Aerobic Acetoxyhydroxylation of Alkenes Co-catalyzed by Organic Nitrite and Palladium

Article abstract of DOI:10.1021/acs.orglett.6b02743

An aerobic acetoxyhydroxylation of alkenes cooperatively catalyzed by organic nitrite and palladium at room temperature using clean and cheap air as the sole oxidant has been developed. Various vicinal diols, diacetoxyalkanes, and dihalogenoalkanes have been synthesized. The gram-scale synthesis has also been approached. Vicinal difluorination and dichlorolation products have also been achieved via this reaction.

Full text of DOI:10.1021/acs.orglett.6b02743

Letter
pubs.acs.org/OrgLett
Aerobic Acetoxyhydroxylation of Alkenes Co-catalyzed by Organic
Nitrite and Palladium
Xian-Min Chen, Xiao-Shan Ning, and Yan-Biao Kang*
Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China
S
* Supporting Information
ABSTRACT: An aerobic acetoxyhydroxylation of alkenes coop-
eratively catalyzed by organic nitrite and palladium at room
temperature using clean and cheap air as the sole oxidant has
been developed. Various vicinal diols, diacetoxyalkanes, and
dihalogenoalkanes have been synthesized. The gram-scale
synthesis has also been approached. Vicinal difluorination and
dichlorolation products have also been achieved via this reaction.
a
Table 1. Reaction Conditions
mong oxidative functionalizations of alkenes, dihydrox-
Aylation is an important access to vicinal diols that is usually
approached by one-step Upjohn reaction1a and its asymmetric
version Sharpless dihydroxylation,1b two-step Prev
́
ost−Wood-
ward reaction,2 and ring opening of epoxides. As drawbacks,
very toxic and expensive OsO4 or stoichiometric silver carbo-
b
entry
Pd cat.
other conditions
3 (%)
c
1
2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2(NO2)2
Pd(PhCN)2Cl2
PdCl2
none
53
52
12
49
38
8
́
nates are used in Upjohn or Prevost−Woodward reactions,
with O2
respectively. Recently, great progress has been achieved for the
dihydroxylation reaction under osmium-free conditions.3−7
In addition to transition-metal catalysis, the proton-catalyzed
diacetoxylation of alkenes using hypervalent iodane reagents or
peracids has been reported.3 A diacetoxylation of alkenes with
Pd/Cu/AgNO2 as the co-catalytic system has been reported
recently.4 After the pioneering work on Pd-catalyzed aerobic
dioxygenation of alkenes,5 the reaction mechanism was
discussed decades ago.8 In all cases, the NOx species plays
key role in Pd−NO-catalyzed aerobic processes.9,10 Previously,
we have reported an anti-Markovnikov−Wacker oxidation
t
3
no BuONO
4
none
5
none
6
Pd(OAc)2
none
7
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
under argon
2.5 mol % [Pd]
tBuONO 7.5%
tBuONO 20%
K2CO3, MeOH
7
8
35
28
53
9
10
d
11
55 (2a)
51 (4a)
e
12
Ac2O, 50 °C
a
t
11,12
t
Conditions: 1a (0.5 mmol), cat. (7.5 mol %), BuONO (20 mol %),
AcOH (5 mL), 25 °C, air (1 atm), 4 h. Combined yields of 3a and
3b, no 2a or 4a observed. Determined by H NMR with an internal
standard (PhCH2CH2CO2Et). 3a/3b = 21/32 with BnOH decom-
using BuONO as a redox co-catalyst (eq 1).
Herein, we
b
1
c
d
e
posed from 1a. Worked up with K2CO3 (conditions A). Worked up
with Ac2O (condition B).
have extended this catalytic system to a synthetically practical
acetoxyhydroxylation of alkenes with air at room temperature,
providing a divergent access to diols and diacetoxyalkanes.
Initially, the reaction conditions of acetoxyhydroxylation
of 1a co-catalyzed by Pd and BuONO have been investigated.
Acetoxyhydroxylation products 3a and 3b were obtained in
have been established with 7.5 mol % of Pd(CH3CN)2Cl2,
20 mol % of BuONO, 1 atm of air, at 25 °C with hydrolysis
(conditions A) or acetylation (conditions B) workup.
Under the standard conditions A, a variety of vicinal diols
were obtained in generally good yields (Scheme 1). A wide
range of functional groups tolerate the reaction conditions.
For example, 10-undecenoic acid 1h without a protecting group
was subjected to the dihydroxylation conditions to give the
desired diol 2h in 84% yield at room temperature. The dihy-
droxylation of Weinreb amide 1k afforded the corresponding
t
t
53% total yield (Table 1, entry 1). Pd(CH3CN)2(NO2)2
t
without BuONO afforded 3 in low yields (entry 3). The
reaction in the absence of oxygen gave only 7% yield (entry 7).
Acetoxyhydroxylation intermediates are divergent precursors
of vicinal diol 2a or diacetoxyalkane 4a.2 With hydrolysis or
acetylation workup, either 2a and 4a was obtained in 55% and
51% yields, respectively (entries 11 and 12). The standard
conditions for a divergent access to diols and diacetoxyalkanes
Received: September 12, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b02743
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Letter
Scheme 1. Dihydroxylation of Alkenes
Scheme 2. Diacetoxylation from Alkenes
diol 2k in 86% yield. Other functional groups or protecting
groups such as benzyloxy, bromo, TBDPS, carbonyl, and
sulfonyl groups have all survived and provided target diols in
good to high yields (2a, 2e, 2i, 2j, 2m, 2n, and 2o). With
respect to the nonfunctionalized alkenes such as 1-hexene,
1-octene, and 1-dodecene, the desired diols could also been
obtained in good yields (2b−d).
