decrease in the enantioselectivity was observed, the reaction
with bistrisylamide of cyclopentane-1,2-diamine 1f also pro-
ceeded enantioselectively (71% ee) to give the N-monoal-
lylated product 2f in a good yield (85%). In the reaction of
1,2-diphenylethylenediamine derivative 1g, similar to the
case of 1e, the product 2g was obtained with high enantio-
selectivity (90% ee, 63% yield). In the reactions of 1e-g, a
very small amount of bisallylated trisylamide was observed
as a side product (less than 3% yield).
Scheme 4
Unfortunately, under the same conditions, N-monoallyla-
tion of 1,3-bistrisylamide derivatives 1h,i proceeded with
poor enantioselectivity (18% ee and 27% ee) to give the
products 2h,i (53% and 69% yield, Scheme 2).
As an application of the present reaction, we next
attempted conversion of the desymmetrization product to a
known medicinal agent (Scheme 3). Two trisyl groups of
diamine bistrisylamide 1j with 0.6 equiv of allyl acetate gave
N-monoallylated product in 58% yield together with recovery
of 1j (37%). The ee of recovered 1j was estimated to be
92%, which indicates an s value ) 15.8. Moreover, the major
enantiomer of 1j (92% ee) was confirmed as the (1R,2R)-
isomer by comparison with the authentic sample prepared
through bistrisylation of (1R,2R)-1,2-diaminocyclohexane
(commercially available).13
Scheme 3
In conclusion, we have succeeded in the development of
new synthetic methodology for optically active vicinal di-
amine derivatives through enantioselective N-monoallylation
with a chiral π-allyl-Pd catalyst. The present reaction is the
first example of asymmetric desymmetrization of meso-di-
amine derivatives through catalytic asymmetric reaction,
which provides a new promising method for synthesis of
chiral vicinal diamines. In addition, in the reaction of a ni-
trogen nucleophile with a chiral π-allyl-Pd complex, although
asymmetric induction at the allylic reagent site is well-
known,7,14 that at the nitrogen nucleophile site has not thus
far been reported except for the synthesis of atropisomeric
anilides recently reported by us and Curran group.15 Thus,
the present reaction should provide a new prototype in the
field of chiral π-allyl-Pd chemistry.
Supporting Information Available: Experimental pro-
cedures and characterization data for compounds 1a-j,
2a,c-i, and 4-6 and a reaction scheme for the determination
of the absolute configuration of 2a,d,g. This material is
2e were removed by Birch reduction,10 and the obtained
diamine 3 was subsequently converted to (3,4-dichloro-
phenyl)acetamide 4. Acylation of 3 with the phenylacetyl
chloride at rt proceeded regioselectively at the primary amino
group without the formation of the regioisomer and bisacyl
derivative. The N-allylation of 4, followed by the ring-closing
metathesis using the Grubbs catalyst and the hydrogenation
using the Lindlar catalyst, gave pyrrolidinylcyclohexylamide
6 which is known as a selective σ-receptor agonist.5,11
On the basis of this conversion, the absolute configuration
of the major enantiomer of 2e (90% ee) which was obtained
by the use of the (R,R)-Trost ligand, was confirmed to be
(1R,2S). In addition, the major enantiomer of desymmetri-
zation product 2g having high optical purity (90% ee) was
determined as (1R,2S)-isomer by comparing with the authen-
tic sample derived from commercially available (1S,2R)-2-
amino-1,2-diphenylethanol (see the Supporting Information).12
The present N-monoallylation using chiral π-allyl-Pd
complex was also applied to kinetic resolution of racemic
vicinal diamine derivative (Scheme 4). Under the above con-
ditions, N-monoallylation of racemic-trans-cyclohexane-1,2-
OL048498N
(9) The reverse of the enantioselectivity in the reaction of 1e was
confirmed by converting 2e to 2a (see the Supporting Information). The
absolute configuration of the major enantiomer of the product 2d was also
determined by conversion to 2a (see the Supporting Information), while
that of 2c was not determined.
(10) Neipp, C. E.; Humphrey, J. M.; Martin, S. F. J. Org. Chem. 2001,
66, 531.
(11) Radesca, L.; Bowen, W. D.; Paolo, L. D.; De Costa, B. R. J. Med.
Chem. 1991, 34, 3058.
(12) The absolute configuration of the product 2f was not determined.
(13) Takahashi, H.; Kawakita, T.; Ohno, M.; Yoshioka, M.; Kobayashi,
S. Tetrahedron 1992, 48, 5691.
(14) For selected examples, see: (a) Hayashi, T.; Yamamoto, A.; Ito,
Y.; Nishioka, E.; Miura, H.; Yanagi, K. J. Am. Chem. Soc. 1989, 111, 6301.
(b) Hayashi, T.; Kishi, K.; Yamamoto, A.; Ito, Y. Tetrahedron Lett. 1990,
31, 1743. (c) Matt, P. V.; Loiseleur, O.; Kock, G.; Pfaltz, A.; Lefeber, C.;
Feucht, T.; Helmchen, G. Tetrahedron: Asymmetry 1994, 5, 573. (d) Togni,
A.; Burckhardt, U.; Gramlich, V.; Pregosin, P. S.; Salzmann, R. J. Am.
Chem. Soc. 1996, 118, 1031. (e) Trost, B. M.; Kruger, A. C.; Bunt, R. C.;
Zambrano, J. J. Am. Chem. Soc. 1996, 118, 6520. (f) Sudo, A.; Saigo, K.
J. Org. Chem. 1997, 62, 5508.
(15) (a) Kitagawa, O.; Kohriyama, M.; Taguchi, T. J. Org. Chem. 2002,
67, 8682. (b) Terauchi, J.; Curran, D. P. Tetrahedron: Asymmetry 2003,
14, 587.
Org. Lett., Vol. 6, No. 20, 2004
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