Letter
Iron-Catalyzed α,β-Dehydrogenation of Carbonyl Compounds
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ABSTRACT: An iron-catalyzed α,β-dehydrogenation of carbonyl com-
pounds was developed. A broad spectrum of carbonyls or analogues, such as
aldehyde, ketone, lactone, lactam, amine, and alcohol, could be converted to
their α,β-unsaturated counterparts in a simple one-step reaction with high
yields.
serves as both a Lewis acid and a redox catalyst. Herein, we
report the recent results in detail.
n organic synthesis, α,β-unsaturated carbonyl compounds
Iare useful building blocks. α,β-Dehydrogenation of carbonyl
compounds is among the most straightforward and practical
processes for the construction of α,β-unsaturated carbonyl
compounds. In earlier reports, either two- or multiple-step
procedures or the involvement of stoichiometric halogen-
containing oxidants, such as DDQ and hypervalent iodine
reagents, was necessary.1,2
Recently, catalytic approaches using transition metals,
especially palladium, have been well demonstrated as efficient
and powerful tools for the α,β-desaturation of a wide range of
carbonyl compounds.3−15 Other transition metals including
copper,16,17 ruthenium,18 platinum,19 iridium,20 and nickel21
have also been successfully applied as the catalyst (Scheme 1a).
The economical and ample supply of iron salts make them
ideal catalysts in both academic research and industrial
applications.22 Recently, iron-catalyzed dehydrogenation re-
actions of organic molecules, such as formic acid, alcohols, and
amines, for the alternative energy storage systems or
ecofriendly synthetic methods have been reported (Scheme
1b).23−28 However, the utilization of this earth-abundant metal
for the catalysts of α,β-dehydrogenation is exceedingly rare.
As part of our ongoing research interest in developing a
practical method to access α,β-unsaturated carbonyl com-
pounds via a dehydrogenation process,3,29 we envisioned that it
is possible to use iron as a bifunctional catalyst, in which it
Our investigations started with the reaction of 3-phenyl-
propanal 1a to cinnamaldehyde 2a in the presence of 10 mol %
FeCl3, 10 mol % 1,10-phenanthroline 3a, and 1 equiv of
TEMPO; 81% of 2a was obtained (Scheme 2). After
evaluations of a series of iron salts (see the Supporting
Information), FeCl3 proved to be best catalyst. Additives,
oxidants, and solvents were also investigated (see the
2 were finally chosen as the standard conditions for further
investigations.
The scope of aldehydes was first investigated. Both alkyl-
and aryl-substituted aldehydes could be converted to their α,β-
unsaturated counterparts (Scheme 2). When α-disubstituted
aldehyde 1b was subjected to the standard conditions, the
dehydrogenation product 2b was isolated in 61% yield.
Aldehydes bearing heterocyclic substituents, such as 2-, 3-, or
4-pyridyl (1c−1e), thiophenyl (1f), and methylfuryl (1g),
were all suitable. Aldehydes bearing either electron-rich or
electron-deficient aryl substituents (1h−1u) could also be
oxidized to the corresponding products. Dehydrogenation of
N-methyl-6-oxo-N-phenylhexanamide 1v with 2 equiv of
TEMPO afforded α,β-, γ,δ-dehydrogenation product 2v.
When cyclohexanecarbaldehyde 1w was treated with 3 equiv
of TEMPO, benzaldehyde 2w was obtained. Dehydrogenation
of 3-cyclohexylpropanal 1x under standard conditions
produced the corresponding α,β-dehydrogenation product 2x
in 67% yield. When the straight-chain aliphatic aldehyde
dodecanal 1y was subjected to the standard conditions, α,β-
dehydrogenation occurred albeit with low yield. The α,β-, γ,δ-
unsaturated product 2z was observed with prolonged reaction
time. After 17 h of reaction in the presence of 2 equiv of
Scheme 1. α,β-Dehydrogenation of Carbonyl Compounds
Received: January 6, 2021
Published: February 12, 2021
© 2021 American Chemical Society
Org. Lett. 2021, 23, 1611−1615
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