Under the standard conditions B, the palladium-catalyzed
diacetoxylation of various alkenes 1 affords the corresponding
products in generally good yields (Scheme 2). Compared to the
dihydroxylation reaction demonstrated in the middle column of
Scheme 2, similar yields were given with the same acetoxyhy-
droxylation intermediates. Various functional groups or protecting
groups tolerate the reaction conditions. For example, diacetox-
ylation products 4h and 4k were obtained from the corresponding
unsaturated carboxylic acid 1h and Weinreb amid 1k in 88% and
85% yields, respectively. The alkenes bearing benzyloxy, bromo,
and sulfonyl groups and TBDPS could also survive under standard
conditions B to provide the desired products in good to high
yields (4a, 4e, 4m, 4n, and 4o). Phthalimidyl butene gave corre-
sponding diacetoxylation product 4l in high yield.
Figure 1. Unsuccessful substrates.
afforded vicinal difluorides 5a and 5b in 57% and 61% yields,
respectively (Scheme 3). Vicinal dichlorides 6a and 6b were
obtained with thionyl chloride in acceptable yields.
Scheme 3. Dihalogenation of Alkenes
This reaction can be scaled up to gram scale. For example,
10-undecenoic acid 1h was subjected to both dihydroxylation
and diacetoxylation conditions, and the corresponding diol 2h
and diacetoxyl acid 4hrespectively, were obtained in high yields
(Scheme 4).
This reaction has the limitation on the alkenes with con-
junctive electron-withdrawing groups as well as internal alkenes.
The substrates listed in Figure 1 gave trace products. Cyclo-
hexene 1p gave cyclohex-2-en-1-one as the major product.
Styrene and methyl acrylate 1t partially polymerized during the
reaction. With respect to the intramolecular reaction, cycli-
zation product 4v was afforded from ethyl pent-4-enoate 1v,
although the yield was only 22% (eq 2).
Scheme 4. Gram-Scale Synthesis
1
In the H NMR monitoring experiment, the formation of
acetoxyhydroxylation products 3iA and 3iB was observed
(Scheme 5, top). Similar results were given under the Grubbs
conditions4 without acetyl anhydride. The reaction in the
Alkenes 1 are good precursors for vicinal difluorides or
dichlorides. Difluorination of diols 2 with DAST (Et2NSF3)
B
DOI: 10.1021/acs.orglett.6b02743
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Letter
A plausible mechanism was proposed on the basis of
monitoring experiments and kinetic study (Scheme 6). AcOH
Scheme 5. NMR Monitoring Experiments
Scheme 6. Proposed Mechanism
attacks complex A to generate either B or B′, followed by
release of Pd0 through the formation of intermediate D.
Rearrangement of D affords acetoxyhydroxylation isomers E
and E′, which is supported by the 1H NMR monitoring
experiment in Scheme 6. Compound E is further hydrolyzed to
diol 2, and E′ is acetylated to diacetoxylation product 4.
The catalytically active Pd(II) species is regenerated by the
oxidation by NO2, which is regenerated from the oxidation of
NO with O2 (air). The use of a radical could be supported by a
radical-trapping experiment (eq 3).13
presence of Ac2O under Grubbs conditions gave 4i as the major
product, probably due to the result of acetylization of mono-
acetoxyl intermediates 3i. Therefore, we believe similar reaction
pathways must be involved for both cases.
Using the acetoxyhydroxylation reaction of 1a to 3a and 3b
as the model reaction, the kinetic study was performed to
investigate the effects of the catalyst and reagents. A first-order
dependence or initial rate on the amount of Pd(CH3CN)2Cl2
was established (Figure 2A), suggesting Pd(II) should be the
In conclusion, we have developed a direct acetoxyhydrox-
ylation of alkenes cooperatively catalyzed by BuONO and
t
palladium using clean and cheap air as the sole oxidant at room
temperature, providing a divergent access to various vicinal
diols, diacetoxyalkanes, and dihalogenoalkanes. As a syntheti-
cally practical method, gram-scale synthesis has also been pro-
vided. Vicinal difluorination and dichlorolation products could
be achieved via this reaction.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.6b02743.
Figure 2. Dependence of the initial rate on (A) first-order dependence
on [Pd(CH3CN)2Cl2], (B) zeroth-order dependence on [1a], and
(C) zeroth-order dependence on [tBuONO].
Experimental details and spectroscopic data for all
products (PDF)
catalytically active species in this reaction. The zeroth-order
AUTHOR INFORMATION
Corresponding Author
■
dependence on [1a] or [tBuONO] suggests that neither
t
alkene 1a nor BuONO participates in the rate-determining
*E-mail: ybkang@ustc.edu.cn.
Notes
step (Figure 2B,C). Thus, NO and its oxidation form NO2
should not bind on the Pd center to work as a whole to parti-
cipate in the rate-determining step.
The authors declare no competing financial interest.
C
DOI: 10.1021/acs.orglett.6b02743
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Organic Letters
Letter
ACKNOWLEDGMENTS
■
We thank the National Natural Science Foundation of China
(NSFC 21672196, 21404096, U1463202) and Anhui Provin-
cial Natural Science Foundation (1608085MB24) for financial
support.
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DOI: 10.1021/acs.orglett.6b02743
Org. Lett. XXXX, XXX, XXX−XXX