Selective C-H bond electro-oxidation of benzylic acetates and alcohols to benzaldehydes

Article abstract of DOI:10.1039/c7ob02300f

A chemical oxidant-free and mediator-free, direct electro-oxidation of both benzylic alcohols and benzylic esters are reported. The scope of the reaction is explored as a function of both steric and electronic effects. Expansion of the scope to non-benzylic and heteroaryl substrates is investigated. Functionalisation of esters and alcohols selectively to the aldehyde oxidation level using a traceless electron approach is reported.

Full text of DOI:10.1039/c7ob02300f

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ISSN 1477-0520
COMMUNICATION
Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
rsc.li/obc

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Selective C-H Bond Electro-oxidation of Benzylic Acetates and
Alcohols to Benzaldehydes
Mateus R. Baroneab and Alan M. Jonesc*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
A chemical oxidant-free and mediator-free, direct electro-oxidation of both benzylic alcohols and benzylic esters are
reported. The scope of the reaction is explored as a function of both steric and electronic effects. Expansion of the scope
to non-benzylic and heteroaryl substrates are investigated. Functionalisation of esters and alcohols selectively to the
aldehyde oxidation level using a traceless electron approach is reported.
www.rsc.org/
mediator would minimise chemical waste associated with the
reaction. We have recently investigated the Shono-type
oxidation of C-H bonds adjacent to a tertiary amide13 and our
Introduction
The controlled and chemo-selective oxidation of primary
alcohols to aldehydes and secondary alcohols to the
corresponding ketones are fundamental reactions in organic
synthesis.1 In turn, these aldehydes and ketones serve as
precursors for a variety of complexity generating reactions.2
However, the controlled oxidation of primary alcohols to
aldehydes can be problematic due to over-oxidation to the
carboxylic acid oxidation state.3 There are a range of versatile
chemical oxidants available to the academic and industrial
chemist that enable this transformation to be performed on
demand.4 However, the majority of these oxidation reactions
are stoichiometric in nature and therefore suffer from the
generation of quantities of chemical waste.5
initial foray into this area began with attempting to expand the
scope of the amide oxidation to esters (Figure 1). It is known
that the Shono electro-oxidation of amides proceeds through
an N-acyl iminium species (
A
).14 It was therefore postulated
15 could form under
that a transient O-acyloxonium species (
B
)
similar electro-oxidative conditions in esters bearing an ɑ-
methylene or methide group.
Recently, the field of electrosynthesis has undergone a
renaissance6 and has found application in a variety of organic
synthetic transformations, such as: C-H bond activation,7 total
synthesis,8 Diels-Alder reaction9 amongst others.10
A
fundamental advantage of the electrosynthesis approach is the
replacement of the need to use stoichiometric oxidants and
instead the oxidation reaction is performed on the electrode
surface via quantum mechanical tunelling11 or through a
mediator in solution.12
Figure 1. Context: Expanding the scope of amide C-H bond functionalisation from
amides (A) to esters (B).
To address the challenge of identifying a cleaner oxidation,
we explored the use of electrosynthesis to replace the need
for both a chemical oxidant and mediator in these REDOX
transformations. The simultaneous removal of oxidant and
This unstable O-acyloxonium species (
further with adventious water to form the aldehyde product
and a carboxylic acid as a by-product via intermediate ( ).
B) would in turn react
C
Alternatively, an ester and aldehyde product could potentially
form when conducted in an alcohol. To the best of our
knowledge there are only limited reports of electro-oxidative
cleavage of an ester group.16
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Results and discussion
To probe whether this methodological leap was indeed
feasible, a collection of benzylic acetates were prepared
including the parent benzyl acetate 1a, a mild electron
donating example 1b and a mild electron withdrawing example
1c (structures shown in Table 2). Cyclic voltammetry was
recorded for 1a (Figure 2).
