Asymmetric synthesis of axially chiral biaryls by nickel-catalyzed Grignard cross-coupling of dibenzothiophenes

Article abstract of DOI:10.1021/jo035880p

Catalytic asymmetric Grignard cross-coupling of 1,9-disubstituted dibenzothiophenes (6a-c) and dinaphthothiophene (6d) with aryl- and alkyl-Grignard reagents (7) proceeded with high enantioselectivity (up to 95% ee) in the presence of a nickel catalyst (3-6 mol %) coordinated with 2-diphenylphosphino-1,1′-binaphthyl (H-MOP) or oxazoline-phosphine ligand (i-Pr-phox) in THF to give 2-mercapto-2′-substituted-1,1′-biphenyls (8a-c) and 2-mercapto-2′-substituted-1,1′-binaphthyls (8d) in high yields. The mercapto group in the axially chiral cross-coupling products was converted into several functional groups by way of the methylsulfinyl group. The rate of flipping in dinaphthothiophene was measured by variable-temperature ³¹P NMR analysis of methyl-phenylphosphinyldinaphthothiophene derivative (21).

Full text of DOI:10.1021/jo035880p

Asym m etr ic Syn th esis of Axia lly Ch ir a l Bia r yls by
Nick el-Ca ta lyzed Gr ign a r d Cr oss-Cou p lin g of Diben zoth iop h en es
Yong-Hwan Cho, Asato Kina, Toyoshi Shimada, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, J apan
thayashi@kuchem.kyoto-u.ac.jp
Received December 28, 2003
Catalytic asymmetric Grignard cross-coupling of 1,9-disubstituted dibenzothiophenes (6a -c) and
dinaphthothiophene (6d ) with aryl- and alkyl-Grignard reagents (7) proceeded with high enantio-
selectivity (up to 95% ee) in the presence of a nickel catalyst (3-6 mol %) coordinated with
2-diphenylphosphino-1,1′-binaphthyl (H-MOP) or oxazoline-phosphine ligand (i-Pr-phox) in THF
to give 2-mercapto-2′-substituted-1,1′-biphenyls (8a -c) and 2-mercapto-2′-substituted-1,1′-binaph-
thyls (8d ) in high yields. The mercapto group in the axially chiral cross-coupling products was
converted into several functional groups by way of the methylsulfinyl group. The rate of flipping
in dinaphthothiophene was measured by variable-temperature 31P NMR analysis of methyl-
phenylphosphinyldinaphthothiophene derivative (21).
In tr od u ction
vanadium complexes6 has been also reported. The other
is enantioposition-selective cross-coupling of achiral bi-
aryl ditriflates where the axially chiral biaryls can be
prepared by the selective substitution of one of two
enantiotopic triflate groups.7
Axially chiral biaryls have found extensive use in chiral
auxiliaries for a variety of asymmetric reactions. Al-
though considerable attention has been paid to their
preparation by asymmetric synthesis,1 direct synthetic
methods giving the enantiomerically enriched biaryls
from achiral substrates are still rare. The asymmetric
synthesis of axially chiral biaryls can be grouped into two
categories according to the mode of generation of the axial
chirality. One is cross- or homo-coupling of two aryl units
where the axial chirality is generated at the formation
of the biaryl skeleton. The best examples are nickel2- or
palladium3-catalyzed asymmetric cross-coupling of aryl
halides with aryl Grignard reagents or arylboronic acids.
Oxidative coupling of 2-naphthol derivatives catalyzed
by copper-chiral amine complexes4,5 or chiral oxo-
Recently, we have reported the third type of catalytic
asymmetric synthesis of axially chiral 1,1′-binaphthyls,
which is realized by asymmetric Grignard cross-coupling
of dinaphtho[2,1-b:1′,2′-d]thiophene with the Grignard
reagents in the presence of a nickel catalyst coordinated
with a chiral oxazoline-phosphine ligand.8 In this type
of reaction, the axial chirality is generated at the cleavage
of the carbon-sulfur bond in the thiophene ring.9
Here we wish to report a full description of this type
of catalytic asymmetric cross-coupling, including its
reaction of 1,9-disubstituted dibenzothiophenes (6a -c)
and dinaphthothiophene (6d ). Also described are the
conversion of the cross-coupling products into useful
axially chiral compounds, the proposal of a stereochem-
ical pathway in the catalytic cycle, and measurement of
the flipping rate of the dinaphthothiophene.
(1) (a) Noyori, R.; Takaya, H. Acc. Chem. Res. 1990, 23, 345. (b)
Rosini, C.; Franzini, L.; Raffaelli, A.; Salvadori, P. Synthesis 1992, 503.
(c) Pu, L. Chem. Rev. 1998, 98, 2405. (d) Hayashi, T. Acc. Chem. Res.
2000, 33, 354. (e) McCarthy, M.; Guiry, P. J . Tetrahedron 2001, 57,
3809.
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Soc. 1988, 110, 8153. (b) Hayashi, T.; Hayashizaki, K.; Kiyoi, T.; Ito,
Y. Tetrahedron Lett. 1989, 30, 215.
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M.; Koga, K. J . Org. Chem. 1999, 64, 2264. (b) Li, X.; Yang, J .;
Kozlowski, M. C. Org. Lett. 2001, 3, 1137.
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Z.; Liu, Q.; Gong, L.; Cui, X.; Mi, A.; J iang, Y. Angew. Chem., Int. Ed.
2002, 41, 4532. (c) Chu, C.-Y.; Uang, B.-J . Tetrahedron: Asymmetry
2003, 14, 53.
(7) (a) Hayashi, T.; Niizuma, S.; Kamikawa, T.; Suzuki, N.; Uozumi,
Y. J . Am. Chem. Soc. 1995, 117, 9101. (b) Kamikawa, T.; Uozumi, Y.;
Hayashi, T. Tetrahedron Lett. 1996, 37, 3161. (c) Kamikawa, T.;
Hayashi, T. Tetrahedron 1999, 55, 3455.
(3) (a) Nicolaou, K. C.; Li, H.; Boddy, C. N. C.; Ramanjulu, J . M.;
Yue, T.-Y.; Natarajan, S.; Chu, X.-J .; Bra¨se, S.; Ru¨bsam, F. Chem. Eur.
J . 1999, 5, 2584. (b) Cammidge, A. N.; Cre´py, K. V. L. Chem. Commun.
2000, 1723. (c) Yin, J .; Buchwald, S. L. J . Am. Chem. Soc. 2000, 122,
12051. (d) Castanet, A.-S.; Colobert, F.; Broutin, P.-E.; Obringer, M.
Tetrahedron: Asymmetry 2002, 13, 659. (e) Herrbach, A.; Marinetti,
A.; Baudoin, O.; Gue´nard, D.; Gue´ritte, F. J . Org. Chem. 2003, 68,
4897.
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1991, 231. (b) Smrcina, M.; Lorenc, M.; Hanus, V.; Sedmera, P.;
Kocovsky, P. J . Org. Chem. 1992, 57, 1917. (c) Smrcina, M.; Pola´kowa´,
J .; Vyskocil, S.; Kocovsky, P. J . Org. Chem. 1993, 58, 4534. (d) Smrcina,
M.; Vyskocil, S.; Maca, B.; Pola´sek, M.; Claxtone, T. A.; Abbott, A. P.;
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3313. (f) Brussee, J .; J ansen, A. C. A. Tetrahedron Lett. 1983, 24, 3261.
(8) Shimada, T.; Cho, Y.-H.; Hayashi, T. J . Am. Chem. Soc. 2002,
124, 13396.
(9) Similar asymmetric ring-opening reactions of biaryl lactones
have been extensively studied: (a) Bringmann, G.; Breuning, M.;
Tasler, S. Synthesis 1999, 525. (b) Bringmann, G.; Breuning, M.;
Pfeifer, R.-M.; Schenk, W. A.; Kamikawa, K.; Uemura, M. J . Organo-
met. Chem. 2002, 661, 31. (c) Bringmann, G.; Tasler, S.; Pfeifer, R.-
M.; Breuning, M. J . Organomet. Chem. 2002, 661, 49.
10.1021/jo035880p CCC: $27.50 © 2004 American Chemical Society
Published on Web 04/29/2004
J . Org. Chem. 2004, 69, 3811-3823
3811

Cho et al.
3a -c.15 In the presence of 20 mol % of NiCl2(dppp), the
dimethylation of 2 with methylmagnesium iodide was
completed at room temperature in 12 h to give 80% yield
of 2,2′-dimethoxy-6,6′-dimethyl-1,1′-biphenyl (3a ).16 Pal-
ladium-catalyzed cross-coupling of 2 with butyl- and
phenylzinc chloride in the presence of PdCl2(dppf) at 65
°C for 48 h gave the corresponding cross-coupling prod-
ucts 3b and 3c in 60% and 55% yield, respectively.
Treatment of 2,2′-dihydroxybiphenyls 4, which were
obtained by treatment of dimethyl ethers 3 with BBr3 in
CH2Cl2, with N,N-dimethylthiocarbamoyl chloride17 in
the presence of 2.2 equiv of triethylamine and 10 equiv
of pyridine at 65 °C for 12 h gave the corresponding
thiocarbamoyl esters 5a and 5b in 90% and 93% yield,
respectively. Under similar conditions with triethylamine
and pyridine, the esterification of 4c with N,N-dimethyl-
thiocarbamoyl chloride did not proceed. It was found that
the use of sodium hydride in DMF at higher temperature
(85 °C) as the optimized reaction condition gave 5c in
75% yield.14a,17 We examined sodium hydride for the
preparation of 5a and 5b to shorten the reaction time,
but only poor yields (<30% yield) of the desired products
were obtained.
SCHEME 1
SCHEME 2
Resu lts a n d Discu ssion
It has been well-documented that organosulfur com-
pounds undergo the cross-coupling with organometallic
reagents in the presence of transition metal catalysts.10,11
In 1979, Wenkert reported that thiophenes participate
in the nickel-catalyzed cross-coupling.12
The preparation of dibenzothiophenes 6 was carried
out under optimized conditions for the Newman-Kwart
rearrangement.13,17 Thus, heating 5a -c without solvents
in an autoclave at 290 °C for 12 h gave the corresponding
1,9-disubstituted dibenzothiophenes 6a -c in high yields
(Scheme 4).
The reaction of dibenzothiophene with methylmagne-
sium iodide and phenylmagnesium bromide in the pres-
ence of 10 mol % of NiCl2(PPh3)2 in benzene at 80 °C gave
73% yield of 2,2′-dimethyl-1,1′-biphenyl and 52% yield
of 2,2′-diphenyl-1,1′-biphenyl, respectively (Scheme 1).
These results suggest that axially chiral biaryls can
be produced by the cross-coupling of a dibenzothiophene
derivative containing substituents at 1- and 9-positions
which will prevent the rotation around the biaryl axis
from taking place. Use of a transition metal catalyst
coordinated with a proper chiral ligand will give us a
chance to obtain enantiomerically enriched biaryls
(Scheme 2).
To realize the catalytic asymmetric synthesis of axially
chiral biaryl compounds from dibenzothiophenes by cross-
coupling, three 1,9-disubstituted dibenzothiophenes were
prepared as substrates. Staiger has recently reported the
synthesis of dinaphtho[2,1-b;1′,2′-d]thiophene by thermal
rearrangement of 2,2′-bis(N,N-dimethylthiocarbamoyl-
oxy)-1,1′-binaphthyl, readily accessible from 2,2′-dihy-
droxy-1,1′-binaphthyl.13 These procedures were applied
to the preparation of 1,9-disubstituted dibenzothiophenes.
Synthetic procedures to the 1,9-disubstituted dibenzo-
thiophenes are depicted in Scheme 3. Triflation of 2,2′-
dihydroxy-6,6′-dimethoxy-1,1′-biphenyl (1), whose prepa-
ration has been reported by Delogu,14 gave bis(triflate) 2
in 90% yield. Nickel- or palladium-catalyzed cross-
coupling of bis(triflate) 2 with organomagnesium or -zinc
reagents gave the corresponding cross-coupling products
First, we examined the Grignard cross-coupling of 1,9-
dimethyldibenzothiophene (6a ) under the conditions
reported by Wenkert.12a Thus, in the presence of 10 mol
% of NiCl2(PPh3)2, dibenzothiophene 6a was allowed
to react with 10 equiv of 4-methylphenylmagnesium
bromide (7m ) in benzene at 80 °C for 12 h. Hydrolysis
gave 2-mercapto-2′-(4-methylphenyl)-6,6′-dimethyl-1,1′-
biphenyl (8a m ) in 5% yield and 2,2′-bis(4-methylphenyl)-
6,6′-dimethyl-1,1′-biphenyl (9a m ) in 85% yield (Scheme
5).
It was found that the reaction in THF at 40 °C proceeds
with much higher selectivity in giving monoarylation
product 8a m . Thus, the reaction of 6a with 10 equiv of
7m in the presence of a nickel catalyst generated from 6
mol % of Ni(cod)2 and 18 mol % of triphenylphosphine in
THF at 40 °C for 24 h gave the monoarylation product
8a m in 75% yield and starting material was recovered
in 20% yield without formation of the diarylation product
9a m (entry 1 in Table 1). The use of 10 equiv of the
Grignard reagent is required to ensure the high conver-
sion of the thiophene.8 A nickel-phosphine complex
generated in situ from Ni(cod)2 and phosphine ligand was
an effective catalyst for this type of cross-coupling. To
examine the ability of several ligands for the asymmetric
cross-coupling, it is more convenient to use the in situ
catalysts than isolated complexes containing chiral
(10) For a review, see: Luh, T.-Y.; Ni, Z.-J . Synthesis 1990, 89.
(11) (a) Okamura, H.; Miura, M.; Takei, H. Tetrahedron Lett. 1979,
43. (b) Wenkert, E.; Ferreira, T. W. J . Chem. Soc., Chem. Commun.
1982, 840. (c) Wenkert, E.; Fernandes, J . B.; Michelotti, E. L.; Swindell,
C. S. Synthesis 1983, 701.
(12) (a) Wenkert, E.; Ferreira, T. W.; Michelotti, E. L. J . Chem. Soc.,
Chem. Commun. 1979, 637. (b) Tiecco, M.; Tingoli, M.; Wenkert, E. J .
Org. Chem. 1985, 50, 3828.
(15) (a) Tuyet, T. M. T.; Harada, T.; Hashimoto, K.; Hatsuda, M.;
Oku, A. J . Org. Chem. 2000, 65, 1335. (b) Harada, T.; Tuyet, T. M. T.;
Oku, A. Org. Lett. 2000, 2, 1319. (c) Harada, T.; Yoshida, T.; Inoue,
A.; Takeuchi, M.; Oku, A. Synlett 1995, 283.
(13) Staiger, C. L.; Loy, D. A.; J amison, G. M.; Schneider, D. A.;
Cornelius, C. J . J . Am. Chem. Soc. 2003, 125, 9920.
(14) (a) Delogu, G.; Fabbri, D.; Dettori, M. A. Tetrahedron: Asym-
metry 1998, 9, 2819. (b) Delogu, G.; Fabbri, D. Tetrahedron: Asymmetry
1997, 8, 759.
(16) Weber, E.; Pollex, R.; Czugler, M. J . Org. Chem. 1992, 57, 4068.
(17) (a) Fabbri, D.; Delogu, G.; De Lucchi, O. J . Org. Chem. 1993,
58, 1748. (b) Albrow, V.; Biswas, K.; Crane, A.; Chaplin, N.; Easun,
T.; Gladiali, S.; Lygo, B.; Woodward, S. Tetrahedron: Asymmetry 2003,
14, 2813.
3812 J . Org. Chem., Vol. 69, No. 11, 2004

