyzed Hartwig–Buchwald amination using ( )-1a
Pd2(dba)3
( )-1
Br
NH2
H
N
Cs2CO3
+
R
R2
1
PhMe, 100 °C
18 h
R1
R2
11
12
13
Entry
R1
R2
Product
Yieldb (%)
1
NO2
NO2
Ac
CN
NO2
Me
Me
Me
Me
OMe
13a
13b
13c
13d
13e
98
93
93
92
91
2c
3
4
5
a
The reactions were carried out on 0.25 mmol scale of 11 with 1.2 equiv of 12
and 1.4 equiv of Cs2CO3 in the presence of Pd2(dba)3 (1 mol %) and ligand ( )-1
(3 mol %) in PhMe (1.0 mL) at 100 °C for 18 h under Ar.
Figure 1. ORTEP diagram of ( )-1.
b
Isolated yields.
c
This reaction was carried out using ( )-BINAP instead of ( )-1.
alpak IA) of a semi-preparative scale. Optically active (+)-1 and (ꢁ)-1
were obtained in an enantiomerically pure form.19
We investigated the ability of bisphosphine ( )-1 as a ligand for
the palladium-catalyzed Suzuki–Miyaura reaction of aryl chlorides
8 with arylboronic acids 9. This reaction was carried out in the
presence of 2.5 mol % of Pd2dba3, 7.5 mol % of ( )-1, and CsCO3 as
a base in dioxane (Table 1).20 When the reaction was carried out
using 1-chloro-4-nitrobenzene with phenylboronic acid, 4-nitrobi-
phenyl (10a) was obtained in good yield (Table 1, entry 1). The ef-
fect of various aryl chlorides and arylboronic acids in the Suzuki–
Miyaura reaction was investigated (Table 2, entries 2–5). The reac-
tion gave corresponding products 10b–e in moderate to good
yields.
We also investigated the ability of bisphosphine ( )-1 as a li-
gand for the palladium-catalyzed Hartwig–Buchwald amination
of aryl bromides 11 with aniline derivatives 12. This reaction was
carried out in the presence of 1 mol % of Pd2dba3, 2 mol % of ( )-
1, and CsCO3 as a base in PhMe (Table 2).21 The reaction of various
aryl bromides and aniline derivatives gave corresponding products
13a–d with good yields. When ( )-BINAP was used instead of ( )-1
as a ligand, the yield of 13a was slightly decreased (Table 2, entry1
vs entry 2).
Figure 2. ORTEP diagram of palladium complex 14 (one molecule of chloroform
omitted for clarity).
To investigate the nature of the catalyst structure of palladium
complex with ( )-1, a single-crystal of palladium complex 14 was
obtained from the reaction of ( )-1 and PdCl2(MeCN)2.22 The
X-ray analysis of 14 showed that the two phosphine atoms are
coordinated to palladium (Fig. 2), the bite angle of P–Pd–P is
92.5°, and the dihedral angle of the biaryl atropisomeric backbone
is 62.5°. This dihedral angle is significantly narrower than that of
BINAP-PdCl2 complex (70.2°).23
In summary, a new atropisomeric dihydrobenzofuran-based
bisphosphine ligand ( )-1 was prepared, and the resolution of
these isomers was achieved using HPLC with a chiral stationary
phase column. We described the use of an efficient ligand for the
palladium-catalyzed Suzuki–Miyaura reaction and Hartwig–Buch-
wald amination. Further studies to explore the scope of chiral li-
gand 1 in asymmetric catalytic reactions are currently underway.
Table 1
Palladium-catalyzed Suzuki–Miyaura reaction using ( )-1a
R2
Pd2(dba)3
( )-1
Cl
B(OH)2
Cs2CO3
+
Dioxane, 80 °C
R1
R2
R1
References and notes
8
9
10
1. (a)Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York, 2000;
(b)Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto,
H., Eds.; Springer: New York, 1999; (c) Noyori, R. Asymmetric Catalysis in
Organic Synthesis; John Wiley & Sons: New York, 1994.
2. (a) Takaya, H.; Akutagawa, S.; Noyori, R. Org. Synth. 1989, 67, 20; (b) Takaya, H.;
Mashima, K.; Koyano, K.; Yagi, M.; Kumobayashi, H.; Taketomi, T.; Akutagawa,
S.; Noyori, R. J. Org. Chem. 1986, 51, 629; (c) Miyashita, A.; Yasuda, A.; Takaya,
H.; Toriumi, K.; Ito, T.; Souchi, T.; Noyori, R. J. Am. Chem. Soc. 1980, 102, 7932.
