Formyloxyacetoxyphenylmethane and 1,1-diacylals as versatile O-formylating and O-acylating reagents for alcohols

Article abstract of DOI:10.1016/j.tet.2018.09.014

Formyloxyacetoxyphenylmethane, symmetric 1,1-diacylals and mixed 1-pivaloxy-1-acyloxy-1-phenylmethanes have been used as moisture stable O-formylating and O-acylating reagents for primary and secondary alcohols, allylic alcohols and phenols under solvent/catalyst free conditions to afford their corresponding esters in good yield.

Full text of DOI:10.1016/j.tet.2018.09.014

Accepted Manuscript
Formyloxyacetoxyphenylmethane and 1,1-diacylals as versatile O-formylating and O-
acylating reagents for alcohols
Robert S.L. Chapman, Molly Francis, Ruth Lawrence, Joshua D. Tibbetts, Steven D.
Bull
PII:
S0040-4020(18)31069-X
10.1016/j.tet.2018.09.014
TET 29786
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 25 July 2018
Revised Date: 30 August 2018
Accepted Date: 4 September 2018
Please cite this article as: Chapman RSL, Francis M, Lawrence R, Tibbetts JD, Bull SD,
Formyloxyacetoxyphenylmethane and 1,1-diacylals as versatile O-formylating and O-acylating reagents
for alcohols, Tetrahedron (2018), doi: 10.1016/j.tet.2018.09.014.
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Robert S. L. Chapman, Molly Francis, Ruth Lawrence, Joshua D. Tibbetts and Steven D. Bull
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1
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Tetrahedron
journal homepage: www.elsevier.com
Formyloxyacetoxyphenylmethane and 1,1-diacylals as versatile O-formylating and O-
acylating reagents for alcohols
Robert. S. L. Chapman, Molly Francis, Ruth. Lawrence, Joshua D. Tibbetts and Steven. D. Bull*
Department of Chemistry, University of Bath, Bath, BA27AY, UK.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Formyloxyacetoxyphenylmethane, symmetric 1,1-diacylals and mixed 1-pivaloxy-1-acyloxy-1-
phenylmethanes have been used as moisture stable O-formylating and O-acylating reagents for
primary and secondary alcohols, allylic alcohols and phenols under solvent/catalyst free
conditions to afford their corresponding esters in good yield.
Available online
2009 Elsevier Ltd. All rights reserved
.
Keywords:
formylation
acylation
alcohols
1,1-diacylals
1. Introduction
harsh reaction conditions, that give low yields of ester, .
Problems include long reaction times, harsh reaction
The widespread presence of ester functionalities in fine
chemicals, drug molecules, natural products, polymers and
biodiesels means that acylation reactions of alcohols are one
of the most widely used transformations in organic
chemistry.1 Esters are also useful protecting groups that are
widely used to protect acid and alcohol functionalities for
the synthesis of complex natural products and drug
molecules.2 Formyl esters are particularly useful in this
regard, since they are acid stable and can be hydrolysed
under mild basic conditions in the presence of other ester
functionality.2b Simple esters are traditionally prepared using
Fischer esterification procedures that involve azeotropic
refluxing of an alcohol in the presence of an acid catalyst.1a
More complex esters are normally prepared through reaction
of an alcohol with an activated carboxylic acid derivative,
such as an acyl halide, acid anhydride or activated acyl
conditions,
poor
chemoselectivities
and/or
regioselectivities., low functional group tolerance, the need
to employ expensive, corrosive, toxic and volatile reagents,
use of halogenated or environmentally unfriendly solvents, and
the need to employ excess acylating reagents. All these issues
can result in incomplete conversions, poor yields of ester
and/or formation of by-products that can cause purification
problems, particularly on a large scale. Therefore, there is
still a need to develop cheap reagents for the efficient
O-
