Silica-supported HClO4 promotes catalytic solvent- and metal-free O-H insertion reactions with diazo compounds

Article abstract of DOI:10.1039/c8gc02574f

Solvent-free O-H insertion reactions in the presence of diazo carbonyl compounds were carried-out in very mild conditions. Unlike the traditional metal-catalysed version, employing rhodium acetate dimer, this method uses eco-friendly silica-supported HClO₄ as the catalyst. Only 0.3 mol% of this Br?nsted acid catalyst, that can also be recycled several times, is necessary to guarantee very good yields (up to 97%) in the O-H insertion reactions. Reaction set-up is simple and permitted the preparation of forty-three α-hydroxy and α-alkoxy esters/ketones in just 1 h and at room temperature.

Full text of DOI:10.1039/c8gc02574f

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Silica-supported HClO4 promotes catalytic solvent- and metal-free
O-H insertion reactions with diazo compounds
Rafael Douglas C Galloa and Antonio C. B Burtoloso*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Solvent-free O-H insertion reactions in the presence of diazo carbonyl compounds were carried-out in very mild
conditions. Unlike the traditional metal-catalysed version, employing rhodium acetate dimer, this method uses eco-
friendly silica-supported HClO4 as the catalyst. Only 0.3 mol% of this Brønsted acid catalyst, that can also be recycled
several times, is necessary to guarantee very good yields (up to 97%) in the O-H insertion reactions. Reaction set-up is
simple and permitted the preparation of forty-three α-hydroxy and α-alkoxy esters/ketones in just 1 h and at room
temperature.
www.rsc.org/
in continuation with our studies in the chemistry of diazo
compounds, we would like to report an eco-friendly and
Introduction
The α-hydroxy and alkoxy carbonyl functionality is an
important pattern in many naturally occurring and synthetic
compounds (Figure 1, A).1–4 It is present in several interesting
and promising molecules5–10 that have shown distinct
applications in chemical biology and/or medicinal chemistry.
Since the pioneering studies from Casanova and Reichstein,11
and Yates12 in the fifties, the syntheses of α-hydroxy and α-
alkoxy carbonyl compounds have been achieved mostly using
metal-catalyzed O-H insertion reactions13–19 from the stable
diazo carbonyl compounds. For these reactions, the use of
transition-metal catalysts in chlorinated solvents (or in
benzene/toluene) proved to give the best results so far. The
most used transition-metal catalysts for O-H insertions include
copper and rhodium, but other metals such as gold, iron,
ruthenium, rhenium and gold complexes could also be
employed.13,17,20 Among these, rhodium is by far the best
metal-free protocol to perform O-H insertion reactions, using
only 0.3 mol% of a recyclable silica-immobilized Brønsted acid
catalyst in the absence of solvent (Figure 1, C). Our studies
goes in the direction of sustainable catalysis27,28, opening a
new entry for performing O-H insertion reactions.
metal to perform these reactions efficiently but is scarce and
22
expensive. Some Lewis acids such as BF3·Et2O13, InCl321, SnCl2
,
Sc(OTf)323 and the expensive B(C6F5)3 have also been applied
in O-H insertion reactions, but none of them have the broad
applicability and efficiency (catalyst loading, yield,
temperature and reaction time) when compared to rhodium
catalysts, for example rhodium acetate (Figure 1, B). Although
several modern, scalable and greener methods to prepare
diazo carbonyl compounds were described in the last few
years,25,26 the need of using expensive and scarce catalysts,
and problematic solvents, to perform efficiently many of the
transformations involving these compounds (including O-H
insertion reactions) is still a drawback in some scenarios (for
example, in industry). Herein, to bypass these limitations and
24
Figure 1. (a) Selected important examples of biologically active molecules.
(b) O-H reactions by previous contributions. (c) This work.
Brønsted acid catalysis29 has been resurfaced as a powerful
tool in the discovery of new reactions, in asymmetric catalysis,
as well as a substitute for metal-catalysis in some cases30.
Recent advances have demonstrated the potential of Brønsted
acids in catalyzing some transformations involving diazo
compounds.31–34 Preliminary studies from our laboratory and
the Mattson group showed that O-H insertion reactions could
a.
Instituto de Química de São Carlos, Universidade de São Paulo, CEP 13560-970,
São Carlos, SP, Brasil. E-mail: antonio@iqsc.usp.br
† Electronic supplementary informaꢀon (ESI) available: NMR data and copy of
spectra of all compounds. See DOI:
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be promoted in the presence of the phosphoric acid diphenyl
We also investigated several conditions to find the lowest
phosphate.34 However, high catalyst loadings (30 mol%), possible amount of HClO4-SiO2 without compromising the
excess of the R-OH reagent, long reaction times and very reaction yield (Table 2). Thus, even decreasing the catalyst
reactive diazo compounds were necessary to promote loading from 5 mol% to 0.5 mol%, complete consumption of
acceptable yields of the products, showing that more studies diazo compound
1
was observed along with shorter reaction
should be carried-out.
times and giving insertion product 2 in almost similar yields
(Entries 1-4). With 0.3 mol% of HClO4-SiO2 the product yield was
slightly increased to 89% (Entry 5). No further improvement in
the yield was seen when the catalyst amount was decreased to
0.2 or 0.1 mol% (Entry 6 and 7).
Results and discussion
For our initial study, we decided to choose as the reaction
model the O-H insertion reaction between methyl α-
Table 2. Optimization of HClO4-SiO2 loading
phenyldiazoacetate
1 and benzyl alcohol. Our first experiment
was repeating our previous conditions34 (10 equiv. of alcohol
and 30 mol% of diphenyl phosphate) in this new system.
Moderate yield and long reaction time were observed with this
catalyst (Entry 1). We then screened various Brønsted acids
with different pKa, but similar or poorer results were obtained
(Entries 2–5). The use of the stronger acid H2SO4 (pka = -3.0)
caused an increase in the yield to 69% and a decrease in the
Entry
Catalyst (mol%)
Time (h)
Yield b (%)
1
2
3
4
5
6
7
3
1
1
1
1
1
1
3
83
80
82
80
89
79
70
2
reaction time (12 h for total conversion of 1, Entry 6). These
1
results indicate that the pKa of acid was important for the
desired reaction to occur, stronger acids giving the best
results. Indeed, when we used HClO4 (pka = -10), a 72% yield
was obtained in just 2h (Entry 7). Reducing the catalyst loading
0.5
0.3
0.2
0.1
a Reaction conditions: 1 (0.3 mmol), 10 eq. BnOH, catalyst (X
mol%), 25 °C, time. b Isolated yield.
to 5 mol% provided compound
2 in 73% yield after 12 hours
(total consumption of 1) (Entry 8).
