Iron/ABNO-Catalyzed Aerobic Oxidation of Alcohols to Aldehydes and Ketones under Ambient Atmosphere

Article abstract of DOI:10.1021/acs.joc.6b00009

We report a new Fe(NO₃)₃·9H₂O/9-azabicyclo[3.3.1]nonan-N-oxyl catalyst system that enables efficient aerobic oxidation of a broad range of primary and secondary alcohols to the corresponding aldehydes and ketones at room temperature with ambient air as the oxidant. The catalyst system exhibits excellent activity and selectivity for primary aliphatic alcohol oxidation. This procedure can also be scaled up. Kinetic analysis demonstrates that C-H bond cleavage is the rate-determining step and that cationic species are involved in the reaction.

Full text of DOI:10.1021/acs.joc.6b00009

Note
pubs.acs.org/joc
Iron/ABNO-Catalyzed Aerobic Oxidation of Alcohols to Aldehydes
and Ketones under Ambient Atmosphere
,†
†,‡
†
†,‡
†
,†
Lianyue Wang,* SenSen Shang, Guosong Li, Lanhui Ren, Ying Lv, and Shuang Gao*
†Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian National Laboratory for Clean Energy, Dalian 116023,
China
‡
Graduate School of the Chinese Academy of Sciences, Beijing 100049, China
*
S Supporting Information
ABSTRACT: We report a new Fe(NO ) ·9H O/9-azabicyclo-
3
3
2
[
3.3.1]nonan-N-oxyl catalyst system that enables efficient aerobic
oxidation of a broad range of primary and secondary alcohols to the
corresponding aldehydes and ketones at room temperature with
ambient air as the oxidant. The catalyst system exhibits excellent
activity and selectivity for primary aliphatic alcohol oxidation. This
procedure can also be scaled up. Kinetic analysis demonstrates that
C−H bond cleavage is the rate-determining step and that cationic
species are involved in the reaction.
lcohols are selectively oxidized into the corresponding
advantages of these reactions, most of them use halogenated
hydrocarbon (PhCF , CH Cl , or C H Cl ) as the solvent. In
A
carbonyl compounds, which is one of the most
3
2
2
2
4
2
1
fundamental reactions in organic chemistry. Numerous
this context, our group is particularly interested in Fe/TEMPO
8e
classical methods have been proven to achieve this trans-
formation very well with stoichiometric amounts of oxidants,
catalytic systems for the oxidation of alcohols. Another major
problem of Fe/TEMPO systems is their moderate selectivity
regarding the form of aliphatic aldehydes. As we know, the
oxidation of unactivated primary aliphatic alcohols to aldehydes
is a challenging issue in alcohol oxidation reactions. The
products of the aliphatic aldehydes are more reactive than
aliphatic alcohols and more conducive to over-oxidation to the
carboxylic acids. There are several reports on the highly
selective oxidation of unactivated primary aliphatic alcohols to
among which, MnO , chromium salts, and the Dess−Martin
2
reagent produce large amounts of inorganic and organic toxic
2
waste. With the increasing focus on environmental problems,
molecular oxygen as oxidant has attracted great attention
because of its advantages, such as economy and water as the
only byproduct. In this regard, many of the significant
improvements in catalytic methods have been made for aerobic
alcohol oxidation. Among these, the developed catalyst systems
for the aerobic alcohol oxidation with molecular oxygen as
terminal oxidant are involved in transition metals or
coordination complexes of transition metal, but the use of
noble metals (e.g., Pd, Ru, Au) and commercially unavailable
11
aldehydes. The limitation of the Fe/TEMPO system in
obtaining high selectivity of primary aliphatic aldehydes is
probably caused by the low catalytic activity of TEMPO. We
envisioned that the selectivity and reactivity of primary aliphatic
alcohol oxidation could be improved by replacing TEMPO with
a nitroxyl radical having different redox and steric properties.