acylation of alcohol substrates, particularly if their
esterification reactions can be carried out under solvent
and/or catalyst free conditions.8
We have recently reported that formyloxyacetoxyphe-
nylmethane
formylating agent for the conversion of primary and
secondary amines into formamides under solvent free
conditions at room temperature (Scheme 1a).9a We have also
shown that structurally related 1,1-diacylals and mixed 1-
pivaloyl-1-acylals can be used for the solvent free
conversion of amines into their corresponding amides
(Scheme 1b).9b A review of the literature revealed that
ethylidene diacetate had previously been reported to react
1 (FAPM) can be used as a bench stable
donor.3 However,
O-acylation reactions of acyl chlorides and
2
acid anhydrides are often exothermic,4 often generating
acidic by-products that are incompatible with acid sensitive
functionalities. Effective catalytic trans-esterification
protocols have also been developed for ester formation,
however these approaches often require use of excess or
3
4
5
irreversible acyl donor to drive the
O-acylation reaction to
6
completion.5 Catalytic protocols involving Bronsted/Lewis
acid catalysts, basic catalysts, metal complexes, enzymes
and microwave irradiation conditions have been developed
with primary alcohols (1-butanol, 2-phenylethanol) in
CHCl3 under acid catalysed conditions to afford their
corresponding acetates
7 (no yields reported), acetaldehyde
and acetic acid (Scheme 1c).10 Similarly, phenoxides have
to increase the rate of
O-acylation reactions under milder
conditions.6 Formyl esters are prepared via in situ generation
of reactive formylating species, or through the use of
stoichiometric amounts of formylating agent.7 Although a
been used as nucleophiles to deprotect benzal diacetates
afford their corresponding benzaldehydes, phenoxy acetate
8
to
9
(no yield reported) and acetic acid as side products (Scheme
O
-acylation approaches are available,1 many
1d).11a Catalytic amounts of tetrabutylammonium bromide
wide range of
of these methods suffer from practical disadvantages, or

2
Tetrahedron
have been used to catalyse the methanolysis of 1,1-acylals
enabling formate ester 11a to be isolated in 87% yield after
ACCEPTED MANUSCRIPT
to afford their corresponding aldehydes in good yield.9b
chromatographic purification (Table1, Entry 6). There was
1
no evidence of any competing acylation observed by H
NMR during the course of the optimisation reactions.
Table 1. Optimisation of the FAPM
1 mediated formylation
reaction of 2-(4-methoxyphenyl)ethanol.
Temp
(°C)
Time
(h)
%
Entry
Solvent
Base
Conversion
1
2
3
None
None
EtOAc
rt
24
24
24
None
None
None
15
64
66
40
40
NaHCO3
(2 equiv)
NaHCO3
(2 equiv)
NaHCO3
(2 equiv)
4
5
6
None
None
None
rt
24
24
16
72
40
60
91
100
Conversion levels determined from integration of diagnostic resonances
for 10a and 11a in the 1H NMR spectra of their crude reaction products.
These optimal conditions were then applied for the
formylation of a range of primary, secondary and tertiary
alcohols to produce twelve formate esters 11a-l in 60-88%
O-
Scheme 1 (a) Formyloxyacetoxyphenylmethane (FAPM)
1
as an
2 9a
(b) 1,1-diacylals
phenylmethanes as
amides 5 9b
N-formylating agent for the synthesis of formamides
.
3
N
and mixed 1-pivaloxy-1-acyloxy-1-
-acylating agents for the synthesis of
yield (Scheme 2). Most of these
were carried out by dissolving the alcohol substrates in
FAPM at 60 °C, addition of 2 equiv. of solid NaHCO3
O-formylation reactions
4
.
(c) Ethylidene diacetate
agent for the synthesis of alkyl acetates 7 10
diacetates as an
phenoxy acetates 9 11
6
as an
O
-acetylating
(d) Benzal
1
.
followed by stirring of the heterogeneous reaction mixture at
60 °C for 16 h to afford a formyl ester that were then
purified by chromatography. EtOAc was added as a co-
8
O-acetylating agent for the synthesis of
.