Table 1. Optimization conditions for O-H insertion reactions
Sequentially, we investigated the amount of alcohol required
for the reaction aiming at a better economy of the reagents (Table
3). Thereby, the quantity of alcohol was reduced to 6 equiv. with no
change in product yield (Entry 1). Similar observation regarding
product yield can be noticed in entries 2-7. Therefore, a slight
excess of the alcohol is recommended for better yield of the
insertion product (Entry 7, 95%).
Catalyst
(mol%)
Time
(h)
Entry
Catalyst
pKa
Yieldb (%)
1
2
3
4
5
6
7
8
9
(PhO)2PO2H
AcOH
CSA
3.88
4.76
1.2
−2.6
-2.8
-3.0
-10.0
-10.0
30
30
30
30
30
30
30
5
24
24
24
24
24
12
2
12
2
12
24
51
-
Table 3. Optimization of the alcohol ammounta
55
58
61
69
72
73
83
-
MsOH
TsOH
H2SO4
HClO4
HClO4
HClO4-SiO2
SiO2
Entry
Time (h)
BnOH (eq.)
Yieldb (%)
1
2
3
4
5
6
7
1
1
1
1
1
4
1
6.0 eq.
5.0 eq.
4.0 eq.
3.0 eq.
2.0 eq.
1.0 eq.
1.5 eq.
89
88
90
90
91
85
95
5
5
-
10
11
none
-
a Reaction conditions: 1 (0.3 mmol), 10 eq. BnOH, catalyst (X mol%), 25 °C,
time. b Isolated yield.
Aiming to increase the performance and eliminate by-
products of the reaction, as well as the improvement of acid
manipulation, HClO4 was immobilized on silica (230-400
mesh)35–37
a Reaction conditions: 1 (0.3 mmol), X eq. BnOH, catalyst
(0.3 mol%), 25 °C, 60 min. b Isolated yield.
In the case of alcohols that are solids at 25 oC, there was a need
to find suitable solvents to carry out the reaction. In this context,
some environmentally safe solvents were selected and tested in the
model reaction, employing solid cinnamic alcohol as the nucleophile
(Table 4). After testing several solvents, we noticed that acetone
was the best one and furnished the insertion product in 66% yield
. To our delight, this modification significantly
improved its catalytic efficiency (5 mol%, 83% yield, 2h, Entry 9).
It is important to mention that the reaction did not occur using
only silica as the catalyst (Entry 10) nor without the Brønsted
acid (Entry 11).
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(Entries 1-4). Finally, concentrating the reaction medium three evaporation. In just few cases, where the alcohols employed are
times (solvent volume lowered to 50 μL), compound 3 was obtained non-volatile or solids, column chromatography is necessary. No
in 88% yield (Entry 5).
matter the type of purification, about 80% of all the solvents
employed can also be recovered. It is worth noting that in reaction
Table 4. Solvent screening to use with solid alcohols as nucleophilea scales larger than 50 g of the starting materials, products may be
purified by vacuum distillation, avoiding the use of solvents. The use
of membranes, as described by Szekely38,39, is also an sustainable
alternative to use in large scale preparations.
Table 5. Scope of nucleophile
Volume
(uL)
Yieldb
(%)
Entry
Solvent
Time (h)
1
2
3
4
5
Acetonitrile
Ethyl acetate
Acetone
DMSO
Acetone
150
150
150
150
50
24
24
12
24
4
27
42
66
-
Entry
1
R-OH
Product
Yield b
95%
88
a
Reaction conditions: 1 (0.3 mmol), 1.5 eq. cinnamyl alcohol,
catalyst (0.3 mol%), 25 °C, Solvent, 4 h. b Isolated yield.
With the optimized conditions in hand, we decided to examine
the substrate scope of alcohols, as depicted in Table 5. A discussed
previously, benzyl and cinnamyl alcohols were isolated in excellent
yields (Entries 1 and 2). Other primary and secondary alcohols such
as MeOH, EtOH and i-PrOH smoothly afforded products in very
good yields (Entries 3-5). When tert-butanol was used, product 7
was obtained in 66% yield (Entry 6). This lower yield can be
explained by the steric hindrance of the tert-butyl group of the
alcohol. Excellent yields were also observed when propargyl and
allylic alcohols were used (Entries 7 and 8, 97 and 96% yield,
respectively). It is also noteworthy that even using water as the
nucleophile the insertion product 10 was isolated in 82% yield
(Entry 9).
2c
88%
3
4
5
90%
93%
95%
In addition, we investigated others α-diazo esters and ketones
employing alcohol or water as the nucleophile to understand the
general extension of the envisaged methodology (Figure 2). To
study the scope of diazo compounds, reactions were performed
employing optimized reaction conditions previously mentioned
(Table 3, Entry 7). The α-diazo substrates containing electron donor
groups, both at the ortho and para position of the benzene ring
smoothly delivered our required products 21-27, 34-35 and 42 in
good yields (81-96%). However, when using precursors with
electron withdrawing groups, such as bromine or nitro, there was a
decrease in the yield of the products 28-33, 36-39 and 43 (58-80%).
Additionally, good yields were obtained for insertion reaction with
diazo compound containing different ester group, such as benzyl
(products 40-41 80-83% yield). Using the less reactive diazo ketones
derivatives, as well as aliphatic diazo esters, the insertion products
could be obtained in excellence yield even using water (44-54, 80-
96%). Furthermore, we also repeated the formation of product 25
(Figure 2) in a larger scale (1.0 g of 11). In this scale, compound 25
could be isolated in 90% yield. It is also important to note that 88%
of the excess of the alcohol employed in the reaction can be
recovered. Product purification is also simple and consist in just a
filtration of the heterogeneous reaction mixture (to remove and
recycle the catalyst), followed by ethyl acetate washing and solvent
6
66%
97%
7
8
96%
82%
OH
O
9d
O
10
a
Reaction conditions: 1 (0.3 mmol), 1.5 eq. alcohol, catalyst (0.3
mol%), 25 °C, 1 h. Isolated yield. Solvent acetone, 4h. 10 eq. H2O,
24 h.
b
c
d
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Figure 2. Scope of diazo compounds. Reaction condition: 1.5 equiv ROH or 10 equiv H2O; 0.3 mol% of HClO4-SiO2, 60 mim (ROH), 24 h (H2O), and 25 °C.
