COMMUNICATION
DOI: 10.1002/chem.201302106
Tertiary Amines as Synthetic Equivalents of Vinyl Cations: Zinc Bromide
Promoted Coupling of Propargylamines with a-Isocyanoacetamides to Give
2,4,5-Trisubstituted Oxazoles Initiated by an Internal Redox Process
Yann Odabachian, Qian Wang, and Jieping Zhu*[a]
The Crabbꢀ homologation allows the synthesis of allenes
from in situ generated propargylamines through a 1,5-hy-
can interrupt the Crabbꢀ homologation leading to 2-vinyl
oxazoles 3 by an unprecedented domino 1,5-hydride shift/in-
dride
shift/1,2-elimination
sequence
(Equation (1),
termolecular
trapping/cyclization/elimination
sequence
Scheme 1).[1] Initially developed for the synthesis of mono-
substituted allenes, reaction conditions have now been es-
(Equation (3), Scheme 1). In this transformation, propargyl-
amine 1 acts formally as a synthetic equivalent of a vinyl
cation.[8] We note that a vinyl anion can be easily generated
from tosylhydrazone in the presence of a strong base and is
widely used in organic synthesis (the Shapiro reaction;
Equation (4), Scheme 1).[9] However, to the best of our
knowledge, the use of tertiary aliphatic amines as vinyl
cation synthetic equivalents has not yet been reported.[10]
We began our studies by investigating the reaction be-
tween N,N-diisopropylprop-2-yn-1-amine (1a) and a-isocya-
noacetamide 2a[11] in the presence of different metal salts. It
was found that neither CuI nor ZnACTHNUTRGNENUG(OTf)2 was able to pro-
mote the reaction. However, in the presence of a catalytic
amount of ZnBr2, the reaction produced a small amount of
unexpected 2-vinyl oxazole 3a (Table 1).[12] Intrigued by the
mechanism of this unprecedented reaction and the impor-
tance of oxazoles in natural product and medicinal chemis-
try,[13] the reaction conditions were optimized by varying the
amount of ZnBr2, the solvent, the temperature, and the ad-
ditives. Using the optimized reaction conditions—1a
(1.0 equiv, 0.1M), 2a (2.0 equiv), ZnBr2 (1.5 equiv), toluene,
reflux—oxazole 3a was isolated in 74% yield (Table 1). The
use of a stoichiometric amount of ZnBr2 was necessary for
the success of this transformation, the requirement originat-
Scheme 1. Tertiary propargylamine as a synthetic equivalent of a vinyl
cation: synthesis of 2-vinyl oxazoles.
tablished allowing access to di- and trisubstituted allenes.[2–3]
A recent important discovery came from the research group
of Nakamura who reported the first examples of intermolec-
ular nucleophilic trapping of incipient iminium intermediate
A for the synthesis of N-tethered 1,6-enynes C (Equa-
tion (2), Scheme 1).[4] Although there is recent interest in
the domino 1,5-hydride shift/cyclization of zwitterionic inter-
mediates,[5] examples of using an external nucleophile to
trap the cationic intermediate resulting from intramolecular
hydride shift are rare.[4,6–7] We report herein that isonitriles
ing from product inhibition, oxazoles being known to coor-
[14]
dinate strongly to Zn2+
.
Using 2a as the isocyanide component, the scope of the
tertiary amine was first examined (Table 1). In the case of
N-(pentan-3-yl)-N-(prop-2-yn-1-yl)pentan-3-amine (1b),
a
mixture of two stereoisomers was obtained in 74% yield in
favor of the Z isomer. With N-(sec-butyl)-N-(prop-2-yn-1-
yl)butan-2-amine (1c), less-substituted terminal olefin 3c
was formed together with a small amount of internal alkene
3c’ (3c/3c’, 10:1). Therefore, the regioselectivity of olefin
formation follows the Hofmann rule. Dicycloalkylpropargyl-
amines 1d–1g participated in this reaction without problems
to afford the corresponding products, namely, cyclopent-1-
en-1-yl, cyclohex-1-en-1-yl, cyclohept-1-en-1-yl, and cyclo-
oct-1-en-1-yl oxazoles (3d–g), respectively, in good yields.
Notably, the reaction also worked with N-methyl-propargyl-
amines 1h–1j. In accordance with the notion that a tertiary
[a] Dr. Y. Odabachian, Dr. Q. Wang, Prof. Dr. J. Zhu
Institute of Chemical Sciences and Engineering
Ecole Polytechnique Fꢀdꢀrale de Lausanne
EPFL-SB-ISIC-LSPN, BCH 5304, 1015 Lausanne (Switzerland)
Fax : (+41)21-6939740
Supporting information for this article is available on the WWW
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C H bond is a better hydride donor than a primary C H
Chem. Eur. J. 2013, 00, 0 – 0
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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