Recently, sterically unhindered nitroxyl radicals have begun to
be used (Figure 1). Such nitroxyl radicals have been well used
for the catalytic oxidation in Cu- or transition-metal-free
3
ligands limits their applications. In addition, these catalytic
systems usually use pure O as the oxidant. Substitution of
2
noble metals in catalysts for cheap and abundant metals is of
obvious importance. Therefore, recent efforts have been made
to develop earth-abundant metal catalysts based on first-row
12
catalytic systems and show high reactivity in contrast to
4
−6
7
8
9
transition metals such as Cu,
Co, Fe, and V, which have
been well proven to show effective implementation for aerobic
alcohol oxidation.
Iron as an earth-abundant metal in the geosphere has been
1
0
developed as a catalyst for many organic reactions, but there
are not many reports on Fe as the catalyst for aerobic alcohol
oxidation. The mainly catalytic systems were based on TEMPO
in combination with Fe salts. The Fe/TEMPO catalytic system
Figure 1. Structures of reported nitroxyl radicals. ABNO = 9-
azabicyclo[3.3.1]nonan-N-oxyl, AZADO = 2-azaadamantane-N-oxyl,
nor-AZADO = 9-azanoradamantane-N-oxyl.
8a
for alcohol oxidation was first reported by Wang et al. Further
developments of the Fe/TEMPO catalyst system were reported
by Ma et al. The performance and substrate scope were
Received: January 3, 2016
8d
improved in the presence of NaCl as an additive. Despite the
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.6b00009
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a
Table 1. Optimization of the Reaction Conditions for 1-Octanol Oxidation
b
b
entry
nitroxyl radical
TEMPO
[Fe]
solvent
yield (%)
selectivity (%)
1
2
3
4
5
6
7
Fe(NO ) ·9H O
CH CN
15
31
65
71
74
65
97
3
3
2
3
HO-TEMPO
4-acetamido-TEMPO
Oxo-TEMPO
ABNO
Fe(NO ) ·9H O
CH CN
3
3
2
3
Fe(NO ) ·9H O
CH CN
46
3
3
2
3
Fe(NO ) ·9H O
CH CN
10
3
3
2
3
Fe(NO ) ·9H O
CH CN
87
3
3
2
3
Fe(NO ) ·9H O
CH CN
NR
trace
49
3
3
2
3
ABNO
FeCl ·6H O
CH CN
3
2
3
c
8
ABNO
FeCl ·6H O
CH CN
93
3
2
3
c
9
ABNO
CH CN
trace
trace
trace
39
3
d
10
11
12
13
14
15
16
17
18
19
ABNO
CH CN
3
ABNO
Zn(NO ) ·6H O
CH CN
3
2
2
3
ABNO
Fe(NO ) ·9H O
Toluene
MeOH
86
3
3
2
ABNO
Fe(NO ) ·9H O
trace
87
3
3
2
e
f
ABNO
Fe(NO ) ·9H O
CH CN
97
99
93
99
81
3
3
2
3
ABNO
Fe(NO ) ·9H O
CH CN
90
3
3
2
3
f
f
f
,
g
h
i
ABNO
Fe(NO ) ·9H O
CH CN
59
3
3
2
3
,
,
ABNO
Fe(NO ) ·9H O
CH CN
35
3
3
2
3
TEMPO
4-acetamido-TEMPO
Fe(NO ) ·9H O
DCE
45
3
3
2
c,f
FeCl3
DCE
3
a
b
1
-Octanol (0.25 mmol), CH CN (2 mL); entries 1−12, oxygen balloon as the oxidant. Yield and selectivity were determined by GC analysis using
3
c
d
e
f
biphenyl as internal standard, and the products were confirmed by GC−MS. 10 mol % of NaNO , 30 mol % NaNO , Air balloon. Open air,
reaction time 4 h. 3 mol % of ABNO. 5 mol % of Fe(NO ) ·9H O. 10 mol % of NaCl, NR = no reaction.