solvent when the parent alcohol was insoluble in FAPM 1,
Since the focus of these previous studies concentrated on
using an alcohol as a nucleophile to deprotect acylals to
afford their corresponding aldehydes, we decided to explore
to afford a homogeneous solution, prior to addition of
insoluble NaHCO3. Use of these basic reaction conditions
afforded alkyl formates 11a-b, benzylic formates 11c-d and
allylic formates 11e-f in good 71-88% isolated yield. The
the scope and limitation of using FAPM
412 for the
-formylation and -acylation reactions of
alcohols. Consequently, we now report herein that these
reagents may be used for the -acylation of a range of
1 and 1,1-diacylals
3/
O
O
ability of FAPM
reactive -methoxyphenyl formate 11g in 75% isolated yield
is noteworthy. FAPM also showed good reactivity towards
1 to formylate p-methoxyphenol to afford
p
O
1
primary and secondary alcohols under solvent/catalyst free
conditions to give their corresponding formyl and acyl esters
in good yield.
acyclic and cyclic secondary alcohols affording their
corresponding formates 11h-j in 75-84% yield. Acid
sensitive functional groups were also tolerated under these
conditions, as demonstrated for the synthesis of
O
-silyl-
O-
2. Results and Discussion
formate ester 11k and acetonide-
O-formate ester 11l in 60%
Our initial investigations focused on identifying conditions
and 87% yields, respectively.
that would enable FAPM
for alcohols. Treatment of 2-(4-methoxyphenyl)ethanol 10a
with 1.5 equiv. of FAPM under solvent free conditions at
rt for 24 gave only 15% conversion to 4-
1 to be used as a formylating agent
Our attention then turned to investigating the potential of
employing less reactive 1,1-acylal 3a for the -acetylation of
alcohols. Use of our previously established base catalyzed
O
1
O
-
h
formylation conditions (60 °C, 2 equiv. NaHCO3, 16 h) for the
acetylation of benzyl alcohol with 1,1-diacylal 3a were only
partially successful, affording its corresponding acetate 12a in
only 80% conversion after 16 h. However, a brief optimization
study revealed that treatment of benzyl alcohol with 1.5 equiv.
of 1,1-diacylal 3a and 2 equivalents of K2CO3 at 90 °C for 16 h
gave 100% conversion to afford acetate 12a in 90% yield after
chromatographic purification.
methoxyphenethyl formate 11a (Table 1, Entry 1), whilst
repeating the reaction at 40 °C gave an improved 64%
conversion (Table 1, Entry 2). Inclusion of EtOAc as a
cosolvent at 40 °C had no effect on the extent of conversion
(Table 1, Entry 3), however inclusion of 2 equiv. of
NaHCO3 as a base resulted in improved results, affording
72% and 91% conversion to formate ester 11a at rt (Table 1,
Entry 4) and 40 °C (Table 1, Entry 5), respectively. Finally,
repeating the formylation reaction using 1.5 equiv. of FAPM
1
under solvent free conditions at 60 °C for 16 h resulted in
complete consumption of 2-(4-methoxyphenyl)ethanol,

3
ACCEPTED MANUSCRIPT
(a) 1.5 equiv. FAPM 1, 2 equiv. NaHCO3, 16 h, 60 °C. (b) 1.5
equiv. FAPM 1, 2 equiv. NaHCO3, EtOAc, 16 h, 60 °C.
Scheme 2 FAPM
1
as an
O
-formylating agent for the
synthesis of formate esters 11a-l
.
(a) 1.5 equiv. acylal 3a, 2.0 equiv. K2CO3, 16 h, 90 °C. (b)
1.5 equiv. acylal 3a, 2.0 equiv. K2CO3, 24 h, 90 °C. (c) 3
equiv. acylal 3a, 2.0 equiv. K2CO3, 16 h, 90 °C. (d) 6.0
equiv. acylal 3a, 8.0 equiv. K2CO3, 16 h, 90 °C. (*) Toluene
(2 mL) added. (+) Water (2 mL added)
These optimal conditions were then applied for the
esterification of a range of thirteen primary and secondary
alcohols which gave their corresponding acetates 12a-m in 63-
92% isolated yields (Scheme 3). A wide range of different
Scheme 3 1,1-Diacylal 3a as an
synthesis of acetates 12a-m
O-acylating agent for the
alcohol substrates were successfully
O-acetylated to afford
.
alkyl acetates 12a-c, benzylic acetate 12d, pyridyl acetate 12e
and allylic acetates 12f-h in 68-92% yield. 1,1-Diacylal 3a also
showed good reactivity towards acyclic and cyclic secondary
alcohols affording their corresponding acetates 12i-k in 68-77%
yield. Finally, use of 3 equivalents of 1,1-diacylal 3a resulted in
bis-acetylation of the diol fragment of methyl 4,6-O-
benzylidene-α-D-glucopyran-oside to afford bis-acetate 12l in
65% yield. Similarly, use of 6 equiv. of 1,1-diacylal 3a, resulted
in the tetra-acetylation of the tetrol fragment of methyl α-
glucopyranoside to afford tetra-acetate 12m in 63% isolated
yield.