4 | J. Name., 2012, 00, 1-3
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In view of all experiments performed,
a plausible and mild, solvent free and can be performed in an open vial. High
summarized mechanism for the alcohol insertion reaction in the α- efficiency of the methodology permits the use of a diverse number
diazo carbonyl is depicted in Figure 3. Therefore, Si is coordinated of alcohols (or water), as well as a good variety of diazo compounds
to the oxygen atom of the Cl=O group, owing to the high as substrates. Moreover, the great stability of the silica-supported
oxophilicity of Si, to form a six-membered cyclic structure that catalyst, the need of low loadings of the catalyst and its reusability
increases the electrophilicity of the proton of HClO4.40 Initially, the open the possibility to perform the reaction in large scale, making
diazo compound is protonated by the Brøsnted acid, driving to the the method also attractive on an industrial perspective.
formation of the diazonium intermediate. Sequentially, nucleophilic
attack of the oxygen dislocates molecular nitrogen, followed by
hydrogen abstraction by the conjugate base of the catalyst and
Experimental
regenerating the catalyst.
O
HO
Cl
O
GENERAL PROCEDURES
O
O
O
O
Si
O
O
HO
O
OH
O
R
H
R
R
All solvents were dried and distilled prior to use by standard
procedures. Reagents were purchased at the highest commercial
Si
O
R
R
R
O
N
N
N2
R
O
quality from Sigma-Aldrich and used without further purification,
unless otherwise stated. Diazo compounds employed in this work
are known and were prepared according to the literature.42-48 Ethyl
diazoacetate is commercially available. Reactions were monitored
by thin layer chromatography (TLC), carried out on 0.25 mm silica
gel plates using UV light as visualizing agent and potassium
permanganate in aqueous KOH for staining. Column
chromatography was performed using silica gel 60 (particle size
0.063-0.210 mm). Unless stated otherwise, all the yields refer to
isolated products after flash column chromatography. The solvent
mixtures employed in TLC analysis and in flash column
chromatography purifications are reported as volume by volume
and in percentages. Proton nuclear magnetic resonance (1H NMR)
spectra were recorded using 500 MHz equipment. For 1H NMR
spectra, chemical shifts (δ) are referenced from TMS (0.00 ppm).
Coupling constants (J) are reported in Hz. For multiplicities the
following abbreviations were used: s, singlet; d, doublet; t, triplet;
q, quartet; m, multiplet; dd, double doublet; bs, broad singlet; dt,
double triplet. Carbon nuclear magnetic resonance (13C NMR)
spectra were recorded using a NMR spectrometer at 125 MHz. For
13C NMR spectra, chemical shifts (δ) are given from CDCl3 (77.0
ppm). Infrared spectra were obtained using FT-IR at 4.0 cm-1
resolution and are reported in wavenumbers. Melting points were
determined using a digital melting point apparatus and were not
corrected. High resolution mass spectra (HRMS) were recorded
using electron spray ionization (ESI) (Hybrid linear ion trap–orbitrap
FT-MS and QqTOF/MS).
O
O
O
O
H
O
Cl
O
Cl
O
O
R
H
R
R
O
O
R
OH
R
HO
OH
O
HO
O
H
Si
O
Si
O
Si
O
Si
O
O
N
O
O
O
N
N2
R-OH
Figure 3. Suggested summarized mechanism for the reaction
‘between α-diazo carbonyl and alcohol via Brøsnted acid catalysis.
The reusability of HClO4–SiO2 was also investigated for our best
reaction condition that afforded 2 in 95% yield. The reactions were
repeated 6 times more in the presence of the recovered HClO4–SiO2
to afford, again, 2 in 95%, 94%, 92%, 91%, 90%, and 85% yields,
respectively. The catalytic performance was maintained until the
fifth recycling without any significant loss of activity (90-95% yield).
Some green metrics41 were also calculated for our method,
choosing compound 5 as an example (Table 4).
Table 4. Quantification of Green Chemistry Metrics for compound 5
Entry
green chemistry metricsa
Product 5
1
2
3
4
5
6
7
8
Yield
atom economy
carbon efficiency
93%
87.4%
85.3%
73.7%
18
reaction mass efficiency (RME)
mass intensity (MI)
mass productivity
E factor (MI – 1)
5.5%
17
Solvent consumption
a definitions and calculations for each green chemistry metric are
0.019L/g
described in the supporting information
.
Conclusions
In conclusion, we demonstrated that the OH insertion reaction
of α-diazo compounds, catalyzed by silica-supported HClO4, can be
a robust way to prepare a-hydroxy or alkoxy-carbonyls, avoiding the
use of scarce and expensive catalysts as well as problematic
solvents. High yield of products (up to 97%) could be obtained in
just 0.3 mol% of the catalyst. The reaction set-up is very simple,
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PREPARATION OF DIAZO COMPOUNDS
Methyl (1,3-benzodioxole)diazoacetate 1545
To a mixture of esters (10 mmol) and p-ABSA (12 mmol), in
anhydrous CH3CN (30 mL), was added DBU (14 mmol). The reaction
mixture was stirred at room temperature during overnight. Upon
the complete consumption of the starting materials, the reaction
mixture was diluted with distilled water (20 mL), followed by
extraction with diethyl ether (3 × 10 mL). After washing with 10%
NH4Cl solution (3 × 10 mL) and brine (3 × 10 mL), the combined
organic extracts were dried over MgSO4 and concentrated by rotary
evaporation. The residue was purified by flash chromatography to
afford the diazo esters.
Yield: 84% (924 mg). Orange solid, m.p. 77-78 °C. TLC: Rf = 0.40
(10% EtOAc/hexanes). 1H NMR (500 MHz, CDCl3): δ 7.06 (dd, J = 1.7,
0.4 Hz, 1H), 6.84 – 6.85 (m, 2H), 5.97 (s, 2H), 3.86 (s, 3H).
Methyl 2-(2-bromophenyl)-2-diazoacetate 1346
Yield: 90% (1143 mg). Colourless oil. TLC: Rf
= 0.20 (10%
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.49 – 7.46 (m, 2H),
7.39 – 7.36 (m, 2H), 7.20 – 7.16 (m, 1H), 3.86 (s, 3H).
2-diazo-1-phenylethanone 1847
Methyl phenyldiazoacetate 142
Yield: 84% (910 mg). Yellow solid, m.p. 50-51 °C. TLC: Rf = 0.32 (20%
1
Yield: 81% (755 mg). Red oil. TLC: Rf = 0.47 (10% EtOAc/hexanes).