Asymmetric Synthesis of Axially Chiral Biaryls
SCHEME 3
SCHEME 4
yield and 72% yield, respectively. Palladium catalysts
such as Pd(PPh3)4 did not show any catalytic activity. The
monoarylation product 8a m was also obtained in 69%
yield in the presence of a nickel catalyst containing
bisphosphine ligand, 1,3-bis(diphenylphosphino)propane
(dppp), under the same conditions (entry 2).
Among the chiral ligands examined for the asymmetric
cross-coupling of thiophene 6a with 4-methylphenyl-
magnesium bromide (7m ) (Scheme 6), (S)-2-diphenyl-
phosphino-1,1′-binaphthyl18 (H-MOP) was found to be
most enantioselective (Table 1). Thus, the asymmetric
cross-coupling of 6a with 10 equiv of 7m in THF in the
presence of 6 mol % of Ni(cod)2 and 18 mol % of (S)-
H-MOP at 40 °C for 20 h gave 85% yield of the axially
chiral 2-mercapto-2′-(4-methylphenyl)-6,6′-dimethyl-1,1′-bi-
phenyl (8a m ). The mercapto group in 8a m was converted
into thiocarbamoyl group by treatment with phenyliso-
cyanate and its enantiomeric purity was determined to
be 82% ee by HPLC analysis with a chiral stationary
phase column (entry 4). The absolute configuration was
determined to be S by correlation with the authentic
sample, (S)-(+)-9a m (vide infra). THF was the best
solvent for the present cross-coupling, benzene and
toluene giving a lower yield of 8a m and lower enantio-
selectivity. It was found that the enantiomeric purity of
8a m is not strongly dependent on the reaction temper-
ature (entries 3-5).
A little lower enantioselectivity was observed in the
reactions with use of other H-MOP derivatives, (S)-H-
MOP-xylyl, (S)-H-MOP-tolyl, and (S)-H-MOP-anisyl, which
gave 8a m of 74% ee, 72% ee, and 67% ee, respectively
(entries 6-8). Other chiral phosphine ligands used suc-
cessfully for other types of asymmetric cross-coupling2,3,7
were much less enantioselective than (S)-H-MOP for the
present reaction (entries 9-14). The use of oxazoline-
phosphine ligands did not give any cross-coupling prod-
ucts under the same conditions (entries 13 and 14).
The best reaction conditions found for the asymmetric
cross-coupling of 6a with 7m (Table 1), that is, Ni(cod)2
(6 mol %) and (S)-H-MOP (18 mol %) in THF at 40 °C,
were applied to the reaction of some other 1,9-disubsti-
tuted dibenzothiophenes 6a -c and the Grignard reagents
7.
SCHEME 5
TABLE 1. Nick el-Ca ta lyzed Asym m etr ic Cr oss-Cou p lin g
of 1,9-Dim eth yld iben zoth iop h en e (6a ) w ith
4-Meth ylp h en ylm a gn esiu m Br om id e (7m )a
yield of % ee of
ligand
(equiv to Ni)
temp time
8a m
8a m
entry
(°C)
(h)
(%)b
(config)c
1
2
PPh3 (3.0)
dppp (1.5)
40
40
55
40
20
40
40
40
40
40
40
40
40
40
24
24
10
20
24
24
24
24
24
24
24
24
24
24
75
69
87
85
32
85
84
63
50
78
65
58
0
3
4
5
6
7
8
9
10
11
12
13
14
(S)-H-MOP (3.0)
(S)-H-MOP (3.0)
(S)-H-MOP (3.0)
(S)-H-MOP-xylyl (3.0)
(S)-H-MOP-tolyl (3.0)
(S)-H-MOP-anisyl (3.0)
(R)-MeO-MOP (3.0)
(S)-phephos (1.5)
(S)-(R)-PPF-OMe (3.0)
(R)-BINAP
82 (S)
82 (S)
83 (S)
74 (S)
72 (S)
67 (S)
8 (R)
35 (S)
30 (S)
23 (R)
(S)-i-Pr-phox (1.5)
(R)-Ph-phox (1.5)
0
a
The reaction was carried out with thiophene 6a (0.24 mmol)
and 7m (2.4 mmol) in 5.6 mL of THF in the presence of Ni(cod)2
b
(0.014 mmol) and a ligand. Isolated yield of 8a m by silica gel
chromatography. c Determined by HPLC analysis of the phenyl-
carbamate ester of thiol 8a m with a chiral stationary phase
column (Chiralcel OD-H (hexane/2-propanol ) 90/10)).
The results summarized in Table 2 show that the
monosubstitution products 8 are obtained in high yields
irrespective of the alkyl or phenyl substituents at 1- and
ligands.8 NiBr2 and Ni(acac)2 were also effective as
catalyst precursors.
The reaction of 6a with 7m in the presence of 6 mol %
of a nickel catalyst generated from NiBr2 and Ni(acac)2
with triphenylphosphine in THF at 40 °C for 24 h gave
the corresponding cross-coupling product 8a m in 78%
(18) (a) Uozumi, Y.; Suzuki, N.; Ogiwara, A.; Hayashi, T. Tetra-
hedron 1994, 50, 4293. (b) Hayashi, T.; Hirate, S.; Kitayama, K.; Tsuji,
H.; Torii, A.; Uozumi, Y. J . Org. Chem. 2001, 66, 1441.
J . Org. Chem, Vol. 69, No. 11, 2004 3813

Cho et al.
TABLE 2. Asym m etr ic Cr oss-Cou p lin g of
1,9-Disu bstitu ted Diben zoth iop h en es 6 w ith th e
SCHEME 6
Gr ign a r d Rea gen ts 7 Ca ta lyzed by th e Ni/(S)-H-MOP
Ca ta lysta
yield
% ee
of 8
thiophene
R2MgX
temp time of 8
entry
1 (R1)
7 (R2)
(°C)
(h) (%)b (config)c
1
2
3
4
5
6
7
6a (Me) 7m (4-MeC6H4) 40
20
24
32
24
8
85
88
87
89
90
85
91
82 (S)
81 (S)
35 (S)
78 (S)
36 (R)
36 (R)
53 (R)
6a (Me) 7n (Ph)
6a (Me) 7p (PhCH2)
40
40
6b (Bu) 7m (4-MeC6H4) 40
6c (Ph)
6c (Ph)
6c (Ph)
7m (4-MeC6H4) 40
7m (4-MeC6H4) 55
3
24
7q (Me)
20
a
The reaction was carried out with thiophene 6 (0.24 mmol)
and the Grignard reagent 7 (2.4 mmol) in 5.6 mL of THF in the
presence of Ni(cod)2 (0.014 mmol) and (S)-H-MOP (0.042 mmol).
b
Isolated yield of 8 by silica gel chromatography. c Determined
by HPLC analysis of the phenylcarbamate ester of thiol 8 with a
chiral stationary phase column: (Chiralcel OD-H (hexane/2-
propanol ) 90/10)) for 8a m , 8a n , 8a p , 8bm , 8cm , and 8cq.
SCHEME 7
(entries 5 and 6). The reaction of methylmagnesium
iodide (7q) was completed in 24 h at 20 °C (entry 7). The
higher reactivity of 1,9-diphenyldibenzothiophene (6c)
may be related to a larger torsion angle of thiophene ring
in 6c, which has bulky substituents at 1- and 9-positions.
The more strained thiophene ring system caused by the
larger torsion angle will result in the lower energy of the
carbon-sulfur bond cleavage.19
It is noteworthy that the asymmetric cross-coupling of
1,9-dimethyldibenzothiophene (6a ) and 1,9-diphenyldi-
benzothiophene (6c) proceeded in an opposite sense of
stereorecognition (Scheme 7). Although the designation
of the configuration is S for both of the two cross-coupling
products 8a m and 8cq, the stereochemistry at ring-
opening of the thiophene is opposite. It follows that the
substituents at the 1- and 9-positions play a key role in
the enantioselection.
Higher enantioselectivity was observed in the asym-
metric cross-coupling of dinaphthothiophene (6d ) (Table
3). The reaction of 6d proceeded in the presence of a
smaller amount of the nickel catalyst at a lower reaction
temperature than that of dibenzothiophenes. Bianchini
reported that the energy barrier of carbon-sulfur bond
cleavage of the thiophene ring in dinaphthothiophene by
9-positions. The enantioselectivity was dependent on the
1,9-substituents on the dibenzothiophene 6 and the
Grignard reagents 7. Thus, the enantiomeric purity of
8a m and 8a n obtained for the reaction of 6a with aryl
Grignard reagents, 4-MeC6H4MgBr (7m ) and PhMgBr
(7n ), was 81-82% ee (entries 1 and 2), while that of 8a p
formed by the reaction with the benzylmagnesium bro-
mide (7p ) was as low as 35% ee (entry 3). The dibenzo-
thiophenes substituted with methyl (6a ) and butyl (6b)
gave the monosubstitution products 8 of around 80% ee
on the reaction with 7m (entries 1 and 4), while 1,9-
diphenyldibenzothiophene (6c) gave 8cm of 36% ee
(entries 5 and 6). It was found that 1,9-diphenyldibenzo-
thiophene (6c) is more reactive than the other thiophenes
6a and 6b toward the present nickel-catalyzed cross-
coupling. The reaction of 6c with the Grignard reagent
7m proceeded faster than that of 6a and 6b, giving high
yield of the monoarylation product 8cm within 8 and 3
h in the reaction carried out at 40 and 55 °C, respectively
(19) (a) Vicic, D. A.; J ones, W. D. J . Am. Chem. Soc. 1999, 121, 7606.
(b) Vicic, D. A.; J ones, W. D. J . Am. Chem. Soc. 1997, 119, 10855.
3814 J . Org. Chem., Vol. 69, No. 11, 2004

