Synthesis of ene-allenes via palladium-catalyzed hydride-transfer reaction of propargylic amines under mild conditions

Article abstract of DOI:10.1016/j.tetlet.2005.09.169

The palladium-catalyzed allene transformation reaction from propargylic amines proceeded in the presence of Pd₂(dba)₃· CHCl₃ (5 mol %) and (C₆F₅)₂PC ₂H₄P(C₆

Full text of DOI:10.1016/j.tetlet.2005.09.169

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 8333–8336
Synthesis of ene–allenes via palladium-catalyzed hydride-transfer
reaction of propargylic amines under mild conditions
Hiroyuki Nakamura,* Satoshi Tashiro and Takaya Kamakura
Department of Chemistry, Faculty of Science, Gakushuin University, Mejiro, Tokyo, 171-8588, Japan
Received 27 June 2005; revised 22 September 2005; accepted 28 September 2005
Available online 11 October 2005
Abstract—The palladium-catalyzed allene transformation reaction from propargylic amines proceeded in the presence of
Pd2(dba)3ÆCHCl3 (5 mol %) and (C6F5)2PC2H4P(C6F5)2 (10 mol %) in CHCl3 at room temperature to give the corresponding allenes
in good to high yields. Dicyclohexyl groups substituted on the nitrogen of propargylic amines were found to be effective for the
current transformation and the conjugated ene–allenes 4 were synthesized from the corresponding propargylic amines 3 under mild
conditions.
Ó 2005 Elsevier Ltd. All rights reserved.
Allenes are now one of the attractive building blocks for
organic synthesis.1 Although various synthetic methods
NR2
have been developed for the synthesis of allenes includ-
ing the SN20-type displacement with organocopper
H
species,2 the homologation of 1-alkynes,3 the stereo-
selective reduction of alkynes,4 asymmetric allylations,5,6
NR2
b-eliminations by Horner–Emmons–Wadsworth7 or
sulfinyl radical8 reactions, and palladium-catalyzed
hydrogenolysis,9 development of simple protocols for
the introduction of an allene moiety into electrophiles
is still important subject. In this regard, palladium-cata-
lyzed coupling reactions of aryl halides with allenyl-
stannanes,10 allenylindiums,11 and allenylzincs12 have
been reported so far. We recently found that propargylic
amines underwent the hydride-transfer reaction in the
presence of a palladium catalyst to afford allenes.13 In
this transformation, propargyldiisopropylamine can be
handled as an allenyl anion equivalent and introduced
into various electrophiles to be transformed into allenes
(Scheme 1). Although the transformation can be utilized
for the synthesis of heterocyclic allenes,14 the reactions
required relatively high temperatures (80–100 °C), which
may cause side-reactions or decomposition of sub-
strates. Actually, the reaction of (E)-N,N-diisopropyl-
5-phenylpent-4-en-2-yn-1-amine under the previously
reported conditions did not afford the corresponding
E+
E
Pd-cat. hydrogen
transfer reaction
H
E
Scheme 1. Allenyl anion equivalent.
ene–allene but resulted in the decomposition of com-
pounds. Therefore, development of the allene transfor-
mation, which proceeds under mild conditions, has
been required for a wide use. In this letter, we found that
dicyclohexyl and dicyclopentyl groups substituted on
the nitrogen of propargylic amines are potent for the
current transformation and succeeded in the synthesis
of conjugated ene–allenes via palladium-catalyzed
hydride-transfer reaction from propargylic amines at
room temperature.
Various amines 1a–e were employed for the allene trans-
formation under palladium-catalyzed conditions as
shown in Table 1. The treatment of N,N-diisopropyl-3-
(4-methoxyphenyl)prop-2-ylamine 1a in the presence of
Pd2(dba)3ÆCHCl3 (2.5 mol %) and (C6H5)3P (20 mol %)
in dioxane at room temperature (Condition A)13 affor-
ded 4-methoxyphenylallene in 28% conversion with
11% yield, whereas 57% conversion with 58% yield
was observed in the presence of Pd2(dba)3ÆCHCl3
Keywords: Allene; Palladium catalyst; Propargylic amines; Hydride
transfer.
*
Corresponding author. Tel.: +81 339 860221x6491; fax: +81 359
921029; e-mail: hiroyuki.nakamura@gakushuin.ac.jp
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.09.169