1H NMR (500 MHz; CDCl3): δ 7.49 – 7.47 (m, 2H), 7.39 – 7.36 (m,
2H), 7.19 – 7.18 (m, 1H), 3.86 (s, 3H).
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.77 – 7.75 (m, 2H);
7.56 – 7.52 (m, 1H); 7.46 – 7.43 (m, 2H), 5.91 (s, 1H).
3-diazo-2-oxopropylphosphonate 1948
Methyl 2-diazo-2-(4-methoxypheny)acetate 1143
Yield: 72% (320 mg). Yellow oil. TLC: Rf = 0.20 (EtOAc). 1H
Yield: 86% (886 mg). Orange solid, m.p. 48-50 °C. TLC: Rf = 0.32 NMR (500 MHz, CDCl3): δ 5.61 (s, 1H), 4.19 – 4.13 (m, 4H), 2.95
(d, J = 21.8 Hz, 2H), 1.35 (td, J = 7.1, 0.5 Hz, 6H).48
1
(10% EtOAc/hexanes). H NMR (500 MHz; CDCl3): δ 7.39 (d, J = 9.0
Hz, 2H), 6.95 (d, J = 9.0 Hz, 2H), 3.85 (s, 3H), 3.81 (s, 3H).
PREPARATION OF PERCHLORIC ACID ADSORBED ON SILICA GEL
(HCLO4–SIO2)36
Methyl 4-bromophenyldiazoacetate 1243
The preparation of HClO4–SiO2 was carried out following some
Yield: 90% (1147 mg). Orange solid, m.p. 39-40 °C. TLC: Rf = 0.48
modifications of the originally reported procedure.36 To
a
1
(10% EtOAc/hexanes). H NMR (500 MHz; CDCl3): δ 7.51 (d, J = 8.9
suspension of silica gel (10 g, 230–400 mesh) in EtOAc (20 mL) was
added HClO4 (0.14 g, 1.40 mmol, that correspond to 0.2 g of a 70%
aq. solution of HClO4) and the mixture was stirred magnetically for
30 min at rt. EtOAc was removed under reduced pressure (rotary
evaporator) and the residue was heated at 100 °C for 4 h under
vacuum to afford HClO4–SiO2 (0.14 mmol g−1).
Hz, 2H), 7.36 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H).
Methyl 4-nitrophenyldiazoacetate 1744
Yield: 70% (774 mg). Orange oil. TLC:
Rf = 0.38 (10%
EtOAc/hexanes). 1H NMR (500 MHz; CDCl3): δ 8.23 (d, J = 9.3 Hz,
2H), 7.67 (d, J = 9.2 Hz, 2H), 3.91 (s, 3H).
Methyl 2-methoxyphenyldiazoacetate 1445
GENERAL PROCEDURE FOR O-H INSERTION
To a 4 mL vial equipped with a magnetic stir-bar was added 0.3
mmol of diazo (1 equiv), 1.5 equiv of alcohol (or 10 equiv of the
water) and 0.3 mol% of HClO4.SiO2 (6.4 mg, 0.9 µmol) at room
temperature. The reaction mixture was stirred at this temperature
for 1 h for the alcohols and 24 h for water. Then, the heterogeneous
mixture was filtered and washed with 1-2 mL of ethyl acetate.
Evaporation of the solvent afforded the O-H insertion product with
no need of purification. In the case of reactions employing non-
volatile or solid alcohols, products were purified by flash column
Yield: 95% (979 mg). Orange oil, m.p. 39-40 °C. TLC: Rf = 0.35 (10%
1
EtOAc/hexanes). H NMR (500 MHz; CDCl3): δ 7.55 (dd, J = 7.8, 1.6
Hz, 1H), 7.26 (ddd, J = 8.3, 7.1, 1.7 Hz, 1H), 7.02 (td, J = 7.7, 1.2 Hz,
1H), 6.90 (dd, J = 8.3, 1.0 Hz, 1H), 3.86 (s, 3H), 3.83 (s, 3H).
Benzyl 2-diazo-2-phenylacetate 1643
Yield: 86% (1083 mg). Orange solid, m.p. 63-66 °C. TLC: Rf = 0.47
(10% EtOAc/hexanes). 1H NMR (500 MHz; CDCl3): δ 7.48 (dd, J = 8.5,
1.1 Hz, 2H), 7.41 – 7.32 (m, 7H), 7.17 (t, J = 7.4 Hz, 1H), 5.30 (s, 2H).
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chromatography
[silica
gel
(230-400
mesh)]
using Methyl 2-tert-butoxy-2-phenylacetate 753
cyclohexane:EtOAc or hexanes:EtOAc (9:1) as eluent (In general, 50 Yield: 66% (44 mg). Colourless oil. TLC: Rf
= 0.33 (10%
1
g of silica, 270 mL of hexanes or cyclohexane and 30 mL of ethyl EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.48 – 7.46 (m, 2H),
acetate for 1 g of purified product). The product formation can also 7.35 – 7.28 (m, 3H), 5.09 (s, 1H), 3.70 (s, 3H), 1.26 (s, 9H).
be accompanied by TLC or by the disappearance of the yellow color
of the solution. Methyl-cyclohexane or heptane can also be used in Methyl 2-phenyl-2-(prop-2-ynyloxy)acetate 854
the place of cyclohexane and hexanes.
Yield: 97% (59 mg). Colourless oil. TLC: Rf = 0.15 (10%
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.46 – 7.44 (m, 2H),
Methyl 2-benzyloxy-2-phenylacetate 249
7.40 – 7.36 (m, 3H), 5.22 (s, 1H), 4.29 (dd, J = 16.1 Hz, 1H), 4.14 (dd,
Yield: 95% (73 mg). Colourless oil. TLC: Rf
= 0.25 (10% J = 16.1 Hz, 1H), 3.73 (s, 3H), 2.48 (s, 1H).
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.47 – 7.45 (m, 2H),
7.39 – 7.30 (m, 8H), 4.94 ( s, 1H), 4.60 (d, J = 11.9 Hz, 1H), 4.57 (d, J Methyl 2-(allyloxy)-2-phenylacetate 955
= 11.9 Hz, 1H) 3.71 (s, 3H).
