Palladium/Benzoic Acid Catalyzed Hydroamination of Alkynes

Full text of DOI:10.1021/jo990498r

4570
J . Org. Chem. 1999, 64, 4570-4571
Communications
Ta ble 1. P a lla d iu m /Ben zoic Acid Ca ta lyzed
Hyd r oa m in a tion of Alk yn es
P a lla d iu m /Ben zoic Acid Ca ta lyzed
Hyd r oa m in a tion of Alk yn es
Isao Kadota,† Akinori Shibuya,
Leopold Mpaka Lutete, and Yoshinori Yamamoto*
Research Center for Organic Resources and Materials
Chemistry, Institute for Chemical Reaction Science, and
Department of Chemistry, Graduate School of Science,
Tohoku University, Sendai 980-8578, J apan
Received March 22, 1999
The hydroamination of C-C multiple bonds has been
considered as one of the most efficient methods for the
synthesis of organo-nitrogen compounds, because the addi-
tion process does not produce a waste element in contrast
to the substitution process which inevitably affords a useless
byproduct.1 The palladium-catalyzed intermolecular hydro-
aminations of 1,3-dienes,2 allenes,3 enynes,4 and methyl-
enecyclopropanes5 have been developed to realize the ideal
C-N bond formation. Recently, we reported that certain
alkynes react with carbon pronucleophiles in the presence
of palladium/acetic acid catalyst to give the corresponding
allylation products (formal hydrocarbonation based on the
rearrangement of an alkyne to an allene).6a The hydrocar-
bonation process is similar to the hydroacylation process
reported by Trost et al. for the allylation of acetic acid with
alkynes which gives allylic acetates.6b It occurred to us that
the formal hydrocarbonation may be extended to the formal
hydroamination to provide a new atom-economical procedure
for the synthesis of amines from alkynes.7 Actually, the
reaction of certain aromatic acetylenes 1 with amines 2 in
the presence of 5 mol % Pd(PPh3)4 and 10 mol % PhCO2H
in dioxane at 100 °C gave the corresponding allylic amines
3 in very high to good yields (eq 1).
a
b
Isolated yield. Inseparable mixture of the stereoisomers. The
ratio was determined by 1H NMR analysis.
respectively, in good to high yields (entries 2-4). In all cases,
no regio- or stereoisomers were obtained. No reaction took
place in the absence of benzoic acid. Other examples with
various alkynes are summarized in Table 1. When p-
methoxyphenylalkyne 1b was used as a substrate, the yield
was slightly increased (see entries 3 and 5). The reaction of
substrates which have an electron-withdrawing groups at
the para-position gave a messy mixture. A novel N,O-acetal
3f was synthesized in good yield by the reaction of propar-
gylic ether 1c (entry 6). The reaction of cyclopropylphenyl-
acetylene 1d produced an 85:15 mixture of the E and Z
linear adducts 3g in 72% yield (entry 7). Aliphatic acetylenes
such as 3-hexyne and 1-octyne did not react with amines
under the reaction conditions mentioned above. The reaction
of primary amines 2e and 2f was examined; 3 equiv of 1a
was treated with 2e and 2f under the same reaction
conditions as above to give the 2:1 adducts 3h and 3i,
respectively, in good yields (eq 2).
In an initial experiment, 1-phenyl-1-propyne (1a ) was
treated with 1 equiv of dibenzylamine (2a ), Pd(PPh3)4 (5 mol
%), and benzoic acid8 (10 mol %) in dioxane at 100 °C to
give the allylic amine 3a as a sole product in 98% yield
(Table 1, entry 1). Similarly, the reactions of 1a with
secondary amines 2b-d gave the allylic amines 3b-d ,
† Institute for Chemical Reaction Science.
(1) For recent review of catalytic hydroamination, see: Mu¨ller, T. E.;
Beller, M. Chem. Rev. 1998, 98, 675-703.
(2) Armbruster, R. W.; Morgan, M. M.; Schmidt, J . L.; Lau, C. M.; Riley,
R. M.; Zabrowski, D. L.; Dieck, H. A. Organometallics 1986, 5, 234-237.
(3) (a) Besson, L.; Gore´, J .; Cazes, B. Tetrahedron Lett. 1995, 36, 3857-
3860. (b) Al-Masum, M.; Meguro, M.; Yamamoto, Y. Tetrahedron Lett. 1997,
38, 6071-6074. For lanthanoid-catalyzed intramolecular hydroamination
of allenes, see: (c) Arredondo, V. M.; McDonald, F. E.; Marks, T. J . J . Am.
Chem. Soc. 1998, 120, 4871-4872.
(4) Radhakrishnan, U.; Al-Masum, M.; Yamamoto, Y. Tetrahedron Lett.
1998, 39, 1037-1040.
(5) Nakamura, I.; Itagaki, H.; Yamamoto, Y. J . Org. Chem. 1998, 63,
6458-6459.
(6) (a) Kadota, I.; Shibuya, A.; Gyoung, Y.-S.; Yamamoto, Y. J . Am. Chem.
Soc. 1998, 120, 10262-10263. (b) Trost, B. M.; Brieden, W.; Baringhaus,
K. H. Angew. Chem., Int. Ed. Engl. 1992, 31, 1335-1336. See also ref 9.
(7) For lanthanoid-catalyzed intramolecular hydroamination of alkynes,
see: Li, Y.; Marks, T. J . J . Am. Chem. Soc. 1996, 118, 9295-9306 and
references therein.
The reaction of 1-phenyl-1-propyne (1a ) with dibenzyl-
amine (2a ) is representative. A mixture of 1a (75 µL, 0.6
mmol), 2a (96 µL, 0.5 mmol), Pd(PPh3)4 (29 mg, 0.025 mmol),
and benzoic acid (6 mg, 0.05 mmol) in dry dioxane (2 mL)
(8) The use of acetic acid gave slightly lower yield.
10.1021/jo990498r CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/06/1999