Asymmetric Synthesis of Axially Chiral Biaryls
TABLE 3. Nick el-Ca ta lyzed Asym m etr ic Cr oss-Cou p lin g of Din a p h th oth iop h en e 6d w ith th e Gr ign a r d Rea gen ts 7a
temp
(°C)
time
(h)
yield of
% ee of
entry
R2MgX7 (R2)
ligand (equiv to Ni)
8d (%)b
8d (config)c
1
2
7m (4-MeC6H4)
7m (4-MeC6H4)
7m (4-MeC6H4)
7m (4-MeC6H4)
7m (4-MeC6H4)
7m (4-MeC6H4)
7n (Ph)
7o (4-MeOC6H4)
7q (Me)
7q (Me)
(S)-H-MOP (3.0)
(S)-i-Pr-phox (1.5)
(R)-Ph-phox (1.5)
(S)-(R)-PPF-OMe (3.0)
(S)-phephos (1.5)
(R)-BINAP (1.5)
(S)-i-Pr-phox (1.5)
(S)-i-Pr-phox (1.5)
(S)-i-Pr-phox (1.5)
(S)-H-MOP (3.0)
(S)-i-Pr-phox (1.5)
(S)-phephos (1.5)
20
20
20
20
20
20
20
20
20
10
20
20
10
24
30
12
8
10
24
30
24
24
48
48
93
97
90
88
86
72
92
96
88
97
93
41d
14 (S)
95 (S)
86 (R)
3 (S)
3
4
5
1 (S)
6
2 (S)
7
95 (S)
93 (S)
45 (R)
68 (R)
50 (R)
19 (R)
8
9
10
11
12
7r (Et)
7r (Et)
a
The reaction was carried out with thiophene 6d (0.24 mmol) and 7 (2.4 mmol) in 5.6 mL of THF in the presence of Ni(cod)2 (0.007
mmol) and a ligand. Isolated yield of 8d by silica gel chromatography. c Determined by HPLC analysis of the phenylcarbamate ester of
b
thiol 8d with a chiral stationary phase column (Chiralcel OD-H (hexane/2-propanol ) 90/10) for 8d n , Chiralcel AD (hexane/2-propanol
d
) 90/10) for 8d m , 8d o, 8a q, and 8d r ). The formation of 45% yield of 10 (43% ee) was observed.
SCHEME 8
transition metal complexes is much lower than that of
dibenzothiophene.20 The X-ray analysis21 of dinaphtho-
thiophene (6d ) showed its large torsion angle (25.9°),
which presumably arises from strong repulsion between
the two twisted naphthyl groups.
The reaction of 6d with 4-methylphenylmagnesium
bromide (7m ) in THF in the presence of 3 mol % of Ni-
(cod)2 and 9 mol % of (S)-H-MOP proceeded at 20 °C for
10 h to give 93% yield of (S)-2-mercapto-2-(4-methyl-
phenyl)-1,1′-binaphthyl (S)-(-)-8d m , whose enantiomeric
purity determined by HPLC analysis was 14% ee (entry
1). Considering that the (S)-H-MOP ligand gave the cross-
coupling product 8a m of 82% ee in the reaction of diben-
zothiophene 6a with the Grignard reagent 7m , this low
enantioselectivity is rather surprising. It was found that
oxazoline-phosphines22 are much more enantioselective
than H-MOP for the cross-coupling of dinaphthothiophene
(6d ). Thus, the reaction of 6d with 7m in the presence
of 3 mol % of Ni(cod)2 and 4.5 mol % of (S)-i-Pr-phox in
THF at 20 °C for 24 h gave (S)-8d m of 95% ee in 97%
yield (entry 2). The enantioselectivity was also high (86%
ee) with (R)-Ph-phox as the ligand of the nickel catalyst
(entry 3).
In the reaction with ethylmagnesium bromide (7r ), the
(S)-i-Pr-phox ligand gave a unique result. With other
ligands examined, a considerable amount of the reduced
product 10 was formed in addition to the cross-coupling
product 8d r .
Thus, the reaction catalyzed by the nickel complex of
(S)-i-Pr-phox gave a high yield of (R)-8d r (50% ee)
without any detectable amount of 10 (entry 11), while
the reaction with (S)-phephos23-nickel catalyst gave both
8d r and 10 in 41% and 45% yield, respectively (entry 12).
Interestingly, 8d r has R configuration and 10 has S
configuration (Scheme 8). The opposite configuration is
important for us to understand the reaction mechanism
(see Scheme 10).
Other ligands2,3,7 were much less enantioselective than
the oxazoline-phosphine ligands (entries 4-6). The reac-
tions of 6d with phenylmagnesium bromide (7n ) and
4-methoxyphenylmagnesium bromide (7o) also proceeded
with high enantioselectivity in the presence of the nickel
catalyst coordinated with (S)-i-Pr-phox to give high yields
of the corresponding cross-coupling products (S)-(-)-8d n
of 95% ee and (S)-(-)-8d o of 93% ee, respectively
(entries 7 and 8). For the reaction with methylmagnesium
iodide (7q), (S)-H-MOP was more effective than (S)-i-Pr-
phox (entries 9 and 10). In the presence of the nickel
catalyst of (S)-H-MOP, the cross-coupling of 6d with 7q
at 10 °C for 24 h gave 97% yield of (R)-2-mercapto-2′-
methyl-1,1′-binaphthyl (8d q), which is 68% ee (entry 10).
According to the catalytic cycle generally accepted for
the nickel-catalyzed cross-coupling, oxidative addition of
thiophene 6 to a nickel(0) species forms nickelacycle A19,20
(Scheme 9). Transmetalation of the aryl or alkyl group
from the Grignard reagent 7 to A gives diorganonickel
intermediate B. Reductive elimination from B leads to
the magnesium thiolate C. Aqueous workup gives the
cross-coupling product 8 (Scheme 9).
(20) (a) Bianchini, C.; Fabbri, D.; Gladiali, S.; Meli, A.; Pohl, W.;
Vizza, F. Organometallics 1996, 15, 4604. (b) Bianchini, C.; J ime´nez,
M. V.; Meli, A.; Moneti, S.; Vizza, F.; Herrera, V.; Sanchez-Delgado,
R. A. Organometallics 1995, 14, 2342.
(21) Fabbri, D.; Dore, A.; Gladiali, S.; De Lucchi, O.; Valle, G. Gazz.
Chim. Ital. 1996, 126, 11.
(22) (a) Sprinz, J .; Helmchen, G. Tetrahedron Lett. 1993, 34, 1769.
(b) Von Matt, P.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1993, 32,
566. (c) Dawson, G. J .; Frost, C. G.; Williams, J . M. J . Tetrahedron
Lett. 1993, 34, 3149. (d) Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000,
33, 336.
As has been shown in Tables 2 and 3, the stereochem-
ical outcome is strongly dependent on the Grignard
reagents in the reaction catalyzed by a nickel complex of
H-MOP or i-Pr-phox. The strong dependency indicates
(23) Hayashi, T.; Konishi, M.; Fukushima, M.; Kanehira, K.; Hiroki,
T.; Kumada, M. J . Org. Chem. 1983, 48, 2195.
J . Org. Chem, Vol. 69, No. 11, 2004 3815

Cho et al.
SCHEME 9
SCHEME 10
that the stereochemistry of the corresponding products
is determined at or after the transmetalation step. The
determination before the transmetalation step, namely
at the oxidative addition step, would result in the same
enantioselectivity irrespective of the Grignard reagents
used. The nickelacycle intermediates (S)-A and (R)-A are
probably in a fast equilibration. It is unlikely that the
diorganonickel intermediates B undergo the epimeriza-
tion between (S)-B and (R)-B, because the substituted
groups, Ni(R2)L* and SMgBr, at 2 and 2′ positions are
sterically bulky enough to prevent the biaryl axis from
rotating. The opposite absolute configuration observed
in the reaction with ethylmagnesium bromide (Scheme
8, entry 12 in Table 3) may suggest that the (S)-isomer
of the ethylnickel intermediate (S)-B (Et) undergoes the
reductive elimination preferentially while the (R)-isomer
(R)-B (Et) undergoes the â-hydrogen elimination followed
by reductive elimination from the nickel-hydride (R)-B
(H) leading to the reduction product (S)-10 (Scheme 10).
The axially chiral cross-coupling products 8 obtained
here are versatile intermediates for further transforma-
tion. The reactions starting from (S)-8d n and (R)-8d r are
summarized in Scheme 11. The key compound is (S)-2-
methylsulfinyl-2′-phenyl-1,1′-binaphthyl (12), which was
obtained by methylation of the mercapto group in (S)-
8d n (95% ee, entry 7 in Table 3) followed by oxidation of
the sulfide with peracid. Treatment of (S)-12 with 1.5
equiv of ethylmagnesium bromide according to the pro-
cedures reported by Hoffmann24 at room temperature
generated binaphthylmagnesium bromide (12′) in a high
yield. Use of butyllithium25 in place of ethylmagnesium
bromide resulted a lower yield of a binaphthyllithium
species. The binaphthylmagnesium bromide (12′) was
allowed to react with electrophiles to give the corre-
sponding substitution products in high yields without
racemization. Thus, the reaction with iodine, trimethoxy-
borane, and chlorodiphenylphosphine gave iodide 13,
boronate 14, and phosphine 15, respectively. The phos-
phine 15 of (R)-configuration is known26 to show (+)-
specific rotation ([R]20D +145 (c 1.0, chloroform)), and the
(-)-specific rotation ([R]20 -137 (c 1.0, chloroform)) of
D
the phosphine 15 derived from (-)-8d n demonstrates
that the absolute configuration of the cross-coupling
product (-)-8d n is S. In a similar manner, the mercapto
group in (-)-8d r was converted into the diphenylphos-
phino group by way of the sulfoxide. The configuration
of (-)-17 obtained was assigned to be R by comparison
(24) (a) Hoffmann, R. W.; Nell, P. G. Angew. Chem., Int. Ed. 1999,
38, 338. (b) Hoffmann, R. W.; Ho¨lzer, B.; Knopff, O.; Harms, K. Angew.
Chem., Int. Ed. 2000, 39, 3072.
(25) Lockard, J . P.; Schroeck, C. W.; J ohnson, C. R. Synthesis 1973,
485.
(26) Hayashi, T.; Han, J .-W.; Takeda, A.; Tang, J .; Nohmi, K.;
Mukaide, K.; Tsuji, H.; Uozumi, Y. Adv. Synth. Catal. 2001, 343, 279.
3816 J . Org. Chem., Vol. 69, No. 11, 2004

Asymmetric Synthesis of Axially Chiral Biaryls
SCHEME 11a
SCHEME 12
a
Reaction conditions: (a) MeI, K2CO3, acetone, rt, 99%; (b)
mCPBA, CH2Cl2, 0 °C, 92%; (c) EtMgBr, THF, rt; (d) I2, rt, 67%;
(e) (i) B(OMe)3, (ii) 10% HCl, (iii) pinacol, benzene, reflux 48%; (f)
Ph2PCl, rt 62%; (g) Ni(acac)2, MeMgI, THF 50 °C, 76%.
coupling protocol, the biarylthiols obtained by the present
asymmetric cross-coupling were converted into the com-
pounds whose absolute configurations are known (Scheme
12). For example, the cross-coupling of (-)-8d q (68% ee,
entry 10 in Table 3) with methylmagnesium iodide
catalyzed by Ni(acac)2 gave (S)-(+)-2,2′-dimethyl-1,1′-
of its specific rotation ([R]20D -28 (c 0.3, chloroform)) with
the reported value ([R]20D -85 (c 0.2, chloroform)) for (R)-
17.27
The substitution of the methylsulfinyl group with a
nucleophile is also possible by nickel-catalyzed cross-
coupling.11b,12a For example, the cross-coupling of (S)-
(-)-12 with the methyl Grignard reagent proceeded in
THF at 65 °C to give 76% yield of the methylation product
(R)-(-)-16 in the presence of 10 mol % of Ni(acac)2
(Scheme 11).
Although the mercapto group is less reactive than the
methylsulfinyl group toward the cross-coupling, the
reaction of biarylthiols with the Grignard reagents in the
presence of Ni(acac)2 as a catalyst in refluxing THF or
in benzene at 80 °C gave the cross-coupling products in
moderate to high yields. Taking advantage of this cross-
binaphthyl (18) ([R]20 +36 (c 0.5, chloroform)), the
D
specific rotation of (R)-(-)-18 being reported to be ([R]20
D
-37 (c 1.0, chloroform)).2a The biarylthiol (+)-8a m (82%
ee, entry 4 in Table 1) was converted into 2,2′-bis(4-
methylphenyl)-6,6′-dimethyl-1,1′-biphenyl (9a m ) by the
cross-coupling with 4-methylphenylmagnesium bromide,
and its specific rotation ([R]20 +43 (c 1.0, chloroform))
D
was compared with that ([R]20 +75 (c 1.0, chloroform))
D
of the authentic sample prepared from (S)-2,2′-dihydroxy-
6,6′-dimethyl-1,1′-biphenyl15 (Scheme 13) to determine
that (+)-8a m has S configuration. The absolute configu-
rations of the thiols (+)-8a n (81% ee, entry 2 in Table 2)
and (-)-8cq (53% ee, entry 7 in Table 2) were determined
to be (S)-(+) and (S)-(-), respectively, by correlation with
the authentic sample (S)-(+)-9a n whose preparation is
(27) Uozumi, Y.; Tanahashi, A.; Lee, S.-Y.; Hayashi, T. J . Org. Chem.
1993, 58, 1945.
J . Org. Chem, Vol. 69, No. 11, 2004 3817