A range of 1,1-diacylal reagents 3b-g were then used for the
O
-acylation of benzyl alcohol at 90 °C for 16 h under solvent
free conditions to give five esters 13a-e containing propionyl,
benzoyl, hexanoyl, phenylacetoyl and acryloyl groups in 62-
94% yields, respectively (Scheme 4). The trifluoro-1,1-diacylal
reagent 3g proved to more reactive, with trifluoroacetylation of
benzyl alcohol proceeding at rt after only 1 h to afford
trifluoroacetate 13f in 89% yield.
a) 1.5 equiv. 1,1-diacylal 3a-f, 2.0 equiv. K2CO3, 90 °C, 16
h. (b) 1.5 equiv. 1,1-diacylal 3g, 2.0 equiv. K2CO3, rt, 1 h.
Scheme 4 Symmetric 1,1-diacylals 3b-g as
agents of benzyl alcohol for the synthesis of benzyl esters
13a-f
O-acylating
.

4
Tetrahedron
Following on from our previous success of using 1-
ACCEPTED MANUSCRIPT
pivaloxy-1-acyloxy-1-phenylmethanes for the
amines (Scheme 1b),9b we next decided to investigate
whether mixed 1-pivaloxy-1-acyloxy-1-phenylmethanes
could be used as selective -acyl donors for alcohols. This
N-acylation of
4
O
would avoid wastage of one equivalent of a valuable
acylating group that occurs when symmetric 1,1-acylals 3a-
g
are used for O-acylating reagents. These mixed 1,1-
diacylal reagents were prepared by treatment of
benzaldehyde with 1.5 equiv. of pivaloyl chloride and a
catalytic amount of
pTSA to afford chloro(phenyl)methyl
pivalate 14 13
,
that was then reacted immediately with a
series of carboxylic acids and Et3N in acetone at 40 °C to
afford five mixed 1-pivaloxy-1-acyloxy-1-phenylmethanes
4a-e in 74-84% yield (Scheme 5).9b
(*) Toluene (2 mL) added
Scheme 6. -acylation reactions of 1-pivaloxy-1-acyloxy-1-
O
phenylmethanes 4a-e to afford esters 12a, 13a, 13c, 13e,
13g-l
Scheme 5. Synthesis of mixed 1-pivaloxy-1-acyloxy-1-
phenylmethanes 4a-e
.
These 1-pivaloxy-1-acyloxy-1-phenylmethanes 4a-e were
then used as -acylating reagents for a range of primary
alkyl and allylic alcohols to give 10 primary esters (12a
13a 13c 13e 13g-l) in 62-96% yield (Scheme 6). Selective
-acyl transfer (acetyl, phenylacetyl, propionyl, acryloyl
and furanoyl) was observed for all the mixed 1,1-diacylals
4a-e employed, with no evidence of any competing
O
,
,
,
,
O
O-
pivaloyl transfer having occurred in any of these
reactions.
O-acylation
The
formylating agent
methyl ester ( )-15 as a bifunctional substrate.
of ( )-15 was performed using 1.5 equiv. of 1,1-diacylal 3a
under neutral conditions (70 °C, 16 h)9a to selectively afford
-acetyl- -serine methyl ester (
)-16 ([α]D25 = -9.5; Lit14a = -
10.1) as a single product in 83% yield (Scheme 7).14
formylation of the free hydroxyl group of ( )-16 was then
carried out using 1.5 equiv. of FAPM 1, using our standard
basic conditions (2 equiv. NaHCO3, 60 °C, 16 h, to afford
acetyl- -formyl- -serine methyl ester (
)-17 ([α]D20 = -56.0)
in 78% yield. We initially considered that competing base
mediated -/ -acetyl migration to afford -acetyl- -serine
methyl ester might have occurred, followed by
formylation to afford ( )- -formyl- -acetyl-serine methyl
N
-/
O
- selectivity profiles of the acylating agent 3a and
was then investigated using -serine
-acetylation
1
L
S
N
Scheme 7. Synthesis of
ester ( )-17
N-acetyl-O-formyl-L-serine methyl
S
S
.
