Tert-Butyl Nitrite: Organic Redox Cocatalyst for Aerobic Aldehyde-Selective Wacker-Tsuji Oxidation

Article abstract of DOI:10.1021/acs.orglett.6b01165

An aldehyde-selective aerobic Wacker-Tsuji oxidation is developed. Using tert-butyl nitrite as a simple organic redox cocatalyst instead of copper or silver salts, a variety of aldehydes were achieved as major products in up to 30/1 regioselectivity as well as good to high yields at room temperature.

Full text of DOI:10.1021/acs.orglett.6b01165

Letter
pubs.acs.org/OrgLett
tert-Butyl Nitrite: Organic Redox Cocatalyst for Aerobic Aldehyde-
Selective Wacker−Tsuji Oxidation
Xiao-Shan Ning, Mei-Mei Wang, Chuan-Zhi Yao, Xian-Min Chen, and Yan-Biao Kang*
Center of Advanced Nanocatalysis, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026,
China
S
* Supporting Information
ABSTRACT: An aldehyde-selective aerobic Wacker−Tsuji
oxidation is developed. Using tert-butyl nitrite as a simple
organic redox cocatalyst instead of copper or silver salts, a
variety of aldehydes were achieved as major products in up to
30/1 regioselectivity as well as good to high yields at room
temperature.
acker−Tsuji oxidation1 is a palladium−copper cocata-
During the ammoxidation of methylarenes,10a it was noted
t
Wlyzed process for converting terminal alkenes to that BuONO was a convenient organic NO-source which
ketones,2 normally under aerobic conditions and following
the Markovnikov rule. Copper salts are usually used as
necessary transition metal redox cocatalysts. Despite ketone-
selective Wacker−Tsuji oxidation of terminal olefins having
been well established, the aldehyde-selective version of this
reaction following the anti-Markovnikov rule remains a
challenge.3 Remarkable progress has been made recently4−7
for aerobic8 and nonaerobic9 aldehyde-selective Wacker−Tsuji
oxidation, especially using benzoquinone (BQ) as the oxidant
(Scheme 1). The Pd/Cu/Ag/MNO2 catalytic system gave
aldehydes with generally good selectivity.8
might replace inorganic NO2-salts10b in catalysis. Thus, various
palladium catalysts were investigated in the aerobic oxidation of
t
1a to aldehyde 2a in BuOH at room temperature (Table 1).
Nitrile ligands have obvious effects on the regioselectivity as
well as the conversion of 2a (entries 2−8). Pd(PhCN)2Cl2
gives the best regioselectivity (entry 3). When the reaction was
carried out in the absence of O2, only 10% conversion was
t
obtained with the oxidation by BuONO itself (entry 9). The
reaction selectivity has no dependence on the amounts of
tBuONO (entries 10−13). When excess TBN was used, the
reaction finished in 30 min. This is consistent with the kinetic
study which reveals a zeroth-order dependence of tBuONO on
the initial rate. Despite the fact that an excess amount of
tBuONO has no effect on the conversion of 1a to 2a, palladium
black could be seen in the reactions with a lower loading of
tBuONO; therefore 20 mol % of TBN was used for further
investigation of the substrate scope. The catalyst loading has a
slight effect on the reaction yields (entries 3 and 14−16).
Hypothetically, Pd(CH3 CN)2 ClNO2 or Pd-
(CH3CN)2(NO2)2 could be the catalytically active forms
Scheme 1
t
which is in situ generated from Pd(PhCN)2Cl2 and BuONO
in the reaction mixture. However, the reaction using either
NO2-containing Pd-complex gives only a trace amount of 2a
(entries 17 and 18), suggesting the catalytically active species
should not be the NO2-containing Pd-complexes.11 The
stoichiometric Pd-catalyst gives rise to 14% conversion in the
t
t
absence of BuONO and O2, indicating BuONO should be a
The advantage of using clean and green molecular oxygen as
the sole oxidant under aerobic conditions is that it supports
sustainable chemistry. In fact, inorganic redox cocatalysts such
as CuCl and MNO2 (M: Na, K, Ag) are still used under aerobic
conditions in most cases. Therefore, an aerobic Wacker−Tsuji
oxidation in the absence of metal redox cocatalysts approaches
the concept of green chemistry. Herein, an aldehyde-selective
aerobic Wacker−Tsuji oxidation enabled by a simple organic
redox cocatalyst for regeneration of Pd(II).
After establishing the optimized reaction conditions (5 mol
% of Pd(PhCN)2Cl2, 20 mol % TBN), the scope of aldehyde-
selective Wacker−Tsuji oxidation was evaluated (Scheme 2).
Various terminal alkenes bearing different functional groups
were subjected to the optimized conditions, and aldehyde
t
redox cocatalyst BuONO (TBN) has been developed, where
Received: April 21, 2016
benzoquinone or a copper redox cocatalyst is not involved.