Cho et al.
SCHEME 13
SCHEME 14
SCHEME 15
shown in Scheme 13. Similarly, the absolute configura-
tion of (+)-10 (43% ee, entry 12 in Table 3) was deter-
mined to be (S)-(+) by comparison of the specific rotation
([R]20D +65 (c 0.5, chloroform)) of 2-(4-methylphenyl)-1,1′-
binaphthyl (19) obtained from (+)-10 with that ([R]20
D
+96 (c 1.0, chloroform)) of (S)-(+)-19 derived from known
(S)-2-hydroxy-1,1′-binaphthyl.18a By way of the sulfoxide,
(-)-2-mercapto-2′-(4-methylphenyl)-1,1′-binaphthyl (8dm )
was converted into (-)-19. Treatment of (-)-2-methyl-
sulfinyl-2′-(4-methylphenyl)-1,1′-binaphthyl, prepared from
(-)-8d m according to the procedure described for the
preparation of 12, with ethylmagnesium bromide and
10% HCl gave (-)-19 of 95% ee and the absolute config-
uration of (-)-8d m was assigned to be S by correlation
with the authentic sample (Scheme 13).
Dinaphthothiophene derivative 21 containing the phos-
phinyl group was prepared from 6d according to the
procedures shown in Scheme 15. Lithiation of the 6-posi-
tion of 6d with tert-butyllithium followed by treatment
with iodine gave the 6-iododinaphthothiophene (20). The
reaction of the Grignard reagent prepared from 20 with
phosphinyl chloride in THF gave the desired dinaph-
thothiophene derivative 21.
The rate of the interconversion of 21 was estimated in
the temperature range between -60 and -15 °C by line-
shape analysis of the 31P NMR spectra. At and below ca.
-35 °C, the 31P NMR spectra of 21 gave clearly separated
two signals from two atropisomers, and at higher tem-
perature the single coalesced signal was detected. The
relative molar ratios between the two isomers were
directly obtained at -60, -55, and -50 °C to be ca. 55:
45 constantly. The interconversion rate constants k were
determined between -55 and -15 °C by the line-shape
analysis (shown in the Supporting Information). An
Eyring plot (ln k/T vs 1/T) is linear (R2 > 0.999), and the
activation parameters for the interconversion of 21 are
∆Hq ) 46.1 kJ /mol, ∆Sq ) -196 J /(mol‚K), and ∆Gq
(at -35 °C) ) 46.5 kJ /mol. The ∆Gq value is similar to
the activation barrier of S-methyldinaphthothiophenium
tetrafluoroborate and dinaphthothiophene S-oxide.21 The
∆Gq(at 40 °C) ) 50 kJ /mol and k(at 40 °C) ) 3.0 × 104
Hz at the catalytic reaction temperature were estimated
by the extrapolation of the Eyring plot. In other words,
the flipping of dinaphthothiophene (6d ) is 30 000 times
per second at the reaction temperature and the half-life
for racemization of 6d is calculated to be shorter than
0.0001 s (t1/2 ) 2.31 × 10-5). It is concluded that the
racemization of 6d is much faster than the catalytic cross-
coupling reaction. As shown in Scheme 10, it is most
likely that the stereochemical outcome in the present
asymmetric cross-coupling is determined at the trans-
metalation step after the epimerization of the diastereo-
meric nickelacycle intermediates. A kinetic resolution at
the oxidative addition step would not affect the stereo-
chemical outcome, because the nickelacycle intermediates
are in fast equilibration.
It has been reported21 that the structure of dinaph-
thothiophene (6d ) is not flat but distorted due to the
steric repulsion between the two naphthyl rings. It is
interesting to study the rate of flipping of the dinaph-
thothiophene (6d ), because the flipping rate is related
to the mechanism of stereocontrol in the present asym-
metric cross-coupling reaction where the carbon-sulfur
bond in the thiophene ring is cleaved. If the flipping is
slow compared to the cross-coupling, the present asym-
metric reaction is expected to involve a kinetic resolution
of the starting substrate. If it is fast, the starting
substrate is recognized to be always racemic. The inter-
conversion of various dinaphthoheteroles such as S-
methylthiophenium salt21 and phosphole28 have been
studied by NMR analysis. The dinaphthoheteroles con-
taining substituents on the central heteroatom exist in
solution as a mixture of two diastereomeric enantiomers,
which facilitates the studies of the interconversion by the
NMR analysis. On the other hand, dinaphthothiophene
(6d ) has no substituents on the central atom, and hence
exists as a mixture of two enantiomers. Thus, our
strategy for solving the problem is the introduction of a
chiral substituent on 6d , which makes the dinaphtho-
thiophene become a mixture of two diastereoisomers.
PhMeP(O)- was selected as the substituent because of
its utility in the NMR analysis by using 31P NMR spectra
(Scheme 14).
(28) (a) Yasuike, S.; Iida, T.; Okajima, S.; Yamaguchi, K.; Seki, H.;
Kurita, J . Tetrahedron 2001, 57, 10047. (b) Watson, A. A.; Willis, A.
C.; Wild, S. B. J . Organomet. Chem. 1993, 445, 71.
3818 J . Org. Chem., Vol. 69, No. 11, 2004

Asymmetric Synthesis of Axially Chiral Biaryls
24 h. When the reaction was confirmed to be completed by a
TLC analysis, the mixture was quenched with water at 0 °C.
It was then diluted with diethyl ether and the organic layer
was washed with 10% HCl and brine. The organic layer was
dried over anhydrous MgSO4 and evaporated under reduced
pressure. Silica gel column chromatography (hexane/ethyl
acetate ) 90/10) gave 3.8 g (60% yield) of 2,2′-dimethoxy-6,6′-
dibutyl-1,1′-biphenyl (3b): 1H NMR (CDCl3) δ 0.75 (t, J ) 7.3
Hz, 6H), 1.16 (m, 4H), 1.38 (m, 4H), 2.20 (m, 4H), 3.67 (s, 6H),
6.80 (d, J ) 8.2 Hz, 2H), 6.92 (d, J ) 7.7 Hz, 2H), 7.27 (t, J )
8.0 Hz, 2H); 13C NMR (CDCl3) δ 13.9, 22.5, 32.2, 32.7, 55.5,
107.9, 120.9, 125.5, 127.8, 142.8, 157.1. Anal. Calcd for
Con clu sion
We have developed a new efficient route to axially
chiral biaryls, which have been realized by nickel-
catalyzed asymmetric cross-coupling of thiophene 6 with
the Grignard reagents. Monosubstitution products 8 were
obtained in high yield with high enantiomeric purity. By
replacement of the mercapto group in 8 by some func-
tional groups, the thiols 8 can be converted into useful
chiral building blocks.
C
22H30O2: C, 80.94; H, 9.26. Found: C, 80.86; H, 9.23.
P r ep a r a t ion of 2,2′-Dim et h oxy-6,6′-d ip h en yl-1,1′-b i-
Exp er im en ta l Section
p h en yl (3c).15 3c was prepared in a manner similar to 3b with
phenylzinc chloride. H NMR (CDCl3) δ 3.67 (s, 6H), 6.73 (d,
J ) 7.2 Hz, 4H), 6.81 (d, J ) 7.7 Hz, 2H), 6.84 (d, J ) 8.3 Hz,
2H), 7.02 (t, J ) 7.2 Hz, 4H), 7.08 (t, J ) 7.2 Hz, 2H), 7.26 (t,
J ) 8.0 Hz, 2H); 13C NMR (CDCl3) δ 55.7, 109.5, 122.2, 124.9,
126.1, 127.0, 128.3, 128.9, 141.3, 143.0, 157.9.
Ma ter ia ls. The compounds 2,2′-dihydroxy-6,6′-dimethoxy-
1,1-biphenyl (1),14 (S)-2,2′-dihydroxy-6,6′-dimethyl-1,1′-biphen-
yl,15 and methylphenylphosphinyl chloride29 were prepared
according to the reported procedures. THF, Et2O, toluene, and
benzene were distilled from sodium benzophenone-ketyl under
nitrogen. DMF, triethylamine, and pyridine were dried over
CaH2, and distilled under nitrogen. PdCl2(dppf),30 NiCl2-
(dppp),31 and NiCl2(dppe)32 were prepared according to the
reported procedures.
P r ep a r a tion of 2,2′-Bis(tr iflu or om eth a n esu lfon yloxy)-
6,6′-d im eth oxy-1,1-bip h en yl (2).15 To a solution of 2,2′-
dihydroxy-6,6′-dimethoxy-1,1′-biphenyl (1)14 (6.7 g, 27 mmol)
in 1,2-dichloroethane (150 mL) was added pyridine (5.5 mL,
68 mmol) and triflic anhydride (10 mL, 60 mmol) at 0 °C. The
mixture was allowed to stir at room temperature for 10 h and
quenched with 10% HCl. It was then diluted with ethyl acetate
and the organic layer was washed with saturated NaHCO3
solution and brine, dried over anhydrous MgSO4, and evapo-
rated under reduced pressure. Silica gel column chromatog-
raphy (hexane/ethyl acetate ) 80/20) gave 13 g (90% yield) of
bis(triflate) 2: 1H NMR (CDCl3) δ 3.80 (s, 6H), 7.01 (d, J )
8.6 Hz, 2H), 7.02 (d, J ) 8.3 Hz, 2H), 7.48 (t, J ) 8.6 Hz, 2H);
13C NMR (CDCl3) δ 56.1, 110.4, 112.9, 114.5, 118.2 (q, J ) 3.6
Hz), 130.7, 148.4, 158.5.
P r ep a r a tion of 2,2′-Dim eth oxy-6,6′-d im eth yl-1,1′-bi-
p h en yl (3a ). To a solution of bis(triflate) 2 (9.0 g, 18 mmol)
and NiCl2(dppp)16 (1.9 g, 3.5 mmol) in dry diethyl ether (120
mL) was slowly added methylmagnesium iodide in diethyl
ether (66 mL, 0.11 mol) at 0 °C under nitrogen atmosphere.
The mixture was allowed to stir at room temperature for 12 h
and quenched with water carefully at 0 °C. It was diluted with
ether and the organic layer was washed with 10% HCl and
brine. The separated organic layer was dried over anhydrous
MgSO4 and evaporated under reduced pressure. Silica gel
column chromatography (hexane/ethyl acetate ) 90/10) gave
3.4 g (80% yield) of 2,2′-dimethoxy-6,6′-dimethyl-1,1′-biphenyl
(3a ):33 1H NMR (CDCl3) δ 1.94 (s, 6H), 3.69 (s, 6H), 6.82 (d, J
) 8.2 Hz, 2H), 6.90 (d, J ) 8.2 Hz, 2H), 7.23 (t, J ) 7.8 Hz,
2H); 13C NMR (CDCl3) δ 19.5, 55.7, 108.3, 122.2, 126.2, 127.8,
138.1, 156.9.
P r ep a r a t ion of 2,2′-Dim et h oxy-6,6′-d ib u t yl-1,1′-b i-
p h en yl (3b). To a solution of bis(triflate) 2 (10 g, 20 mmol)
and PdCl2(dppf) (1.4 g, 2.0 mmol) in dry THF (30 mL) was
slowly added diisobutylaluminum hydride solution in hexane
(4.0 mL, 3.9 mmol) at 0 °C and the mixture was stirred at 0
°C for 15 min. n-Butylzinc chloride, which is a white slurry
prepared from n-butyllithium and ZnCl2 in THF (80 mL, 80
mmol), was slowly added at 0 °C. The mixture was refluxed
for 24 h, n-butylzinc chloride solution in THF (40 mL, 40 mmol)
was slowly added, and the mixture was refluxed for another
1
P r ep a r a t ion of 2,2′-Dih yd r oxy-6,6′-d im et h yl-1,1′-b i-
p h en yl (4a ). To a solution of 3a (3.3 g, 14 mmol) in dry CH2Cl2
(120 mL) was slowly added a solution of BBr3 (3.2 mL, 34
mmol) in dry CH2Cl2 (50 mL) at -78 °C under nitrogen
atmosphere. The mixture was allowed to stir at room temper-
ature for 5 h, and quenched carefully with 10% HCl at 0 °C.
It was then extracted with diethyl ether and the organic layer
was dried over anhydrous MgSO4. After evaporation under
reduced pressure, silica gel column chromatography (hexane/
ethyl acetate ) 50/50) gave 2.8 g (97% yield) of 2,2′-dihydroxy-
6,6′-dimethyl-1,1′-biphenyl (4a ):15 1H NMR (CDCl3) δ 2.00 (s,
6H), 4.69 (br, 2H), 6.90 (d, J ) 8.2 Hz, 2H), 6.93 (d, J ) 7.6
Hz, 2H), 7.25 (t, J ) 8.0 Hz, 2H); 13C NMR (CDCl3) δ 19.4,
113.1, 119.5, 122.6, 130.1, 138.9, 153.8. The diols 4b and 4c
were prepared in a similar manner.
2,2′-Dih ydr oxy-6,6′-dibu tyl-1,1′-biph en yl (4b):15a 1H NMR
(CDCl3) δ 0.78 (t, J ) 7.4 Hz, 6H), 1.20 (sextet, J ) 7.5 Hz,
4H), 1.91 (m, 4H), 2.25 (m, 4H), 4.67 (br, 2H), 6.90 (dd, J )
8.2, 1.0 Hz, 2H), 6.95 (dd, J ) 7.6, 1.0 Hz, 2H), 7.29 (t, J ) 8.0
Hz, 2H); 13C NMR (CDCl3) δ 13.7, 22.5, 32.4, 32.8, 113.0, 118.8,
121.5, 130.1, 143.8, 153.8.
2,2′-Dih ydr oxy-6,6′-diph en yl-1,1′-biph en yl (4c):15 1H NMR
(CDCl3) δ 5.18 (br, 2H), 6.63 (dd, J ) 8.2, 1.1 Hz, 4H), 6.83
(dd, J ) 7.7, 1.1 Hz, 2H), 7.03 (dt, J ) 8.2, 1.1 Hz, 4H), 7.05
(d, J ) 7.7 Hz, 2H), 7.12 (t, J ) 7.4 Hz, 2H), 7.31 (t, J ) 8.0
Hz, 2H); 13C NMR (CDCl3) δ 114.4, 122.9, 126.7, 127.4, 128.6,
130.3, 144.0, 154.2.
P r ep a r a tion of 2,2′-Bis(N,N-d im eth ylth ioca r ba m oyl-
oxy)-6,6′-d im eth yl-1,1′-bip h en yl (5a ). To a solution of 4a
(1.8 g, 8.4 mmol), triethylamine (2.6 mL, 19 mmol), and
pyridine (6.8 mL, 84 mmol) in dry THF (50 mL) was added
N,N-dimethylthiocarbamoyl chloride (2.3 g, 19 mmol) at 0 °C
under nitrogen atmosphere. The mixture was allowed to stir
at 65 °C for 24 h. N,N-Dimethylthiocarbamoyl chloride (1.2 g,
9.2 mmol) was added and the mixture was stirred at 65 °C for
another 12 h. The resulting mixture was quenched with
saturated NaHCO3 solution and was extracted with CHCl3.
The separated organic phase was dried over anhydrous MgSO4
and evaporated under reduced pressure. The residue was
purified by column chromatography on silica gel (hexane/ethyl
acetate ) 70/30) to give 2.9 g (90% yield) of 2,2′-bis(N,N-
dimethylthiocarbamoyloxy)-6,6′-dimethyl-1,1′-biphenyl (5a): 1H
NMR (CDCl3) δ 2.13 (s, 6H), 2.89 (s, 6H), 3.22 (s, 6H), 7.12 (d,
J ) 8.1 Hz, 2H), 7.16 (d, J ) 7.5 Hz, 2H), 7.29 (t, J ) 7.9 Hz,
2H); 13C NMR (CDCl3) δ 19.9, 38.0, 42.9, 121.3, 127.3, 127.5,
129.1, 139.2, 151.5, 186.6. Anal. Calcd for C20H24N2O2S2: C,
61.82; H, 6.23. Found: C, 61.78; H, 6.15.
(29) Korpiun, O.; Lewis, R. A.; Chickos, J .; Mislow, K. J . Am. Chem.
Soc. 1968, 90, 4842.
(30) Hayashi, T.; Konishi, M.; Kobori, Y.; Kumada, M.; Higuchi, T.;
Hirotsu, K. J . Am. Chem. Soc. 1984, 106, 158.
(31) Van Hecke, G. R.; Horrocks, W. D., J r. Inorg. Chem. 1966, 5,
8.
(32) Booth, G.; Chatt, J . J . Chem. Soc. 1965, 3238.
(33) Coleman, R. S.; Guernon, J . M.; Roland, J . T. Org. Lett. 2000,
2, 277.
P r ep a r a tion of 2,2′-Bis(N,N-d im eth ylth ioca r ba m oyl-
oxy)-6,6′-d ibu tyl-1,1′-bip h en yl (5b). 5b was prepared from
4b in a manner similar to that for 5a . 1H NMR (CDCl3) δ 0.81
(t, J ) 7.3 Hz, 6H), 1.25 (m, 4H), 1.46 (m, 4H), 2.34 (m, 4H),
2.79 (s, 6H), 3.23 (s, 6H), 7.19 (d, J ) 7.6 Hz, 2H), 7.25 (dd, J
J . Org. Chem, Vol. 69, No. 11, 2004 3819

