Palladium-catalyzed amination of allylic alcohols using anilines

Full text of DOI:10.1021/jo990558t

5000
J . Org. Chem. 1999, 64, 5000-5001
Communications
Ta ble 1. Rea ction of 4-Ch lor o-2-m eth yla n ilin e (1a ) w ith
2-Bu ten -1-ol (2a )a
P a lla d iu m -Ca ta lyzed Am in a tion of Allylic
Alcoh ols Usin g An ilin es
Shyh-Chyun Yang* and Chung-Wei Hung
Graduate Institute of Pharmaceutical Sciences, Kaohsiung
Medical College, Kaohsiung 80708, Taiwan, R.O.C.
Received March 29, 1999
Palladium-catalyzed allylation is an established, efficient,
and highly stereoselective method for C-C, C-N, and C-O
bond formation, which has been widely applied to organic
chemistry.1 The processes have been shown to proceed by
attack of nucleophiles on intermediate η3-allylpalladium(II)
complexes generated by oxidative addition of allylic com-
pounds including allylic halides,2 acetates,3 and carbonates4
to a Pd(0) complex. However, there have been only limited
and sporadic reports dealing with the direct cleavage of the
C-O bond in allylic alcohols on interaction with a transition
metal complex.5 Successful applications using allylic alcohols
directly in catalytic processes are even more limited. This
apparently stems from the poor capability of a nonactivated
hydroxyl to serve as a leaving group.6 Itoh has reported that
palladium-catalyzed nucleophilic substitution of allylic al-
cohols using zinc enolates can proceed efficiently in the
presence of titanium(IV) alkoxides and LiCl.7 This result
prompted us to study the reaction between anilines and
allylic alcohols in order to understand the regio- and
stereocontrol of the reaction; this is important for practical
synthetic applications and also for gaining more insight into
the mechanism. This is, to our knowledge, the first example
of palladium-catalyzed allylation of anilines by the direct
use of allylic alcohols in the presence of Ti(OPri)4.
a
Reaction conditions: 1a (1 mmol), 2a (1.2 mmol), and MS4A
(200 mg) in a solvent (5 mL) at 50 °C for 3 h. Isolated yield. c The
b
E/Z ratio of 3a was determined by GC. Without MS4A. e Reflux
d
for 3 h.
Ta ble 2. Rea ction of An ilin es (1b-h ) w ith 2-Bu ten -1-ol
(2a )a
When a mixture of 4-chloro-2-methylaniline (1a , 1 mmol)
and 2-buten-1-ol (2a , 1.2 mmol) was heated in the presence
of Pd(OAc)2 (0.01 mmol), PPh3 (0.04 mmol), Ti(OPri)4 (0.25
* To whom correspondence should be addressed. E-mail: scyang50@
ksts.seed.net.tw.
(1) (a) Tsuji, J . Organic Synthesis with Palladium Compounds; Springer-
Verlag: Heidelberg, 1980. (b) Trost, B. M.; Verhoeven, T. R. In Compre-
hensive Organometallic Chemistry; Wilkinson, G., Stone, F. G. A., Abel, E.
W., Eds.; Pergamon Press: Oxford, 1982; Vol. 8, p 799. (c) Heck, R. F.
Palladium Reagents in Organic Synthesis; Academic Press: London, 1985.
(d) Trost, B. M.; Fleming, I. In Comprehensive Organic Synthesis; Oppolzer,
W., Ed.; Pergamon Press: New York, 1991; Vol. 5, p 315. (e) Davis, J . A. In
Comprehensive Organometallic Chemistry II; Abel, E. W., Stone, F. G. A.,
Wilkinson, G., Eds.; Pergamon Press: Oxford, 1995; Vol. 9, p 291. (f) Tsuji,
J . Palladium Reagents and Catalysts; Wiley: New York, 1995.
(2) (a) Sakamoto, M.; Shimizu, I.; Yamamoto, A. Bull. Chem. Soc. J pn.
1996, 69, 1065. (b) Connell, R. D.; Rein, T.; Akermark, B.; Helquist, P. J .
Org. Chem. 1988, 53, 3845.
(3) (a) Trost, B. M. Tetrahedron 1977, 33, 371. (b) Trost, B. M. Acc. Chem.
Res. 1980, 13, 385. (c) Backvall, J . E. Acc. Chem. Res. 1983, 16, 335. (d)
Tsuji, J .; Minami, I. Acc. Chem. Res. 1987, 20, 140. (e) Trost, B. M. Angew.
Chem., Int. Ed. Engl. 1989, 28, 1173. (f) Oppolzer, W. Angew. Chem., Int.
Ed. Engl. 1989, 28, 38. (g) Tsuji, J . Synthesis 1990, 739. (h) Trost, B. M.
Pure Appl. Chem. 1992, 64, 315. (i) Backvall, J . E. Pure Appl. Chem. 1992,
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Asymmetry 1992, 3, 1089.
(4) (a) Tsuji, J .; Shimizu, I.; Minami, I.; Ohashi, Y. Tetrahedron Lett.
1982, 23, 4809. (b) Trost, B. M.; Hung, M. H. J . Am. Chem. Soc. 1983, 105,
7757. (c) Takahashi, T.; J inbo, Y.; Kitamura, K.; Tsuji, J . Tetrahedron Lett.
1984, 25, 5921. (d) Tsuji, J .; Shimizu, I.; Minami, I.; Ohashi, Y.; Sugihara,
T.; Takahashi, K. J . Org. Chem. 1985, 50, 1523.
(5) (a) Lumin, S.; Falck, J . R.; Capdevila, J .; Karara, A. Tetrahedron Lett.
1992, 33, 2091. (b) Tsay, S.; Lin, L. C.; Furth, P. A.; Shum, C. C.; King, D.
B.; Yu, S. F.; Chen, B.; Hwu, J . R. Synthesis 1993, 329. (c) Masuyama, Y.;
Kagawa, M.; Kurusu, Y. Chem. Lett. 1995, 1121.
(6) Stary, I.; Stara, I. G.; Kocovsky, P. Tetrahedron Lett. 1993, 34, 179.
(7) Itoh, K.; Hamaguchi, N.; Miura, M.; Nomura, M. J . Chem. Soc., Perkin
Trans. 1 1992, 2833.
a
Reaction conditions: 1 (1 mmol), 2a (0.8 mmol), Pd(OAc)2 (0.01
mmol), PPh3 (0.04 mmol), Ti(OPri)4 (0.25 mmol), and MS4A (200
b
mg) in benzene (5 mL) were refluxed for 3 h. Isolated yield.
c Determined by GC.
mmol), and molecular sieves (MS4A) (200 mg) in benzene
(5 mL) under nitrogen at 50 °C for 3 h, the mixtures of regio-
and stereoisomeric anilines 3a and 4a were formed in 22%
and 29%, respectively (entry 1 in Table 1). The 87/13 E/ Z
ratio of 3a was determined by GC and 1H NMR spectros-
copy: the CH2 signal appeared at δ 3.71 ppm for the
E-isomer and at δ 3.80 ppm for the Z-isomer. This stereo-
chemistry was confirmed by the coupling constant of the
vinylic protons for this major isomer (J ) 15.2 Hz) being
characteristic of E-stereochemistry. The reaction should be
10.1021/jo990558t CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/19/1999

