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ACS Catalysis
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Dehydrogenative Synthesis of Linear α,β‐Unsaturated Aldehydes
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t
with Oxygen at Room Temperature Enabled by BuONO
†
†
‡
†
Mei-Mei Wang, Xiao-Shan Ning, Jian-Ping Qu,* and Yan-Biao Kang*
†
Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China
‡
Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Jiangsu National Synergetic Innovation Center for
Advanced Materials, Nanjing Tech University, Nanjing 211816, China
aromatic aldehydes are generally suitable, in which bases or primary
amine-cocatalysts were not involved.
ABSTRACT: Synthesis of linear α,β-unsaturated aldehydes via a room-
temperature oxidative dehydrogenation has been realized by the
cocatalysis of an organic nitrite and palladium with molecular oxygen as
the sole clean oxidant. Linear α,β-unsaturated aldehydes could be
efficiently prepared under aerobic catalytic conditions directly from
corresponding saturated linear aldehydes. Besides linear products, the
aromatic analogy could also be smoothly achieved by the same standard
method. The organic nitrite redox cocatalyst and alcohol solvent play
Scheme 1. Dehydrogenation to α,β-Unsaturated Aldehydes
key
role
for
realizing
this
method.
KEYWORDS: dehydrogenation, α,β-unsaturated aldehydes, palladium, or-
ganic nitrite, co-catalysis
Linear α,β-unsaturated aldehydes are highly useful synthetic blocks in
organic synthesis. The strategy of direct preparation of linear α,β-un-
saturated aldehydes by corresponding α,β-dehydrogenative oxidation
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exhibits an efficient straightforward pathway. Compared to aromatic
α,β-unsaturated aldehydes, the synthetic methods to linear α,β-unsatu-
rated aldehydes have been less reported. The approaches with hazard-
ous stoichiometric oxidants such as PhSeCl, IBX, and Pd(II)-Ag(I) have
Initially, for comparison, the literature methods were tested in the ox-
idative dehydrogenation of aliphatic aldehyde 1a to the corresponding
α,β-unsaturated aldehyde 2a. All these Pd-catalyses were found
ineffective (Table 1, entries 2-4). The elevated reaction temperature,
basic reaction medium or amine-cocatalysts made the unstable aliphatic
aldehyde 1a consumed via aldol condensation and other side-reaction.
The IBX-oxidative dehydrogenation gave no 2a either (entry 1). Thus
all literature methods tested here failed for the efficient conversion of 1a
to 2a.
1-4
been reported decades ago (Scheme 1). The indirect route with stoi-
chiometric palladium-mediated dehydrogenation, namely Saegusa reac-
tion, transforms enol silyl ethers to linear α,β-unsaturated aldehydes.2
a
As a more general synthetic method, the α,β-dehydrogenative oxidant of
aldehydes with excess IBX (2-iodoxybenzoic acid) has been found to be
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efficient at elevated temperatures in DMSO and PhF. However, this
method is flawed by the limited solubility of IBX in many common or-
ganic solvents as well as the limited scope of aldehyde. With respect to
the transition metal-catalyzed dehydrogenation of aldehydes, despite re-
markable progress has been accomplished by Wang, Stahl, and Huang et
al, the scope of aldehyde has still been limited to few aromatic alde-
When Pd(PhCN)
BuOH gave a moderate yield of 2a (entries 5-7), in which the
conditions have been used in the aldehydes-selective Wacker oxidation
2
Cl
2
used instead of Pd(OAc)
2
, only the reaction in
t
5-8
hydes. So far, the synthesis of linear α,β-unsaturated aldehydes via cat-
9a
in previous report. The reaction in the presence of K
2
CO afforded no
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alytic oxidative α,β-dehydrogenation has still remained unrevealed.
2a (entry 6), indicating bases destroy either aldehyde substrates or α,β-
In another hand, molecular oxygen is a clean and cheap oxidant which
has been widely used in industrial oxidations as well as organic synthesis.
unsaturated aldehydes. The coordinative aprotonic co-solvent such as
PhCN and DMSO inhibited the reaction (entries 7-8). Surprisingly, the
addition of toluene increased the yield to 61% (entry 9). The reaction
under weakly acidic conditions gave rise to the elevation of the yield to
Despite O
2
has many advantages, the activation of O
2
to form reactive
[
O] in transition metal catalysis normally involves the redox cocatalyst
such as copper or the acceleration with a special ligand such as
diazafluoren (DAF).5 Recently, we have reported organic nitrite-Pd-
cocatalyzed anti-Markovnikov Wacker oxidation and aerobic
70% (entry 10). When mesitylene (C
6
H
3
Me ) was used instead of
3
-6
toluene, the yield was further increased to 88% (entry 11). The role of
t
BuOH and mesitylene is not clear. Neither reaction under argon nor in
t
acetoxyhydroxylation of alkenes enabled by the activation of O
BuONO. Herein, we have developed a highly efficient catalytic
2
with
the absence of redox cocatalyst BuONO succeeded (entries 12-13).
t
9-10
The reaction with inorganic redox co-catalyst NaNO
BuONO gave diminished yield of 2a (entry 14). The reaction with 7.5
2
instead of
t
system for a ligand-free aerobic dehydrogenation of saturated aldehydes
to linear α,β-unsaturated aldehydes, in which both aliphatic and
mol % of Pd(PhCN)
2
Cl afforded comparable yield of 2a, thus the
2
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