Cho et al.
) 8.1, 1.0 Hz, 2H), 7.34 (t, J ) 8.1 Hz, 2H); 13C NMR (CDCl3)
δ 13.9, 22.6, 32.0, 32.6, 38.3, 40.0, 100.5, 121.7, 125.3, 127.2,
143.4, 151.1, 186.1. Anal. Calcd for C26H36N2O2S2: C, 66.06;
H, 7.68. Found: C, 65.76; H, 7.65.
phenylmagnesium bromide in THF (1.60 mL, 2.35 mmol) at 0
°C under nitrogen atmosphere. The mixture was allowed to
stir at 40 °C for 24 h and quenched with water. It was then
diluted with CHCl3 and the organic layer was washed with
10% HCl, saturated NaHCO3, and brine. The organic layer was
dried over anhydrous MgSO4 and evaporated under reduced
pressure. Silica gel preparative thin-layer chromatography
(hexane/ethyl acetate ) 98/2) gave 61 mg (85% yield, 82% ee)
of (S)-2-m er ca p to-2′-(4-m eth ylp h en yl)-6,6′-d im eth yl-1,1′-
bip h en yl (8a m ): [R]20D +98 (c 0.5, chloroform) for 8a m of 82%
P r ep a r a tion of 2,2′-Bis(N,N-d im eth ylth ioca r ba m oyl-
oxy)-6,6′-d ip h en yl-1,1′-bip h en yl (5c). To a solution of 4c (1.4
g, 4.1 mmol) in dry DMF (50 mL) was added sodium hydride
(60% oil dispersion; 0.30 g, 10 mmol) in portions at 0 °C, before
N,N-dimethylthiocarbamoyl chloride (1.5 g, 12 mmol) was
added in one portion. The mixture was allowed to stir at 85
°C for 2 h and quenched with 1 N KOH (150 mL) at 0 °C. The
precipitate was collected on a filter and then thoroughly
washed with H2O. The collected solid was dissolved in CHCl3
and the solution was dried over anhydrous MgSO4. After
evaporation of the solvent, the crude solid was recrystallized
from hexane/chloroform to give 1.6 g (75% yield) of 2,2′-bis-
(N,N-dimethylthiocarbamoyloxy)-6,6′-diphenyl-1,1′-biphenyl
(5c): 1H NMR (CDCl3) δ 3.00 (s, 6H), 3.32 (s, 6H), 6.77 (dd, J
) 8.0, 1.3 Hz, 4H), 7.01 (t, J ) 7.7 Hz, 4H), 7.02 (dd, J ) 7.7,
1.3 Hz, 2H), 7.09 (t, J ) 7.3 Hz, 2H), 7.35 (t, J ) 8.0 Hz, 2H),
7.51 (dd, J ) 8.2, 1.3 Hz, 2H); 13C NMR (CDCl3) δ 38.6, 43.3,
122.9, 126.4, 127.0, 127.2, 127.3, 129.2, 139.8, 143.3, 151.7,
1
ee; H NMR (CDCl3) δ 1.78 (s, 3H), 2.04 (s, 3H), 2.25 (s, 3H),
3.21 (s, 1H), 6.85 (d, J ) 7.6 Hz, 1H), 6.96 (d, J ) 8.0 Hz, 2H),
7.00 (t, J ) 7.6 Hz, 1H), 7.11 (d, J ) 8.1, 3H), 7.27-7.31 (m,
2H), 7.36 (t, J ) 7.6 Hz, 1H); 13C NMR (CDCl3) δ 19.8, 20.5,
21.1, 125.6, 126.7, 127.3, 128.0, 128.2, 128.3, 128.5, 129.3,
132.6, 136.1, 136.6, 137.0, 138.0, 138.4, 141.3. Anal. Calcd for
C
21H20S: C, 82.85; H, 6.62. Found: C, 82.70; H, 6.84. (S)-2-
Mer capto-2′-ph en yl-6,6′-dim eth yl-1,1′-biph en yl (8an ): [R]20
D
1
+92 (c 1.0, chloroform) for 8a n of 81% ee; H NMR (CDCl3) δ
1.77 (s, 3H), 2.05 (s, 3H), 3.20 (s, 1H), 6.82 (d, J ) 7.6 Hz,
1H), 6.97 (t, J ) 7.7 Hz, 1H), 7.09 (d, J ) 7.8 Hz, 1H), 7.13-
7.14 (m, 3H), 7.22-7.24 (m, 2H), 7.29 (d, J ) 11.9 Hz, 1H),
7.31 (d, J ) 11.3 Hz, 1H), 7.37 (t, J ) 7.6 Hz, 1H); 13C NMR
(CDCl3) δ 19.8, 20.5, 125.6, 126.6, 126.8, 127.4, 128.1, 128.2,
128.7, 129.5, 132.6, 136.7, 137.0, 137.3, 137.8, 141.3, 141.4.
Anal. Calcd for C20H18S: C, 82.71; H, 6.25. Found: C, 82.61;
H, 6.61. (S)-2-Mer capto-2′-ben zyl-6,6′-dim eth yl-1,1′-biph en -
185.6. Anal. Calcd for
C30H28N2O2S2: C, 69.07; H, 5.60.
Found: C, 69.10; H, 5.27.
P r ep a r a tion of 1,9-Dim eth yld iben zo[2,1-b:1′,2′-d ]th io-
p h en e (6a ). 2,2′-Bis(N,N-dimethylthiocarbamoyloxy)-6,6′-di-
methyl-1,1′-biphenyl (5a ) (2.8 g, 7.2 mmol) was heated in an
autoclave at 290 °C for 12 h. The reaction mixture was cooled
to room temperature and then purified by column chromatog-
raphy on silica gel (hexane/ethyl acetate ) 95/5) to give 1.3 g
(86% yield) of 1,9-dimethyldibenzothiophene (6a ):34 1H NMR
(CDCl3) δ 2.77 (s, 6H), 7.26 (m, 2H), 7.35 (t, J ) 7.6 Hz, 2H),
7.67 (m, 2H); 13C NMR (CDCl3) δ 25.6, 119.9, 126.0, 127.9,
134.3, 135.4, 140.1. Similarly, the thiophenes 6b and 6c were
prepared from 5b and 5c, respectively.
1,9-Dibu tyldiben zo[2,1-b:1′,2′-d]th ioph en e (6b): 1H NMR
(CDCl3) δ 0.86 (t, J ) 7.4 Hz, 6H), 1.27 (sextet, J ) 7.5 Hz,
4H), 1.57-1.62 (m, 4H), 3.08 (m, 4H), 7.35 (d, J ) 6.7 Hz, 2H),
7.39 (t, J ) 7.5 Hz, 2H), 7.65 (dd, J ) 7.6, 1.1 Hz, 2H); 13C
NMR (CDCl3) δ 13.9, 22.8, 33.5, 36.2, 119.7, 125.6, 126.1, 134.7,
139.7, 139.9. Anal. Calcd for C20H24S: C, 81.02; H, 8.16.
Found: C, 81.15; H, 8.24.
1,9-Dip h en yld ib en zo[2,1-b:1′,2′-d ]t h iop h en e (6c): 1H
NMR (CDCl3) δ 6.76 (d, J ) 7.1 Hz, 4H), 6.94 (t, J ) 7.6 Hz,
4H), 7.01 (t, J ) 7.3 Hz, 2H), 7.03 (d, J ) 7.3 Hz, 2H), 7,42 (t,
J ) 7.6 Hz, 2H), 7.78 (d, J ) 7.8 Hz, 2H); 13C NMR (CDCl3) δ
121.0, 125.9, 126.2, 127.6, 127.8, 128.2, 132.5, 140.6, 140.7,
142.9. Anal. Calcd for C24H16S: C, 85.68; H, 4.79. Found: C,
85.41; H, 4.92.
P r ep a r a tion of Din a p h th o[2,1-b:1′,2′-d ]th iop h en e (6d ).
1,1′-Binaphthyl-2,2′-diyl O,O-bis(N,N-dimethylthiocarbamate)
(18.4 g, 39.9 mmol) prepared from 1,1′-binaphthol according
to De Lucchi’s procedures17a was heated in an autoclave at 285
°C for 30 min. The reaction mixture was cooled to room
temperature and the crude solid was recrystallized from
chloroform/methanol to give 9.5 g (68% yield) of dinaphtho-
thiophene (6d ): 1H NMR (CDCl3) δ 7.57 (m, 4H), 7.93 (d, J )
8.6 Hz, 2H), 7.96 (d, J ) 8.6 Hz, 2H), 8.03 (m, 2H), 8.87 (m,
2H); 13C NMR (CDCl3) δ 120.8, 124.8, 125.2, 126.0, 127.4,
128.6, 129.8, 131.4, 132.1, 138.4.
yl (8a p ): [R]20 +4.7 (c 1.0, chloroform) for 8a p of 35% ee; 1H
D
NMR (CDCl3) δ 1.68 (s, 3H), 1.96 (s, 3H), 3.03 (s, 1H), 3.55 (d,
J ) 15.3 Hz, 1H), 3.66 (d, J ) 15.3 Hz, 1H), 6.95 (d, J ) 6.6
Hz, 2H), 6.99 (d, J ) 7.6 Hz, 1H), 7.07 (d, J ) 7.6 Hz, 1H),
7.13 (m, 2H), 7.18 (m, 3H), 7.23 (m, 2H); 13C NMR (CDCl3) δ
19.6, 19.9, 39.4, 125.8, 126.1, 127.0, 127.6, 127.7, 127.9, 128.1,
128.3, 129.4, 131.9, 136.4, 137.5, 137.6, 138.6, 139.3, 140.1.
Anal. Calcd for C21H20S: C, 82.85; H, 6.62. Found: C, 82.68;
H, 6.85. (S)-2-Mer ca p to-2′-(4-m eth ylp h en yl)-6,6′-d ibu tyl-
1,1′-bip h en yl (8bm ): [R]20 +37 (c 1.0, chloroform) for 8bm
D
of 78% ee; 1H NMR (CDCl3) δ 0.75 (t, J ) 7.3 Hz, 3H), 0.80 (t,
J ) 7.4 Hz, 3H), 1.09 (m, 3H), 1.24 (m, 3H), 1.41 (m, 1H), 1.53
(m, 1H), 1.93 (ddd, J ) 14.6, 10.4, 5.5 Hz, 1H), 2.06 (ddd, J )
14.6, 10.4, 5.5 Hz, 1H), 2.23 (s, 3H), 2.27 (ddd, J ) 14.6, 10.4,
5.5 Hz, 1H), 2.39 (ddd, J ) 14.6, 10.4, 5.5 Hz, 1H), 3.21 (s,
1H), 6.88 (d, J ) 7.6 Hz, 1H), 6.94 (d, J ) 8.0 Hz, 2H), 7.05 (t,
J ) 7.7 Hz, 1H), 7.08 (d, J ) 8.0 Hz, 2H), 7.11 (d, J ) 7.7 Hz,
1H), 7.28 (d, J ) 7.6 Hz, 1H), 7.34 (d, J ) 6.7 Hz, 1H), 7.41 (t,
J ) 7.6 Hz, 1H); 13C NMR (CDCl3) δ 13.9, 21.1, 22.7, 22.8,
31.4, 32.1, 32.6, 32.9, 124.9, 125.3, 127.3, 127.8, 128.0, 128.1,
128.2, 128.8, 133.2, 136.0, 136.6, 137.1, 138.6, 141.4, 141.5,
141.7. Anal. Calcd for C27H32S: C, 83.45; H, 8.30. Found: C,
83.25; H, 8.24. (R)-2-Mer ca p to-2′-(4-m eth ylp h en yl)-6,6′-
d ip h en yl-1,1′-bip h en yl (8cm ): [R]20D -18 (c 1.0, chloroform)
for 8cm of 36% ee; 1H NMR (CDCl3) δ 2.28 (s, 3H), 3.23 (s,
1H), 6.66 (dd, J ) 8.3, 1.1 Hz, 2H), 6.89 (m, 6H), 6.95 (dd, J )
6.9, 2.2 Hz, 1H), 7.02 (t, J ) 7.7 Hz, 2H), 7.06 (m, 4H), 7.12
(m, 2H), 7.29 (dd, J ) 7.7, 1.4 Hz, 1H), 7.35 (dd, J ) 7.7, 1.4
Hz, 1H), 7.46 (t, J ) 7.7 Hz, 1H); 13C NMR (CDCl3) δ 21.1,
126.29, 126.34, 127.18, 127.24, 127.3, 127.8, 127.9, 128.1,
128.6, 129.08, 129.12, 129.2, 129.7, 129.9, 133.4, 135.2, 136.1,
136.5, 138.0, 140.6, 140.9, 142.1, 142.4; HRMS (FAB) calcd
for C31H24S (M)+ 428.1598, found 428.1592. (S)-2-Mer ca p to-
2′,6-d ip h en yl-6′-m eth yl-1,1′-bip h en yl (8cq): [R]20 -43 (c
Asym m etr ic Gr ign a r d Cr oss-Cou p lin g of Th iop h en es
6a -d w ith Gr ign a r d Rea gen ts. The reaction conditions and
results are summarized in Tables 1-3. A typical procedure is
given for the reaction of 1,9-dimethyldibenzothiophene (6a )
with 4-methylphenylmagnesium bromide (7m ) in the presence
of Ni(cod)2 and (S)-H-MOP (entry 4 in Table 1).
To a solution of 1,9-dimethyldibenzothiophene (6a ) (50 mg,
0.24 mmol), Ni(cod)2 (3.9 mg, 14 µmol), and (S)-H-MOP (18.6
mg, 42 µmol) in dry THF (4 mL) was added slowly 4-methyl-
D
1.0, chloroform) for 8cq of 53% ee; 1H NMR (CDCl3) δ 2.31 (s,
3H), 3.43 (s, 1H), 6.50 (dd, J ) 8.2, 1.4 Hz, 2H), 6.69 (dd, J )
8.2, 1.4 Hz, 2H), 6.92 (dd, J ) 7.7, 1.2 Hz, 1H), 7.00 (m, 5H),
7.08 (m, 2H), 7.15 (t, J ) 7.8 Hz, 1H), 7.25 (m, 2H), 7.31 (dd,
J ) 7.7, 1.2 Hz, 1H); 13C NMR (CDCl3) δ 20.3, 126.2, 126.3,
126.96, 127.04, 127.2, 127.7, 128.12, 128.14, 128.9, 129.0,
134.2, 136.5, 136.9, 137.8, 140.7, 141.0, 141.6, 142.1. Anal.
Calcd for C25H20S: C, 85.18; H, 5.72. Found: C, 85.07; H, 5.55.
(S)-2-Mer capto-2′-(4-m eth ylph en yl)-1,1′-bin aph th yl (8dm ):
[R]20 -98 (c 1.0, chloroform) for 8d m of 95% ee; 1H NMR
D
(34) Tedjamulia, M. L.; Tominaga, Y.; Castle, R. N.; Lee, M. L. J .
Heterocycl. Chem. 1983, 20, 1485.
(CDCl3) δ 2.11 (s, 3H), 3.15 (s, 1H), 6.82 (d, J ) 8.0 Hz, 2H),
3820 J . Org. Chem., Vol. 69, No. 11, 2004

