C2-symmetric bicyclo[3.3.1]nonadiene as a chiral ligand for rhodium-catalyzed asymmetric arylation of N-(4-nitrobenzenesulfonyl)arylimines

Article abstract of DOI:10.1021/ol0476063

(Chemical Equation Presented) Asymmetric synthesis of diarylmethylamines with high enantioselectivity (95-99percent ee) was realized by use of a new C ₂-symmetric diene ligand, (1R,5R)-2,6-diphenylbicyclo[3.3.1]nona-2,6- diene (Ph-bnd*), for th

Full text of DOI:10.1021/ol0476063

ORGANIC
LETTERS
2005
Vol. 7, No. 2
307-310
C2-Symmetric Bicyclo[3.3.1]nonadiene as
a Chiral Ligand for Rhodium-Catalyzed
Asymmetric Arylation of
N-(4-Nitrobenzenesulfonyl)arylimines
Yusuke Otomaru, Norihito Tokunaga, Ryo Shintani, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity,
Sakyo, Kyoto 606-8502, Japan
thayashi@kuchem.kyoto-u.ac.jp
Received November 22, 2004
ABSTRACT
Asymmetric synthesis of diarylmethylamines with high enantioselectivity (95−99% ee) was realized by use of a new C2-symmetric diene ligand,
(1R,5R)-2,6-diphenylbicyclo[3.3.1]nona-2,6-diene (Ph-bnd*), for the rhodium-catalyzed asymmetric arylation of N-(4-nitrobenzenesulfonyl)arylimines
with arylboroxines.
One of the recent topics in the field of asymmetric catalysis
is the development of chiral diene ligands, which have been
demonstrated to have advantages over other types of chiral
ligands containing phosphorus and/or nitrogen atoms in some
asymmetric reactions catalyzed by transition metal com-
plexes.1 The C2-symmetric dienes based on a bicyclo[2.2.1]-
heptadiene backbone (nbd*), which we have reported in
2003,2 are highly enantioselective chiral ligands for rhodium-
catalyzed asymmetric addition of organoboronic acids to R,â-
unsaturated ketones2 and fumaric and maleic compounds.3
Carreira reported the preparation of several types of C1-
symmetric bicyclo[2.2.2]octadienes and their successful use
for iridium-catalyzed kinetic resolution of allyl carbonates4
and the rhodium-catalyzed asymmetric 1,4-addition.5 Very
recently, we reported6 (R,R)-2,5-diphenylbicyclo[2.2.2]octa-
2,5-diene (Ph-bod*) as a new type of C2-symmetric chiral
diene ligand and its application to rhodium-catalyzed asym-
metric arylation of N-tosylarylimines with arylboroxines
giving diarylmethylamines,7,8 where high enantioselectivity
(95-99% ee) was observed for a variety of substitution
patterns on the aryl groups. One drawback in this report6 is
(5) Defieber, C.; Paquin, J.-F.; Serna, S.; Carreira, E. M. Org. Lett. 2004,
6, 3873.
(6) Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani,
R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584.
(7) Other reports on the catalytic enantioselective arylation of arylimines
giving enantiomerically enriched diarylmethylamines: (a) Hayashi, T.;
Ishigedani, M. J. Am. Chem. Soc. 2000, 122, 976. (b) Hermanns, N.;
Dahmen, S.; Bolm, C.; Bra¨se, S. Angew. Chem., Int. Ed. 2002, 41, 3692.
(c) Kuriyama, M.; Soeta, T.; Hao, X.; Chen, Q.; Tomioka, K. J. Am. Chem.
Soc. 2004, 126, 8128. (d) Hayashi, T.; Kawai, M.; Tokunaga, N. Angew.
Chem., Int. Ed. 2004, 43, 6125.
(1) For a short review: Glorius, F. Angew. Chem., Int. Ed. 2004, 43,
3364.
(2) Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem.
Soc. 2003, 125, 11508.
(3) Shintani, R.; Ueyama, K.; Yamada, I.; Hayashi, T. Org. Lett. 2004,
6, 3425.
(4) Fischer, C.; Defieber, C.; Suzuki, T.; Carreira, E. M. J. Am. Chem.
Soc. 2004, 126, 1628.
(8) Rhodium-catalyzed arylation of N-tosylimines with arylboron reagents
was first reported by Miyaura: (a) Ueda, M.; Miyaura, N. J. Organomet.
Chem. 2000, 595, 31. (b) Ueda, M.; Saito, A.; Miyaura, N. Synlett 2000,
1637.
10.1021/ol0476063 CCC: $30.25
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Published on Web 12/22/2004

