C O MMU N I C A T I O N S
Table 2. Catalyzed Aryl Transfer from 5 to Benzaldehyde (4f)a
Acknowledgment. The Deutsche Forschungsgemeinschaft within
the SFB 380 and the Fonds der Chemischen Industrie are gratefully
acknowledged for financial support. We thank Witco for the
donation of diethyl zinc and N. Hermanns, S. Dahmen, and T.
Focken for helpful discussions.
entry
ArB(ÃH)2 with Ar )
product
% yieldb
%eec,d
Supporting Information Available: Separation conditions of the
diarylmethanols on chiral HPLC system. This material is available free
1
2
3
4
5
6
7
8
9
4-chlorophenyl (5b)
4-biphenyl (5c)
1a
1b
1c
1e
1f
1g
1h
1i
89
75
87
77
<5
84
56
54
94
95 (S)
65
89
45
n.d.
80
31
73
80
4-methylphenyl (5d)
2-methoxyphenyl (5e)
2,6-dimethylphenyl (5f)
4-methoxyphenyl (5g)
1-naphthyl (5h)
References
(1) (a) Meguro, K.; Aizawa, M.; Sohda, T.; Kawamatsu, Y.; Nagaoka, A.
Chem. Pharm. Bull. 1985, 33, 3787. (b) Toda, F.; Tanaka, K.; Koshiro,
K. Tetrahedron: Asymmetry 1991, 2, 873. (c) Stanev, S.; Rakovska, R.;
Berova, N.; Snatzke, G. Tetrahedron: Asymmetry 1995, 6, 183. (d) Botta,
M.; Summa, V.; Corelli, F.; Pietro, G. Di; Lombardi, P. Tetrahedron:
Asymmetry 1996, 7, 1263.
2-bromophenyl (5i)
4-bromophenyl (5j)
1j
(2) (a) Ohkuma, T.; Koizumi, M.; Ikehira, H.; Yokozawa, T.; Noyori, R. Org.
Lett. 2000, 2, 659. (b) Corey, E. J.; Helal, C. J. Tetrahedron Lett. 1995,
36, 9153. (c) Corey, E. J.; Helal, C. J. Tetrahedron Lett. 1996, 37, 4837.
(3) (a) Soai, K.; Kawase, Y.; Oshio, A. J. Chem. Soc., Perkin Trans. 1 1991,
1613. (b) Soai, K.; Niwa, S. Chem. ReV. 1992, 92, 833. (c) For a
diastereoselective version, see: Hu¨bscher, J.; Barner, R. HelV. Chim. Acta
1990, 73, 1068.
a-c See Table 1. d Comparison of the HPLC peak elution order of 1a
with known data revealed that the S enantiomer was formed in excess.
Assuming an analogous mechanism for the aryl transfer and based on the
HPLC elution order, we assume that the other products have S configuration
as well.
(4) (a) Dosa, P. I.; Ruble, J. C.; Fu, G. C. J. Org. Chem. 1997, 62, 444. (b)
Huang, W.-S.; Hu, Q.-S.; Pu, L. J. Org. Chem. 1999, 64, 7940. (c) Huang,
W.-S.; Pu, L. Tetrahedron Lett. 2000, 41, 145. (d) Blacker, J. In Third
International Conference on the Scale Up of Chemical Processes,
Conference Proceedings, Laird, T., Ed.; Scientific Update: UK, 1998; p
74.
Table 3. Catalyzed Aryl Transfer from 5 to Aldehydes (4) in the
Presence of DiMPEGa
(5) (a) Bolm, C.; Mun˜iz, K. Chem. Commun. 1999, 1295. (b) Bolm, C.;
Hermanns, N.; Hildebrand, J. P.; Mun˜iz, K. Angew. Chem., Int Ed. 2000,
39, 3465. (c) Bolm, C.; Kesselgruber, M.; Hermanns, N.; Hildebrand, J.
P. Angew. Chem., Int. Ed. 2001, 39, 1488. (d) Bolm, C.; Kesselgruber,
M.; Grenz, A.; Hermanns, N.; Hildebrand, J. P. New J. Chem. 2001, 25,
13. (e) Bolm, C.; Hermanns, N.; Kesselgruber, M.; Hildebrand, J. P. J.
Organomet. Chem. 2001, 624, 157. (f) For a recent review on catalyzed
asymmetric arylation reactions, see: Bolm, C.; Hildebrand, J. P.; Mun˜iz,
K.; Hermanns, N. Angew. Chem., Int. Ed. 2001, 40, 3284.
(6) (a) Ueda, M.; Miyaura, N. J. Org. Chem. 2000, 65, 4450. (b) Fu¨rstner,
A.; Krause, H. AdV. Synth. Catal. 2001, 343, 343.
(7) Oi, S.; Moro, M.; Inoue, V. Chem. Commun. 1997, 1621.
(8) (a) Oi, S.; Moro, M.; Inoue, Y. Organometallics 2001, 20, 1036. (b)
Murata, M. Shimazaki, R.; Ishikura, M.; Watanabe, S.; Masuda, Y.