Asymmetric Synthesis of Axially Chiral Biaryls
7.08 (d, J ) 8.0 Hz, 2H), 7.14 (m, 3H), 7.27 (m, 3H), 7.43 (t, J
) 7.5 Hz, 1H), 7.64 (dd, J ) 8.5, 3.1 Hz, 2H), 7.71 (d, J ) 8.2
(s, 1H), 7.06 (d, J ) 8.6 Hz, 1H), 7.23 (ddd, J ) 8.1, 7.0, 1.1
Hz, 1H), 7.25 (d, J ) 8.2 Hz, 1H), 7.31 (ddd, J ) 8.1, 7.0, 1.1
Hz, 1H), 7.38 (ddd, J ) 8.1, 7.0, 1.1 Hz, 1H), 7.43 (dd, J ) 8.2,
1.1 Hz, 1H), 7.49 (ddd, J ) 8.1, 7.0, 1.1 Hz, 1H), 7.51 (d, J )
8.7 Hz, 1H), 7.64 (dd, J ) 8.2, 1.3 Hz, 1H), 7.82 (d, J ) 8.7 Hz,
1H), 7.85 (d, J ) 8.2 Hz, 1H), 7.96 (d, J ) 8.3 Hz, 1H), 7.99 (d,
J ) 8.3 Hz, 1H); 13C NMR (CDCl3) δ 120.8, 125.0, 125.2, 125.6,
125.76, 125.83, 126.0, 126.2, 126.5, 126.7, 127.0, 127.9, 128.28,
128.30, 128.4, 128.5, 131.5, 131.9, 133.8, 134.1.
Hz, 1H), 7.92 (d, J ) 8.2 Hz, 1H), 8.01 (d, J ) 8.5 Hz, 1H); 13
C
NMR (CDCl3) δ 21.1, 124.9, 125.9, 126.1, 126.2, 126.8, 126.85,
126.93, 128.1, 128.2, 128.3, 128.4, 128.65, 128.67. 128.9, 131.2,
131.3, 132.1, 133.0, 133.1, 133.3, 134.2, 136.3, 138.3, 140.0.
Anal. Calcd for C27H20S: C, 86.13; H, 5.35. Found: C, 86.02;
H, 5.42. (S)-2-Mer ca p to-2′-p h en yl-1,1′-bin a p h th yl (8d n ):
[R]20 -79 (c 1.0, chloroform) for 8d n of 95% ee; 1H NMR
D
(CDCl3) δ 3.19 (s, 1H), 7.06 (m, 3H), 7.13 (d, J ) 8.5 Hz, 1H),
7.21 (m, 4H), 7.32 (m, 2H), 7.35 (d, J ) 8.5 Hz, 1H), 7.51 (ddd,
J ) 8.1, 7.0, 1.1 Hz, 1H), 7.69 (dd, J ) 8.5, 4.4 Hz, 2H), 7.77
(d, J ) 8.2 Hz, 1H), 7.99 (d, J ) 8.2 Hz, 1H), 8.08 (d, J ) 8.5
Hz, 1H); 13C NMR (CDCl3) δ 124.8, 125.8, 126.10, 126.13,
126.68, 126.72, 126.74, 126.9, 127.4, 128.0, 128.14, 128.19,
128.6, 128.7, 128.8, 131.1, 131.2, 132.0, 133.0, 133.0, 133.2,
134.0, 139.0, 141.1. Anal. Calcd for C26H18S: C, 86.15; H, 5.01.
Found: C, 85.96; H, 5.29. (S)-2-Mer ca p t o-2′-(4-m et h oxy-
p h en yl)-1,1′-bin a p h th yl (8d o): [R]20D -91 (c 1.0, chloroform)
for 8d o of 93% ee; 1H NMR (CDCl3) δ 3.18 (s, 1H), 3.65 (s,
3H), 6.58 (d, J ) 8.8 Hz, 2H), 7.11 (m, 3H), 7.14 (d, J ) 9.0
Hz, 1H), 7.21 (ddd, J ) 8.2, 7.0, 1.2 Hz, 1H), 7.29 (ddd, J )
8.2, 7.0, 1.2 Hz, 1H), 7.33 (ddd, J ) 8.2, 7.0, 1.2 Hz, 1H), 7.36
(d, J ) 8.7 Hz, 1H), 7.47 (ddd, J ) 8.2, 7.0, 1.2 Hz, 1H), 7.66
(d, J ) 8.5 Hz, 1H), 7.70 (d, J ) 8.5 Hz, 1H), 7.77 (d, J ) 8.2
P r ep a r a tion of (S)-2-Meth ylth io-2′-p h en yl-1,1′-bin a p h -
th yl (11). To a stirred solution of (S)-8d n (1.1 g, 3.1 mmol,
95% ee) in acetone (25 mL) were added iodomethane (0.20 mL,
3.4 mmol) and potassium carbonate (1.3 g, 9.2 mmol) and the
mixture was allowed to stir for 12 h at room temperature
under nitrogen atmosphere. When the reaction was completed,
the reaction mixture was quenched with water and extracted
with CHCl3. After drying over anhydrous MgSO4 and evap-
oration, the purification of the crude solid by column chroma-
tography (hexane/ethyl acetate ) 95/5) on silica gel gave 1.2
g (99% yield) of (S)-2-methylthio-2′-phenyl-1,1′-binaphthyl
(11): [R]20 -50 (c 1.0, chloroform) for 11 of 95% ee; 1H NMR
D
(CDCl3) δ 2.29 (s, 3H), 7.01 (m, 3H), 7.15 (m, 4H), 7.22 (t, J )
8.0 Hz, 1H), 7.27 (t, J ) 8.0 Hz, 1H), 7.34 (t, J ) 7.5 Hz, 1H),
7.39 (d, J ) 8.8 Hz, 1H), 7.46 (t, J ) 7.5 Hz, 1H), 7.66 (d, J )
8.5 Hz, 1H), 7.79 (d, J ) 8.2 Hz, 1H), 7.81 (d, J ) 8.8 Hz, 1H),
7.96 (d, J ) 8.2 Hz, 1H), 8.05 (d, J ) 8.5 Hz, 1H); 13C NMR
(CDCl3) δ 16.0, 123.1, 124.8, 125.8, 126.3, 126.4, 126.5, 126.6,
127.2, 127.9, 128.1, 128.3, 128.4, 128.5, 128.8, 130.8, 132.5,
132.8, 133.2, 133.7, 133.7, 136.5, 139.8, 141.3. Anal. Calcd for
Hz, 1H), 7.96 (d, J ) 8.2 Hz, 1H), 8.04 (d, J ) 8.2 Hz, 1H); 13
C
NMR (CDCl3) δ 55.0, 112.9, 124.8, 125.8, 125.9, 126.0, 126.74,
126.77, 126.8, 128.0, 128.10, 128.14, 128.3, 128.7, 128.8, 129.9,
131.2, 132.1, 132.9, 133.0, 133.2, 133.5, 134.0, 139.5, 158.3.
HRMS (FAB) calcd for C27H20OS (M + H)+ 393.1313, found
393.1324. (R)-2-Mer ca p to-2′-m eth yl-1,1′-bin a p h th yl (8d q):
C
27H20S: C, 86.13; H, 5.35. Found: C, 86.10; H, 5.62.
P r ep a r a tion of (S)-2-Meth ylsu lfin yl-2′-p h en yl-1,1′-bi-
[R]20 -19 (c 1.0, chloroform) for 8d q of 68% ee; 1H NMR
D
n a p h th yl (12). To a solution of 15 (1.2 g, 3.1 mmol) in dry
CH2Cl2 (25 mL) was added m-chloroperbenzoic acid (0.58 g,
3.4 mmol) at 0 °C. The reaction mixture was stirred for 15
min at 0 °C, before it was quenched with saturated NaHCO3
solution and extracted with CH2Cl2. The separated organic
layer was dried over anhydrous MgSO4 and evaporated. The
purification by column chromatography (hexane/ethyl acetate
) 1/1) on silica gel gave 1.1 g (92% yield) of (S)-2-methyl-
sulfinyl-2′-phenyl-1,1′-binaphthyl (12) as a 1:1 mixture of
diastereomers. Anal. Calcd for C27H20OS: C, 82.62; H, 5.14.
Found: C, 82.55; H, 5.39. Separation of the diastereomers was
carried out by silica gel preparative thin-layer chromatography
with hexane/ethyl acetate (1/1 to 0/1). One of the diastereo-
mers: [R]20D +19 (c 0.7, chloroform) for 12 of 95% ee; 1H NMR
(CDCl3) δ 2.09 (s, 3H), 6.96 (d, J ) 8.6 Hz, 1H), 7.06 (m, 5H),
7.28 (t, J ) 7.5 Hz, 1H), 7.44 (m, 2H), 7.49 (t, J ) 7.5 Hz, 1H),
7.59 (ddd, J ) 8.2, 6.2, 2.0 Hz, 1H), 7.69 (d, J ) 8.6 Hz, 1H),
8.00 (m, 3H), 8.08 (d, J ) 8.6 Hz, 1H), 8.10 (t, J ) 8.6 Hz,
2H); 13C NMR (CDCl3) δ 42.1, 118.9, 125.9, 126.0, 126.9, 127.1,
127.2, 127.4, 127.5. 127.8, 128.56, 128.58, 128.66, 128.68,
129.4, 129.6, 130.0, 132.6, 132.6, 133.5, 134.0, 134.2, 140.3,
(CDCl3) δ 2.08 (s, 3H), 3.15 (s, 1H), 6.97 (d, J ) 8.6 Hz, 1H),
7.08 (d, J ) 8.6 Hz, 1H), 7.20 (ddd, J ) 8.2, 7.0, 1.3 Hz, 1H),
7.23 (ddd, J ) 8.1, 7.0, 1.1 Hz, 1H), 7.36 (ddd, J ) 8.1, 7.0, 1.1
Hz, 1H), 7.40 (ddd, J ) 8.1, 7.0, 1.1 Hz, 1H), 7.51 (d, J ) 8.7
Hz, 2H), 7.81 (d, J ) 8.7 Hz, 1H), 7.85 (d, J ) 8.1 Hz, 1H),
7.89 (t, J ) 8.1 Hz, 2H); 13C NMR (CDCl3) δ 19.9, 124.2, 125.1,
125.2, 125.3, 126.6, 126.8, 126.9, 127.4, 128.07, 128.09, 128.2,
128.4, 128.9, 130.6, 131.6, 132.1, 132.4, 133.0, 133.1, 135.2.
Anal. Calcd for C21H16S: C, 83.96; H, 5.37. Found: C, 83.84;
H, 5.64. (R)-2-Mer capto-2′-eth yl-1,1′-bin aph th yl (8dr ): [R]20
D
1
-5 (c 0.8, chloroform) for 8d r of 50% ee; H NMR (CDCl3) δ
1.07 (t, J ) 7.6 Hz, 3H), 2.36 (dq, J ) 15.1, 7.6 Hz, 1H), 2.43
(dq, J ) 15.1, 7.6 Hz, 1H), 3.17 (s, 1H), 7.00 (dd, J ) 8.5, 1.0
Hz, 1H), 7.05 (dd, J ) 8.5, 1.1 Hz, 1H), 7.20 (ddd, J ) 8.2, 6.7,
1.1 Hz, 1H), 7.24 (ddd, J ) 8.2, 6.7, 1.1 Hz, 1H), 7.37 (ddd, J
) 8.2, 6.7, 1.1 Hz, 1H), 7.41 (ddd, J ) 8.2, 6.7, 1.1 Hz, 1H),
7.52 (d, J ) 8.6 Hz, 1H), 7.59 (d, J ) 8.6 Hz, 1H), 7.82 (d, J )
8.6 Hz, 1H), 7.85 (d, J ) 8.2 Hz, 1H), 7.90 (d, J ) 8.2 Hz, 1H),
7.96 (d, J ) 8.6 Hz, 1H); 13C NMR (CDCl3) δ 14.6, 26.6, 125.1,
125.3, 125.5, 125.6, 126.6, 126.8, 127.2, 128.0, 128.1, 128.2,
128.3, 128.7, 131.0, 131.5, 132.1, 132.4, 132.9, 133.1, 133.6,
140.9. Anal. Calcd for C22H18S: C, 84.03; H, 5.77. Found: C,
84.07; H, 6.06.
140.5, 142.0. The other diastereomer: [R]20 -482 (c 1.1,
D
1
chloroform) for 12 of 95% ee; H NMR (CDCl3) δ 1.86 (s, 3H),
6.98 (d, J ) 8.6 Hz, 1H), 7.08 (m, 5H), 7.23 (ddd, J ) 8.2, 7.1,
1.1 Hz, 1H), 7.42 (m, 2H), 7.46 (ddd, J ) 8.2, 7.1, 1.1 Hz, 1H),
7.61 (ddd, J ) 8.2, 7.1, 1.1 Hz, 1H), 7.71 (d, J ) 8.6 Hz, 1H),
7.95 (d, J ) 8.2 Hz, 1H), 8.01 (d, J ) 8.7 Hz, 2H), 8.10 (d, J )
8.6 Hz, 1H), 8.14 (d, J ) 8.7 Hz, 1H); 13C NMR (CDCl3) δ 41.5,
100.5, 119.8, 126.3, 126.8, 127.2, 127.3, 127.7, 127.8, 127.8,
127.9, 128.2, 128.6, 129.4, 129.6, 130.6, 130.7, 132.5, 132.9,
134.0, 134.1, 136.3, 139.4, 140.9, 141.2.
P r epar ation of (S)-2-Iodo-2′-ph en yl-1,1′-bin aph th yl (13).
To a solution of 12 (0.34 g, 0.87 mmol) as a diastereomeric
mixture (1:1) in dry THF (30 mL) was slowly added ethyl-
magnesium bromide in diethyl ether (0.70 mL, 1.3 mmol) at 0
°C. The resulting mixture was stirred at room temperature
for 35 min and iodine (0.44 g, 1.7 mmol) was added. The
reaction mixture was allowed to stir at room temperature for
12 h under nitrogen atmosphere and quenched with water. It
was then diluted with ethyl acetate, and the organic layer was
washed with saturated Na2S2O3 solution and water, dried over
Asym m etr ic Gr ign a r d Cr oss-Cou p lin g of Din a p h th o-
th iop h en e (6d ) w ith Eth ylm a gn esiu m Br om id e (7r ) in
th e P r esen ce of (S)-p h ep h os. To a solution of dinaphtho-
thiophene (6d ) (57 mg, 0.20 mmol), Ni(cod)2 (1.7 mg, 6.0 µmol),
and (S)-phephos (11 mg, 9.0 µmol) in dry THF (4 mL) was
added slowly ethylmagnesium bromide in Et2O (1.1 mL, 2.0
mmol) at 0 °C under nitrogen atmosphere. The mixture was
allowed to stir at 20 °C for 48 h, and quenched with water. It
was diluted with CHCl3 and the organic layer was washed with
10% HCl, saturated NaHCO3, and brine. The organic layer was
dried over anhydrous MgSO4 and evaporated under reduced
pressure. Silica gel preparative thin-layer chromatography
(hexane/ethyl acetate ) 90/10) gave 26 mg (41% yield, 19%
ee) of (R)-2-mercapto-2′-ethyl-1,1′-binaphthyl (8d r ) ([R]20D -1.8
(c 1.1, chloroform) for 8d r of 19% ee) and 27 mg (45% yield,
43% ee) of (S)-2-m er ca p to-1,1′-bin a p h th yl (10):20a [R]20D -16
1
(c 0.8, chloroform) for 10 of 43% ee; H NMR (CDCl3) δ 3.23
J . Org. Chem, Vol. 69, No. 11, 2004 3821