Yield: 96% (59 mg). Colourless oil. TLC: Rf = 0.17 (10%
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.46 – 7.44 (m, 2H),
Methyl 2-(cinnamyloxy)-2-phenylacetate 3
7.38 – 7.33 (m, 3H), 5.94 (ddt, J = 17.2, 10.4, 5.8 Hz, 1H), 5.29 (dq, J
Yield: 88% (75 mg). Colourless oil. TLC: Rf
=
0.36 (10% = 17.2, 1.6 Hz, 1H), 5.23 (ddd, J = 10.4, 2.8, 1.2 Hz, 1H), 4.95 (s, 1H),
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.47 (dd, J = 8.0, 1.3 4.06 (dt, J = 5.8, 1.3 Hz, 2H), 3.71 (s, 3H).
Hz, 2H), 7.39 – 7.29 (m, 7H), 7.24 (tt, J = 6.3, 1.3 Hz, 1H), 6.59 (d, J =
15.9 Hz, 1H), 6.30 (dt, J = 15.9, 6.3 Hz, 1H), 5.00 (s, 1H), 4.26 – 4.18 Methyl 2-hydroxy-2-phenylacetate 1056
(m, 2H), 3.70 (s, 3H). 13C NMR (125 MHz, CDCl3) δ: 171.4, 136.5, Yield: 82% (41 mg). Colourless oil. TLC: Rf
= 0.20 (10%
1
136.4, 133.7, 128.88, 128.81, 128.6, 128.0, 127.5, 126.7, 125.1, EtOAc/hexanes). H NMR (500 MHz; CDCl3): δ 7.41 – 7.39 (m, 2H),
79.8, 70.2, 52.4. IR νmax (cm-1): 3029, 2950, 2856, 1745, 1445, 1264, 7.36 – 7.30 (m, 3H), 5.16 (s, 1H), 3.71 (s, 3H), 3.69 (s, 1H).
1205, 1173, 1115, 1069, 1016, 969, 736, 695. HRMS (ESI-TOF)
calculated for C18H18O3Na [M+Na] 305.1154; found 305,1142.
Methyl 2-hydroxy-2-(4-methoxyphenyl)acetate 2157
Yield: 80% (48 mg). White solids. TLC: Rf
= 0.17 (20%
Methyl 2-methoxy-2-phenylacetate 450
EtOAc/hexanes). 1H NMR (500 MHz, CDCl3): δ 7.33 (d, J = 8.5 Hz,
Yield: 90% (49 mg). Colourless oil. TLC: Rf
= 0.31 (10% 2H), 6.89 (d, J = 8.8 Hz, 2H), 5.13 (s, 1H), 3.80 (s, 3H), 3.75 (s, 3H),
1
EtOAc/hexanes). H NMR (500 MHz; CDCl3): δ 7.45 – 7.43 (m, 2H), 3.39 (brs, 1H).
7.39 – 7.33 (m, 3H), 4.78 (s, 1H), 3.72 (s, 3H), 3.41 (s, 3H).
Methyl 2-methoxy-2-(4-methoxyphenyl)acetate 2258
Yield: 91% (57 mg). Colourless oil. TLC: Rf
=
0.30 (10% EtOAc/hexanes). 1H NMR (500 MHz, CDCl3): δ 7.32 (d, J = 9.0 Hz,
Ethoxy-phenyl-acetic acid methyl ester 551
= 0.29 (10%
Yield: 93% (54 mg). Colourless oil. TLC: Rf
1
EtOAc/hexanes). H NMR (500 MHz; CDCl3): δ 7.47 – 7.45 (m, 2H), 2H), 6.89 (d, J = 9.0 Hz, 2H), 4.72 (s, 1H), 3.80 (s, 3H), 3.71 (s, 3H),
7.38 – 7.33 (m, 3H), 4.89 (s, 1 H), 3.71 (s, 3H), 3.60 (dq, J = 14.0, 7.0 3.38 (s, 3H).
Hz, 1H), 3.51 (dq, J = 14.0, 7.0 Hz, 1H), 1.27 (t, J = 7.0 Hz, 3H).
Methyl 2-ethoxy-2-(4-methoxy phenyl)acetate 2334
Isopropoxy-phenyl-acetic acid methyl ester 652
Yield: 95% (59 mg). Colourless oil. TLC: Rf = 0.23 (10%
1
Yield: 95% (60 mg). Colourless oil. TLC: Rf
=
0.32 (10% EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.38 – 7.36 (m, 2 H),
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.47 – 7.45 (m, 2H), 6.89 – 6.88 (m, 2 H), 4.83 (s, 1 H), 3.79 (s, 3 H), 3.70 (s, 3 H), 3.59 –
7.36 – 7.33 (m, 3H), 5.00 (s, 1H), 3.70 (s, 3H), 3.70 – 3.65 (m, 1H), 3.46 (m, 2 H), 1.26 (t, J = 7.0 Hz, 3 H).
1.25 (d, J = 6.1 Hz, 3H), 1.20 (d, J = 6.1 Hz, 3H).
Methyl 2-isopropanoxy-2-(4-methoxyphenyl)acetate 2459
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Yield: 93% (66 mg). Colourless oil. TLC: Rf
= 0.25 (10% 7.35 – 7.33 (m, 2H), 5.92 (ddt, J = 17.2, 10.4, 5.8 Hz, 1H), 5.28 (dq, J
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.39 – 7.36 (m, 2 H), = 17.2, 1.6 Hz, 1H), 5.24 (dq, J = 10.4, 2.7, 1.2 Hz, 1H), 4.90 (s, 1H),
6.90 – 6.87 (m, 2 H), 4.94 (s, 1H), 3.79 (s, 3H), 3.70 (s, 3H), 3.68 – 4.06 – 4.04 (m, 2H), 3.71 (s, 3H).
3.63 (m, 1H), 1.23 (d, J = 6.1, 3H), 1.18 (d, J = 6.1, 3H).
Methyl 2-(4-bromophenyl)-2-methoxyacetate 30
Methyl 2-(benzyloxy)-2-(4-methoxyphenyl)acetate 2534
Yield: 80% (62 mg). Colourless oil. TLC: Rf
= 0.28 (10%
Yield: 93% (80 mg). Colourless oil. TLC: Rf
= 0.30 (10% EtOAc/hexanes). 1H NMR (500 MHz, CDCl3): δ 7.52 – 7.48 (m, 2H),
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.38 – 7.28 (m, 7 H), 7.34 – 7.31 (m, 2H), 4.74 (s, 1H), 3.72 (s, 3H), 3.41 (s, 3H). 13C NMR
6.91 – 6.88 (m, 2 H), 4.88 (s, 1 H), 4.56 (dd, J = 11.9 Hz, 2 H), 3.80 (s, (125 MHz, CDCl3) δ: 170.8, 135.3, 131.9, 128.9, 123.0, 81.9, 57.5,
3 H), 3.71 (s, 3 H).
52.5. IR νmax (cm-1): 2995, 2951, 2930, 2828, 1748, 1486, 1259,
1210, 1172, 1106, 1070, 1010, 821, 765. HRMS (ESI-TOF) calculated
for C10H11BrO3H [M+H] 258,9970; found 258.9975.