2
2
g
h
i
3
3
2
TEMPO owing both to the smaller steric hindrance around the
n-oxyl radical and increased stability in the condition of
oxidation. Inspired by these studies, we can make a reasonable
conjecture that such nitroxyl radicals might be able to solve the
limitation of poor selectivity for primary aliphatic alcohol
oxidation in Fe catalytic systems. To the best of our knowledge,
this is no report on the use of less hindered nitroxyl radicals in
Fe catalytic systems for alcohol oxidation.
conditions compared with the reported literature (Table 1,
8c
entry 3). These results demonstrated that the catalytic activity
of TEMPO and 4-substituted TEMPOs was not so effective to
selectively oxidize unactivated aliphatic alcohols to the
aldehydes under the present reaction conditions. It is worth
noting that overoxidation of the aldehyde did not occur and
that n-octyl nitrite was a main byproduct in our reaction
conditions. It was reported that only Fe(NO ) ·9H O can
3
3
2
8b
Herein, we report a new, highly selective, and active
achieve the oxidation of benzyl alcohol. However, in our case,
no reaction occurred without ABNO, and n-octyl nitrite was
not detected (Table 1, entry 6). When FeCl ·6H O was utilized
Fe(NO ) /ABNO (9-azabicyclo[3.3.1]nonan-N-oxyl) catalyst
3
3
system for the aerobic oxidation of alcohols. A broad range of
alcohols, including unactivated aliphatic, allylic, and benzylic
alcohols, are oxidized to the corresponding aldehydes and
ketones in high yields at room temperature with ambient air as
the oxidant. For primary aliphatic alcohols, overoxidation to the
corresponding carboxylic acids was not observed. The catalyst
system exhibits a wide range of functional-group compatibility,
including alkenes, alkynes, halides, heterocyclic atoms, nitro
groups, and alkyl ethers. Our catalytic system uses the
traditional organic solvent acetonitrile without the use of
environmentally unfriendly halogenated solvents (PhCF3,
CH Cl , or C H Cl ). These very mild reaction conditions
3
2
as catalyst, this led to a trace yield (Table 1, entry 7). As
suggested by some authors, NO is playing a key role in Fe/
x
TEMPO systems. NaNO was added into the FeCl ·6H O/
2
3
2
ABNO catalytic system resulting in good selectivity of the
desired product, but moderate yield was obtained (Table 1,
entry 8). To test whether only NO can achieve this catalytic
x
process, only NaNO2 and Zn(NO ) ·6H O were used,
3
2
2
respectively (Table 1, entries 9−11). Only trace product was
obtained, indicating that Fe3+ is necessary for the achievement
of the catalytic reaction. Other solvents such as toluene showed
good selectivity under the same reaction conditions (Table 1,
entry 12).The use of a polar solvent such as MeOH resulted in
trace product (Table 1, entry 13). An important improvement
for the aerobic oxidation system applicability is to take the place
2
2
2
4
2
make the present catalysts useful, particularly for practical
applications in organic synthesis. In addition, a plausible overall
mechanism for the present catalytic system was discussed.
Kinetic isotope effects (KIE) and Hammett values were also
studied in this work.
of pure O with air since this reduces cost and is also safer.
2
While optimization of the reaction conditions employs an
oxygen balloon, the reaction can also be conducted under air
balloon and even under open air, albeit with slightly longer
reaction time (Table 1, entries 14 and 15). The effect of catalyst
loadings was also investigated. When the amount of Fe(NO3)3·
The investigation began with 1-octanol as the model
substrate with a comparison of the catalytic efficiencies of
different diversities of nitroxyl radicals using 10 mol %
Fe(NO ) ·9H O in CH CN as the solvent under oxygen
3
3
2
3
atmosphere at room temperature. The results are summarized
in Table 1. ABNO showed a relatively high selectivity under
our screening conditions (Table 1, entries 1−5). 4-Acetamido-
TEMPO provided a moderate selectivity under our reaction
9H O and ABNO was reduced, the yields were decreased, but
2
good selectivity was still obtained (Table 1, entries 16 and 17).
