Scheme 4. Stereochemical Pathway of the Asymmetric
Table 1. Rhodium-Catalyzed Asymmetric Arylation of Imines
3 with Arylboroxines 4a
Arylation
yield (%)b % eec
imine boroxine
of
amine
of
entry
3
4
ligand
(R)-binap
(R)-segphos
(S)-p-phos
amined
1
2
3
4
5
6
7
8
9
3a
3a
3a
3a
3a
3a
3a
3a
3b
3c
3d
3e
3f
3g
3h
3h
3h
3h
3b
4m
4m
4m
4m
4m
4m
4m
4m
4m
4m
4m
4m
4m
4m
4n
15 (5am) 34 (S)
<5 (5am)
15 (5am) 49 (R)
(S)-phosphoramidite 68 (5am) 23 (S)
(R,R)-Bn-nbd*
(R,R)-Bn-bod*
(R,R)-Ph-bod*
88 (5am) 81 (S)
99 (5am) 70 (S)
96 (5am) 89 (S)
96 (5am) 98 (S)
98 (5bm) 98 (S)
98 (5cm) 99 (S)
95 (5dm) 95 (S)
95 (5em) 98 (S)
94 (5fm) 96 (S)
99 (5gm) 95 (S)
96 (5hn)f 99 (R)
94 (5ho)f 98 (R)
99 (5hp)f 99 (R)
98 (5hq) 99 (R)
99 (5bp) 98 (R)
(R,R)-Ph-bnd* (2)
(R,R)-Ph-bnd* (2)
(R,R)-Ph-bnd* (2)
(R,R)-Ph-bnd* (2)
(R,R)-Ph-bnd* (2)
(R,R)-Ph-bnd* (2)
(R,R)-Ph-bnd* (2)
(R,R)-Ph-bnd* (2)
(R,R)-Ph-bnd* (2)
(R,R)-Ph-bnd* (2)
(R,R)-Ph-bnd* (2)
(R,R)-Ph-bnd* (2)
10
11
12
13e
14e
15
16g
17
18h
19
4o
4p
4q
4p
addition to electron-deficient olefins.20 (2) The rhodium
complexes of the diene ligands are catalytically much more
active than those of the phosphorus ligands for the addition
of phenylboroxine (4m) to the N-4-nitrobenzenesulfon-
ylimine of 4-chlorobenzaldehyde 3a, the yields of the
phenylation product 5am all being higher than 95% with
the diene ligands (entries 5-8). (3) Of the diene ligands,
Ph-bnd* (2) is most enantioselective, giving (S)-5am with
98% ee (entry 8). (4) The additions of phenylboroxine (4m)
to imines substituted with 4-bromo (3b), 4-methoxy (3c),
4-carbomethoxy (3d), and 2-methyl (3e) all proceeded with
high enantioselectivity to give the corresponding N-sulfon-
ylphenyl(aryl)methylamines with high (95-99% ee) enan-
tioselectivity (entries 9-12). High enantioselectivity (95-
96% ee) was also observed in the phenylation of imines 3f
and 3g, which were derived from 1-naphthaldehyde and
2-thiophenecarboxaldehyde, respectively (entries 13 and 14).
(5) The asymmetric arylation of benzaldehyde imine 3h with
substituted phenyl groups was also successful using aryl-
boroxines containing 4-chloro (4n), 4-methoxy (4o), 3-meth-
oxy (4p), and 2-methyl (4q) groups (entries 15-18). The
arylation products 5hn, 5ho, and 5hp obtained here are the
enantiomers of 5am, 5cm, and 5em, respectively, which were
obtained by the asymmetric phenylation using phenyl-
boroxine (4m).
a Reaction was carried out in dioxane at 60 °C for 6 h with 1.2 equiv of
boroxine 4 in the presence of 20 mol % KOH, 1 equiv (with respect to
boron) of H2O, and 3 mol % (Rh) of [RhCl((R,R)-Ph-bnd*(2))]2 or a catalyst
generated from [RhCl(C2H4)2]2 and a chiral ligand. b Isolated yields by
column chromatography on silica gel (hexane/ethyl acetate ) 2/1).