Using a sensitive measurement of 10 mVs-1 scan rate it was
observed in both electrolyte systems (LiClO4 and Bu4NClO4)17
that oxidation waves for all three substrates were observed
with +1.0 V (1a), +1.2 V (1b) and +0.9 V (1c) oxidation
potentiasl (relative to Ag/AgCl) and a slightly improved peak
current (Ip) measurement in Bu4NClO4. On the basis of this
positive oxidation result, screening of potential conditions to
enable viable electro-oxidation of model benzylic acetate 1a
was attempted (Table 1).
In the first instance, potentiostatic conditions were
screened with 1a (entries 1-8) using both Bu4NClO4 and LiClO4
as the electrolyte. The applied voltage was varied around the
observed oxidation potential for 1a (cyclic voltammetry
measurement, +1.0 V) with up to an extra 300 mV applied to
compensate for expected iR drop across the electrode
surface.18 In all cases, the reaction was performed until Fmol-1
equivalent to 4 electrons per mole of substrate was passed or
starting material consumption was observed. Near the
oxidation potential of 1a trace conversion to the desired
aldehyde 2a was observed in both electrolyte systems (entries
3-4 and 6-7, respectively). However, at higher applied voltages
degradation products were observed (entries
5 and 8,
Entry
Electrolyte
Current (mA)
Conversion (%)
Solvent
Voltage (mV)
+900
1
2
3
4
5
6
7
8
9
Bu4NClO4
Bu4NClO4
Bu4NClO4
Bu4NClO4
Bu4NClO4
LiClO4
LiClO4
LiClO4
Bu4NClO4
MeCN/MeOH
MeCN/MeOH
MeCN/MeOH
MeCN/MeOH
MeCN/MeOH
MeCN/MeOH
MeCN/MeOH
MeCN/MeOH
MeCN/MeOH
-
-
-
-
-
-
-
-
20
0
0
<5
<5
+1000
+1100
+1200
+1300
+1100
+1200
+1300
-
degradation
<10
<10
degradation
27
10
11
12
13
14
15
16
Bu4NClO4
Bu4NClO4
LiClO4
20
10
20
20
10
10
-
34
49
25
57
84
38
0
MeOH
MeOH
MeCN/MeOH
MeOH
MeOH
MeOH/H2O
MeOH
-
-
-
-
-
-
-
LiClO4
LiClO4
LiClO4
LiClO4
2 | J. Name., 2012, 00, 1-3
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approach was
respectively), coupled with excessive time 6 h) and a concomitant improvement in reaction yield in both
required for sufficient charge to be passed (24 h to 5 days), a electrolyte systems (entries 11 vs 10 and 14 vs 13,
controlled voltage ruled out in this system early on. Switching respectively). Lowering the current rate further led to modest
to a galvanostatic approach, using the same electrolyte improvements in conversion but unacceptable lengthening of
systems and reticulated vitreous carbon (RVC) electrodes the reaction time. It became clear that lithium perchlorate was
produced more promising results (entries 9-15).
superior to tetrabutylammonium perchlorate (entry 14 vs 11)
In particular, it was observed that a single solvent system plus coupled with its ease of separation from organic products
gave higher yields than the previously optimized solvent was selected as the electrolyte. To probe whether additional
system for the Shono oxidation,13 acetonitrile-methanol water improved the reaction yield (entry 15) based on a
(entries 9 vs 10 and 12 vs 13, respectively). Lowering the postulated mechanism led to a reduced yield versus entry 14.
current density across the electrode surface from an applied Furthermore, passing no electrical current led to no reaction
20 mA to 10 mA, led to a doubling in reaction time (approx. 5- (entry 16). To test the hypothesis that C-H bond
Table 3. Results of direct alcohol electro-oxidation to aldehydes (c.e. = current efficiency).
oxidation adjacent to an ester was possible, a collection of a simple aqueous base wash removed the acid by-product.