3. (a) Schmid, R.; Cereghetti, M.; Heiser, B.; Schönholzer, P.; Hansen, H.-J. Helv.
Chim. Acta 1988, 71, 897; (b) Schmid, R.; Foricher, J.; Cereghetti, M.;
Schönholzer, P. Helv. Chim. Acta 1991, 74, 370; (c) Schmid, R.; Broger, E. A.;
Cereghetti, M.; Crameri, Y.; Foricher, J.; Lalonde, M.; Müller, R. K.; Scalone, M.;
Schoettel, G.; Zutter, U. Pure Appl. Chem. 1996, 68, 131.
Entry
R1
R2
H
OMe
H
OMe
OMe
Reaction time (h)
Product
Yieldb (%)
1
2
3
4
5
NO2
NO2
Ac
Ac
CN
24
24
24
48
48
10a
10b
10c
10d
10e
91
88
59
80
94
a
The reactions were carried out on 0.20 mmol scale of 8 with 1.5 equiv of 9 and
2.0 equiv of Cs2CO3 in the presence of Pd2(dba)3 (2.5 mol %) and ligand ( )-1
(7.5 mol %) in dioxane (0.6 mL) at 80 °C under Ar.
b
Isolated yields.

T. Mino et al. / Tetrahedron Letters 50 (2009) 2239–2241
2241
4. (a) Laue, C.; Schroeder, G.; Arlt, D.; Grosser, R. (Bayer AG), EP643.065, 1995;
Chem. Abstr. 1995, 123, 112406b.; (b) Namyslo, J. C.; Kaufmann, D. E. Chem. Ber.
1997, 1327.
5. Sollewijn Gelpke, A. E.; Kooijman, H.; Spek, A. L.; Hiemstra, H. Chem. Eur. J.
1999, 2472.
J = 9.7 Hz, C ꢂ 4), 132.2 (d, J = 9.7 Hz, C ꢂ 4), 132.3 (d, J = 10.0 Hz, C ꢂ 4), 133.9
(d, J = 35.5 Hz, C ꢂ 2), 135.3 (d, J = 36.2 Hz, C ꢂ 2), 158.7 (d, J = 15.2 Hz, C ꢂ 2);
31P NMR (CDCl3) d: 29.9; FAB-MS m/z (rel intensity): 639 (M++1, 14); HRMS
(FAB-MS) m/z calcd for C40H32O4P2+H 639.1854, found 639.1886.
18. Preparation of ( )-2,20-diphenylphosphino-1,10-bi-5,6-dihydrobenzofuran (( )-
6. Botman, P. N. M.; Fraanje, J.; Goubitz, K.; Peschar, R.; Verhoeven, J. W.; van
Maarseveen, J. H.; Hiemstra, H. Adv. Synth. Catal. 2004, 346, 743.
BICMAP, ( )-1): To a mixture of phosphine oxide ( )-7 (232.5 mg,
0.364 mmol) and triethylamine (1.82 mL, 13.1 mmol) in m-xylene (4.9 mL)
was added trichlorosilane (1.10 mL, 10.9 mmol) at 0 °C under an Ar
atmosphere. The reaction mixture was stirred for 6 h at 110 °C. After being
cooled to room temperature, the mixture was quenched with 6 M NaOH aq
(10 mL) and diluted with chloroform and water. The organic layer was dried
over MgSO4, and concentrated under reduced pressure. The residue was
purified by silica gel chromatography (elution with n-hexane/ethyl
acetate = 10/1): 116.7 mg, 0.192 mmol, 53%; white solid; mp 229–231 °C; 1H
NMR (CDCl3) d: 2.90–3.04 (m, 2H), 3.06–3.22 (m, 2H), 3.74 (dd, J = 8.8 and
18.7 Hz, 2H), 4.24–4.36 (m, 2H), 6.60 (dt, J = 1.7 and 7.6 Hz, 2H), 7.08 (d,
J = 7.6 Hz, 2H), 7.13–7.34 (m, 20H); 13C NMR (CDCl3) d: 29.8 (s, C ꢂ 2), 70.7 (s,
C ꢂ 2), 124.0 (t, J = 2.2 Hz, C ꢂ 4), 124.7 (s, C ꢂ 2), 126.7 (s, C ꢂ 2), 127.8 (d,
J = 1.2 Hz, C ꢂ 2), 127.9 (t, J = 3.5 Hz, C ꢂ 4), 128.0 (s, C ꢂ 2), 128.1 (t, J = 3.1 Hz,
C ꢂ 4), 133.3 (t, J = 10.3 Hz, C ꢂ 4), 134.0 (t, J = 10.5 Hz, C ꢂ 4), 137.3 (dd, J = 3.6,
4.6 Hz, C ꢂ 2), 137.7 (dd, J = 5.4 and 6.9 Hz, C ꢂ 2), 138.6 (dd, J = 6.2 and 7.3 Hz,