In order to make further comparison with the reported
8c,d
literature,
the reactions were performed with catalysts from
B
DOI: 10.1021/acs.joc.6b00009
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a,b
the literature used under open air conditions (Table 1, entries
Scheme 2. Oxidation of Activated Alcohols
18 and 19). The results obtained amplify the higher activity of
the present catalyst system.
Under the optimized reaction conditions, we explored the
substrate scope of this catalytic oxidation system. On the basis
of our initial efforts to achieve high selectivity of unactivated
alcohol oxidation, the oxidation of aliphatic alcohols with
various functional groups was examined. The results are
summarized in Scheme 1. Linear and annular unactivated
Scheme 1. Oxidation of Primary and Secondary Unactivated
a,b
Alcohols
a
b
Alcohol (0.25 mmol), CH CN (2 mL). Yield and selectivity were
3
determined by GC analysis using biphenyl as internal standard and
c
d
e
confirmed by GC−MS. 3 mol % of ABNO. 1 mol % of ABNO. 5
mol % of ABNO. Values in parentheses are the isolated yields. Entries
are shown as follows: reaction time, yield (isolated yield), selectivity.
be quantitatively oxidized to the corresponding aldehydes
(
Scheme 2, 19−21). Compared with primary benzylic alcohols,
secondary benzylic alcohols are less reactive. Excellent results
can be achieved in the case of increased loading of ABNO
(
Scheme 2, 23−27). Although a slightly lower yield of product
was obtained for the oxidation of cinnamyl alcohol (Scheme 2,
8), this reaction was highly efficient for propargylic alcohol
2
oxidation (Scheme 2, 29). 3-Thiophene-ylmethanol, usually
regarded as difficult substrate, was oxidized into the desired
product in good yield (Scheme 2, 30).
a
b
Alcohol (0.25 mmol), CH CN (2 mL). Yield and selectivity were
3
Our previous work and the pertinent literature have given a
determined by GC analysis using biphenyl as internal standard, and
the products were confirmed by GC−MS. Values in parentheses are
the isolated yields. Entries are shown as follows: reaction time, yield
8a,d,e
plausible mechanism for the Fe/TEMPO catalytic system.
We speculate that the present aerobic alcohol oxidation shows a
similar reaction process: (1) substrate oxidation mediated by
Fe(III) and ABNO via an Fe(III) alkoxide intermediate and (2)
catalyst oxidation in which Fe(II) and reduced ABNO are
(
isolated yield), selectivity.
3−
primary alcohols were smoothly oxidized to the desired
aldehydes with high yields and selectivity (Scheme 1, 1−14).
A wide range of functional groups such as aryl (Scheme 1, 9),
alkyl ethers (Scheme 1, 11), alkyl halides (Scheme 1, 12),
alkenes (Scheme 1, 13), and alkynyl (Scheme 1, 14) were
tolerated under the optimized reaction conditions, and the
corresponding aldehydes were obtained in good to moderate
yields with excellent selectivity. Most importantly, secondary
aliphatic alcohols could also be oxidized to the desired ketones
in good to excellent yields under our mild conditions (Scheme
oxidized by O via NO generated in situ by NO . In order to
2 x
gain more insight into the present alcohol oxidation system, we
then investigated the kinetic isotope effect (KIE). 1-Phenyl-
ethanol and its deuterated alcohol were selected as test
substrates. A linear relationship exists between −ln(1 − C)
and reaction time, indicating that the reaction is first order with
respect to 1-phenylethanol as shown in Figure 1S. The KIE
value for this Fe/ABNO-catalyzed oxidation of secondary
alcohol was 2.1. Intramolecular competition experiment for the
oxidation of PhCHDOH was also carried out. The KIE was
determined to be 3.7 as an average of two measurements. From
these results, we concluded that C−H cleavage is the rate-
determining step. To pursue a better understanding of the
transition state, Hammett correlation study was conducted with
various para-substituted benzyl alcohols. A linear relationship
was obtained between the logarithm of the initial rate and the σ
value of the para-substituent (Figure 2S). The resulting
Hammett parameter ρ is −1.8, thus suggesting the reaction
exhibits preferential oxidation of electron-rich alcohols and
carbocation is involved, which is also consistent with the
observation that electron-donating substituents accelerate the
overall rate of oxidation.