benzylic esters were prepared. Our initial results using the However, there were still limitations to this approach for
optimised procedure are detailed in Table 2. It was found using example electro-oxidation of cyclic benzylic ester 1d or
the optimised conditions, appreciable amounts of the desired homologated ester 1e, did not afford the aldehyde 2d and 2e
aldehyde (2a 2c) were obtained from the benzylic acetates respectively. These limitations coupled with the use of an acyl
1a-1c). To address, the mechanism issue identified in Figure 1, ancillary group still did not meet our green chemistry
,
-
(
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standards due to the additional manipulation step required to Electro-oxidation of the benzyl alcohol reveals a benzyl radical,
prepare the acetate. We therefore considered whether a subsequent oxidation of the hydroxyl group will deliver an
stabilising group on the heteroatom adjacent to the C-H bond aldehyde after deprotonation. Similarly, the benzylic acetate
was indeed essential to electro-oxidation. Promisingly, cyclic system could proceed via analogous initial steps to an O-
voltammetry measurements on benzyl alcohol 3a showed an acyloxonium species that could be trapped with water or
oxidation wave at +1.2 V relative to Ag/AgCl.19 Using our methanol to deliver
a hemiacetal or acetal species,
previously optimised conditions for the ester electro-oxidation respectively. In turn, the hemi-acetal or acetal intermediate
we explored the direct mediator-free oxidation on a range of would collapse upon work-up to deliver the aldehyde (Scheme
commercially available alcohols (Table 3).
1B). We have shown that mild electron withdrawing and
It was possible to cleanly convert benzyl alcohol (3a) to donating groups are tolerated in both systems but those that
benzaldehyde (2a) under the mild conditions of lithium strongly donate or withdraw electrons were less compatible
perchlorate in methanol in near quantitative yield and in with direct electro-oxidation. Nitrogen containing heterocycle
improved yield compared to the chemical manipulation of
forming the benzyl acetate (99% vs 80%, respectively).20 The conversion (<5%) to the aldehyde. However, changing the
scope of this reaction was further investigated via exploration benzene ring to thiophene was successful, affording
(3n) and non-benzylic substrates (3k-3m) gave trace
a
of the effects of electron withdrawing and donating group aldehyde 2h in quantitative yield, demonstrating the utility of
around the ring system and steric effects around the reacting the approach in other classes of heterocyclic systems.
centre. The use of a chlorine atom as an electron withdrawing
group in the ortho- (2f, 81%), meta- (2g, 55%) and para- (2h,
Conclusion
86%) positions was well tolerated. The use of a methyl group
as a mild electron donating group in the ortho- (2i, 66%), meta-
The use of mediator-free, galvanostatic, direct electro-
(
2j, 99%) and para- (2b, 83%) positions also afforded good to
oxidation of benzylic alcohols and acetates shows scope on a
range of substrates and offers an alternative and
complementary approach to the preparation of valuable
aldehydes. Mechanistic investigations to determine the
sequence of electro-oxidation steps are now underway.
excellent yields of the aldehyde.
Intriguingly, a strong electron donating group para to the
reacting centre (from para-methoxy benzyl alcohol, 3i (not
shown)) resulted in a greatly reduced yield of aldehyde 2k
(27%). The relatively low yield of 2k compared with other
benzaldehydes is likely to be due to the para-methoxy group
stabilizing the carbon-centred benzylic radical leading to
further unproductive reaction pathways and oxidative
Experimental section
General methods
decomposition of 2k
.
Reactions were carried out under nitrogen. Organic solutions
were dried over MgSO4. Starting materials were purchased
from commercial suppliers and were used without further
purification. Solvents were dried over molecular sieves (3-4Å)
Flash silica chromatography was performed using Sigma-
Aldrich high-purity grade, pore size 60 Å, 200-400 mesh
1
particle size silica gel. H and 13C NMR spectra were recorded
on a JEOL ECS 400 NMR Spectrometer at 400 MHz or Bruker
AVIII 300 or 400 MHz spectrometers. Chemical shifts (δ) are
reported relative to TMS (δ=0) and/or referenced to the
solvent in which they were measured. All chemical shifts (δ)
are reported in parts per million, and coupling constants (J) are
reported in Hertz. Low and High-resolution mass spectrometry
analysis were obtained using an Agilent 6450 LC-MS/MS
system. Infrared (IR) spectra were recorded on
a
ThermoScientific Nicolet Impact-380 ATR-FTIR spectrometer.