N
L
S
3. Conclusions
O-
S
In summary, we have shown that formyloxyacetoxyphenyl-
methane
tolerant
1
and 1,1-diacylals
3 can be used as moisture-
N-
O
-acylating reagents for primary and secondary
O
L
S
alcohols under solvent-free conditions to afford their
corresponding esters in good yields. This -acylation
methodology has been extended to enable mixed pivaloyl
1,1-acylals to be used as efficient -acylating agents for
O
N
O
O
L
N-
4
O
S
N
O
the selective transfer of a range of acyl donor groups to a
wide range of alcohols. We have also demonstrated the
ester 18 as an alternative product. However, analysis of the
13C NMR spectrum of the formylation product revealed
inherent
for the selective
followed by -formylation of its primary alcohol group to
selectively afford orthogonally protected -acetyl- -formyl
serine ester product ( )-17
N
-/
O
- selectivity of these acylal acylating reagents
resonances at
presence of the ester, amide and formyl ester groups of (
17.9 This is in contrast to the 13C NMR chemical shifts for
the methyl esters and formamide groups of ( )-18, that
169-174 region of its
δ
170.0, 169.9 and 160.3, consistent with the
S)-
N-acetylation of serine methyl ester
O
S
N
O
would be expected to appear in the
13C NMR spectrum.9
δ
S
.

5
the reaction stirred at 90 °C for 16 or 24h. Toluene or
ACCEPTED MANUSCRIPT
4. Experimental
DMSO (2 mL) was added as a cosolvent when the alcohol
substrate was insoluble in the formylating reagent at 60 °C.
The crude reaction mixture was then purified by column
chromatography to give the isolated ester.
Unless preparative details are given, reagents and solvents
were obtained from commercial suppliers. All reactions
were performed without air exclusion, at room temperature
with magnetic stirring unless otherwise stated. Anhydrous
MgSO4 or Na2SO4 were used as drying agents for organic
solutions. Petrol refers to petroleum ether with a boiling
range of 40-60 °C. Thin layer chromatography (TLC) was
carried out using Macherey-Nagel aluminium-backed plates,
precoated with silica. Compounds were visualised by
quenching of UV fluorescence at 254 nm or, where
necessary, by staining with potassium permanganate,
phosphomolybdic acid (PMA) or vanillin dip, followed by
gentle heating. Purification by flash column chromatography
was performed using high-purity grade 60 Å silica gel (60 Å
pore size, 40-75 ꢀm particle size). Capillary melting points
were determined using a Stuart digital SMP10 melting point
apparatus and are reported to the nearest °C. An Optical
Activity Ltd AA-10 Series Automatic Polarimeter with a
path length of 1 dm was used to measure optical rotations,
with concentration (c) quoted in g/100 mL. Nuclear
Magnetic Resonance (NMR) spectroscopy experiments were
performed in deuterated solvent at 298 K on either a Brüker
Avance 250, 300, 400 or 500 MHz spectrometer or an
Agilent ProPulse 500 MHz spectrometer, with proton
General Procedure C: Synthesis of 1,1-diacylals
para-Toluenesulphonic acid (mono hydrate) (0.18 g, 0.94
mmol) was added to a mixture of benzaldehyde (1.0 g, 9.4
mmol) and anhydride (18.8 mmol) at rt. The reaction was
stirred for 12 h and then diluted with Et2O (50 mL) and
washed with saturated Na2CO3 (3 x 20 mL). The organics
were dried (MgSO4) and concentrated in vacuo to give the
title compound which was used in subsequent steps without
further purification unless otherwise stated.