the difficulty in removing the tosyl group from nitrogen on
the diarylmethylamines. Thus, reductive deprotection of
phenyl(4-chlorophenyl)methylamine tosylamide with, for
example, Li/NH3 or SmI2/HMPA resulted in the formation
of a significant amount of diphenylmethylamine.6,9 It is
anticipated that the use of a 4-nitrobenzenesulfonyl group10
in place of a tosyl group makes the deprotection much easier.
Unfortunately, however, the enantioselectivity of the asym-
metric arylation catalyzed by the rhodium/(R,R)-Ph-bod*
complex was significantly lower for N-4-nitrobenzene-
sulfonylimines, as exemplified by the phenylation of the
sulfonylimines of 4-chlorobenzaldehyde where the enantio-
selectivitywas98and89%eefortosylimineand4-nitrobenzene-
sulfonylimine, respectively (Scheme 1) (vide infra). Here we
Scheme 3. Rhodium-Catalyzed Asymmetric Arylation of
Imines 3 with Arylboroxines 4
Scheme 1. Asymmetric Phenylation Catalyzed by Rhodium/
Ph-bod*
report a new C2-symmetric chiral diene, 2,6-diphenylbicyclo-
[3.3.1]nona-2,6-diene (Ph-bnd*), which is a chiral ligand
suitable for the rhodium-catalyzed asymmetric arylation of
N-4-nitrobenzenesulfonylimines.
Scheme 2 shows the synthetic pathway to the 2,6-
diphenylbicyclo[3.3.1]nona-2,6-diene (Ph-bnd*). Racemic
Scheme 2. Preparation of Ph-bnd* (2)
with a phenylcerium reagent generated from phenyllithium
and cerium trichloride in THF followed by dehydration of
the resulting diol with phosphoryl chloride and pyridine to
give 95% yield of racemic 2,6-diphenylbicyclo[3.3.1]nona-
2,6-diene (Ph-bnd* 2). Resolution of dl-2 was efficiently
carried out by use of a chiral stationary phase column
(Chiralcel OJ) to give both enantiomers, (+)-Ph-bnd* (2)
and (-)-Ph-bnd* (2).12 The absolute configuration of the (+)-
isomer was assigned to be (R,R)- by consideration of the
stereochemical reaction pathway in the catalytic asymmetric
arylation shown in Schemes 3 (vide infra). Treatment of
(R,R)-(+)-Ph-bnd* (2) with [RhCl(C2H4)2]2 in benzene at 50
°C for 12 h gave 87% yield of the diene-rhodium complex
[RhCl((R,R)-Ph-bnd* (2))]2.13
diketone, bicyclo[3.3.1]nonane-2,6-dione (1), prepared ac-
cording to the procedures reported by Schaefer,11 was treated
(9) Loss of chloride was also observed during the reductive removal of
2,4,6-triisopropylbenzenesulfonyl group with SmI2/HMPA: see ref 7d.
(10) (a) Fukuyama, T.; Jow, C.-K.; Cheung, M. Tetrahedron Lett. 1995,
36, 6373. (b) Kan, T.; Fukuyama, T. Chem. Commun. 2004, 353. (c) Greene,
T. W.; Wuts, P. G. M. ProtectiVe Groups in Organic Synthesis, 3rd ed.;
Wiley: New York, 1999; p 609.
(11) Schaefer, J. P.; Honig, L. M. J. Org. Chem. 1968, 33, 2655. See
also: Meerwein, H.; Schu¨rmann, W. Justus Liebigs Ann. Chem. 1913, 398,
196.
(12) R,R)-(+)-Ph-bnd*: [R]20 +39 (c 0.58, CHCl3).
D
308
Org. Lett., Vol. 7, No. 2, 2005

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
309

tions have been unambiguously determined, gave the phen-
ylation product 5am of (S)-configuration. The similarity in
the structure of these dienes supports the assignment of the
absolute configuration of diene 2. The coordination of imine
3 with its si-face to the rhodium bearing (R,R)-Ph-bnd* (2)
as a chiral ligand is much more favorable than the coordina-
tion with its re-face because of the steric repulsions shown
in Scheme 4. The si-face coordination will lead to the
phenylation products of (S)-configuration.
The 4-nitrobenzenesulfonyl group was readily removed
from diarylmethylamines 5 without racemization or any side
reactions in high yields. Thus, for example, treatment of the
4-nitrobenzenesulfonamide 5am with benzenethiol and
potassium carbonate in DMF10 gave 96% yield of free amine
(S)-phenyl(4-chlorophenyl)methylamine (6a) (Scheme 5).
The deprotection of 5bm, which contains bromide on the
phenyl ring, was also successful to give the corresponding
free amine (S)-6a in 96% yield.
In summary, high enantioselectivity and high catalytic
activity were observed in the rhodium-catalyzed asymmetric
arylation of N-4-nitrobenzenesulfonylimines with aryl-
boroxines by use of a C2-symmetric new diene ligand, 2,6-
diphenylbicyclo[3.3.1]nona-2,6-diene (Ph-bnd*), to give high
yields of diarylmethylamines with 95-99% ee.
Acknowledgment. This work has been supported in part
by a Grant-in-Aid for Scientific Research, the Ministry of
Education, Culture, Sports, Science and Technology, Japan
(21 COE on Kyoto University Alliance for Chemistry). N.T.
thanks the Japan Society for the Promotion of Science for
the award of a fellowship for graduate students.
Scheme 5. Deprotection of 4-Nitrobenzenesulfonyl Group
Supporting Information Available: Experimental pro-
cedures and spectroscopic and analytical data for the
substrates and products. This material is available free of
charge via the Internet at http://pubs.acs.org.
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Org. Lett., Vol. 7, No. 2, 2005