Electrosynthesis and cyclic voltammetry were performed using
a Metrohm Autolab PGSTAT100N + 10 Amp Booster (Metrohm
Autolab, U.K.) with an undivided electrochemical cell. Data was
processed using Autolab Nova software (version 2.0). The
electrode system for electrosynthesis consisted of two
reticulated vitreous carbon (RVC) electrodes (supplier: ERG
Aerospace; specifications: 45 pores per inch (PPI); 800 square
foot per cubic foot; size 20 x 11 x 5 mm) for galvanostatic
reactions plus an additional pseudo Ag/AgCl reference
The result for a strongly electron withdrawing group in the
4-position of the substrate 3j afforded only trace conversion to
the desired product as a result of the highly electron
withdrawing nature of the para-nitro group. Based on the
experimental results above and EPR literature21 of related
systems a tentative mechanism can be proposed (Scheme 1).
4 | J. Name., 2012, 00, 1-3
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23
electrode for potentiostatic reactions. Please see13 for further Benzyl acetate
(1a)
details and images of the reaction set-up.
The title compound was afforded as a clear oil (0.85 g, 56%)
1
using general procedure A. H NMR (400 MHz, CDCl3) δ 7.42-
7.29 (m, 5H), 5.12 (s, 2H), 2.11 (s, 3H) ppm; 13C NMR (100.1
MHz, CDCl3) δ 171.0, 136.0, 128.7, 128.4, 128.3, 66.4, 21.1
ppm; m/z (ESI) = 151 [M+H]+. Spectroscopic data are in
General procedures and safety statements
(A) Preparation of Benzyl acetates22
A round bottom flask equipped with a magnetic stirrer was
charged with the appropriate benzyl alcohol (10.0 mmol) and
acetic anhydride (15.0 mmol). The reaction mixture was
accordance with literature.
24
4-Methylbenzyl acetate (1b)
o
The title compound was afforded as a clear oil (0.78 g, 48%)
1
using general procedure A. H NMR (400 MHz, CDCl3) δ 7.34-
refluxed (85 C) for 15 h. Upon cooling to room temperature
the reaction mixture was poured into water (50 mL). The
aqueous phase was extracted with ethyl acetate (30 mL x 3).
The combined organic phase was washed with 1 M aq HCl (30
mL), saturated aq NaHCO3 (30 mL), water (30 mL) and brine
(30 mL), and dried (MgSO4). The solvent was evaporated under
reduced pressure to afford the title compound without further
purification.
7.23 (m, 2H), 7.23-7.10 (m, 2H), 5.07 (s, 2H), 2.36 (s, 3H), 2.08
(s, 3H) ppm; 13C NMR (100.1 MHz, CDCl3) δ 171.1, 138.2, 133.0,
129.3, 128.5, 66.4, 21.3, 21.2 ppm; m/z (ESI) = 165 [M+H]+.
Spectroscopic data are in accordance with literature.
