DOI: 10.1002/asia.201403092
Communication
Synthesis Design
An Unexpected Double Diels–Alder Reaction of (E)-2-Bromo-4-
aryl-1,3-pentadiene Involving [1,5]-Hydrogen Migration and HBr
Elimination: Synthesis of Bicyclo[2.2.2]octene Derivatives
Pingping Huang, Lingyan Liu,* Weixing Chang, and Jing Li*[a]
Diels–Alder (DDA) reaction was unexpectedly developed be-
Abstract: An unexpected double Diels–Alder (DDA) reac-
tion of (E)-2-bromo-4-aryl-1,3-pentadiene was developed
tween this conjugated diene and N-phenylmaleimide (2a), re-
sulting in a “butterfly-like” bicyclo[2.2.2]octene derivative that
and resulted in a series of “butterfly-like” bicyclo[2.2.2]oc-
has broad applications in the fields of medicine and molecular-
sieve materials (Scheme 1).[4] In the last few decades, other
tene derivatives in moderate to good yields without the
need for a metal catalyst. The proposed mechanism in-
volves a [1,5]-sigmatropic hydrogen migration and HBr
elimination. Through this decisive [1,5]-hydrogen shift
step, the electronic properties and steric hindrance of the
conjugated diene substrate are completely altered and
the DDA reaction of this potential diene synthon is suc-
cessfully achieved.
The Diels–Alder (D–A) reaction, which is a concerted [4+2] cy-
cloaddition reaction of a conjugated diene with a dienophile,
is one of the most important carbon–carbon bond-forming re-
actions in synthetic organic chemistry.[1] It provides chemists
with one of the best tools for the construction of six-mem-
bered rings and has nearly singular capability of establishing
large numbers of stereochemical centers in one step.[2] In view
of its utility, the D–A reaction has been a major focus in the
Scheme 1. An unexpected DDA reaction.
development of diverse diene substrates. A variety of 1,3-
dienes with bromo substitution at the 2-position and aryl and
methyl groups at the 4-position are now available through
a simple procedure developed by our research group.[3] We
chose the D–A reaction to explore the application of this con-
jugated diene. The diene possesses some noteworthy proper-
ties: 1) it has multiple substituents with large steric hindrance
(Me and aryl groups at the same carbon atom, C4); 2) it has an
electron-withdrawing group (2-Br), which is an inverse-elec-
tron-demand substrate; and 3) it easily dimerizes and oligo-
merizes. These properties pose a great challenge for the D–A
reaction from the perspective of configuration, electronic
nature, and steric hindrance. Nonetheless, a novel double
dienes have been developed to synthesize bicyclo[2.2.2]octene
derivatives.[5] The 1,4-elimination of small molecules (such as
CO2, CO, RCONH2, or RCOOH) is generally involved in this syn-
thesis, but a group shift is not. However, herein, the methyl
and phenyl groups located at the same carbon atom, C4, were
adjusted to be located at different carbon atoms, C4 and C2
(Scheme 1).
This result intrigued us to conduct a thorough study of this
DDA reaction. Our experimental parameters were finely
screened (Table 1). Interestingly, when only 1.5 equivalents of
2a were used, the bicyclo[2.2.2] product could still be ob-
tained with a small amount of polymerization owing to the
diene’s instability at 1308C in anisole (Table 1, entry 1). Because
two molecules of 2a were always involved, the amount of di-
enophile was adjusted for high conversion of the diene. As ex-
pected, the DDA reaction yield gradually improved with in-
creasing amounts of 2a (Table 1, entries 2–4). Notably, the use
of 3.0 equivalents of 2a yielded up to 73% of the bicy-
clo[2.2.2]octene derivative. Prolonging the reaction time to
20 h, on the contrary, the yield decreased to 61% under the
standard conditions (Table 1, entry 5). Changing the solvent
[a] P. Huang, Dr. L. Liu, W. Chang, Prof. J. Li
State Key Laboratory of Elemento-Organic Chemistry
The Department of Chemistry, Nankai University
Collaborative Innovation Center of
Chemical Science and Engineering (Tianjin)
Weijin Road 94#, Nankai District
Tianjin 300071 (P.R. China)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/asia.201403092.
Chem. Asian J. 2015, 00, 0 – 0
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