Communications
J . Org. Chem., Vol. 64, No. 13, 1999 4571
Sch em e 1
The reaction of the alkynes 4a and 4b, having a monopro-
tected amino group at the terminus of the carbon chain,
under the standard conditions mentioned above gave the
pyrrolidine derivatives 5a and 5b, respectively, in good
yields (eq 3). Similarly, the benzylamine derivative 6a
cyclized to produce piperidine 7 in 81% yield (eq 4). Interest-
ingly, the tosylamide counterpart 6b gave the linear diene
8 in 80% yield. Perhaps, the tosyl group would decrease the
nucleophilicity of the nitrogen atom, hampering the cycliza-
tion. The diene 8 would be produced from the corresponding
π-allylpalladium species via â-elimination.
was stirred overnight at 100 °C. The reaction mixture was
then filtered through a short silica gel column using ether
as an eluent, and the filtrate was concentrated. The residue
was purified by a silica gel column chromatography (hexane/
EtOAc, 10:1) to give 3a (154 mg, 98%).
A plausible catalytic cycle of this hydroamination is
illustrated in Scheme 1. The initial step would be hydro-
palladation of 1a with the hydridopalladium species 9
generated from Pd0 and benzoic acid (catalytic cycle I).9 The
resulting vinylpalladium species 10 would produce phenyl-
allene 11 and the active catalyst 9 via â-elimination.10
Hydropalladation of 11 with 9 would give the π-allylpalla-
dium species 12 which would react with amine 2 to give the
product 3 along with the hydridopalladium 9 (cycle II).11
The usefulness of this transformation is demonstrated by
the intramolecular version of the hydroamination reaction.
In conclusion, we have developed a simple and efficient
method for the synthesis of various acyclic and cyclic allylic
amines using palladium/benzoic acid catalyst. Application
of this efficient process to alkaloid synthesis is presently
under investigation.
Ack n ow led gm en t. This work was financially sup-
ported by the Grant-in-Aid for Scientific Research from the
Ministry of Education, Science and Culture of J apan.
(9) Trost, B. M.; Rise, F. J . Am. Chem. Soc. 1987, 109, 3161-3163.
(10) For palladium-catalyzed isomerization of alkynes to allenes, see: (a)
Sheng, H.; Lin, S.; Huang, Y. Tetrahedron Lett. 1986, 27, 4893-4894. (b)
Trost, B. M.; Schmidt, T. J . Am. Chem. Soc. 1988, 110, 2301-2303. (c) Lu,
X.; J i, J .; Ma, D.; Shen, W. J . Org. Chem. 1991, 56, 5774-5778.
(11) For the allylation of acetic acid with alkynes via a π-allylpalladium
intermediate, see ref 6b and Al-Masum, M.; Yamamoto, Y. J . Am. Chem.
Soc. 1998, 120, 3809-3810.
Su p p or tin g In for m a tion Ava ila ble: Characterization data
of compounds 3a -i, 5a , and 7. This material is available free of
charge via the Internet at http://pubs.acs.org.
J O990498R