25
4-Chlorobenzyl acetate (1c)
The title compound was afforded as a clear oil (0.98 g, 53%)
1
using general procedure A. H NMR (400 MHz, CDCl3) δ 7.34-
(B) Electrosynthetic oxidation reactions
7.30 (m, 2 H), 7.30-7.25 (m, 2H), 5.05 (s, 2H), 2.08 (s, 3H) ppm;
13C NMR (100.1 MHz, CDCl3) δ 170.9, 134.5, 134.2, 129.7,
128.8, 65.6, 21.1 ppm; m/z (ESI) = 185 [M35Cl+H]+, 187
[M37Cl+H]+. Spectroscopic data are in accordance with
A sealable electrochemical cell equipped with a magnetic
stirrer was added anhydrous methanol (10 mL), Lithium
perchlorate (0.53 g [0.50 M]) and the alcohol (0.5 mmol [0.05
M]) or the benzyl acetate (0.05 M) under study. Two
reticulated vitreous carbon (RVC) electrodes were inserted
into the solution at a distance of approximately 0.5 cm from
each other and the vial sealed. The solution was cooled to 0 oC
(ice-bath) and degassed with nitrogen. A fixed current (10 mA)
was passed through the solution in an ice bath until the
desired charge (Q) was achieved (on average t = 5.5 h). Upon
completion of the reaction, the solvent was evaporated (at 35
oC), the residual oil was partitioned between water (10 mL)
and ethyl acetate (5 mL x 3). The combined organic extracts
were dried (MgSO4) and evaporated. Analytical quality sample
of the aldehyde/ketone was obtained by column
chromatography (SiO2; cyclohexane-ethyl acetate) to afford
the title compound.
literature.
26
Phenylethyl acetate (1e)
The title compound was afforded as a clear oil (0.58 g, 36%)
1
using general procedure A. H NMR (400 MHz, CDCl3) δ 7.34-
7.19 (m, 5 H), 4.27 (t, J = 7.0 Hz, 2H), 2.99 - 2.83 (t, J = 7.0 Hz,
2H), 2.03 (s, 3 H) ppm; m/z (ESI) = 165 [M+H]+. Spectroscopic
data are in accordance with literature.
27
Benzaldehyde (2a)
The title compound was afforded as a colourless oil (52 mg,
99%) using general procedure B (from benzyl alcohol, 3a).
Alternatively, the title compound (42 mg, 80%) was prepared
1
using general procedure B (from benzyl acetate, 1a). H NMR
(300 MHz, CD3OD) δ 10.01 (s, 1H), 7.91-7.85 (m, 2H), 7.68-7.63
(m, 1H), 7.60-7.45 (m, 2H) ppm; 13C NMR (100.1 MHz, CD3OD)
δ 192.6, 136.4, 134.6, 129.9, 129.1 ppm; m/z (ESI) 106 [M]+.
(C) Cyclic voltammetry studies
An undivided glass cell equipped with a rectangular reticulated
vitreous carbon (RVC) anode (11 cm2) and rectangular RVC
cathode (11 cm2), arranged opposite to one another at a
distance of 3.0 mm with a Ag/AgCl pseudo reference electrode
placed 1.0 mm from the working electrode. To this reaction
vessel was added the analyte under study (5.0 mM) in the
organic solvent(s) (total volume 6.0 mL) and electrolyte (e.g.
tetrabutylammonium perchlorate (0.5 M)). Scan rate was
varied using the Autolab Nova 2.0 software.
Spectroscopic data are in accordance with literature.
28
4-Methylbenzaldehyde (2b)
The title compound was afforded as a colourless oil (50 mg,
83%) using general procedure B (from 4-methylbenzyl alcohol,
3b). Alternatively, the title compound (90 mg, 75%) was
prepared using general procedure B (from 4-methylbenzyl
acetate, 1b). 1H NMR (300 MHz, CD3OD) δ 9.95 (s, 1H), 7.77 (d,
J = 8.0 Hz, 2H), 7.32 (d, J= 8.0 Hz, 2H), 2.43 (s, 3H) ppm; 13C
NMR (100.1 MHz, CD3OD) δ 191.9, 145.5, 134.2, 129.8, 129.7,
21.7 ppm; m/z (ESI) 121 [M+H]+. Spectroscopic data are in
CAUTION: Perchlorates – May intensify fire. In combination
with flammable solvents, all sources of ignition should be
avoided. During the concentration stage of the work-up, low
temperature rotary evaporation with a suitable shield should
be employed. The aqueous layer (after extraction) was treated
with excess sodium sulphite prior to disposal.
accordance with literature.
