Angewandte
Communications
Chemie
Synthetic Methods
Ketenimines from Isocyanides and Allyl Carbonates: Palladium-
Catalyzed Synthesis of b,g-Unsaturated Amides and Tetrazoles
Guanyinsheng Qiu+, Mathias Mamboury+, Qian Wang, and Jieping Zhu*
Abstract: The reaction of allyl ethyl carbonates with isocya-
nides in the presence of a catalytic amount of Pd(OAc)2
provided ketenimines through b-hydride elimination of the
allyl imidoylpalladium intermediates. The insertion of the
isocyanide into the p-allyl Pd complex proceeded via an
unusual h1-allyl Pd species. The resulting ketenimines were
hydrolyzed to b,g-unsaturated carboxamides during purifica-
tion by flash column chromatography on silica gel or converted
in situ into 1,5-disubstituted tetrazoles by [3+2] cycloaddition
with hydrazoic acid or trimethylsilyl azide.
T
here has been increased interest in the exploitation of
isocyanides as a one-carbon-atom synthons in transition-
metal-catalyzed insertion reactions in the last decade.[1]
Isoelectronic with carbon monoxide, isocyanides possess
additional advantages of being tunable both electronically
and sterically, and are easy to handle. Following the seminal
contribution by Whitby and co-workers on the palladium-
catalyzed three-component reaction of isocyanides, aryl
halides, and amines,[2] a tin-free version of the synthesis of
amidines as described by Kosugi, Migita, and co-workers,[3]
many elegant transformations have been reported.[4,5] All
these reactions involved the generation of aryl or vinyl
Scheme 1. Palladium-catalyzed isocyanide insertion reactions. dba=di-
benzylideneacetone, dppe=1,2-bis(diphenylphosphanyl)ethane,
TMS=trimethylsilyl.
to take place under stoichiometric conditions,[13] we hypothe-
sized that a catalytic process leading to a ketenimine B could
be developed if b-hydride elimination from an alkyl imidoyl-
palladium intermediate A could be facilitated [Eq. (2)].[14] We
report herein that the reaction of allyl ethyl carbonates 1 with
isocyanides 2 in the presence of a catalytic amount of
Pd(OAc)2 indeed afforded vinyl ketenimines 3, which were
hydrolyzed upon flash column chromatography (FCC) on
silica gel to b,g-unsaturated carboxamides 4 [Scheme 1,
Eq. (3)]. We also document a three-component synthesis of
1,5-disubstituted tetrazoles 5 by in situ trapping of the
ketenimines 3 with hydrazoic acid (HN3) or TMSN3 [Eq. (4)].
We began our studies by using cinnamyl ethyl carbonate
(1a) and tert-butyl isocyanide (2a) as test substrates (Table 1).
In the presence of palladium acetate (0.1 equiv) and triphe-
nylphosphine (0.2 equiv), the reaction of 1a and 2a in THF at
508C afforded ketenimine 3a in 76% yield, as determined by
NMR spectroscopy. FCC of the crude ketenimine 3a afforded
the b,g-unsaturated carboxamide 4a in 50% yield.[15] Since
one-carbon homologation of allyl carbonates to give amides
4a is a useful transformation in organic synthesis,[16] we set out
to optimize the reaction conditions with regard to the yield of
amide 4a. The incorporation of a phosphine ligand was
detrimental to the desired transformation (Table 1, entries 1–
5), and a decrease in the catalyst loading increased the
reaction efficiency. With 0.01 equivalent of Pd(OAc)2, keten-
imine 3a was formed in 95% yield (as determined by NMR
spectroscopy); after FCC, 4a was isolated in 87% yield
(Table 1, entry 9). In this case, the crude ketenimine, after
evaporation of solvent, was pure enough to be fully charac-
terized (1H and 13C NMR, IR, HRMS). Even with
imidoylpalladium species, followed by ligand exchange and
2
À
reductive elimination with the formation of a key C(sp )
C(sp2) bond. Transformations leading to the formation of
3
2
À
a C(sp ) C(sp ) bond via an alkyl imidoylpalladium inter-
mediate, however, remain scarce.[5a,6]
The reaction of isocyanides with carbenes[7] and metallo-
carbenes[8] to generate ketenimines has been exploited in the
past.[9] In connection with our ongoing project aimed at
exploring new reactivity profiles of the isocyano functional-
ity,[10] we became interested in developing a new synthesis of
ketenimines[11] from isocyanides. In 2001, Yamamoto and co-
workers reported a palladium-catalyzed three-component
reaction of an aryl isocyanide, an allyl carbonate, and TMSN3
[Scheme 1, Eq. (1)].[12] Selective insertion of the isocyanide
À
into the Pd N3 bond in the [(p-allyl)PdN3] complex was the
key step in the formation of N-allyl cyanamides. Since the
À
insertion of an isocyanide into a (p-allyl) Pd bond is known
[*] Dr. G. Qiu,[+] M. Mamboury,[+] Dr. Q. Wang, Prof. Dr. J. Zhu
Laboratory of Synthesis and Natural Products, Institute of Chemical
Sciences and Engineering, Ecole Polytechnique Fꢀdꢀrale de Lausanne
EPFL-SB-ISIC-LSPN, BCH 5304, 1015 Lausanne (Switzerland)
E-mail: jieping.zhu@eplf.ch
[+] These authors contributed equally.
Supporting information for this article can be found under:
Angew. Chem. Int. Ed. 2016, 55, 1 – 6
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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