Communications
J . Org. Chem., Vol. 64, No. 14, 1999 5001
Ta ble 3. Rea ction of 4-Ch lor o-2-m eth yla n ilin es (1a ) w ith
Sch em e 1
Allyl Alcoh ols (2b-f)a
Ti(OPri)4, and MS4A are summarized in Table 3. All of the
allylic alcohols examined underwent amination smoothly to
give the corresponding N-allylanilines in overall yields
ranging from 75 to 99%. Since both regioisomeric alcohols
2a and 2b gave identical mixtures of the anilines 3a and
4a in similar ratios, the reaction is considered to proceed
via π-allylpalladium intermediates.
A possible mechanism for the formation of N-allylanilines
from 1 and 2 is illustrated in Scheme 1, in which the
substituent on allyl alcohol is omitted. Alcohol 2 or an allyl
titanate, formed by an alcohol exchange reaction between 2
and isopropoxide in Ti(OPri)4,7 reacts with Pd(0) species
generated in situ8 to afford a π-allylpalladium intermediate
10. Subsequently, the reaction of 11 with aniline 1 followed
by reductive elimination gives N-allylaniline. It is possible
that 11 could be formed by ligand exchange between 10 and
the Ti(HNAr)n(OR)4-n species generated in the reaction
medium.
a
Reaction conditions: 1a (1 mmol), 2 (1.2 mmol), Pd(OAc)2 (0.01
mmol), PPh3 (0.04 mmol), Ti(OPri)4 (0.25 mmol), and MS4A (200
b
mg) in benzene (5 mL) were refluxed for 3 h. Isolated yield.
c Determined by GC.
accompanied by formation of water. Addition of molecular
sieves (MS4A) for its removal showed a positive effect (entry
2). It was confirmed that the reaction did not occur in the
absence of Ti(OPri)4 (entry 3) or phosphine species (entry
4). Note that the products could also be afforded in good yield
in the reaction under reflux (entry 6) or an increase in the
amount of palladium catalyst (2.5 mol %) (entry 5). Six
solvents were investigated: MeCN, THF, HMPA, DMF, and
toluene, with benzene giving the best results (entries 1 and
6-10). Use of MeCN, THF, DMF, or toluene medium led to
4a and a single stereoisomer E-3a .
The results collected in Table 2 show the amination of
2-buten-1-ol (2a ) worked well with anilines containing both
electron-withdrawing and electron-donating groups, giving
generally high yields of the corresponding allylic anilines.
Results for amination of a number of allylic alcohols 2b-f
with 4-chloro-2-methylaniline (1a ) using Pd(OAc)2, PPh3,
Ack n ow led gm en t. We gratefully acknowledge the
National Science Council of the Republic of China for
financial support.
Su p p or tin g In for m a tion Ava ila ble: Experimental proce-
dures and characterization data. This material is available free
of charge via the Internet at http://pubs.acs.org.
J O990558T
(8) Ti(OPri)4 may be acceleration of the reduction of Pd(OAc)2 to Pd(0)
species: Satoh, T.; Itoh, K.; Miura, M.; Nomura, M. Bull. Chem. Soc. J pn.
1993, 66, 2121.