28
4-Chlorobenzaldehyde (2c)
The title compound was afforded as a white powder (60 mg,
86%) using general procedure B (from 4-chlorobenzyl alcohol,
3c). Alternatively, the title compound (48 mg, 68%) was
prepared using general procedure A (from 4-chlorobenzyl
CAUTION: Passing an electrical current through flammable
organic solvent – The potentiostat and wiring should be
regularly inspected for faults and pass all relevant electrical
tests prior to use.
1
acetate, 1c). H NMR (300 MHz, CDCl3) δ 10.00 (s, 1H), 7.94-
7.78 (m, 2H), 7.71-7.43 (m, 2H) ppm; 13C NMR (100.1 MHz,
CDCl3) δ 190.1, 140.7, 134.5, 130.1, 129.2 ppm; m/z (ESI) 139
[M-H]+. Spectroscopic data are in accordance with literature.
28
2-Chlorobenzaldehyde (2f)
Spectroscopic data
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The title compound was afforded as a colourless oil (57 mg, A.M.J. thanks the Royal Society of London (United Kingdom)
81%) using general procedure B (from 2-chlorobenzyl alcohol, for the award of a research grant (RG150135). The authors
1
3d). H NMR (300 MHz, CDCl3) δ 10.48 (s, 1H), 7.92-7.89 (m, thank the analytical services at Manchester Metropolitan
1H), 7.56-7.50 (m, 1H), 7.49 -7.42 (m, 2H) ppm; 13C NMR (100.1 University and the Centre for Chemical and Materials Analysis
MHz, CDCl3) δ ppm 190.0, 138.2, 135.2, 132.5, 130.7, 129.5, in the School of Chemistry at the University of Birmingham for
127.4 ppm; m/z (ESI) 139 [M-H]+; Hi-Res LC–MS (ESI) m/z calcd analytical support. The NMR instruments used in this research
for C7H5OCl [M-H]+ 138.9956, found 138.9961. Spectroscopic were obtained through Birmingham Science City: Innovative
data are in accordance with literature.
28
3-Chlorobenzaldehyde (2g)
Uses for Advanced Materials in the Modern World (West
Midlands Centre for Advanced Materials Project 2), with
The title compound was afforded as a colourless oil (39 mg, support from Advantage West Midlands (AWM) and part
55%) using general procedure B (from 3-chlorobenzyl alcohol). funded by the European Regional Development Fund (ERDF).
1H NMR (300 MHz, CDCl3) δ 9.97 (s, 1H) 7.89-7.83 (m, 1H) 7.79-
7.73 (m, 1H) 7.51 - 7.45 (m, 2H) ppm; 13C NMR (100.1 MHz,
Notes and references
CDCl3) δ 190.8, 137.8, 135.4, 134.5, 130.5, 129.4, 127.8 ppm;
m/z (ESI) 139 [M-H]+. Spectroscopic data are in accordance
1
(a) G. Tojo, M. I. Fernandez, Oxidation of Alcohols to
Aldehydes and Ketones: Guide to Current Common
A
with literature.
29
Practice, Springer, New York, 2006; (b) G. Franz, R. A.
Sheldon, Oxidation, in: Ullmann’s Encyclopaedia of Industrial
Chemistry, VCH-Verlag, Weinheim, 2000; (c) R. C. Larock,
Comprehensive Organic Transformations, 2nd Ed, Wiley,
New York, 1999.
Thiophene-2-carbaldehyde (2h)
The title compound was afforded as a pale yellow oil (55 mg,
99%) using general procedure B (from 2-thiophenemethanol).
