Palladium-Catalyzed Reaction of N-Allylbenzotriazoles with Amines: A Novel Method for the Preparation of Allylamines

Full text of DOI:10.1021/jo980200h

5
232
J . Org. Chem. 1998, 63, 5232-5234
Notes
P a lla d iu m -Ca ta lyzed Rea ction of
Sch em e 1
N-Allylben zotr ia zoles w ith Am in es: A
Novel Meth od for th e P r ep a r a tion of
Allyla m in es
Alan R. Katritzky,* J iangchao Yao, and Ming Qi†
Center for Heterocyclic Compounds,
Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
Received February 4, 1998
Allylamines are common moieties in biologically active
compounds1 and important intermediates in organic
synthesis. Many syntheses of allylamines have been
documented including (i) reaction of alkenyl cuprates
in the above reactions usually proceeds efficiently, the
convenience of the method depends on the availability
of the starting materials.
In recent years benzotriazole has been demonstrated
to be a useful synthetic auxiliary,15 with versatility
endowed by the benzotriazole group being capable of
2
with iminium salts, R-aminoethers or R-aminothioethers,
(
ii) reaction of Grignard reagents with allyl-R-aminoni-
3
4
triles, and (iii) the amination of dienes and allylic
halides.1
a,5
The most general approach is based on the
transition metal catalyzed reaction of amines with allylic
1
6
17
6
7
acting as a nucleofuge, proton activator, electron
substrates including allyl acetates, allyl carboxylates,
donor18 and radical, or carbanion precursor. Since
R-mono- and R,R-disubstituted allylbenzotriazoles can be
prepared in high yields through lithiation and alkylation
of N-allylbenzotriazole,1 we became interested in ex-
ploring the possibility of using benzotriazole as a leaving
group in metal-catalyzed allylic amination reaction. The
success of such a reaction would be advantageous in
terms of both the availability of substrates and the
structural diversity of the products.
19
20
8
9
10
allyl ethers, allyl alcohols and diethyl allyl phosphates.
Besides the aforementioned oxygen-containing leaving
groups, amine,1 nitro, or ammonium moieties have
1
12
13
7a
also been employed as the leaving group in transition
metal catalyzed allylation.14 While the amination step
†
Trega Biosciences, Inc., 9880 Campus Point Drive, San Diego, CA
9
2121.
1) (a) Cheikh, R. B.; Chaabouui, R.; Laurent, A.; Mison, V.; Nafti,
A. Synthesis 1983, 685. (b) Kondo, T.; Nakai, H.; Goto, T. Tetrahedron
973, 29, 1801.
2) Germon, C.; Alexakis, A.; Normant, J . F. Bull. Soc. Chim. Fr.,
Part 2 1984, 377.
(
1
(
Resu lts a n d Discu ssion
3) Ahlbrecht, H.; Dollinger, H. Synthesis 1985, 743.
The first step of an allylation is the cleavage of a C-N
bond to form the allylic metal complex. However, under
the conditions of the recent literature method which used
1
6) (a) Walker, W. E.; Manyik, R. M.; Atkins, K. E.; Farmer, M. L.
11c,d
nickel(0) as catalyst in DMF solution at 80 °C,
1
-allylbenzotriazole (1a ) and 1,2,3,4-tetrahydroisoquino-
line (2), which were chosen as the model substrates, did
not react (Scheme 1). When a base was added we were
able to detect the desired product 3 by GCMS, but the
reaction did not proceed completely. The major side
reaction was the isomerization of 1-allylbenzotriazole (1a )
2
1
(
9) Atkins, K. E.; Walker, W. E.; Manyik, R. M. Tetrahedron Lett.
970, 3821.
10) Tanigawa, Y.; Nishimura, K.; Kawasaki A.; Murahashi S.-I.
Tetrahedron Lett. 1982, 23, 5549.
11) (a) Wenkert, E.; Fernandes, J . B.; Michelotti, E. L.; Swindell,
1
(15) Katritzky, A. R.; Lan, X.; Yang, J . Z.; Denisko, O. Chem. Rev.
1998, 98, 409.
(16) (a) Katritzky, A. R.; Rachwal, S.; Hitchings, G. J . Tetrahedron
1991, 47, 2683. (b) Katritzky, A. R.; Fan, W.-Q. J . Org. Chem. 1990,
55, 3205.
(17) (a) Katritzky, A. R.; Li, J .; Malhotra, N. Liebigs Ann. Chem.