1
, 15 and 16). Moreover, the oxidation of challenging hindered
secondary alcohols furnished the expected products in excellent
yields (Scheme 1, 17 and 18).
Having obtained good results for the oxidation of unactivated
alcohols, we next examined the ability of the Fe(NO ) ·9H O/
3
3
2
ABNO catalytic system to catalyze the oxidation of certain
activated alcohols. The results are summarized in Scheme 2. By
reducing the amount of ABNO, excellent results could also be
obtained, as could be expected. All benzylic alcohols with
electron-donating and -withdrawing groups were oxidized into
the corresponding aldehydes or ketones with excellent
selectivity (Scheme 2, 19−30). As expected, electron-deficient
benzylic alcohols were less reactive than electron-rich benzylic
alcohols. It is worth noting that primary benzylic alcohols can
Finally, we demonstrated the gram-scale application of this
catalytic system. Benzyl alcohol was used as a test substrate.
C
DOI: 10.1021/acs.joc.6b00009
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Reaction of benzyl alcohol (25 mmol, 2.7 g) was performed
are given below. Spectral parameters are consistent with literature
values.
1
4
with 0.2 mol % of ABNO and 5 mol % of Fe(NO ) ·9H O in
3
3
2
Representative Procedures for the Measurement of Kinetic
Isotope Effects. Kinetic Isotope Effect for 1-Phenethyl Alcohol. To
a 10 mL, dried culture tube were added Fe(NO ) ·9H O (0.025
CH CN under ambient atmosphere at room temperature. The
3
desired product was obtained in 95% isolated yield with >99%
selectivity within 16 h. These results suggest that in the case of
a low catalytic amount of ABNO our system shows high
activity, selectivity, and practicability for the aerobic oxidation
of alcohols.
3
3
2
mmol, 10 mg), ABNO (1.25 mL, 0.01 M), 1-phenethyl alcohol or 1-
deuterated-1-phenylethanol (0.25 mmol), and 0.75 mL of CH CN.
3
The resulting suspension was stirred at room temperature open to air.
Reaction sample spectra were collected every 30 min and determined
by GC.
In summary, we have developed a highly efficient Fe(NO ) ·
H O/ABNO-catalyzed oxidation systems for a variety of
2
3
3
9
For Benzyl Alcohol. To a 10 mL, dried culture tube were added
Fe(NO ) ·9H O (0.025 mmol, 10 mg), ABNO (1.25 mL, 0.01 M),
alcohols. The catalyst system exhibits a wide substrate
tolerance. The oxidation reaction is carried out under ambient
atmosphere and at room temperature. This catalytic system
takes safety into account and avoids using any ligand and base,
which is beneficial for its use in pharmaceuticals, fragrances, and
food additives. The distinctive feature of this catalytic system is
that unactivated alcohols can be smoothly oxidized into the
aldehydes and ketones with excellent selectivity. The utilization
of a low catalytic amount of ABNO (0.2 mol %) in a scaled-up
reaction can afford an excellent yield of the desired product.
The present catalyst system might also be useful for other types
of functional-group transformations.
3
3
2
PhCHDOH (0.25 mmol, 27.3 mg), and 0.75 mL and CH CN. The
3
resulting suspension was stirred at room temperature open to air until
the starting material was consumed as determined by GC. The crude
reaction was filtered through a silica plug with EtOAc. The solvent was
removed by evaporation (in many cases, some solvent remained to
1
avoid evaporation of any aldehyde products), and an H NMR
spectrum of the reaction mixture was acquired to determine the ratio
of products.