General Procedure D: O-acylation of alcohols
Alcohol (1.0 mmol) was added to the acylation reagent (1.5
mmol) and K2CO3 (0.270 g, 2.0 mmol). Toluene (2 mL) was
added as a cosolvent when the alcohol substrate was
insoluble in the formylating reagent at 60 °C. The reaction
was then stirred at 90 °C for 16 or 24h. The crude reaction
mixture was then purified by column chromatography to
give the isolated ester.
General Procedure E: Synthesis of mixed acylals
Trimethylacetyl chloride (0.813 mL, 6.60 mmol) was added
dropwise to a mixture of benzaldehyde (0.489 g, 4.40 mmol)
and p-toluenesulfonic acid (0.083 g, 0.44 mmol) at rt and the
1
decoupling for all 13C NMR spectra. H and 13C NMR
chemical shifts, δ, are quoted in parts per million (ppm) and
referenced against the residual, non-deuterated solvent peak.
Ratios of formamide rotamers were determined by
reaction mixture stirred for 3 h. The reaction was then
quenched via addition of saturated NaHCO3 (10 mL) and
diluted with Et2O (50 mL). The reaction was then extracted
with saturated NaHCO3(aq) (3 x 20 mL), the organic layer
dried (MgSO4) and concentrated in vacuo to afford
chloro(phenyl)methyl pivalate 14 (1.0 g, 4.40 mmol) as a
yellow oil that was carried forward to the next step without
further purification. Triethylamine (0.60 mL, 4.40 mmol)
was added dropwise to a solution of chloro(phenyl)methyl
pivalate 14 (4.40 mmol) and carboxylic acid (4.40 mmol) in
acetone (10 mL). The reaction was stirred at 40 °C for 12 h,
over which time a white ppt formed. The reaction mixture
was filtered through Celite® and concentrated in vacuo to
afford a crude reaction product that was purified by silica
gel chromatography to give the desired mixed acylal.
1
comparison of the integrals for equivalent peaks in their H
NMR spectra.
A PerkinElmer Spectrum 100 FTIR
spectrometer with Universal ATR FTIR accessory was used
to record infrared (IR) spectra; with samples run neat and
the most relevant, characteristic absorbances quoted as ν in
cm-1. High resolution mass spectrometry (HRMS) results
were acquired on an externally calibrated Bruker Daltonics
micrOTOFTM time-of-flight mass spectrometer coupled to an
electrospray source (ESI-TOF). Molecular ions were
detected in positive mode as either the protonated or
sodiated form, with Bruker Daltonics software,
DataAnalysisTM
(Formyloxy)(phenyl)methyl
used
to
process
acetate
the
1
data.
and
phenylmethylene diacetate 3a were prepared using our
previously described protocols.9
4-Methoxy phenethyl alcohol formate 11a
General procedure A was followed to afford the title
compound (0.127 g, 0.71 mmol) as a clear oil in 71% yield.
General Procedure A: O-formylation of alcohols
Alcohol
(1.0
mmol)
was
added
to
1H NMR (300 MHz, CDCl3) δ 8.05 (s, 1H, (C=O)
H
), 7.19 -
), 4.36 (t, = 7.0
Hz, 2H, CH2(OC=O)), 3.81 (s, 3H, CH3), 2.93 (t, = 7.2 Hz,
(formyloxy)(phenyl)methyl acetate
1
(0.291 g, 1.5 mmol)
7.10 (m, 2H, Ar
H), 6.91 - 6.81 (m, 2H, Ar
H
J
and NaHCO3 (0.168 g, 2.0 mmol), and the reaction stirred at
60 °C for 16 h. EtOAc (2mL) was added as a cosolvent
when the alcohol substrate was insoluble in the fomylating
reagent at 60 °C. The crude reaction mixture was then
purified by column chromatography to give the desired
formate ester.
J
13
2H, CH2CH2(OC=O)). C NMR (75 MHz, CDCl3) δ 161.0,
158.4, 129.8, 129.3, 113.9, 64.6, 55.2, 34.0.
Analytical data in accordance with the literature.7h
Citronellyl formate 11b
General procedure A was followed to afford the title
compound (0.153 g, 0.83 mmol) as a clear oil in 83% yield.