1992, 843. (b) Katritzky, A. R.; Wu, J .; Kuzmierkiewicz, W.; Rachwal,
S. Liebigs Ann. Chem. 1994, 1. (c) Katritzky, A. R.; Wu, H.; Xie, L.;
J iang, J . J . Heterocycl. Chem. 1995, 32, 595.
(
(
C. S. Synthesis 1983, 701. (b) Murahashi, S.-I.; Imada, Y.; Nishimura,
K. Tetrahedron 1994, 50, 453. (c) Trost, B. M.; Spagnol, M. D. J . Chem.
Soc., Perkin Trans. 1 1995, 2083. (d) Bricout H.; Carpentier, J .-F.;
Mortreux, A. J . Chem. Soc., Chem. Commun. 1997, 1393.
(12) (a) Tamura, R.; Hegedus, L. S. J . Am. Chem. Soc. 1982, 104,
3
727. (b) Ono, N.; Hamamoto, I.; Kaji, A. J . Chem. Soc., Chem.
(18) (a) Katritzky, A. R.; Rachwal, S.; Caster, K. C.; Mahni, F.; Law,
K. W.; Rubio, O. J . Chem. Soc., Perkin Trans. 1 1987, 781. (b)
Katritzky, A. R.; Lan, X.; Fan, W.-Q. Synthesis 1994, 445.
(19) (a) Aurrecoechea, J . M.; Lopez, B.; Fernandez, A.; Arrieta, A.;
Cossio, F. P. J . Org. Chem. 1997, 62, 1125. (b) Aurrecoechea, J . M.;
Fernandez-Acebes, A. Tetrahedron Lett. 1993, 34, 549.
(20) (a) Katritzky, A. R.; Qi, M.J . Org. Chem. 1997, 62, 4116. (b)
Katritzky, A. R.; Qi, M.; Feng, D.; Nichols, D. A. J . Org. Chem. 1997,
62, 4121.
Commun. 1982, 821. (c) Tamura, R.; Hayashi, K.; Kai, Y.; Oda, D.
Tetrahedron Lett. 1984, 25, 4437.
(13) (a) Trost, B. M.; Keinan, E. J . Org. Chem. 1980, 45, 2741. (b)
Hosomi, A.; Hoashi, K.; Kohra, S.; Tominaga, Y.; Otaka, K.; Sakurai,
H. J . Chem. Soc., Chem. Commun. 1987, 570. (c) Moreno-Manas, M.;
Morral, L.; Pleixats, R. J . Heterocycl. Chem. 1997, 34, 241.
(14) Godleski, S. A. In Comprehensive Organic Synthesis; Trost, B.
M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 4, p 585.
S0022-3263(98)00200-X CCC: $15.00 © 1998 American Chemical Society
Published on Web 06/29/1998

Notes
J . Org. Chem., Vol. 63, No. 15, 1998 5233
Sch em e 2
Sch em e 3
by GC analysis (from 80/20 to 98/2). The definite
assignment of these isomers are difficult, as the alkene
1
protons in all of these compounds overlapped in their H
NMR spectra. For compound 8, only one isomer was
obtained and the coupling constant of the alkene proton
is 15.9 Hz, so we concluded that 8 is the E-alkene and
by analogy deduced that the major isomers in 7a -d are
also the E-alkenes.
When a primary amine was used as the nucleophile,
both mono- (9) and diallylamines (10) were formed
(
Scheme 3). However, under the standard conditions, the
Ta ble 1. P r ep a r a tion of Allyla m in es 7 a n d 8
reaction of 5g and ammonia failed to produce the desired
primary allylamine.
start prod-
yield
(%)
matl
uct
R1
R2
R3
R4
R5
In conclusion, we found that benzotriazole can be used
as a leaving group in the palladium-catalyzed allyl
amination. This new methodology provides a general
access to a wide range of allylamines. Compared to the
previous available methods, a practical advantage of the
present route is that N-(substituted allyl)benzotriazoles
can be readily prepared.
5
5
5
5
5
5
5
1
1
a
b
c
d
e
f
7a
7b
7c
7d
7e
7f
8
Me
Et
n-Bu
Bn
H
H
H
H
H
o-CH2C6H4(CH2)2-
85
80
70
70
75
H
H
H
n-C8H17
Bn
Me
Bn
Et
Et
n-Bu n-Bu
H
-(CH2)5-
o-CH2C6H4(CH2)2-
-(CH2)5-
a
H
H
H
H
H
H
H
H
Me
Ph
H
20
g
75
80
87
7h
7i
Bn
Bn
H
n-C8H17
n-C8H17
Exp er im en ta l Section
a
7
0% of 7a also found.