C ꢂ 2), 158.6 (t, J = 6.4 Hz, C ꢂ 2); 31P NMR (CDCl3) d: ꢁ13.0; EI-MS m/z (rel
intensity): 606 (M+, 0.08); HRMS (FAB-MS) m/z calcd for C40H32O2P2+H
607.1956, found 607.1953; HPLC: Daicel CHIRALPAKÒ IA (0.46 / ꢂ 25 cm, UV
7. (a) Saito, T.; Sayo, N.; Xiaoyaong, Z.; Yokozawa, T. (Takasago International
Corporation), EP 0850945, 1998.; (b) Saito, T.; Yokozawa, T.; Ishizaki, T.; Moroi,
T.; Sayo, N.; Miura, T.; Kumobayashi, H. Adv. Synth. Catal. 2001, 343, 264.
8. (a) Pai, C.-C.; Li, Y.-M.; Zhou, Z.-Y.; Chan, A. S. C. Tetrahedron Lett. 2002, 43,
2789; (b) Duprat de Paule, S.; Jeulin, S.; Ratovelomanana-Vidal, V.; Genêt, J.-P.;
Champion, N.; Dellis, P. Tetrahedron Lett. 2003, 44, 823.
9. For reviewes, see: (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457; (b)
Stanforth, S. P. Tetrahedron 1998, 54, 263; (c) Suzuki, A. In Metal-Catalyzed
Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim,
1998; pp 49–97; (d) Suzuki, A. J. Organomet. Chem. 1999, 576, 147; (e) Llord-
Williams, P.; Giralt, E. Chem. Soc. Rev. 2001, 30, 145.
10. For reviewes, see: (a) Hartwig, J. F. Angew. Chem., Int. Ed. 1998, 37, 2046; (b)
Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L. Acc. Chem. Res. 1998, 31,
805; (c) Yang, B. Y.; Buchwald, S. L. J. Organomet. Chem. 1999, 576, 125.
11. Shekhar, S.; Ryberg, P.; Hartwig, J. F.; Mathew, J. S.; Blackmond, D. G.; Strieter,
E. R.; Buchwald, S. L. J. Am. Chem. Soc. 2006, 128, 3584.
12. Price: $91, 100 g, Matrix Scientific Inc.
13. Song, Z. J.; Zhao, M.; Frey, L.; Li, J.; Tan, L.; Chen, C. Y.; Tscaen, D. M.; Tillyer, R.;
Grabowski, E. J. J.; Volante, R.; Reider, P. J.; Kato, Y.; Okada, S.; Nemoto, T.; Sato,
H.; Akao, A.; Mase, T. Org. Lett. 2001, 3, 3357.
254 nm, hexane/ethanol = 97: 3, 0.3 mL/min), tR = 22.3 (CD: kext
and 25.9 min (CD: kext ) 254 (+)); X-ray diffraction analysis data of ( )-1.
Colorless prismatic crystals from hexane/CHCl3, orthorhombic space group
Pnc2, a = 12.1145(12) Å, b = 14.5546(15) Å, c = 8.9488(9) Å, = 90°, b = 90°,
= 90°, V = 1577.9(3) Å3, Z = 4, = 1.277 g/cm3, ) = 1.73 cmꢁ1. The
(Mo K
(De) 254 (ꢁ))
(De
14. Preparation of 2-bromoethoxy-1,4-dibromobenzene (4): To the mixture of 3
(6.33 g, 21.4 mmol), triphenylphosphine (6.18 g, 23.5 mmol) in acetonitrile
(29.4 mL) was added carbon tetrabromide (7.82 g, 23.5 mmol) at room
temperature. After stirring for 3.5 h, the mixture was concentrated under
reduced pressure. The residue was purified by silica gel chromatography
(elution with n-hexane/ethyl acetate = 8/1): 7.04 g, 19.6 mmol, 92%; white
solid; mp 57–59 °C; 1H NMR (CDCl3) d: 3.68 (t, J = 6.4 Hz, 2H), 4.32 (t, J = 6.4 Hz,
2H), 7.00–7.03 (m, 2H), 7.40 (d, J = 8.8 Hz, 1H); 13C NMR (CDCl3) d: 28.1, 69.2,
111.4, 117.2, 121.5, 125.7, 134.4, 155.2; EI-MS m/z (rel intensity) 358 (M+, 19).