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b01165
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
a
Table 1. Reaction Conditions
Scheme 2. Reaction Scope
b
b
entry
[Pd] (mol %)
tBuONO (mol %) 2a/3a
2a (%)
1
2
3
4
5
6
7
8
−
20
−
−
12/1
0
Pd(PhCN)2Cl2
none
20
0
Pd(PhCN)2Cl2
71
76
59
73
75
60
10
14
72
72
71
71
77
82
3
Pd(p-MePhCN)2Cl2
Pd(p-CF3PhCN)2Cl2
Pd(C4H9CN)2Cl2
Pd(tBuCN)2Cl2
20
11/1
20
4.5/1
10/1
6/1
20
20
Pd(MeCN)2Cl2
20
7.5/1
5/1
c
9
Pd(PhCN)2Cl2
20
10
11
12
13
Pd(PhCN)2Cl2
5
14/1
10/1
14/1
14/1
10/1
13/1
10/1
1.5/1
1/1
Pd(PhCN)2Cl2
10
Pd(PhCN)2Cl2
30
Pd(PhCN)2Cl2
100
20
d
14
Pd(PhCN)2Cl2 (2.5)
Pd(PhCN)2Cl2 (5)
Pd(PhCN)2Cl2 (7.5)
Pd(CH3CN)2Cl(NO2)
Pd(CH3CN)2(NO2)2
Pd(PhCN)2Cl2
e
15
20
f
16
20
17
18
none
none
none
20
2
g
19
2/1
14
h
j
20
Pd(PhCN)2Cl2
2/1
40
i
j
21
Pd(PhCN)2Cl2
20
2.3/1
70
a
b
Reaction conditions: 1a (0.5 mmol). By 1H NMR (400 MHz) using
c
d
1,4-dioxane as internal standard. Under argon. With 2.5 mol % of
[Pd], 180 min. With 5 mol % of [Pd], 90 min. With 7.5 mol % of
e
f
g
[Pd], 90 min. With 100 mol % [Pd] in the absence of TBN and O2.
h
i
t
t
MeOH instead of BuOH as solvent. EtOH instead of BuOH as
j
solvent. The ratio and yield refer to the total yield of 2a and acetal.
products were obtained with as high as 30:1 regioselectivity in
generally good to high isolated yields. Various functional
groups or protecting groups could be tolerated under these
reaction conditions. For example, aldehydes 2a and 2b bearing
PhO- and PhCO2-groups were isolated in 76% and 75% yields
with high regioselectivity, providing an easy access to ω-
hydroxy aldehydes from corresponding unsaturated alcohol
derivatives. The unstable protecting groups such as MOM
remained unchanged in the oxidation (2e−f, 2n). Even
nitrogen-containing substrates smoothly gave the desired
aldehydes in high yields with up to 30:1 selectivity (2g−j).
The unstable TsO-aldehyde 2o was also obtained in 77% yield
with 24:1 selectivity.
a
Condition A: 1 (0.5 mmol), Pd(PhCN)2Cl2 (5 mol %), tBuONO (20
mol %), tBuOH, O2 (1 atm), isolated yields. Ratios refer to aldehyde/
b
c
ketone. Pd(PhCN)2Cl2 (10 mol %). Pd(PhCN)2Cl2 (7.5 mol %).
d
Same as condition A except EtOH instead of tBuOH and 10 mol % of
t
[Pd] were used. Ratios refer to acetal/ketone.
When EtOH was used as solvent instead of BuOH, acetal
products were achieved in good to high yields with as high as
8.8:1 regioselectivity (4a−b).
With respect to the internal alkenes, 1p has been subjected to
the reaction conditions (eq 1) and the normal Wacker product
3p was obtained in 88% yield, indicating this reaction condition
is also suitable for internal alkenes with ketone-selective
products.
with 5 mol % of the Pd-catalyst (Scheme 3). More than 2 g of
aldehydes 2a and 2i were obtained with 13:1 and 23:1
selectivity in high yields. With respect to the acetal-selective
oxidation, 4b was obtained with 6.8:1 regioselectivity (acetal/
ketone) in 80% yield.
To explore the effects of the palladium catalyst and the role
t
of BuONO, the dependence of the initial rate on the
concentrations of [Pd], [tBuOH], [1a], and [tBuONO] was
examined by a kinetic study (Figure 1A−1D). A first-order
dependence of the initial rate on the amount of the palladium
catalyst was established (Figure 1A). There is no induction
phase observed in conversion−time plots, indicating Pd(II) in
[Pd(PhCN)2Cl2] should be the catalytically active form which
directly catalyzed this reaction. A first-order dependence of the
The aldehyde-selective Wacker−Tsuji oxidation in gram-
scale could also result in high regioselectivity and high yields
B
DOI: 10.1021/acs.orglett.6b01165
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 3. Gram-Scale Reactions
Scheme 4. Control Experiments
large amount of PhCN which obviously inhibited the reaction
(Scheme 4, bottom). The excess PhCN has another negative
effect on the ratios of 2a and 3a. In the control reactions, 20
t
mol % Pd-catalyst without BuONO gave 6.3/1 selectivity,
whereas the increase in the amount of the Pd-catalyst resulted
in an obvious decrease of the aldehyde/ketone ratios.