1
3
1
d1-Benzyl alohol: colorless oil; H NMR (400 MHz, CDCl ) δ
3
13
7.21−7.11 (m, 5H), 4.40 (s, 1H), 3.07 (s, 1H); C NMR (101 MHz,
CDCl ) δ 140.9, 128.5, 127.6, 127.1, 64.8, 64.7, 64.4.
3
1
4
1
1
-Phenyl-1-deuteroethanol: colorless oil; H NMR (400 MHz,
CDCl ) δ 7.27−7.19 (m, 4H), 7.19−7.12 (m, 1H), 2.49 (s, 1H), 1.34
3
13
(
s, 3H); C NMR (101 MHz, CDCl ) δ 145.8, 128.5, 127.4, 125.5,
3
EXPERIMENTAL SECTION
7
0.1, 69.9, 69.7, 24.8
4e
■
1
Benzaldehyde: colorless oil; yield 2.5 g, 95%; H NMR (400 MHz,
General Information. All chemicals were purchased from Reagent
Co. and used without further purification. The yield and selectivity
CDCl ) δ 9.88 (s, 1H), 7.75 (d, J = 8.1 Hz, 2H), 7.49 (dd, J = 11.9, 4.1
3
13
1
Hz, 1H), 7.39 (t, J = 7.5 Hz, 2H); C NMR (101 MHz, CDCl ) δ
were obtained by GC. All products were confirmed by GC−MS. H
3
NMR and 13C NMR spectra were recorded on a 400 MHz NMR
191.6, 135.3, 133.4, 128.6, 127.9.
1
5
2
-Adamantanone (Scheme 1, 17): white solid, yield 36 mg, 95%;
spectrometer in CDCl with TMS as an internal reference (δTMS =
3
1
1
H NMR (400 MHz, CDCl ) δ 2.53 (s, 2H), 2.09−1.92 (m, 12H);
C NMR (101 MHz, CDCl ) δ 218.8, 47.0, 39.3, 36.4, 27.5.
0
7
.00 ppm; CDCl : δC = 77.1 ppm; residual CHCl in CDCl : δH =
3
3
3
3
3
.26 ppm).
General Procedure for Aerobic Alcohol Oxidation. To a 10
mL, dried culture tube were added Fe(NO ) ·9H O (0.025 mmol, 10
3
1
6
1
Camphor (Scheme 1,18): white solid; yield 32 mg, 85%; H NMR
(400 MHz, CDCl ) δ 2.34 (d, J = 18.2 Hz, 1H), 2.07 (t, J = 4.2 Hz,
3
3
2
3
mg), ABNO (1.25 mL, 0.01 M), alcohol (0.25 mmol), and 0.75 mL of
1H), 2.00−1.88 (m, 1H), 1.83 (d, J = 18.2 Hz, 1H), 1.70−1.60 (m,
1
3
CH CN. The resulting suspension was stirred at room temperature
1H), 1.46−1.26 (m, 2H), 0.94 (s, 3H), 0.90 (s, 3H), 0.82 (s, 3H); C
3
open to air. The progress of the reaction was monitored by GC using
biphenyl as an internal standard. After completion of the reaction, the
diethyl ether was added to the resulting mixture. The mixture was
NMR (101 MHz, CDCl ) δ 57.8, 46.9, 43.3, 43.1, 29.9, 27.1, 19.8,
3
19.2, 9.3.
1
7
4′-Methylypropiophenone (Scheme 2,26): colorless oil; yield 34
mg, 92%; H NMR (400 MHz, CDCl ) δ 7.76 (d, J = 8.0 Hz, 2H),
1
dried over anhydrous MgSO and then filtered through a short column
4
3
of silica gel to remove the inorganic salts. CH CN and diethyl ether
were removed by rotary evaporation, and the product was further
7.14 (d, J = 7.8 Hz, 2H), 2.89−2.83 (m, 2H), 2.29 (s, 3H), 1.11 (td, J
3
= 7.2, 1.4 Hz, 3H); 13C NMR (101 MHz, CDCl ) δ 200.4, 143.6,
3
purified by column chromatography over silica gel with a mixture of
ethyl acetate/hexane as eluent. H and C NMR spectra data of all
isolated products were in accord with the literature.