15. Preparation of 6-diphenylphosphino-2,3-dihydrobenzofuran (5): To the solution
of bromide 4 (0.356 g, 1.00 mmol) in THF (2 mL) was added slowly n-BuLi in
hexane (0.60 mL, 1.00 mmol, 1.66 M) at ꢁ80 °C for 10 min under an Ar
atmosphere. After the mixture was stirred for 2 h, n-BuLi in hexane (0.60 mL,
1.00 mmol, 1.66 M) was added slowly at ꢁ80 °C for 10 min again. After the
mixture was stirred for 1.5 h, chlorodiphenylphosphine (0.20 mL, 1.10 mmol)
was added, and stirring was continued for 23 h at ꢁ80 °C. The mixture was
quenched with satd NH4Cl aq at 0 °C and diluted with ethyl acetate at room
temperature. The organic layer was washed with brine, dried over MgSO4, and
concentrated under reduced pressure. The residue was purified by silica gel
chromatography (elution with n-hexane/ethyl acetate = 20/1): 0.201 g,
0.66 mmol, 66%; white solid; mp 76–78 °C; 1H NMR (CDCl3) d: 3.20 (t,
J = 8.7 Hz, 2H), 4.55 (t, J = 8.7 Hz, 2H), 6.69 (d, J = 7.1 Hz, 1H), 6.87 (ddd, J = 1.3,
7.6 and 8.7 Hz, 1H), 7.17 (dd, J = 0.8 and 7.5 Hz, 1H), 7.24–7.35 (m, 10H); 13C
NMR (CDCl3) d: 29.6, 71.1, 114.1 (d, J = 16.7 Hz), 124.9 (d, J = 16.7 Hz), 126.5 (d,
J = 24.9 Hz), 128.1, 128.4 (d, J = 7.1 Hz, C ꢂ 4), 128.6 (s, C ꢂ 2), 133.6 (d,
J = 19.5 Hz, C ꢂ 4), 137.0 (d, J = 10.8 Hz), 137.3 (d, J = 10.8 Hz, C ꢂ 2), 160.4 (d,
J = 7.7 Hz); 31P NMR (CDCl3) d: ꢁ4.1; EI-MS m/z (rel intensity): 304 (M+, 100);
HRMS (FAB-MS) m/z calcd for C20H17OP 304.1017, found 304.0995.
16. Preparation of 6-diphenylphosphinyl-2,3-dihydrobenzofuran (6): To the solution
of phosphine 5 (0.304 g, 1.00 mmol) in chloroform (5 mL) was added slowly
30% aqueous H2O2 (2.0 mL) then stirred for 2 h. After this, water was added to
the mixture and the organic layer was separated. The organic layer was dried
over MgSO4, and concentrated under reduced pressure. The residue was
purified by silica gel chromatography (elution with n-hexane/ethyl acetate = 1/
3): 0.317 g, 0.99 mmol, 99%; white solid; mp 127–128 °C; 1H NMR (CDCl3) d:
3.26 (t, J = 8.8 Hz, 2H), 4.59 (t, J = 8.8 Hz, 2H), 6.99 (d, J = 12.4 Hz, 1H), 7.18–7.32
(m, 2H), 7.41–7.57 (m, 6H), 7.62–7.72 (m, 4H); 13C NMR (CDCl3) d: 29.6, 71.3,
112.4 (d, J = 12.2 Hz), 124.8 (d, J = 10.1 Hz), 125.1 (d, J = 14.7 Hz), 128.4 (d,
J = 12.0 Hz, C ꢂ 4), 131.7 (d, J = 2.6 Hz), 131.8 (d, J = 2.8 Hz, C ꢂ 2), 132.0 (d,
J = 10.0 Hz, C ꢂ 4), 133.1, 133.3 (s, C ꢂ 2), 160.1, (d, J = 17.2 Hz); 31P NMR
(CDCl3) d: 30.0; EI-MS m/z (rel intensity): 320 (M+, 54); HRMS (FAB-MS) m/z
calcd for C20 H17O2P+H 321.1044, found 321.1039.
a
c
q
l
a
structure was solved by the direct method of full-matrix least-squares, where
the final R and Rw were 0.0338 and 0.0863 for 2118 reflections.