Gen er a l. Compounds 5a -g were prepared by the literature
to 1-(propenyl)benzotriazole (4). We tested other cata-
lysts [Pd(PPh , Pd(OAc) /PPh ] and solvents (THF,
toluene, CH CN, 1,4-dioxane, MeOH, EtOH, n-BuOH,
and DMA) and found that best conditions for the allyl
methods.1 For NMR and other chemical information see our
7a
3
)
4
2
3
20a
previous paper.
3
Gen er a l P r oced u r e for th e P r ep a r a tion of Allyla m in es
3, 7a -f,h ,i, a n d 8-10. Under argon, a mixture of allylbenzo-
amination were using methanol as solvent, K
KOH as base, and Pd(OAc) (3 mol %) and PPh
) as catalyst. Without Pd(OAc) /PPh
2
CO
(9 mol
catalyst, the
3
or
triazole (5.3 mmol), amine (1.1 g, 5.8 mmol), Pd(OAc)
2
(40 mg,
0
.18 mmol), PPh (140 mg, 0.53 mmol), and K CO (1.0 g) in
3 2 3
2
3
MeOH (15 mL) was refluxed for 4-48 h. The reaction mixture
was cooled to room temperature, quenched with water (20 mL),
and extracted with ether (3 × 40 mL). The solvent was removed
under vacuum, and the residual oil was purified by column
chromatography on neutral alumina (hexane:triethylamine 100:
3) to afford the desired products.
%
2
3
reaction of 1a and 2 only gave isomerization product 4.
Under such conditions the isomeric 2-allylbenzotriazole
(
1b) also reacts with amines and therefore it is not
necessary to separate 1a and 1b. The mixture 1a and
b reacts with secondary amines such as dibenzylamine
2
1
N-Allyl-1,2,3,4-tetr a h yd r oisoqu in olin e (3): 85% yield,
1
1
colorless oil; H NMR δ 2.75 (t, 2H, J ) 5.9 Hz), 2.93 (t, 2H, J
and dioctylamine to give tertiary allylamines 7h ,i in good
yields (Scheme 2, Table 1); however, N,N-diphenylamine
failed to react with 1 to produce the corresponding
allylamine.
)
)
7
5.7 Hz), 3.18 (d, 2H, J ) 6.4 Hz), 3.64 (s, 2H), 5.22 (d, 1H, J
10.4 Hz), 5.26 (d, 1H, J ) 18.3 Hz), 5.93-6.02 (m, 1H), 7.02-
13
.13 (m, 4H); C NMR d 29.0, 50.2, 55.9, 61.4, 117.7, 125.5,
126.0, 126.5, 128.6, 134.2, 134.7, 135.3.
Under the standard reaction conditions, R-mono- and
R,R-disubstituted allylbenzotriazoles 5a -e reacted with
various secondary amines to give the allylamines 7a -e
in good yields (Scheme 2, Table 1). The reaction proceeds
regiospecifically, with amine attack at the least substi-
tuted carbon to give only the γ-amination product. The
starting materials 5a -e were prepared from N-allylben-
N-(2-Bu ten yl)-1,2,3,4-ter a h yd r oisoqu in olin e (7a ): color-
1
less oil; a mixture of E- and Z-isomers (E/ Z ) 80/20); H NMR
δ 1.73 (d, 3H, J ) 5.4 Hz), 2.73 (t, 2H, J ) 5.9 Hz), 2,89 (t, 2H,
J ) 5.3 Hz), 3.10 (d, 2H, J ) 5.4 Hz) [3.17 (d, 2H, J ) 5.4 Hz,
E-isomer)], 3.60 (s, 2H) [3.61 (s, 2H, Z-isomer)], 5.62-5.67 (m,
13
2
H), 7.01-7.33 (m, 4H); C NMR δ 17.8, 29.1 [29.11, Z-isomer],
50.5, 55.9 [55.4, Z-isomer], 60.6, 125.4, 126.0, 126.5, 127.8, 128.6,
128.9, 134.3, 134.6. Anal. Calcd for C19 39N: C, 83.37; H, 9.15;
H
N, 7.48. Found: C, 83.19; H, 9.37; N, 7.48.
zotriazole (1) and alkyl bromides in almost quantitatively
yields;17a the crude products were used for the subsequent
reactions without further purification.