Synthesis 2002, 717.
(9) For an enantioselective Rh-catalyzed aryl transfer reaction using phenyl-
boronic acid as aryl source (41% ee), see: Sakai, M.; Ueda, M.; Miyaura,
N. Angew. Chem., Int. Ed. 1998, 37, 3279.
(10) Presumably, the Lewis-acidic achiral metal salts, which are formed during
the transmetalation, catalyze the aryl transfer as well and afford racemic
products. By this parallel reaction the overall enantioselectivity of the
process is reduced.
entry
ArB(ÃH)2 with Ar )
phenyl (5a)
4-chlorophenyl (5b)
4-biphenyl (5c)
4-methylphenyl (5d)
4-methoxyphenyl (5g)
1-naphthyl (5h)
2-bromophenyl (5i)
4-bromophenyl (5j)
phenyl (5a)
Ar′CHO
product
% yieldb
%eec
1
2
3
4
5
6
7
8
9
4a
4f
4f
4f
4f
4f
4f
4f
4d
1a
1a
1b
1c
1g
1h
1i
93
61
75
91
86
91
58
48
85
97 (R)
97 (S)
97
96
90
85
88
96
98
1j
1d
a In toluene, 10 mol % of 2, 10 mol % of DiMPEG, 7.2 equiv of ZnEt2,
and 2.4 equiv of ArB(OH)2 with respect to Ar′CHO. b,c See Table 1.
could lead to a significant increase in enantioselectivity at low
catalyst loading,15 we decided to investigate the influence of such
modifiers in this new protocol as well. Gratisfyingly, this improved
the process even further. Thus, by the addition of 10 mol % of
DiMPEG (M ) 2000 g‚mol-1) to the reaction mixture, higher ee
values were achieved for a wide range of substrates (Table 3).
In particular, arylboronic acids, which previously gave unsatisfy-
ing results, showed a strong effect. For example, the aryl transfer
starting from 1-naphthylboronic acid (5h) and benzaldehyde (1f)
now afforded 1h in 91% yield having 85% ee (Table 3, entry 6).
In the absence of the polyether, this reaction gave 1h in only 56%
yield and 31% ee (Table 2, entry 7).
In summary, we developed a flexible method for the catalyzed
synthesis of optically active diarylmethanols with very high
enantiomeric excesses from readily available starting materials.
Noteworthy is the fact that with a single catalyst both enantiomers
of the product are accessible simply by choosing the appropriate
combination of arylboronic acid or aldehyde as aryl donor and
acceptor, respectively.
(11) (a) Ishiyama, T.; Murata, M.; Miyaura, N. J. Org. Chem. 1995, 60, 7508.
(b) Ishiyama, T.; Itoh, Y.; Kitano, T.; Miyaura, N. Tetrahedron Lett. 1997,
38, 3447. (c) Murata, M.; Watanabe, S.; Masuda, Y. J. Org. Chem. 1997,
62, 6458. (d) Murata, M.; Oyama, T.; Watanabe, S.; Masuda, Y. J. Org.
Chem. 2000, 65, 164. (e) Baidoin, O.; Gue´nard, D.; Gue´ritte, F. J. Org.
Chem. 2000, 65, 9268.
(12) For recent developments in this area, see: Li, W.; Nelson, D. P.; Jensen,
M. S.; Hoerrner, S.; Cai, D.; Larsen, R. D.; Reider, P. J. J. Org. Chem.
2002, 67, 5394 and references therein.
(13) For B-to-Zn exchange reactions involving alkenylboranes, see: (a) Srebnik,
M. Tetrahedron Lett. 1991, 32, 2449. (b) Oppolzer, W.; Radinov, R. N.
HelV. Chim. Acta 1992, 75, 170. (c) Oppolzer, W.; Radinov, R. N. J. Am.
Chem. Soc. 1993, 115, 1593. (d) Langer, F.; Schwink, L.; Devasagayaraj,
A.; Chavant, P.-Y.; Knochel, P. J. Org. Chem. 1996, 61, 8229. (e) Boudier,
A.; Bromm, L. O.; Lotz, M.; Knochel, P. Angew. Chem., Int. Ed. 2000,
39, 4414. (f) Dahmen, S.; Bra¨se, S. Org. Lett. 2001, 3, 4119.
(14) A toluene solution (3 mL) of the boronic acid (2.4 equiv) is mixed with
neat diethylzinc (7.2 equiv) in a sealed vessel under argon atmosphere.
After 12 h of stirring at 60 °C, the vessel is cooled to 10 °C and a toluene
solution of ferrocene 2 (10 mol %) is added. The mixture is stirred for
additional 15 min and the aldehyde (1 equiv) is subsequently added. After
stirring overnight followed by standard workup as described earlier,5 the
diarylmethanols are obtained in analytically pure form after column
chromatography (silica gel, pentane:diethyl ether ) 85:15).
(15) Bolm, C.; Hermanns, N.; Rudolph, J., manuscript in preparation.
JA028518L
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J. AM. CHEM. SOC. VOL. 124, NO. 50, 2002 14851