Methyl 2-(allyloxy)-2-(4-methoxyphenyl)acetate 26
Yield: 95% (68 mg). Colourless oil. TLC: Rf
= 0.25 (10%
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.39 – 7.35 (m, 2H),
6.91 – 6.88 (m, 2H), 5.93 (ddt, J = 17.2, 10.3, 5.8 Hz, 1H), 5.25 (ddq, J
= 24.2, 10.4, 1.4 Hz, 2H), 4.89 (s, 1H), 4.03 (dt, J = 5.8, 1.3 Hz, 2H),
3.80 (s, 3H), 3.71 (s, 3H). 13C NMR (125 MHz, CDCl3) δ: 171.6, 160.0,
133.9, 128.8, 128.5, 118.3, 114.2, 79.3, 70.3, 55.43, 52.37. IR νmax
(cm-1): 3003, 2954, 2839, 1748, 1611, 1512, 1461, 1437, 1246, 1210,
1172, 1093, 1030, 930, 832 796, 755. HRMS (ESI-TOF) calculated for
C13H16NaO4 [M+Na] 259.0946; found 259,0936.
Methyl 2-(4-bromophenyl)-2-ethoxyacetate 31
Yield: 77% (63 mg). Colourless oil. TLC: Rf
= 0.27 (10%
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.51 – 7.48 (m, 2H),
7.36 – 7.33 (m, 2H), 4.85 (s, 1H), 3.72 (s, 1H), 3.71 (s, 3H), 3.60 (dq, J
= 9.1, 7.0 Hz, 1H), 3.50 (dq, J = 9.1, 7.0 Hz, 1H), 1.28 (t, J = 7.0 Hz,
3H). 13C NMR (125 MHz, CDCl3) δ: 171.1, 135.8, 131.8, 128.9, 122.8,
80.3, 65.6, 52.51, 15.22 IR νmax (cm-1): 2977, 2952, 2928, 2880,
1751, 1487, 1258, 1208, 1170, 1110, 1071, 1011, 819, 764. HRMS
(ESI-TOF) calculated for C11H13BrO3Na [M+Na] 294.9946; found
294.9946.
Methyl 2-(4-methoxyphenyl)-2-(prop-2-yn-1-yloxy)acetate 27
Yield: 97% (69 mg). Colourless oil. TLC: Rf
= 0.18 (10%
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.39 – 7.35 (m, 2H),
6.92 – 6.88 (m, 2H), 5.16 (s, 1H), 4.28 (dd, J = 16.0, 2.4 Hz, 1H), 4.11
(dd, J = 16.0, 2.4 Hz, 1H), 3.81 (s, 3H), 3.72 (s, 3H). 13C NMR (125
MHz, CDCl3) δ: 171.0, 160.3, 129.2, 127.52, 114.3, 78.7, 78.3, 76.8,
75.6, 56.0, 55.45, 55.48. IR νmax (cm-1): 3281, 3001, 2954, 2919,
2848, 1742, 1609, 1510, 1446, 1247, 1172, 1087, 1022, 828, 754.
HRMS (ESI-TOF) calculated for C13H14ONa [M+Na] 257.0790; found
257.0751.
Methyl 2-(4-bromophenyl)-2-phenethoxyacetate 32
Yield: 75% (79 mg). Colourless oil. TLC: Rf
= 0.22 (10%
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.51 – 7.48 (m, 2H),
7.36 – 7.29 (m, 7H), 4.89 (s, 1H), 4.58 (s, 2H), 3.70 (s, 3H). 13C NMR
(125 MHz, CDCl3) δ: 170.9, 136.9, 135.4, 131.9, 129.1, 128.6,
128.21, 128.20, 122.9, 79.0, 71.4, 52.5. IR νmax (cm-1): 3063, 3031,
2951, 2870, 1749, 1487, 1257, 1208, 1171, 1093, 1071, 1011, 822,
761, 738, 698. HRMS (ESI-TOF) calculated for C17H18BrO3 [M+H]
349,0439; found 349,0493.
Methyl 2-(4-bromophenyl)-2-hydroxyacetate 2860
Yield: 76% (80 mg). Colourless oil. TLC: Rf
= 0.17 (10%
Methyl 2-(4-bromophenyl)-2-(prop-2-yn-1-yloxy)acetate 33
EtOAc/hexanes). 1H NMR (500 MHz, CDCl3): δ 7.50 (d, J = 8.3 Hz,
2H), 7.31 (d, J = 8.4 Hz, 2H), 5.14 (d, J = 5.4 Hz, 1H), 3.77 (s, 3H), 3.49
(d, J = 5.2 Hz, 1H).
Yield: 78% (66 mg). Colourless oil. TLC: Rf
= 0.24 (10%
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.54 – 7.49 (m, 2H),
7.35 – 7.32 (m, 2H), 5.18 (s, 1H), 4.30 (dd, J = 16.1, 2.4 Hz, 1H), 4.17
(dd, J = 16.1, 2.4 Hz, 1H), 3.73 (s, 3H), 2.49 (t, J = 2.4 Hz, 1H). 13C
NMR (125 MHz, CDCl3) δ: 170.4, 134.5, 132.0, 129.3, 123.3, 78.3,
78.0, 76.0, 56.5, 52.6. IR νmax (cm-1): 3292, 2953, 1744, 1487, 1437,
Methyl 2-allyloxy-2-(4-bromophenyl)acetate 2961
Yield: 73% (59 mg). Colourless oil. TLC: Rf
= 0.27 (10%
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.51 – 7.48 (m, 2H),
8 | J. Name., 2012, 00, 1-3
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1211, 1093, 1011, 822, 767, 678, 639. HRMS (ESI-TOF) calculated 7.39 – 7.26 (m, 7H), 7.22 – 7.18 (m, 1H), 5.42 (s, 1H), 4.61 (q, J =
for C12H11BrO3Na [M+Na] 304.9789; found 304.9767.