8334
H. Nakamura et al. / Tetrahedron Letters 46 (2005) 8333–8336
Table 1. Effect of substituents on the nitrogen of propargylic amines
NR1R2
condition
MeO
MeO
2
1a-e
Entry
1
NR1R2
Conditiona
Conversion (%)
Yield of b 2 (%)
A
B
28
57
11
58
1a
N
N
N
1b
1c
2
3
A
B
53
71
96
89
A
B
C
58
67
>99
86
90
>99
N
4
A
B
82
73
Trace
7
MeO
1d
N
Me
5
A
B
44
66
98
71
1e
MeO
a Condition A: Pd2(dba)3ÆCHCl3 (2.5 mol %) and (C6H5)3P (20 mol %) in dioxane at room temperature for 4 days; Condition B: Pd2(dba)3ÆCHCl3
(2.5 mol %) and (C6F5)2PC2H4P(C6F5)2 (10 mol %) in CHCl3 at room temperature for 4 days; Condition C: Pd2(dba)3ÆCHCl3 (5 mol %) and
(C6F5)2PC2H4P(C6F5)2 (10 mol %) in CHCl3 at room temperature for 4 days.
b Isolated yield.
(2.5 mol %) and (C6F5)2PC2H4P(C6F5)2 (10 mol %) in
CHCl3 at room temperature (Condition B).14 Dicyclo-
pentylamine 1b and dicyclohexylamine 1c were more
effective for the allene transformation, and 4-meth-
oxyphenylallene was obtained in 71% and 67% conver-
sions with 89% and 90% yields, respectively, under the
condition B (entries 2 and 3). Surprisingly, the allene
transformation proceeded quantitatively when 5 mol %
of Pd2(dba)3ÆCHCl3 was employed (Condition C in
entry 3). N-Cyclohexyl-N-(2-methoxycyclohexyl)-3-(4-
methoxyphenyl)prop-2-ylamine 1d and N-cyclohexyl-
N-(1-phenylethyl)-3-(4-methoxyphenyl)prop-2-ylamine
1e, which would be expected chelation of a palladium
through the nitrogen and the oxygen, did not accelerate
the reaction rate very much (entries 4 and 5).
the corresponding allenes in 60–95% yields (entries 4–
6). The reaction of 1,4-di-[3-(dicyclohexylamino)prop-
1-yl]benzene afforded 1,4-diallenylbenzene in 56% yield
along with the monoallene transformation product
in 34% yield (entry 7). We also examined the transfor-
mation reaction from heterocyclic propargylamines. 3-
Allenylquinone and 3-allenylbenzo[b]thiophene were
obtained in 99% and 77% yields with 46% and 99%
conversions, respectively (entries 8 and 9). Propargylic
alcohols, which were synthesized from the correspond-
ing aldehydes and the lithium acetylide of N,N-di-
cyclohexylpropargylamine, were transformed into the
allenylcarbinols in 66–86% yields with high conversions
(entries 10 and 11).
The procedure for the current transformation under
mild conditions enabled us to synthesize the conjugated
ene–allenes, which are labile at high temperatures.15 The
results are shown in Table 3. The conjugated propargy-
lic amine 3a underwent the allene transformation reac-
tion in CHCl3 at room temperature for 7 days to
afford the corresponding conjugated ene–allene 4a in
88% yield with 75% conversion (entry 1). Various conju-
gated propargylic amines 3b–e were employed for the
allene transformation at room temperature and the
We next investigated the synthesis of various allenes
from the corresponding propagylic dicyclohexylamines.
The results are summarized in Table 2. Propargylic di-
cyclohexylamines, which have a strong electron-donat-
ing group on the phenyl ring, underwent the allene
transformation reaction to give the corresponding
allenes in good to high yields with high conversion
(entries 1–3). 3,5-Dimethylphenyl-, 4-acetylphenyl-,
and 2-naphthyl propargyldicyclohexylamines also gave

H. Nakamura et al. / Tetrahedron Letters 46 (2005) 8333–8336
8335
Table 2. Palladium-catalyzed allene transformation from the propar-
Table 3. Synthesis of the conjugated ene–allenes 4a
gyldicyclohexylamines at room temperature
allene
transformation
NCy2
Pd2(dba)3•CHCl3 (5 mol%)
(C6F5)2PC2H4P(C6F5)2 (10 mol%)
NCy2
R
R
CHCl3, r.t., 4 d
3
4
Entry Propargylic amine
Conversion Yieldsa
Entry Compound 3
Conversion Yield
(%)
(%)
(%)
of 4
(%)
NCy2
1
>99
>99
NCy2
1
3a
75
88
73
MeO
NCy2
NCy2
2
>99
78
>99
79
3b
2
100
88
AcNH
t-Bu
NCy2
NCy2
MeO2C
3
3c
3
57
O
MeO
O
NCy2
NCy2
Me
3d
4
72
85
30
76
4
58
95
N
i-Pr
Me
NCy2
5
NCy2
3e
C10H21
5
58
83
79
60
MeO
Me
6b
84
85
NCy2
3f
O
O
NCy2
a Condition: Pd2(dba)3ÆCHCl3 (5 mol %) and (C6F5)2PC2H4P(C6F5)2
(10 mol %) in CHCl3 at room temperature for 7 days.
b The reaction was carried out at 50 °C.
6
NCy2
7
>99
46
56 (34)b
Cy
Pd(0)
N
4
Cy2N
3
NCy2
8
99
7
N
R
R
Cy
Cy
NCy2
N
N
9
>99
>99
>99
77
66
86
Pd
Pd(0)
H
S
H
6
5
NCy2
Scheme 2. Proposed mechanism.
10
11
OH
MeO
Dicyclohexyl groups substituted on the nitrogen of
propargylic amines are effective for the current transfor-
mation. According to our proposed mechanism as
shown in Scheme 2, the imine 716 was generated along
with the ene–allenes 4 from 3 via the iminium ion inter-
mediates 6. Therefore, it is considered that a stable for-
mation of cyclic imines 7 would accelerate the catalytic
cycle in the current allene transformation.
NCy2
OH
a Isolated yield.
b The monoallene transformation product was obtained in 34% yield.
corresponding ene–allenes 4b–e were obtained in 30–
76% yields (entries 2–5). In the case of compound 3f,
the reaction carried at 50 °C gave the better yield than
that at room temperature (entry 6).
References and notes
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We succeeded in the synthesis of ene–allenes from the
corresponding propargylic amines at room temperature.

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H. Nakamura et al. / Tetrahedron Letters 46 (2005) 8333–8336
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decomposition of the compound.
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GC–MS analysis at the end of the reactions.