134.4, 129.2, 128.1, 31.6, 21.6, 8.3.
1
13
9f
1-Phenyl-2-propyn-1-one (Scheme 2 ,29): yellow solid; yield 28
1
mg, 86%; H NMR (400 MHz, CDCl ) δ 8.09 (d, J = 7.3 Hz, 2H),
3
1
3
Methods for Determination of Kinetic Isotope Effects.
7.56 (t, J = 7.4 Hz, 1H), 7.43 (t, J = 7.7 Hz, 2H), 3.37 (s, 1H); C
Synthesis of d -Benzyl Alcohol. A solution of benzaldehyde (0.212
1
NMR (101 MHz, CDCl ) δ 177.5, 136.2, 134.6, 129.8, 128.8, 80.9,
3
g, 2 mmol) in MeOH (20 mL) was cooled to 0 °C under N . NaBD4
2
80.3.
(0.17 g, 4 mmol) was added portionwise over 1 h. The reaction was
allowed to warm to room temperature with stirring. After 2 h, the
mixture was cooled to 0 °C and quenched by the careful addition of
HCl (1 M) followed by extraction with ethyl acetate (100 mL). The
ASSOCIATED CONTENT
■
*
S
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.6b00009.
collected organic layers were dried with NaSO and filtered, and the
4
solvent was evaporated. The crude material was purified by silica
column chromatography (ethyl acetate/hexane = 1/20) to afford d1-
benzyl alcohol (0.194 g, 90% yield). Characterization data are given
Measurement of kinetic isotope effects, Hammett plots,
1
3
below. Spectral parameters are consistent with literature values.
and NMR spectra of the isolated products (PDF)
Synthesis of 1-Deutero-1-phenylethanol. A solution of acetophe-
none (0.24 g, 2 mmol) in MeOH (25 mL) was cooled to 0 °C under
N . NaBD (0.17 g, 4 mmol) was added portionwise over 1 h. The
2
4
AUTHOR INFORMATION
■
*
reaction was allowed to warm to room temperature with stirring. After
h, the mixture was then cooled to 0 °C and quenched by the careful
2
Corresponding Authors
E-mail: lianyuewang@dicp.ac.cn.
*E-mail: sgao@dicp.ac.cn.
addition of HCl (1 M) followed by extraction with ethyl acetate (100
mL). The collected organic layers were dried with NaSO and filtered,
4
and the solvent was evaporated. The crude material was purified by
silica column chromatography (ethyl acetate/hexane = 1/20) to afford
Notes
1-deutero-1-phenylethanol (0.207 g, 85% yield). Characterization data
The authors declare no competing financial interest.
D
DOI: 10.1021/acs.joc.6b00009
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(
10) (a) Bolm, C.; Legros, J.; Le Paih, J.; Zani, L. Chem. Rev. 2004,
ACKNOWLEDGMENTS
■
1
04, 6217−6254. (b) Sherry, B. D.; Fu
̈
rstner, A. Acc. Chem. Res. 2008,
o, O. G.; Bolm, C. Chem. Soc.
We gratefully acknowledge financial support from the National
Natural Science Foundation of China (No. 21403219).
4
1, 1500−1511. (c) Correa, A.; Manchen
̃
Rev. 2008, 37, 1108−1117. (d) Enthaler, S.; Junge, K.; Beller, M.
Angew. Chem., Int. Ed. 2008, 47, 3317−3321. (e) Bauer, I.; Knolker, H.
J. Chem. Rev. 2015, 115, 3170−3387.
11) For leading references based on Cu/TEMPO systems, see ref
b,d,e. For copper/ dialkylazodicarboxylate systems: see ref 5e. For
̈
REFERENCES
■
(
4
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DOI: 10.1021/acs.joc.6b00009
J. Org. Chem. XXXX, XXX, XXX−XXX