General Procedure B: O-Acetylation of alcohols
Alcohol (1.0 mmol) was added to phenylmethylene diacetate
3a (0.291 g, 1.5 mmol) and K2CO3 (0.270 g, 2.0 mmol) and
1H NMR (300 MHz, CDCl3) δ 8.06 (s, 1H, (C=O)
H), 5.19 -
4.98 (m, 1H, C=C
H), 4.29 - 4.11 (m, 2H, CH2O(C=O)H),

6
Tetrahedron
2.12 - 1.83 (m, 2H,), 1.81 - 1.64 (m, 4H), 1.61 (s, 3H,
122.0, 114.6, 55.0. Analytical data in accordance with
ACCEPTED MANUSCRIPT
C=CCH3), 1.58 - 1.29 (m, 3H), 1.27 - 1.14 (m, 1H), 0.93 (d,
J
literature.179
= 6.4 Hz, 3H, CHCH3). 13C NMR (75 MHz, CDCl3) δ
161.2, 131.4, 124.5, 62.5, 36.9, 35.3, 29.4, 25.7, 25.4, 19.3,
17.6.
1-Phenylethanol formate 11h
Analytical data in accordance with the literature.7h
General procedure A was followed to afford the title
compound (0.112 g, 0.75 mmol) as a pale yellow oil in 75%
1
yield. H NMR (300 MHz, CDCl3) δ 8.11 (s, 1H, (C=O)
H
),
(OC=O)),
= 7.2 Hz, 3H, CH3). C NMR (75MHz, CDCl3) δ
2-Bromobenzyl alcohol formate 11c
7.42 - 7.28 (m, 5H, Ar
1.60 (d,
H), 6.18 - 5.85 (m, 1H, CH
13
General procedure A was followed to afford the title
compound (0.172 g, 0.80 mmol) as a yellow oil in 80%
J
160.4, 140.8, 128.6, 128.1, 126.1, 72.2, 22.1. Analytical data
1
in accordance with the literature.7h
yield. H NMR (500 MHz, CDCl3) δ 8.19 (s, 1H, (C=O)
H
),
= 2.0, 7.8
), 7.25 -
), 5.31 (s, 2H, CH2). C NMR (126 MHz,
CDCl3) δ 160.5, 134.5, 132.9, 130.1, 130.0, 127.6, 123.5,
65.2. IR (thin film)
max (cm-1): 1719 (C=O);.14
7.61 (dd,
Hz, 1H, Ar
7.20 (m, 1H, Ar
J
= 1.2, 8.1 Hz, 1H, Ar
H), 7.45 (dd, J
H
), 7.34 (dt, = 1.2, 7.5 Hz, 1H, ArH
J
Menthol formate 11i
13
H
General procedure A was followed to afford the title
compound (0.143 g, 0.78 mmol) as a yellow oil in 78%
ν
yield. 1H NMR (300 MHz, CDCl3) δ 8.08 (d,
J
= 0.8 Hz, 1H,
(OC=O)), 2.07 -
= 2.6, 7.0, 13.9 Hz, 1H, C ),
1.76 - 1.64 (m, 2H, CH2), 1.59 - 1.33 (m, 2H, CH2), 1.14 -
0.98 (m, 2H, CH), 0.95 - 0.84 (m, 7H, C & CH(CH3)2),
0.77 (d,
= 6.8 Hz, 3H, CH3). 13C NMR (75 MHz, CDCl3) δ
(C=O)H
), 4.81 (dt,
J = 4.3, 10.8 Hz, 1H, CH
Biphenyl-4-methanol formate 11d
1.97 (m, 1H, C
H), 1.91 (dtd,
J
H
General procedure A was followed to afford the title
compound (0.170 g, 0.80 mmol) as a crystalline white solid
H
1
in 80% yield. H NMR (300 MHz, CDCl3) δ = 8.18 (t,
J =
J
0.9 Hz, 1H, (C=O)
(m, 4H, Ar ), 7.41 - 7.34 (m, 1H, Ar
H2O(C=O)). 13C NMR (75 MHz, CDCl3) δ 160.8, 141.5,
140.5, 134.1, 128.9, 128.8, 127.5, 127.4, 127.1, 65.5. IR
(thin film)
max (cm-1): 1702 (C=O);15
H), 7.65 - 7.57 (m, 4H, Ar
H), 7.50 - 7.42
160.9, 74.1, 46.8, 40.8, 34.1, 31.4, 26.0, 23.2, 22.0, 20.7,
16.0. Analytical data in accordance with the literature.7a
H
H), 5.27 (s, 2H,
C
Carveol formate 11j
ν
General procedure A was followed to afford the title
compound as a yellow oil (0.150 g, 0.84 mmol) in 84%
yield. The formate ester was obtained as a mixture of
diastereomers (1:1) in the same ratio as the starting material.