Cho et al.
anhydrous MgSO4, and evaporated under reduced pressure.
The residue was chromatographed on silica gel (hexane/ethyl
acetate ) 98/2) to give 0.27 g (67% yield) of (S)-2-iodo-2′-
phenyl-1,1′-binaphthyl (13) and 52 mg (18% yield) of 2-phenyl-
1,1′-binaphthyl35 as a byproduct. [R]20D -105 (c 1.0, chloroform)
for 13 of 95% ee; 1H NMR (CDCl3) δ 7.03 (m, 3H), 7.12 (d, J )
8.6 Hz, 1H), 7.16 (m, 2H), 7.25 (m, 2H), 7.30 (ddd, J ) 8.1,
7.0, 1.1 Hz, 1H), 7.42 (ddd, J ) 8.1, 7.0, 1.1 Hz, 1H), 7.49 (ddd,
J ) 8.1, 7.0, 1.1 Hz, 1H), 7.52 (d, J ) 8.8 Hz, 1H), 7.64 (d, J
) 8.6 Hz, 1H), 7.80 (d, J ) 8.2 Hz, 1H), 7.85 (d, J ) 8.6 Hz,
1H), 7.98 (d, J ) 8.2 Hz, 1H), 8.07 (d, J ) 8.6 Hz, 1H); 13C
NMR (CDCl3) δ 101.1, 125.9, 126.1, 126.3, 126.6, 126.7, 126.9,
127.27, 127.32, 128.0, 128.5, 128.6, 129.0, 131.9, 132.7, 134.5,
P r ep a r a tion of (S)-2′-Meth yl-2-p h en yl-1,1′-bin a p h th yl
(16).36 To a solution of 12 (90 mg, 0.23 mmol) and 10 mol % of
N(acac)2 (5.0 mg, 0.02 mmol) in dry THF (5.0 mL) was added
methylmagnesium iodide in diethyl ether (0.60 mL, 1.2 mmol).
The mixture was allowed to stir at 50 °C for 8 h under nitrogen
atmosphere. After being cooled to 0 °C, the reaction mixture
was quenched with saturated NH4Cl solution. It was then
diluted with CHCl3 and the organic layer was washed with
saturated NaHCO3 solution and brine, dried over anhydrous
MgSO4, and evaporated under reduced pressure. The purifica-
tion by silica gel preparative thin-layer chromatography
(hexane/ethyl acetate ) 95/5) gave 60 mg (76% yield) of (S)-
2′-methyl-2-phenyl-1,1′-binaphthyl (16): [R]20 -113 (c 1.0,
D
1
chloroform) for 16 of 95% ee; H NMR (CDCl3) δ 1.91 (s, 3H),
135.4, 137.6, 139.0, 141.1, 141.5. HRMS (FAB) calcd for C26H17
I
7.03 (m, 5H), 7.12 (d, J ) 8.6 Hz, 1H), 7.22 (m, 2H), 7.27 (t, J
) 8.6 Hz, 2H), 7.35 (ddd, J ) 8.7, 4.1, 3.6 Hz, 1H), 7.46 (ddd,
J ) 8.2, 7.1, 1.0 Hz, 1H), 7.66 (d, J ) 8.5 Hz, 1H), 7.74 (d, J
) 8.5 Hz, 1H), 7.81 (d, J ) 8.2 Hz, 1H), 7.96 (d, J ) 8.2 Hz,
1H), 8.03 (d, J ) 8.5 Hz, 1H); 13C NMR (CDCl3) δ 20.4, 124.6,
125.7, 126.0, 126.4, 126.4, 126.6, 127.36, 127.44, 127.86,
127.90, 127.93, 128.4, 128.5, 128.7, 131.6, 132.7, 132.8, 134.0,
134.5, 134.6, 139.3, 141.7.
(M)+ 456.0375, found 456.0381.
P r ep a r a tion of (S)-2-P h en yl-1,1′-bin a p h th yl-2′-bor on ic
Acid P in a col Ester (14).35 To a solution of 12 (0.11 g, 0.30
mmol) in dry THF (5.0 mL) was slowly added ethylmagnesium
bromide in diethyl ether (0.20 mL, 0.42 mmol) at 0 °C. The
resulting mixture was stirred at room temperature for 35 min
and trimethyl borate (73 mg, 0.70 mmol) was added. The
reaction mixture was allowed to stir at room temperature for
12 h under nitrogen atmosphere and all volatiles were
evaporated under reduced pressure. To the residue was added
10% HCl (10 mL) and it was then extracted with diethyl ether.
The extracts were washed with water, dried over anhydrous
Na2SO4, and evaporated under reduced pressure. The residue
was dissolved in dry toluene (50 mL) and 2,3-dimethyl-2,3-
butanediol (77 mg, 0.70 mmol) was added. The solution was
heated at 120 °C for 15 h, using a Dean-Stark trap under
nitrogen atmosphere. The solvent was removed under reduced
pressure and the concentrated residue was chromatographed
on silica gel (hexane/ethyl acetate ) 90/10) to give 61 mg (48%
yield) of (S)-2-phenyl-1,1′-binaphthyl-2′-boronic acid pinacol
ester (14) and 42 mg (45% yield) of 2-phenyl-1,1′-binaphthyl
P r ep a r a tion of (R)-2-Dip h en ylp h osp h in o-2′-eth yl-1,1′-
bin a p h th yl (17). To a solution of (R)-2-methylsufinyl-2′-ethyl-
1,1′-binaphthyl (30 mg, 0.10 mmol), obtained by methylation
of the mercapto group in (R)-2-mercapto-2′-ethyl-1,1′-binaph-
thyl (8d r ) followed by oxidation of the sulfide with mCPBA
according to the procedures described for the preparation of
12, in dry THF (3.0 mL) was slowly added ethylmagnesium
bromide in diethyl ether (0.10 mL, 0.10 mmol) at 0 °C. The
resulting mixture was stirred at room temperature for 35 min
and chlorodiphenylphosphine (40 mg, 0.20 mmol) was added.
The reaction mixture was allowed to stir at room temperature
for 12 h under nitrogen atmosphere and quenched with
saturated NH4Cl. It was then diluted with benzene and the
organic layer was washed with saturated NaHCO3 solution
and brine, dried over anhydrous MgSO4, and evaporated under
reduced pressure. The residue was purified by column chro-
matography on silica gel (hexane/ethyl acetate ) 95/5) to give
18 mg (45% yield) of (R)-2-diphenylphosphino-2′-ethyl-1,1′-
as a byproduct. [R]20 -128 (c 1.0, chloroform) for 14 of 95%
D
ee; 1H NMR (CDCl3) δ 0.75 (s, 6H), 0.95 (s, 6H), 6.97 (m, 3H),
7.19 (m, 5H), 7.40 (m, 3H), 7.59 (d, J ) 8.4 Hz, 1H), 7.79 (m,
3H), 7.91 (d, J ) 8.1 Hz, 1H), 7.99 (t, J ) 8.4 Hz, 1H); 13C
NMR (CDCl3) δ 24.0, 24.5, 83.0, 125.1, 125.6, 125.8, 126.0,
126.3, 126.5, 126.9, 127.0, 127.2, 127.3, 127.4, 127.8, 128.0,
129.3, 130.1, 132.6, 132.8, 134.1, 134.4, 136.3, 139.2, 142.3,
144.1.
binaphthyl (17): [R]20 -28 (c 0.3, chloroform) for 17 of 50%
D
ee (lit.27 [R]20 -85 (c 0.2, chloroform) for (R)-17 of >99% ee);
D
1H NMR (CDCl3) δ 0.90 (t, J ) 7.6 Hz, 3H), 2.17 (m, 2H), 6.80
(d, J ) 8.5 Hz, 1H), 6.98 (dt, J ) 7.2, 1.5 Hz, 1H), 7.02 (dt, J
) 7.2, 1.5 Hz, 2H), 7.13 (dt, J ) 7.2, 1.5 Hz, 2H), 7.23 (m, 8H),
7.30 (t, J ) 7.2 Hz, 1H), 7.47 (m, 2H), 7.51 (d, J ) 8.5 Hz,
1H), 7.84 (d, J ) 8.2 Hz, 1H), 7.87 (d, J ) 8.5 Hz, 1H), 7.88 (d,
J ) 8.2 Hz, 1H), 7.94 (d, J ) 8.5 Hz, 1H); 31P{1H} NMR (CDCl3)
δ -14.3.
P r ep a r a t ion of (S)-2-Dip h en ylp h osp h in o-2′-p h en yl-
1,1′-bin a p h th yl (15). To a solution of 12 (0.22 g, 0.55 mmol)
in dry THF (15 mL) was slowly added ethylmagnesium
bromide in diethyl ether (0.40 mL, 0.82 mmol) at 0 °C. The
resulting mixture was stirred at room temperature for 35 min
and chlorodiphenylphosphine (0.24 g, 1.1 mmol) was added.
The reaction mixture was allowed to stir at room temperature
for 12 h under nitrogen atmosphere and quenched with
saturated NH4Cl solution. It was then diluted with benzene
and the organic layer was washed with saturated NaHCO3
solution and brine. It was then dried over anhydrous MgSO4,
and evaporated under reduced pressure. The residue was
purified by column chromatography on silica gel (hexane/ethyl
acetate ) 95/5) to give 0.18 g (62% yield) of (S)-2-diphenyl-
phosphino-2′-phenyl-1,1′-binaphthyl (15) and 63 mg (35%
P r ep a r a tion of (S)-2,2′-Dim eth yl-1,1′-bin a p h th yl (18).
To a solution of (R)-8d q (68% ee, 50 mg, 0.17 mmol) and
Ni(acac)2 (13 mg, 0.05 mmol) in dry benzene (4 mL) was added
methylmagnesium iodide in Et2O (0.40 mL, 0.83 mmol) at 0
°C. The reaction mixture was allowed to stir at 80 °C for 5 h
and quenched with H2O. It was diluted with CHCl3 and the
organic layer was washed with 10% HCl, saturated NaHCO3,
and brine. The organic layer was dried over anhydrous MgSO4
and evaporated under reduce pressure. Silica gel preparative
thin-layer chromatography (hexane/ethyl acetate ) 95/5) gave
35 mg (75% yield, 70% ee) of (S)-2,2′-dimethyl-1,1′-binaphthyl
yield) of 2-phenyl-1,1′-binaphthyl as a byproduct. [R]20 -137
(18): [R]20D +36 (c 0.5, chloroform) for 18 of 70% ee (lit.2a [R]20
D
D
(c 1.0, chloroform) for 15 of 95% ee (lit.26 [R]20 +145 (c 1.0,
-37 (c 1.0, chloroform) for (R)-18 of 95% ee); 1H NMR (CDCl3)
δ 2.03 (s, 6H), 7.04 (d, J ) 8.5 Hz, 2H), 7.20 (t, J ) 8.2 Hz,
2H), 7.39 (t, J ) 8.2 Hz, 2H), 7.50 (d, J ) 8.5 Hz, 2H), 7.88 (d,
J ) 8.2 Hz, 2H), 7.90 (d, J ) 8.2 Hz, 2H).
D
chloroform) for (R)-15 of >99% ee); 1H NMR (CDCl3) δ 6.60 (t,
J ) 6.9 Hz, 2H), 6.77 (d, J ) 8.6 Hz, 1H), 6.91 (m, 4H), 6.97
(t, J ) 8.2 Hz, 1H), 7.03 (m, 5H), 7.11 (m, 3H), 7.17 (t, J ) 7.5
Hz, 1H), 7.22 (dd, J ) 8.6, 2.7 Hz, 1H), 7.33 (t, J ) 7.3 Hz,
1H), 7.35 (t, J ) 7.7 Hz, 1H), 7.43 (d, J ) 8.6 Hz, 1H), 7.49 (t,
J ) 7.7 Hz, 1H), 7.67 (d, J ) 8.6 Hz, 1H), 7.75 (d, J ) 8.6 Hz,
1H), 7.86 (d, J ) 8.1 Hz, 1H), 7.92 (d, J ) 8.1 Hz, 1H), 8.06 (d,
J ) 8.6 Hz, 1H); 31P{1H} NMR (CDCl3) δ -13.8.
P r ep a r a tion of 6-Meth ylp h en ylp h osp h in yld in a p h th o-
[2,1-b:1′,2′-d ]t h iop h en e (21). To a solution of dinaphtho-
thiophene (6d ) (400 mg, 1.4 mmol) in dry THF (40 mL) was
added a solution of tert-butyllithium in pentane (3.8 mL, 5.6
(36) Yin, J .; Rainka, M. P.; Zhang, X.-X.; Buchwald, S. L. J . Am.
Chem. Soc. 2002, 124, 1162.
(35) Schilling, B.; Kaufmann, D. E. Eur. J . Org. Chem. 1998, 701.
3822 J . Org. Chem., Vol. 69, No. 11, 2004

