J. Am. Chem. Soc. 1999, 121, 8943-8944
8943
Scheme 1
Asymmetric Coupling of Phenols with Arylleads
Susumu Saito, Taichi Kano, Hiroo Muto,
Masakazu Nakadai, and Hisashi Yamamoto*
Graduate School of Engineering, Nagoya UniVersity
CREST, Japan Science and Technology Corporation (JST)
Chikusa, Nagoya 464-8603, Japan
ReceiVed March 1, 1999
The optically pure biaryl axis has been the subject of increasing
interest, due to its role as a pivotal element in a rapidly growing
number of not only pharmacologically potent natural products1
but also chiral metal catalysts2 and artificial helical polymers.3
Despite a broad spectrum of classical4 and modern5 procedures
for the chemical connection of aromatic moieties, the development
of efficient aryl-coupling methods that enable the directed
construction of even highly sterically demanding bi- and polyaryls
in optically active form6 has become of great importance. We
report here the first example of the diastereo- and enantioselective
direct coupling of aryllead compounds with phenol derivatives.
Pinhey suggested that the coupling reaction of phenols with
aryllead triacetates7 is facilitated by the participation of excess
pyridine (ca. 10 equiv) or analogous bases in CHCl3.8 Thereafter,
Barton carefully optimized the reaction conditions, particularly
for the use of aryllead compounds which incorporate electron-
rich aryl groups.9 Our initial plan was guided by a reconsideration
of an alternative base additive which could open the way to the
future discovery of a chiral analogue, with a goal of the efficient
asymmetric synthesis. Since 2,6-bis(2-isopropylphenyl)-3,5-dim-
ethylphenol (3a)10 has been demonstrated to be an effective chiral
auxiliary in the diastereoselective aldol reaction of the corre-
sponding chiral acetate,10a we first investigated the synthetic
efficiency of 3a with several different bases (toluene, room
temperature, 2 h) (Scheme 1). The rate-enhancing effect was most
prominent with at least 3 equiv of 1,4-diazabicyclo[2.2.2]octane
(DABCO) or quinuclidine (3a, 80% and 95%, respectively) but
less efficient with primary amines (i-PrNH2, 3a, 75%; 4, 7%).
An attempt to use other tertiary amines, including NEt3 and i-Pr2-
NEt (4, 11% and 10%, respectively), and secondary (i-Pr2NH; 4:
31%) as well as bidentate amines (trans-1,2-diphenyldiamino-
ethane and trans-1,2-diaminocyclohexane; 4, 7% and 5% yield,
Table 1. Asymmetric Coupling of 1a with 2a in the Presence of
Chiral Basea
yield
(%)b
ee
yield
(%)b
ee
entry base
(%)c entry
base
(%)c
1
2
3
4
5
6
7
8
16d
8d
0
10
4
5
6
7
9
3d
32e
92e
0
20
40
strychnine
brucine
14d
2d
4
a Reactions were carried out using 2a (2.5 equiv), 1 (1 equiv), and
a base (3 equiv) in toluene at room temperature for 3 h. b Unless
otherwise specified, of isolated, purified dicoupling product 3a.
c Determined by HPLC analysis. d Of isolated, purified monocoupling
product 4. e The ratio of dl and meso products ) >99:<1.
(1) Evans, D. A.; Wood, M. R.; Trotter, W.; Richardson, T. I.; Barrow, J.
C.; Katz, J. L. Angew. Chem., Int. Ed. Engl. 1998, 37, 2700. (b) Nicolaou, K.
C.; Natarajan, S.; Li, H.; Jain, N. F.; Hughes, R.; Solomon, M. E.; Ramanjulu,
J. M.; Boddy, C. N. C.; Takayanagi, M. Angew. Chem., Int. Ed. Engl. 1998,
37, 2708. (c) Meyers, A. I.; Willemsen, J. J. Chem. Commun. 1997, 1673. (d)
Chau, P.; Czuba, I. R.; Rizzacasa, Bringmann, G.; Gulden, K.-P.; Scha¨ffer,
M. J. Org. Chem. 1996, 61, 7101.
respectively) proved totally fruitless. This process using DABCO
or quinuclidine exhibited high dl-selectivity (>99% de); in
comparison, Suzuki coupling was carried out and gave consis-
tently lower dl-selectivities as well as lower chemical yields.11,12
On the basis of the structural features of quinuclidine, we next
elucidated the potential for an asymmetric version of this process
using optically active bases (Table 1). We found that brucine was
essential to achieve rate enhancement in addition to high
diastereoselectivity. Moreover, we obtained the best enantiomeric
excess (ee) so far (40% ee).13 The participation of even a small
amount of H2O retarded the rate, as exemplified by the use of
brucine hydrate. Protocols which used toluene were preferable,
although the use of other solvents also gave reasonable yields
(2) (a) Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds. ComprehensiVe
Asymmetric Catalysis; Springer-Verlag: Berlin Heidelberg, in press. (b)
Noyori, R., Ed. Asymmetric Catalysis in Organic Synthesis; John Wiley &
Sons: New York, 1994.
(3) See ref 7 in Supporting Information.
(4) (a) Tamao, K.; Sumitani, K.; Kiso, Y.; Zembayashi, N.; Fujioka, A.;
Kodama, S.; Nakajima, I.; Minato, A.; Kumada, M. Bull. Chem. Soc. Jpn.
1976, 49, 1958. (b) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508.
(5) See ref 8 in Supporting Information.
(6) See ref 9 in Supporting Information.
(7) (a) Bell, H. C.; Kalman, J. R.; Pinhey, J. T. Aust. J. Chem. 1979, 32,
1521. (b) Kozyrod, R. P.; Morgan, J.; Pinhey, J. T. Aust. J. Chem. 1985, 38,
1147. For the preparation of aryllead compounds 2a-d, see: (c) Morgan, J.;
Pinhey, J. T. J. Chem. Soc., Perkin Trans. 1 1990, 715.
(8) (a) Bell, H. C.; Pinhey, J. T.; Sternhell, S. Aust. J. Chem. 1979, 32,
1551. (b) Pinhey, J. T. Aust. J. Chem. 1991, 44, 1353. (c) Pinhey, J. T. Pure
Appl. Chem. 1996, 68, 819.
(11) 2,6-Dibromo-3,5-dimethylanisole (17) and boronic acids 18a-c were
subjected to Suzuki coupling to give the corresponding terphenyl adducts
19a-c with moderate yields and diastereoselectivities. See Supporting
Information and also ref 10b.
(9) Barton, D. H. R.; Donnelly, D. M. X.; Guiry, P. J.; Finet, J.-P. J. Chem.
Soc., Perkin Trans. 1 1994, 2921.
(12) The diastereoselectivity (dl:meso) was unambiguously ascertained by
(10) (a) Saito, S.; Hatanaka, K.; Kano, T.; Yamamoto, H. Angew. Chem.,
Int. Ed. Engl. 1998, 37, 3378. For preliminary preparation of 3a,b, see: (b)
Saito, S.; Kano, T.; Hatanaka, K.; Yamamoto, H. J. Org. Chem. 1997, 62,
5651.
1H NMR and HPLC analysis. See ref 10b.
(13) The ee % of each adduct was determined by chiral HPLC analysis.
The rather low yield by slow reaction with strychnine is probably due to its
insolubility in toluene.
10.1021/ja990646v CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/10/1999