Therefore, Pd(II) should be the catalytically active species for
initializing the Wacker−Tsuji oxidation and NO plays the role
of redox cocatalyst for the regeneration of Pd(II) from Pd(0).
A plausible mechanism for this aldehyde-selective Wacker−
Tsuji oxidation is proposed on the basis of control experiments
and kinetic study (Scheme 5). A Pd(II)-catalyzed oxidation is
proposed on the basis of kinetic study and previous work.
tBuOH (solvent) attacks A to form intermediate B, followed by
β-elimination to afford C. Enol ether C is protonated to 2
under equilibrium. A catalytically active Pd(II) species is
Figure 1. Dependence of the initial rate on (A) [Pd(PhCN)2Cl2]
(first-order); (B) [tBuOH] (first-order); (C) [1a] (zeroth-order); (D)
[tBuONO] (zeroth-order). Conditions: 1a, Pd(PhCN)2Cl2 (5−12.5
mol %), tBuONO (20 mol % for A−C, 6.5−9.5 mol % for D), tBuOH,
O2 (1 atm). For details, see Supporting Information.
t
amount of BuOH (solvent) on the initial rate was established
(Figure 1B). The zeroth-order dependence of [1a] or the
t
amount of BuONO on the initial rate was established (Figure
t
1C−1D), indicating that neither BuONO nor 1a participates
in the rate-determining step of this catalysis; therefore,
tBuONO should not directly bond to Pd and stay outside of
the catalytic cycle.
t
regenerated by oxidation with NO2. Herein BuONO works as
a redox cocatalyst, replacing the copper-redox cocatalyst in
previous work. The unreactive behavior of Pd-
(CH3CN)2ClNO2 or Pd(CH3CN)2(NO2)2 suggests that the
model of Pd(CH3CN)2Cl(NO2) direct insertion to CC
bonds11 proposed previously by computation should be ruled
out. The zeroth-order dependence of the initial rate on the
tBuONO is a donor of nitric oxide (NO), a stable neutral
t
radical which is easily oxidized to NO2 by O2. Thus, BuONO
plays the role of redox cocatalyst in this aerobic oxidation
reaction. Radical scavenger 5 [2,4,6-tri-tert-butylphenol]
inhibits this aldehyde-selective Wacker−Tsuji oxidation of 1a
to 2a (Scheme 4). The 5-NO adduct was isolated in 70% yield
t
amount BuONO and the first-order dependence of the initial
rate on the amount tBuOH support the Heck-type of formation
intermediate B, which is further supported by the control
experiment with stoichiometric Pd-catalyst in the absence of
tBuONO and O2.
t
with respect to BuONO. Actually, the reaction with 5-NO
t
instead of BuONO afforded 2a in 66% conversion, explaining
the incomplete inhibition of the reaction by radical scavenger 5.
The stoichiometric amount of the Pd-catalyst resulted in 14%
conversion of 1a in the absence of TBN and O2 (Scheme 4,
middle). A large amount of palladium black was observed in the
reactions in the absence of tBuONO and O2. The formation of
a large amount of palladium black gave rise to the liberation of a
In conclusion, we have developed an aldehyde-selective
aerobic Wacker−Tsuji oxidation at room temperature under
copper- or silver-free conditions enabled by the catalytic
amount of tert-butyl nitrite as a simple organic redox cocatalyst.
C
DOI: 10.1021/acs.orglett.6b01165
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
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A variety of aldehydes were achieved in generally high
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ASSOCIATED CONTENT
* Supporting Information
■
Alsters, P. L.; Browne, W. R.; Feringa, B. L. Angew. Chem., Int. Ed.
2013, 52, 5561−5565. (c) Teo, P.; Wickens, Z. K.; Dong, G.; Grubbs,
R. H. Org. Lett. 2012, 14, 3237−3239. (d) Yamamoto, M.; Nakaoka,
S.; Ura, Y.; Kataoka, Y. Chem. Commun. 2012, 48, 1165−1167.
(e) Dong, G.; Teo, P.; Wickens, Z.; Grubbs, R. H. Science 2011, 333,
1609−1612.
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.6b01165.
Experimental details and spectroscopic data for all
products (PDF)
(10) (a) Liu, J.; Zheng, H.-X.; Yao, C.-Z.; Sun, B.-F.; Kang, Y.-B. J.
Am. Chem. Soc. 2016, 138, 3294−3297. (b) Ge, J.-J.; Yao, C.-Z.; Wang,
M.-M.; Zheng, H.-X.; Kang, Y.-B.; Li, Y. Org. Lett. 2016, 18, 228−231.
(11) Jiang, Y.-Y.; Zhang, Q.; Yu, H.-Z.; Fu, Y. ACS Catal. 2015, 5,
1414−1423.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: ybkang@ustc.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Natural Science Foundation of China
(NSFC 21404096, U1463202), the Fundamental Research
Funds for the Central Universities of China (WK2060190026,
WK3430000001), and the Anhui Provincial Natural Science
Foundation (1608085MB24) for financial support.
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DOI: 10.1021/acs.orglett.6b01165
Org. Lett. XXXX, XXX, XXX−XXX