J . Org. Chem. 2000, 65, 8063-8065
8063
P a lla d iu m -Ca ta lyzed Rea ction s of N-Allylben zotr ia zoles w ith
Am in es a n d Su lfon a m id es: A F a cile Rou te to F u n ction a lized
Allyla m in es a n d N-Allylsu lfon a m id es
Alan R. Katritzky,* J iangchao Yao, and Olga V. Denisko
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
Received April 24, 2000
A variety of functionalized N-allylamines and N-allylsulfonamides are synthesized by Pd(II)-
catalyzed intermolecular amination of the corresponding N-allylbenzotriazoles.
In tr od u ction
also shown that this reaction can occur intramolecularly,
providing a convenient approach to the synthesis of
-vinyl-pyrrolidines and -piperidines, which are impor-
Compounds containing the allylamino moiety are
abundant in nature and very often reveal significant
biological activity.1 This, and the obvious importance of
allylamines as precursors and intermediates in the
2
tant construction blocks for many biologically active
,2
17
compounds. However, in these previous reports we
discussed exclusively inter- and intramolecular amina-
tions of allylbenzotriazoles bearing no additional func-
tionalities. Numerous naturally occurring allylamines, for
example, piperidine-based alkaloids micropine and epi-
organic synthesis of a wide variety of naturally occurring
compounds,3
-5
has caused extensive development of
methods for their preparation in the last two decades.
The most general approach is based on transition metal
catalyzed amination of various allylic derivatives, pref-
2
micropine, contain additional functional groups, most
often hydroxy, amino, and carboxylic groups, which could
possibly effect the reaction. Thus, from the point of view
of the possible application of â,γ-unsaturated benzotria-
zolyl-containing compounds in the total synthesis of
natural products, it is important to study the effects of
various functionalities on the course of the reaction. A
similar investigation on such reactions with allyl acetates
6
-11
12,13
erentially allyl acetates,
but also allyl halides,
allyl
9
9
8
carbonates, allyl ethers, diethyl allyl phosphates, and
N-allyl-2,4,6-triphenylpyridinium salts.14
Recently, the ring-opening of methylenecyclopropanes
in the presence of Pd(II) catalyst with the formation of
allyl palladium complex, which could be subsequently
1
5
13
aminated, has been described. Although a variety of
transition metal catalysts have been employed, such as
Cu(II)-Cu(0) system12 or Ni(0) catalysts,9 palladium
catalysts have been the most widely exploited.
has been recently carried out.
Resu lts a n d Discu ssion
We found that the benzotriazolyl group in allyl benzo-
triazoles is sufficiently mobile to be substituted by
aliphatic and benzylic amines in the analogous amination
reaction in the presence of palladium(II) acetate.16 It was
We first investigated the influence of hydroxy groups
at various positions in the allylic substrate or the amine
on the course of the amination reaction and the yields of
the products. For the preparation of the starting materi-
als required for this investigation, well-known methods
were used.18 Thus, 4-hydroxy-substituted allylbenzotria-
zoles 2 and 4 were prepared in high yields by R-lithiation
of allylbenzotriazoles 1 and 3, respectively, and subse-
quent quenching with aldehydes and ketones (Scheme
1). Oxirane ring opening with lithiated 1 led to the
formation of 5-hydroxy-3-benzotriazolylpent-1-ene (5) in
(1) Takahata, H.; Bandoh, H.; Hanayama, M.; Momose, T. Tetra-
hedron: Asymmetry 1992, 3, 607.
(
(
2) Bayquen, A. V.; Read, R. W. Tetrahedron 1996, 52, 13467.
3) Trost, B. M.; Godleski, S. A.; Gen eˆ t, J . P. J . Am. Chem. Soc. 1978,
1
00, 3930.
(4) Beier, C.; Schaumann, E. Synthesis 1997, 1296.
(5) Kadota, I.; Kawada, M.; Muramatsu, Y.; Yamamoto, Y. Tetra-
hedron: Asymmetry 1997, 8, 3887.
8
5% yield.
(
(
6) Trost, B. M.; Keinan, E. J . Am. Chem. Soc. 1978, 100, 7779.
7) Connell, R. D.; Rein, T.; Åkermark, B.; Helquist, P. J . Org. Chem.
Based on our previously reported results,16 we chose
1
988, 53, 3845.
8) Murahashi, S.-I.; Imada, Y.; Taniguchi, Y.; Kodera, Y. Tetrahe-
dron Lett. 1988, 29, 2973.
9) Bricout, H.; Carpentier, J .-F.; Mortreux, A. J . Chem. Soc., Chem.
Commun. 1995, 1863.
10) Cerezo, S.; Cortes, J .; Moreno-Ma n˜ as, M.; Pleixats, R.; Roglans,
A. Tetrahedron 1998, 54, 14869.
the catalytic system Pd(OAc)
2
-PPh
3
2 3
-K CO -MeOH,
(
which was shown to provide the best results in the Pd-
catalyzed aminations of unsubstituted 1-allylbenzotria-
zole. We have now found that, under such conditions,
hydroxy-substituted allylbenzotriazoles 2 and 4 react
readily with aliphatic and benzylic amines to afford the
corresponding hydroxy-substituted allylamines 6a -e in
very good yields (Scheme 2). Elaboration of the allylben-
(
(
(11) Sirisoma, N. S.; Woster, P. M. Tetrahedron Lett. 1998, 39, 1489.
(12) Baruah, J . B.; Samuelson, A. G. Tetrahedron 1991, 47, 9449.
(13) Gatti, R. G. P.; Larsson, A. L. E.; B a¨ ckvall, J .-E. J . Chem. Soc.,
Perkin Trans. 1 1997, 577.
14) Moreno-Ma n˜ as, M.; Morral, L.; Pleixats, R. J . Heterocycl. Chem.
997, 34, 241.
15) Nakamura, I.; Itagaki, H.; Yamamoto, Y. J . Org. Chem. 1998,
3, 6458.
16) Katritzky, A. R.; Yao, J .; Qi, M. J . Org. Chem. 1998, 63, 5232.
(
1
(
(17) Katritzky, A. R.; Yao, J .; Yang, B. J . Org. Chem. 1999, 64, 6066.
(18) Katritzky, A. R.; Li, J .; Malhotra, N. Liebigs Ann. Chem. 1992,
843.
6
(
1
0.1021/jo0006268 CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/21/2000