11.8 Hz, 2H), 3.72 (s, 3H). 13C NMR (125 MHz, CDCl3) δ: 170.7, 137.0,
136.2, 133.0, 130.2, 129.3, 128.5, 128.3, 128.1, 128.0, 124.1, 78.6,
Methyl 2-hydroxy-2-(2-methoxyphenyl)acetate 3460
71.8, 52.5. IR νmax (cm-1): 3031, 2951, 2924, 2868, 2852, 1746, 1435,
Yield: 92% (54 mg). Colourless oil. TLC: Rf
=
0.13 (10% 1206, 1094, 1022, 748, 695. HRMS (ESI-TOF) calculated for
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.33 – 7.27 (m, 2H),
C16H15BrO3Na [M+Na] 357,0102; found 357,0047.
6.99 – 6.91 (m, 2H), 5.31 (s, 1H), 3.85 (s, 3H), 3.75 (s, 3H).
Methyl 2-(allyloxy)-2-(2-bromophenyl)acetate 39
Methyl 2-isopropoxy-2-(2-methoxyphenyl)acetate 35
Yield: 78% (67 mg). Colourless oil. TLC: Rf = 0.26 (10%
Yield: 84% (60 mg). Colourless oil. TLC: Rf
=
0.25 (10% EtOAc/hexanes). 1H NMR (500 MHz, CDCl3): δ 7.56 (ddd, J = 15.3,
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.45 (dd, J = 7.6, 1.7 7.9, 1.5 Hz, 2H), 7.34 (td, J = 7.6, 1.2 Hz, 1H), 7.20 (ddd, J = 8.0, 7.4,
Hz, 1H), 7.32 – 7.27 (m, 1H), 6.98 (td, J = 7.5, 1.0 Hz, 1H), 6.90 (dd, J 1.7 Hz, 1H), 5.94 (ddt, J = 17.2, 10.3, 5.9 Hz, 1H), 5.41 (s, 1H), 5.31
= 8.3, 0.7 Hz, 1H), 5.44 (s, 1H), 3.86 (s, 3H), 3.71 (s, 3H), 1.26 (d, J = (dq, J = 17.1, 1.5 Hz, 1H), 5.24 (dq, J = 17.1, 1.5 Hz, 1H), 4.08 (dt, J =
6.1 Hz, 3H), 1.18 (d, J = 6.1 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ: 5.9, 1.3 Hz, 2H), 3.73 (s, 3H), 7.56 (ddd, J = 15.3, 7.9, 1.5 Hz, 2H),
172.3, 157.0, 129.6, 128.3, 126.1, 120.9, 110.9, 72.3, 71.2, 55.8, 3.71 (s, 3H). 13C NMR (125 MHz, CDCl3) δ: 170.7, 136.3, 133.7,
52.1, 22.3, 22.2. IR νmax (cm-1): 3070, 2952, 2923, 2863, 1749, 1435, 130.2, 129.1, 128.0, 124.0, 118.6, 78.4, 71.0, 52.5. IR νmax (cm-1):
1250, 1207, 1090, 1019, 929, 752. HRMS (ESI-TOF) calculated for 3070, 2952, 2923, 2863, 1749, 1469, 1435, 1250, 1207, 1125, 1090,
C13H18O4Na [M+Na] 261.1103; found 261.1100.
1019, 929, 752. HRMS (ESI-TOF) calculated for C12H13BrO3Na
[M+Na] 306.9946; found 306.9928.
Methyl 2-(2-bromophenyl)-2-hydroxyacetate 36
Yield: 62% (46 mg). Colourless oil. TLC: Rf
=
0.11 (10% Benzyl 2-hydroxy-2-phenylacetate 4062
1
EtOAc/hexanes). H NMR (500 MHz; CDCl3): δ 7.58 (dd, J = 8.0, 1.1 Yield: 80% (59 mg). White solid, m.p: 96–98 °C. TLC: Rf = 0.20 (10%
1
Hz, 1H), 7.38 (dd, J = 7.7, 1.8 Hz, 1H), 7.33 (td, J = 7.6, 1.1 Hz, 1H), EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.45 – 7.28 (m, 8H),
7.22 – 7.18 (m, 1H), 5.58 (s, 1H), 3.77 (s, 3H), 3.58 (s, 1H). 13C NMR 7.22 – 7.17 (m, 2H), 5.24 (d, J = 12.4 Hz, 1H), 5.22 (d, J = 5.9 Hz, 1H),
(125 MHz, CDCl3) δ: 173.8, 137.7, 133.4, 130.2, 129.0, 127.9, 123.6, 5.14 (d, J = 12.3 Hz, 1H), 3.42 (d, J = 5.8 Hz, 2H).
72.5, 53.3. IR νmax (cm-1): 3455, 2954, 2920, 2854, 1733, 1437, 1217,
1187, 1080, 1018, 749. HRMS (ESI-TOF) calculated for C9H9BrO3Na Benzyl 2-benzyloxy-2-phenylacetate 4163
[M+Na] 266.9633; found 266.9622.
Yield: 83% (83 mg). Colourless oil. TLC: Rf = 0.45 (10%
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.46 – 7.45 (m, 2H),
7.34 – 7.27 (m, 11H), 7.22 – 7.19 (m, 2H), 5.17 (d, J = 12.4 Hz, 1H),
0.16 (10% 5.11 (d, J = 12.4 Hz, 1H), 4.97 (s, 1H), 4.59 (s, 2H).
Methyl 2-(2-bromophenyl)-2-methoxyacetate 37
Yield: 71% (56 mg). Colourless oil. TLC: Rf
=
1
EtOAc/hexanes). H NMR (500 MHz; CDCl3): δ 7.59 (dd, J = 8.1, 1.2
Hz, 1H), 7.49 (dd, J = 7.8, 1.7 Hz, 1H), 7.34 (td, J = 7.4, 1.1 Hz, 1H), Methyl 2-(benzo[d][1,3]dioxol-5-yl)-2-methoxyacetate 4264
7.21 (ddd, J = 8.0, 7.4, 1.7 Hz, 1H), 5.28 (s, 1H), 3.74 (s, 3H), 3.43 (s, Yield: 81% (55 mg). Colourless oil. TLC: Rf
= 0.32 (10%
1
3H). 13C NMR (125 MHz, CDCl3) δ: 170.6, 136.0, 133.1, 130.3, 128.9, EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 6.90 – 6.87 (m, 2H),
128.0, 124.2, 81.0, 57.8, 52.5. IR νmax (cm-1): 2994, 2951, 2928, 6.80 – 6.78 (m, 1H), 5.96 (s, 2H), 5.08 (s, 1H), 3.76 (s, 3H), 3.44 (s,
2828, 1747, 1436, 1193, 1103, 1011, 752. HRMS (ESI-TOF) 1H).
calculated for C10H11BrO3Na [M+Na] 280.9789; found 280.9746.