Asymmetric Synthesis of Axially Chiral Biaryls
mmol) at -78 °C under nitrogen atmosphere. The reaction
mixture was allowed to stir at -78 °C for 5 h and iodine (2.1
g, 8.5 mmol) was added. The mixture was stirred at room
temperature for an additional 17 h and quenched with
saturated Na2SO3. After removal of THF under reduced
pressure, the mixture was diluted with water and extracted
with ethyl acetate. The organic layer was washed with brine,
dried over anhydrous MgSO4, and evaporated under reduced
pressure to give a mixture of 6-iododinaphthothiophene (20)
(66% yield determined by 1H NMR) and 6d . This mixture was
used for the subsequent reaction without further purification.
To a solution of the Grignard reagent prepared from the
above iodide compound and magnesium (32 mg, 1.3 mmol) in
dry THF (1.3 mL) was added phenylmethylphosphinyl chlo-
ride29 (0.25 g, 1.5 mmol). The reaction mixture was allowed to
stir at 65 °C for 10 h and quenched with aqueous NH4Cl. The
resulting mixture was extracted with ethyl acetate and the
organic layer was washed with brine. The separated organic
layer was dried over anhydrous MgSO4 and evaporated under
reduced pressure. The residue was chromatographed on silica
gel (ethyl acetate only) to give 36 mg (6% yield) of 6-methyl-
phenylphosphinyldinaphthothiophene (21): 1H NMR (CDCl3
at 27 °C) δ 2.32 (d, J ) 13.3 Hz, 3H), 7.48 (m, 2H), 7.55 (m,
3H), 7.63 (m, 2H), 7.87 (m, 4H), 8.00 (d, J ) 9.4 Hz, 1H), 8.11
(d, J ) 9.4 Hz, 1H), 8.40 (d, J ) 14.2 Hz, 1H), 8.75 (d, J ) 9.4
Hz, 1H), 8.85 (d, J ) 9.4 Hz, 1H); 13C NMR (CDCl3 at 27 °C)
δ 15.9 (d, J ) 74.4 Hz), 120.6, 125.1, 125.4, 125.6 (d, J ) 100.2
Hz), 125.9, 126.0, 126.1, 127.0, 128.0, 128.8, 128.8 (d, J ) 9.4
Hz), 129.6, 129.7, 130.0, 130.8 (d, J ) 10.3 Hz), 131.1 (d, J )
10.3 Hz), 131.1 (d, J ) 4.1 Hz), 132.1, 132.2 (d, J ) 3.0 Hz),
132.4 (d, J ) 8.3 Hz), 132.9 (d, J ) 8.3 Hz), 133.1 (d, J ) 102.2
Hz), 137.5 (d, J ) 7.3 Hz), 139.8; 31P NMR (CDCl3 at 27 °C) δ
37.8; HRMS (FAB) calcd for C27H19OPS (M + H)+ 423.0973,
found 423.0974.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for the determination of absolute configurations of the
compounds 9a m , 9a n , and 19, and variable-temperature 31P
NMR spectra of 21. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O035880P
J . Org. Chem, Vol. 69, No. 11, 2004 3823