1H NMR (400 MHz, CDCl3) δ 9.95 (d, J = 1.3 Hz, 1H), 7.78
(ddd, J = 5.0, 3.8, 1.2 Hz, 2H), 7.22 (dd, J = 5.0, 3.8 Hz,
1H) ppm; 13C NMR (100.1 MHz, CDCl3) δ 183.0, 144.0, 136.3,
135.1, 128.3 ppm; m/z (ESI) 111 [M-H]+. Spectroscopic data are
2
3
4
(a) D. Lee, J. K. Sello, S. L. Schreiber, Org. Lett., 2000, 2, 709;
(b) A. F. Abdel-Magid, S. J. Mehrman, Org. Process Res. Dev.,
2006, 10, 971.
M. Sankar, E. Nowicka, E. Carter, D. M. Murphy, D. W.
Knight, D. Bethell, G. J. Hutchings, Nature Comm., 2014, 5,
3332.
(a) D. Könning, T. Olbrisch, F. D. Sypaseuth, C. C. Tzschucke,
M. Christmann, Chem. Commun., 2014, 50, 5014; (b) J. E.
Steves, S. S. Stahl, J. Am. Chem. Soc., 2013, 135, 15742; (c) S.
in accordance with literature.
27
2-Methylbenzaldehyde (2i)
The title compound was afforded as a colourless oil (39 mg,
65%) using general procedure B (from 2-methylbenzyl alcohol).
1H NMR (300 MHz, CDCl3) δ 10.29 (s, 1H), 7.82 (d, J = 7.3 Hz,
1H), 7.51-7.31 (m, 3H), 2.69 (s, 3H) ppm; 13C NMR (100.1 MHz,
CDCl3) δ 192.7, 140.2, 133.9, 133.5, 131.9, 131.5, 126.1, 20.1
ppm; m/z (ESI) 121 [M+H]+; Hi-Res LC–MS (ESI) m/z calcd for
C8H8O [M+H]+ 121.0648, found 121.0644. Spectroscopic data
B.
Ley,
J.
Marsden, Synthesis, 1994, 639.
Norman,
W.
P.
Griffith,
S.
P.
5
6
A. N. Campbell, S. S. Stahl, Acc. Chem. Res., 2012, 45, 851.
(a) E. J. Horn, B. R. Rosen, P. S. Baran, ACS Cent. Sci., 2016,
302; (b) E. J. Horn, B. R. Rosen, Y. Chen, J. Tang, K. Chen, M.
2
,
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are in accordance with literature.
30
3-Methylbenzaldehyde (2j)
Kawamata,
10.1021/acs.chemrev.7b00397
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S.
Baran,
Rev.
doi:
The title compound was afforded as a clear oil (59 mg, 99%)
using general procedure B (from 3-methylbenzyl alcohol). 1H
NMR (300 MHz, CDCl3) δ 9.98 (s, 1H), 7.77- 7.58 (m, 2H) 7.48-
7.38 (m, 2H), 2.43 (s, 3H) ppm; 13C NMR (100.1 MHz, CDCl3) δ
192.8, 138.4, 136.5, 135.4, 130.1, 129.0, 127.3, 21.5 ppm; m/z
(ESI) 121 [M+H]+. Spectroscopic data are in accordance with
7
(a) S. Liang, C.-C. Zeng, H.-Y. Tian, B.-G. Sun, X.-G. Luo, F. Z.
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4-Methoxybenzaldehyde (2k)
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The title compound was afforded as a colourless oil (18 mg,
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B
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alcohol). H NMR (300 MHz, CDCl3) δ ppm 9.88 (s, 1H) 7.88-
7.78 (m, 2H) 7.09-6.95 (m, 2H) 3.89 (s, 3H); 13C NMR (100.1
MHz, CDCl3) δ 190.4, 164.3, 131.5, 129.8, 113.9, 55.6 ppm;
m/z (ESI) 135 [M-H]+; Hi-Res LC–MS (ESI) m/z calcd for C8H8O2
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Conflicts of interest
There are no conflicts to declare.
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Acknowledgements
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