Methyl 2-methoxy-2-(4-nitrophenyl)acetate 4346
Methyl 2-(benzyloxy)-2-(2-bromophenyl)acetate 38
Yield: 52% (36 mg). Colourless oil. TLC: Rf
= 0.28 (10%
Yield: 69% (70 mg). Colourless oil. TLC: Rf
=
0.16 (10% EtOAc/hexanes). 1H NMR δ 8.24 (d, J = 8.9 Hz, 2H), 7.65 (dd, J = 8.9,
1
EtOAc/hexanes). H NMR (500 MHz; CDCl3): δ 7.58 – 7.56 (m, 2H), 0.5 Hz, 2H), 4.89 (s, 1H), 3.75 (s, 3H), 3.47 (s, 3H).
This journal is © The Royal Society of Chemistry 20xx
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Ethyl (E)-(3-phenylallyloxy)acetate 4972
2-methoxyacetophenone 4465
Yield: 84% (56 mg). Colourless oil. TLC: Rf = 0.33 (10%
1
Yield: 87% (35 mg). Yellonw oil. TLC: Rf
=
0.45 (20% EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.41 – 7.37 (m, 2H),
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.95 – 7.93 (m, 2H), 7.34 – 7.30 (m, 2H), 7.26 (s, 1H), 6.63 (d, J = 15.9 Hz, 1H), 6.30 (dt, J
7.61 – 7.57 (m, 1H), 7.49 – 7.46 (m, 2H), 4.72 (s, 2H), 3.52 (s, 3H).
= 15.9, 6.3 Hz, 1H), 4.27 (dd, J = 6.3, 1.4 Hz, 2H), 4.23 (q, J = 7.1 Hz,
2H), 4.1 (s, 2 H), 1.29 (t, J = 7.1 Hz, 3H).
2-(benzyloxy)-1-phenylethan-1-one 4566
Yield: 86% (56 mg). White solid, m.p: 60 °C. TLC: Rf = 0.47 (10% Ethyl benzyloxyacetate 5073
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.93 – 7.91 (m, 2H), Yield: 90% (53 mg). Colourless oil. TLC: Rf
= 0.36 (10%
1
7.60 – 7.56 (m, 1H), 7.48 – 7.44 (m, 2H), 7.41 – 7.35 (m, 4H), 7.34 – EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 7.38 − 7.29 (m, 5H),
7.28 (m, 1H), 4.76 (s, 2H), 4.70 (s, 2H).
4.62 (s, 2H), 4.21 (q, J = 7.2 Hz, 2H), 4.08 (s, 2H), 1.27 (t, J = 7.1 Hz,
3H).
Ethyl 2-hydroxyacetate 4667
Yield: 80% (25 mg). Colourless oil. TLC: Rf
=
0.22 (20% Diethyl 3-methoxy-2-oxopropylphosphonate 5474
1
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 4.27 (q, J = 7.2, 2H), Yield: 96% (65 mg). Colourless oil. TLC: Rf = 0.26 (EtOAc). H NMR
4.15 (s, 2H), 1.31 (t, J = 7.2 Hz, 3H).
(500 MHz, CDCl3): δ 4.19 – 4.13 (m, 6H), 3.44 (s, 3H), 3.15 (d, J =
22.8 Hz, 2H), 1.35 (t, J = 7.1 Hz, 6H).
Ethyl 2-methoxyacetate 4768
Yield: 91% (37 mg). Colourless oil. TLC: Rf
=
0.40 (10% Hydroxy-3 oxo-2 propylphosphonate de diethyle 5346
1
EtOAc/hexanes). 1H NMR (500 MHz, CDCl3): δ 4.23 (q, J = 7.1 Hz, Yield: 90% (57 mg). Colourless oil. TLC: Rf = 0.18 (EtOAc). H NMR
2H), 4.07 (s, 2H), 3.60 (q, J = 7.0 Hz, 2H), 1.29 (t, J = 7.1 Hz, 3H), 1.26 (500 MHz, CDCl3): δ 4.39 (s, 2H), 4.20 – 4.11 (m, 4H), 4.05 (s, 1H),
(t, J = 7.0 Hz, 3H).
3.21 (d, J = 22.6 Hz, 2H), 1.34 (t, J = 7.1 Hz, 6H).
Ethyl isopropoxyacetate 4869
GENERAL PROCEDURE FOR CATALYST RECYCLING
Yield: 92% (41 mg). Colourless oil. TLC: Rf
= 0.41 (10%
EtOAc/hexanes). 1H NMR (500 MHz, CDCl3): δ 4.22 (q, J = 7.1 Hz, The catalyst was reused as follow: after the completion of the
2H), 4.07 (s, 2H), 3.68 (hept, J = 6.1 Hz, 1H), 1.29 (t, J = 7.1 Hz, 3H), reaction, catalyst was separated by filtration and washed with ethyl
1.21 (d, J = 6.1 Hz, 6H).
acetate. After that, it was dried on vacuum for 10 minutes.
2-(Allyloxy)ethyl acetate 5170
Conflicts of interest
Yield: 89% (41 mg). Colourless oil. TLC: Rf
= 0.45 (10%
There are no conflicts to declare.
1
EtOAc/hexanes). H NMR (500 MHz, CDCl3): δ 5.96 – 5.89 (m, 1H),
5.31 (dq, J = 17.2, 1.6 Hz, 1H), 5.26 (dq, J = 10.3, 1.5, 1H), 4.23 (q, J =
7.1, 2H), 4.10 (dt, J = 5.8, 1.3 Hz, 2H), 4.08 (s, 2H), 1.29 (t, J = 7.1 Hz,
3H).
Acknowledgements
The authors would like to acknowledge Fundação de Amparo à
Pesquisa do Estado de Sao Paulo (FAPESP) for research financial
support (2017/23329-9) (2013/18009-4).
Ethyl 2-(prop-2-yn-1-yloxy)acetate 5271
Notes and references
Yield: 90% (39 mg). Colourless oil. TLC: Rf
= 0.39 (10%
EtOAc/hexanes). 1H NMR (500 MHz, CDCl3): δ 4.32 (d, J = 2.4 Hz,
2H), 4.24 (q, J = 7.1 Hz, 2H), 4.20 (s, 2H), 2.48 (t, J = 2.4 Hz, 1H), 1.30
(t, J = 7.1 Hz, 3H).
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