γ-Substituted allylbenzotriazoles 5f,g can also be em-
ployed in this reaction. 1-(Benzotriazol-1-yl)-2-butene
N-Meth yl-N-(2-p en ten yl)octyla m in e (7b): colorless oil; a
1
mixture of E- and Z-isomers (E/ Z ) 90/10); H NMR δ 0.91-
1
3
.03 (m, 6H), 1.31-1.49 (m, 12H), 2.06-2.08 (m, 2H), 2.22 (s,
H), 2.31-2.33 (m, 2H), 2.94-2.96 (m, 2H) [3.01-3.03 (m, 2H,
Z-isomer)], 5.51-5.62 (m, 2H); 13C NMR δ 13.6, 14.1, 22.7, 25.4,
27.4, 27.5, 29.3, 29.6, 31.8, 42.0, 57.4 [54.2, Z-isomer], 60.1, 126.1,
(5f) reacted with 2 to give a mixture of R- and γ-amina-
1
35.5 [134.3, Z-isomer]; HRMS (EI) calcd for C14
H29N 211.2300,
tion products 7a and 7f, while the reaction of 5g and
piperidine afforded the R-amination product 8 selectively.
The reaction probably proceeds through the allylic-
palladium complex intermediate, and the amine attacks
the least substituted terminus of the allyl group.14
Compounds 7a -d were isolated as mixtures of E- and
Z-isomers; the ratio of the two isomers was determined
found 211.2414.
N,N-Diben zyl-2-h ep ten yla m in e (7c): colorless oil; a mix-
1
ture of E- and Z-isomers (E/ Z ) 80/20); H NMR δ 0.91 (t, 3H,
J ) 4.6 Hz), 1.32-1.37 (m, 4H), 2.02-2.06 (m, 2H), 3.01 (d, 2H,
(21) Morphy, J . R.; Rankovic, Z.; Rees, D. C. Tetrahedron Lett. 1996,
37, 3209.

5
234 J . Org. Chem., Vol. 63, No. 15, 1998
Notes
1
J ) 6.3 Hz) [3.87 (d, 2H, J ) 5.9 Hz, Z-isomer)], 3.57 (s, 4H)
N,N-Dioctyla llyla m in e (7i): colorless oil; H NMR δ 0.88
(t, 6H, J ) 6.6 Hz), 1.18-1.43 (m, 24H), 2.39 (t, 4H, J ) 7.7
Hz), 3.07 (d, 2H, J ) 6.4 Hz), 5.09 (d, 1H, J ) 10.7 Hz), 5.15 (d,
1H, J ) 18.4 Hz), 5.85-5.88 (m, 1H); 13C NMR δ 14.1, 22.7, 27.0,
27.6, 29.3, 29.6, 31.9, 53.8, 57.3, 116.7, 136.3. Anal. Calcd for
[
3.33 (s, 4H, Z-isomer)], 5.53-5.59 (m, 2H), 7.21-7.39 (m, 10H);
1
3
C NMR δ 13.9, 22.2, 31.6, 32.1, 55.5, 57.6, 126.7, 127.1, 128.1,
1
28.8, 134.1, 139.9. Anal. Calcd for C21H27N: C, 85.95; H, 9.27;
N, 4.77. Found: C, 86.36; H, 9.81; N, 5.03.
N,N-Dieth yl-4-p h en yl-2-bu ten yla m in e (7d ): colorless oil;
C
19
H
39N: C, 81.06; H, 13.96; N, 4.98. Found: C, 81.33; H, 13.77;
1
a mixture of Z- and E-isomers (E/ Z ) 98/2); H NMR δ 1.03 (t,
N, 5.20.
1
6
H, J ) 7.1 Hz), 2.52 (q, 4H, J ) 7.2 Hz), 3.07 (d, 2H, J ) 6.5
N-(3-P h en yla llyl)-p ip er id in e (8): colorless oil; H NMR δ
1.45-1.59 (m, 2H), 1.61-1.65 (m, 4H), 2.35-2.55 (m, 4H), 3.14
(d, 2H, J ) 6.6 Hz), 6.34-6.35 (m, 1H), 6.50 (d, 1H, J ) 15.9
Hz), 7.2-7.4 (m, 5H); 13C NMR δ 24.2, 25.8, 54.4, 61.7, 126.2,
127.0, 127.2, 128.4, 132.6, 137.0. Anal. Calcd for C14H19N: C,
83.53; H, 9.51; N, 6.96. Found: C, 83.21; H, 9.60; N, 6.99.