19. Optical resolution of ( )-BICMAP (( )-1): Chiral HPLC was carried out with a
Daicel CHIRALPAKÒ IA column (10 mm f ꢂ 250 mm) with hexane/
ethanol = 98:2 eluent. A solution of 2.9 mg of ( )-1 in 2 mL of hexane was
injected for each batch with flow rate of 0.8 mL/min. Enantiomers were eluted
at 45.5 and 51.0 min: (+)-1; 0.79 mg, 27%; >99% ee; ½a D20
ꢃ
+38 (c 0.0275, EtOH);
HPLC (Daicel CHIRALPAKÒ IA, 0.46 / ꢂ 25 cm, UV 254 nm), tR = 21.0 min
(hexane/ethanol = 97:3, 0.3 mL/min) (CD: kext (De) 254 (ꢁ)); (ꢁ)-1: 0.87 mg,
30%; 98.6% ee; ½a D20
ꢃ
ꢁ37 (c 0.0230, EtOH); HPLC (Daicel CHIRALPAKÒ IA, 0.46 /
ꢂ 25 cm, UV 254 nm), tR = 23.5 min (hexane/ethanol = 97:3, 0.3 mL/min) (CD:
kext (De) 254 (+)).
20. General procedure for the palladium-catalyzed Suzuki–Miyaura reaction: To a test
tube, arylchloride 8 (0.20 mmol), arylboronic acid 9 (0.30 mmol), Pd2(dba)3
(0.005 mmol, 4.6 mg), ligand ( )-1 (0.015 mmol, 9.1 mg), Cs2CO3 (0.40 mmol,
130.3 mg) and dioxane (0.60 mL) were added under an Ar atmosphere. The
mixture was stirred at 80 °C. After 24 or 48 h, the reaction mixture was diluted
with ethyl acetate and water. The organic layer was washed with brine and
dried over MgSO4. The filtrate was concentrated with a rotary evaporator and
the residue was purified by column chromatography (elution with n-hexane/
ethyl acetate = 100–20/1). All prepared compounds 10 were known and
identified by 1H NMR, 13C NMR, and MS.
21. General procedure for the palladium-catalyzed Hartwig–Buchwald amination: To
a test tube, arylbromide 11 (0.25 mmol), aniline 12 (0.3 mmol), Pd2(dba)3
(0.0025 mmol, 2.3 mg), ligand ( )-1 (0.0075 mmol, 4.6 mg), Cs2CO3
(0.35 mmol, 114.1 mg) and PhMe (1.0 mL) were added under an Ar
atmosphere. The mixture was stirred at 100 °C. After 18 h, the reaction
mixture was diluted with ethyl acetate and water. The organic layer was
washed with brine and dried over MgSO4. The filtrate was concentrated with a
rotary evaporator and the residue was purified by column chromatography
(elution with n-hexane/ethyl acetate = 6:1). All prepared compounds 13 were
known and identified by 1H NMR, 13C NMR, and MS.