c Determined by HPLC analysis with a chiral stationary phase column
(Chiralcel OD-H: hexane/2-propanol ) 4/1 for 5am, 5bm, 5em, 5hn, and
5hp; hexane/2-propanol ) 2/1 for 5cm, 5fm, 5gm, 5ho, 5hq, and 5bp;
hexane/2-propanol ) 1/1 for 5dm.). d Absolute configuration of 5am was
determined by conversion into known free amine (S)-phenyl(4-chloro-
phenyl)methylamine. The configurations of other amines were assigned by
consideration of the stereochemical reaction pathway. e With 6 mol %
catalyst, 2.4 equiv of 4m, and 40 mol % KOH for 12 h. f Products 5hn,
5ho, and 5hp are enantiomers of 5am, 5cm, and 5em, respectively. g With
1.8 equiv of 4o for 9 h. h With 2.4 equiv of 4q for 12 h.
The results obtained for the asymmetric arylation of N-4-
nitrobenzenesulfonylimines 314 with arylboroxines 4 in the
presence of [RhCl((R,R)-Ph-bnd* (2))]2 (3 mol % Rh) and
aqueous potassium hydroxide in dioxane (Scheme 3) are
summarized in Table 1, which also contains the data obtained
with other chiral diene and chiral phosphorus ligands for
comparison. Table 1 contains the following significant
features. (1) Catalytic activity and enantioselectivity in the
present arylation are very low with chiral phosphorus
ligands,15 binap,16 segphos,17 p-phos,18 and a phosphoramid-
ite19 (entries 1-4), all of which have been reported to be
highly effective for the rhodium-catalyzed asymmetric 1,4-
The (S)-configuration of the arylation product 5am
obtained with (+)-Ph-bnd* (2) indicates that the absolute
configuration of (+)-2 is (R,R). Thus, the dienes, (R,R)-Bn-
nbd*, (R,R)-Bn-bod*, and (R,R)-Ph-bod*, whose configura-
(13) 1H NMR (CDCl3): δ 1.28 (s, 4H), 2.24 (s, 4H), 2.29 (d, J ) 15.1
Hz, 4H), 3.50 (dt, J ) 15.1 and 3.7 Hz, 4H), 4.70 (d, J ) 2.9 Hz, 4H),
7.22-7.29 (m, 12H), 7.50 (d, J ) 7.2 Hz, 8H). 13C{1H} NMR (CDCl3): δ
32.94, 34.61, 41.47, 72.68 (d, J ) 11.4 Hz), 86.22 (d, J ) 14.5 Hz), 126.54,
126.64, 127.77, 144.77 (d, J ) 2.1 Hz).
(14) Prepared from aromatic aldehydes and 4-nitrobenzenesulfonamide
in the presence of tetraethoxysilane: Love, B. E.; Raje, P. S.; Williams II,
T. C. Synlett 1994, 493.
(18) Shi, Q.; Xu, L.; Li, X.; Jia, X.; Wang, R.; Au-Yeng, T. T.-L.; Chan,
A. S. C.; Hayashi, T.; Cao, R.; Hong, M. Tetrahedron Lett. 2003, 44, 6505.
(19) Boiteau, J.-G.; Minnaard, A. J.; Feringa, B. L. J. Org. Chem. 2003,
68, 9481.
(15) Low efficiency of the chiral phosphorus ligands has been also
observed in the arylation of N-tosylimines: see ref 6.
(16) Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayashi,
H.; Taketomi, T.; Akutagawa, S.; Noyori, R. J. Org. Chem. 1986, 51, 629.
(17) Saito, T.; Yokozawa, T.; Ishizaki, T.; Moroi, T.; Sayo, N.; Miura,
T.; Kumobayashi, H. AdV. Synth. Catal. 2001, 343, 264.
(20) For reviews: (a) Hayashi, T.; Yamasaki, K. Chem. ReV. 2003, 103,
2829. (b) Fagnou, K.; Lautens, M. Chem. ReV. 2003, 103, 169. (c) Bolm,
C.; Hildebrand, J. P.; Muniz, K.; Hermanns, N. Angew. Chem., Int. Ed.
2001, 40, 3284.
Org. Lett., Vol. 7, No. 2, 2005
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