Hz), 3.37 (d, 2H, J ) 6.5 Hz), 5.59-5.69 (m, 2H), 7.16-7.32 (m,
1
3
5
1
6
H); C NMR δ 11.6, 38.9, 46.5, 55.0, 125.9, 128.3, 128.4, 128.7,
32.0, 141.3. Anal. Calcd for C14 21N: C, 82.70; H, 10.41; N,
.89. Found: C, 82.65; H, 10.19; N, 6.64.
-(1-P ip er id in yl)-3-bu tyl-2-h ep ten e (7e): colorless oil; H
NMR δ 0.89-0.93 (m, 6H), 1.31-1.61 (m, 14H), 1.99 (t, 4H, J )
H
1
1
1
N-Allyld od ecyla m in e (9): 55% yield, colorless oil; H NMR
7
1
3
.0 Hz), 2.26-2.46 (m, 4H), 2.93 (d, 2H, J ) 6.6 Hz), 5.24 (t,
δ 0.90 (t, 3H, J ) 6.0 Hz), 1.22-1.40 (m, 18H), 1.45-1.55 (m,
2H), 2.61 (t, 2H, J ) 7.1 Hz), 3.26 (d, 2H, J ) 6.1 Hz), 5.09 (d,
1H, J ) 10.2 Hz), 5.17 (d, 1H, J ) 17.1 Hz), 5.89-5.95 (m, 1H);
1
3
H, J ) 5.7 Hz); C NMR δ 13.9, 14.0, 22.5, 22.8, 24.5, 26.0,
0.2, 30.3, 30.7, 36.6, 54.6, 56.7, 121.4, 142.4. Anal. Calcd for
1
3
C
16
H
31N: C, 80.94; H, 13.16; N, 5.90. Found: C, 81.07; H, 13.51;
N, 6.18.
N-(1-Bu ten -3-yl)-1,2,3,4-ter a h yd r o-isoqu in olin e (7f): col-
C NMR δ 14.1, 22.7, 27.4, 29.3, 29.6, 30.2, 31.9, 49.5, 52.6,
115.5, 137.1. Anal. Calcd for C15 31N: C, 79.92; H, 13.86; N,
6.21. Found: C, 80.25; H, 13.56; N, 5.91.
H
1
1
orless oil; H NMR δ 1.28 (d, 3H, J ) 6.6 Hz), 2.73-2.75 (m,
N,N-Dia llyld od ecyla m in e (10): 20% yield, colorless oil; H
NMR δ 0.88 (t, 3H, J ) 5.4 Hz), 1.22-1.32 (m, 18H), 1.40-1.44
(m, 2H), 2.40 (t, 2H, J ) 6.6 Hz), 3.07 (d, 4H, J ) 6.3 Hz), 5.10
(d, 2H, J ) 9.2 Hz), 5.14 (d, 2H, J ) 16.4 Hz), 5.81-5.87 (m,
2H); 13C NMR δ 14.1, 22.7, 26.9, 27.5, 29.3, 29.55, 29.6, 31.9,
2
(
1
1
H), 2.86-2.89 (m, 2H), 2.92-3.12 (m, 1H), 3.74 (s, 2H), 5.16
d, 1H, J ) 9.5 Hz), 5.21 (d, 1H, J ) 19.7 Hz), 5.91-5.98 (m,
H), 7.03-7.12 (m, 4H); 13C NMR δ 17.2, 29.6, 47.5, 52.7, 62.4,
15.6, 125.4, 125.9, 126.0, 126.6, 126.7, 128.6, 140.4. Anal.
Calcd for C13
H
17N: C, 83.37; H, 9.15; N, 7.48. Found: C, 83.17;
53.4, 56.9, 117.1, 135.9. Anal. Calcd for C18H35N: C, 81.44; H,
H, 9.37; N, 7.48.
13.29; N, 5.28. Found: C, 81.46; H, 13.55; N, 5.33.
1
N,N-Diben zylla llyla m in e (7h ): colorless oil; H NMR δ 3.10
d, 2H, J ) 5.4 Hz), 3.61 (s, 4H), 5.15 (d, 1H, J ) 10.2 Hz), 5.25
d, 1H, J ) 18.7 Hz), 5.88-6.02 (m, 1H), 7.25-7.45 (m, 10H); C
(
(
Ack n ow led gm en t. We thank Professor Marcial
Moreno-Ma n˜ as (Barcelona) for his interest in this work
and for his helpful comments.
1
3
NMR δ 56.3, 57.7, 117.3, 126.8, 128.2, 128.68, 128.73, 136.0.
Anal. Calcd for C17 19N: C, 86.03; H, 8.07; N, 5.90. Found:
C, 85.56; H, 7.92; N, 5.28.
H
J O980200H