22. Preparation of palladium complex ( )-14. To
a solution of PdCl2(MeCN)2
(7.78 mg, 0.03 mmol) in CHCl3 (2.0 mL) was added ( )-1 (18.2 g,
a
0.03 mmol) in a CHCl3 (2.0 mL) at room temperature and stirred for 2 h. The
reaction mixture was evaporated under reduced pressure. The residue was
purified by silica gel chromatography (elution with CHCl3/MeOH = 20:1):
25.5 mg, 0.0282 mmol, 94%; yellow solid; mp 258–259 °C; 1H NMR (CDCl3) d:
2.71–2. 87(m, 2H), 2.93–3.09 (m, 2H), 4.31–4.51 (m, 4H), 6.45 (dd, J = 7.8 and
11.9 Hz, 2H), 6.72 (dd, J = 1.9 and 7.8 Hz, 2H), 7.27–7.48 (m, 12H), 7.63–7.75
(m, 4H), 7.87–8.08 (m, 4H); 13C NMR (CDCl3) d: 29.4 (s, C ꢂ 2), 71.2 (s, C ꢂ 2),
118.6 (dd, J = 4.0, 10.4 Hz, C ꢂ 4), 124.6 (d, J = 53.9, C ꢂ 2), 124.9 (d, J = 12.3 Hz,
C ꢂ 2), 126.6 (d, J = 4.4 Hz, C ꢂ 2), 127.8 (dd, J = 11.7, 29.3 Hz, C ꢂ 8), 128.6 (d,
J = 5.4 Hz, C ꢂ 2), 129.9 (d, J = 62.1 Hz, C ꢂ 2), 130.8 (d, J = 2.9 Hz, C ꢂ 2), 131.2
(d, J = 2.1 Hz, C ꢂ 2), 135.0 (d, J = 10.4 Hz, C ꢂ 4), 135.6 (s, C ꢂ 2), 135.8 (s,
C ꢂ 2), 158.6 (dd, J = 1.0 and 12.3 Hz, C ꢂ 2); 31P NMR (CDCl3) d: 26.9; FAB-MS
m/z (rel intensity) 747([MꢁCl]+, 5); HRMS (FAB-MS) m/z calcd for
C40H32O2ClP2Pd 747.0601, found 747.0557; X-ray diffraction analysis data of
14 (Fig. 2): Yellow plate crystals from hexane/CHCl3, C40H32O2Cl2P2PdꢄCHCl3,
monoclinic space group P21/n, a = 11.5010(7) Å, b = 19.5208(12) Å,
17. Preparation of 2,20-diphenylphosphinyl-1,10-bi-5,6-dihydrobenzofuran (( )-7): To
the solution of phosphine oxide 6 (0.961 g, 3.00 mmol) in THF (24 mL) was
added slowly t-BuLi in pentane (2.1 mL, 3.34 mmol, 1.59 M) at ꢁ80 °C for
10 min under an Ar atmosphere. After the mixture was stirred for 3 h, ferric
chloride (FeCl3) (0.593 g, 3.60 mmol) in THF (2 mL) was added. After the
mixture was stirred for 13 h at room temperature, it was concentrated under
reduced pressure. The residue was added to 6 M HCl aq (10 mL) and
chloroform. The organic layer was washed with 6 M NaOH aq (10 mL) and
brine, dried over MgSO4, and concentrated under reduced pressure. The
residue was purified by silica gel chromatography (elution with chloroform/
methanol = 40/1): 0.549 g, 0.86 mmol, 57%; white solid; mp 156–158 °C; 1H
NMR (CDCl3) d: 2.92–3.18 (m, 4H), 3.78 (dd, J = 8.7 and 18.7 Hz, 2H), 4.17–4.28
(m, 2H), 6.76 (dd, J = 7.6 and 13.8 Hz, 2H), 7.03 (dd, J = 2.6 and 7.7 Hz, 2H),
7.23–7.31 (m, 4H), 7.32–7.51 (m, 8H), 7.57–7.66 (m, 4H), 7.68–7.76 (m, 4H);
13C NMR (CDCl3) d: 29.8 (s, C ꢂ 2), 70.5 (s, C ꢂ 2), 121.6 (d, J = 3.2 Hz, C ꢂ 2),
123.8 (d, J = 15.8 Hz, C ꢂ 2), 126.4 (d, J = 12.7 Hz, C ꢂ 2), 127.8 (d, J = 12.2 Hz,
C ꢂ 8), 130.2 (d J = 105.2 Hz, C ꢂ 2), 130.3 (d, J = 2.6 Hz, C ꢂ 2), 130.9 (d,
c = 16.6287(10) Å,
a
= 90°, b = 92.8320(10)°,
c
= 90°, V = 3728.7(4) Å3, Z = 4,
q
= 1.609 g/cm3,
l
(Mo The structure was solved by the
K
a
) = 9.79 cmꢁ1
.
direct method of full-matrix least-squares, where the final R and Rw were
0.0367 and 0.0837 for 8391 reflections.
23. Mikami, K.; Aikawa, K.; Kainuma, S.; Kawakami, Y.; Saito, T.; Sayo, N.;
Kumonayashi, H. Tetrahedron: Asymmetry 2004, 15, 3885.