6766
J . Org. Chem. 1996, 61, 6766-6767
Sch em e 1
P a lla d iu m -Ca ta lyzed Ca r bon yla tion of
P r op a r gyla m in es. Selective In ser tion of
Ca r bon Mon oxid e in to a Ca r bon -Nitr ogen
Bon d
Yasushi Imada† and Howard Alper*
Department of Chemistry, University of Ottawa,
10 Marie-Curie, Ottawa, Ontario, Canada K1N 6N5
Received J uly 18, 1996
The selective insertion of carbon monoxide into an
unactivated carbon-nitrogen bond of amine to form an
amide provides a novel and convenient process for
homologation and functionalization of nitrogen-contain-
ing organic molecules. Many attempts have been made
to achieve this attractive process, and some nitrogen
heterocycles have been found to undergo carbonylative
ring expansion with efficiency.1 However, the palladium-
catalyzed homologation of allylamines is the only ex-
ample involving an acyclic system.2
Ta ble 1. P a lla d iu m -Ca ta lyzed Ca r bon yla tion of
P r op a r gyla m in es to 2,4- a n d 2,3-Dien a m id esa
Propargyl alcohols and their esters have been used as
reactants in a number of metal-catalyzed carbonylation
reactions.3 For example, propargyl esters such as car-
bonates and phosphates are readily carbonylated to give
the corresponding 2,3-dienoates. We have also found that
propargyl alcohols are carbonylated directly to give 2,4-
dienoates4 or furanones,5 depending on the reaction
conditions. Much less attention has been paid to the
carbonylation of propargylamines, with several examples
of cyclization reactions reported, including the rhodium-
catalyzed hydroformylation to pyrroles6 and silylformy-
lation to R-(silylmethylene) â-lactams7 as well as the
palladium-catalyzed oxidative alkoxycarbonylation to
4-(alkoxycarbonyl)pyrrolidones or R-[(alkoxycarbonyl)-
methylene] â-lactams.8 We now wish to report that tris-
(dibenzylideneacetone)dipalladium, with added 1,3-bis-
(diphenylphosphino)propane (dppp) and p-toluenesulfonic
acid, catalyzes the selective insertion of carbon monoxide
into a carbon-nitrogen bond of propargylamines 1 to give
the corresponding 2,4-dienamides 2 or 2,3-dienamides 3
(Scheme 1).
When N-(3-methyl-1-butyn-3-yl)aniline (1a) was treated
with carbon monoxide (600 psi) and a catalytic system
consisting of Pd2(dba)3‚CHCl3, dppp, and p-TsOH in
dichloromethane at 100 °C for 6 h, pure N-phenyl-4-
methyl-2,4-pentadienamide (2a ) was isolated in 66% yield
by column chromatography. It is noteworthy that the
stereochemistry of the R,â-double bond is exclusively E
a
Reaction conditions: propargylamine, Pd2(dba)3‚CHCl3 (2 mol
%), dppp (4 mol %), p-TsOH (4 mol %), dichloromethane, 100 °C,
b
6 h. Propargylamines were synthesized using known methodol-
ogy.9,10 c Products were identified by spectroscopic methods [IR,
MS, NMR (1H, 13C)]. Isolated yield. e 60:40 (2E,4E)/(2E,4Z). f 48
d
h reaction.
) 15.3 Hz). The reaction in the absence of p-TsOH gave
the amide 2a in low yield. Bidentate phosphines such
as dppp and 1,4-bis(diphenylphosphino)butane were ef-
fective as added ligands, while other bidentate and
monodentate phosphines, or the absence of any phos-
phines, showed quite low activities for the formation of
2a . The reaction proceeds well in dichloromethane or
benzene but not in THF.
1
as confirmed by the H NMR coupling constant (3J H2-H3
† Present address: Department of Chemistry, Faculty of Engineer-
ing Science, Osaka University, 1-3, Machikaneyama, Toyonaka, Osaka
560, J apan.
(1) For a review, see: Khumtaveeporn, K.; Alper, H. Acc. Chem. Res.
1995, 28, 414.
(2) Imada, Y.; Nishimura, K.; Murahashi, S.-I. Tetrahedron 1994,
50, 453.
The carbonylation of propargylamines proceeded
smoothly to give 2,4-dienamides 2 in 50-70% yield for
both secondary and tertiary acyclic propargylamines
containing a terminal acetylene unit, and the results are
listed in Table 1 (entries 1-4). Cyclic propargylamine
1e also underwent carbonylation to give the cyclic di-
enamide 2e (Table 1, entry 5); however, 48 h was
required to complete the reaction presumably due to
steric effects. In all cases, 2E isomers were formed
exclusively. On the other hand, propargylamines bearing
either a substituent at the acetylene terminus or an
(3) For a review, see: Tsuji, J .; Mandai, T. Angew. Chem., Int. Ed.
Engl. 1995, 34, 2589.
(4) Huh, K.-T.; Orita, A.; Alper, H. J . Org. Chem. 1993, 58, 6956.
(5) El Ali, B.; Alper, H. J . Org. Chem. 1991, 56, 4099.
(6) Campi, E. M.; J ackson, W. R.; Nilsson, Y. Tetrahedron Lett. 1991,
32, 1093.
(7) Matsuda, I.; Sakakibara, J .; Nagashima, H. Tetrahedron Lett.
1991, 32, 7431.
(8) Bonardi, A.; Costa, M.; Gabriele, B.; Salerno, G.; Chiusoli, G. P.
Tetrahedron Lett. 1995, 36, 7495.
(9) Imada, Y.; Yuasa, M.; Nakamura, I.; Murahashi, S.-I. J . Org.
Chem. 1994, 59, 2282.
(10) Alami, M.; Ferri, F.; Linstrumelle, G. Tetrahedron Lett. 1993,
34, 6403.
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