Perillyl alcohol formate 11e
General procedure A was followed to afford the title
compound (0.159 g, 0.88 mmol) as a yellow oil in 88%
1H NMR (300 MHz, CDCl3) δ 8.17 (d,
(C=O) ), 8.14 (s, 1H, (C=O)
J
= 1.1 Hz, 1H,
H), 5.82 - 5.75 (m, 1H), 5.68 -
20
1
yield. [α]D = -62.5 in MeOH. H NMR (300 MHz, CDCl3)
δ 8.11 (s, 1H, (C=O) ), 5.86 - 5.76 (m, 1H, CH2C=C ),
4.77 - 4.70 (m, 2H, C=CH2), 4.57 (s, 2H, CH2O(C=O)), 2.26
- 2.06 (m, 4H, CH2), 2.05 - 1.94 (m, 1H, C ), 1.93 - 1.80
(m, 1H, C ), 1.75 (s, 3H, CH3), 1.60 - 1.41 (m, 1H, C ).
13C NMR (75 MHz, CDCl3) δ 161.0, 149.4, 132.0, 126.8,
H
H
H
5.53 (m, 2H), 5.44 - 5.37 (m, 1H), 4.78 - 4.74 (m, 2H), 4.74
- 4.70 (m, 2H), 2.40 - 2.06 (m, 5H), 2.04 - 1.82 (m, 4H),
1.76 - 1.68 (m, 10H), 1.68 - 1.63 (m, 3H), 1.61 - 1.56 (m,
1H). 13C NMR (75 MHz, CDCl3) δ 161.1 (α), 161.0 (β),
148.5 (α), 148.1 (β), 132.1 (α), 130.2 (β), 128.6 (α), 126.5
(β), 109.5 (α), 109.4 (β), 73.1 (α), 70.5 (β), 40.2 (α), 35.7
(β), 33.9 (α), 33.7 (β), 30.8 (α), 30.7 (β), 20.8 (α), 20.5 (β),
H
H
H
108.8, 68.0, 40.7, 30.4, 27.2, 26.3, 20.7. IR (thin film) ν max
(cm-1): 1722 (C=O); HRMS (ESI): m/z calculated for
C11H16O2: requires: 181.1228 for [M+H]+; found: 181.1210.
20.5 (α), 18.8 (β). IR (thin film)
ν
max (cm-1): 1717 (C=O);
HRMS (ESI): m/z calculated for C11H16O2: requires:
181.1228for [M+H]+; found: 181.1190.
Geranyl formate 11f
General procedure A was followed to afford the title
compound to give the title compound (0.155 g, 0.85 mmol)
as a pale yellow oil in 85% yield. H NMR (300 MHz,
4-((tert-butyldimethylsilyl)oxy)butan-2-yl formate 11k
1
General procedure A was followed to afford the title
CDCl3) δ 8.08 (s, 1H, (C=O)
C=C CH2O), 5.20 - 5.00 (m, 1H, C=C
7.2 Hz, 2H, CH2O(C=O)), 2.17-2.06 (m, 4H, CH2
H
), 5.45 - 5.31 (m, 1H
CH2), 4.70 (d,
H2), 1.76
compound (0.140 g, 0.60 mmol) as a yellow oil in 60%
1
H
H
J =
yield. H NMR (500 MHz, CDCl3) δ 8.04 (s, 1H, C(O)
H
),
OC(O)H), 3.70 – 3.62 (m, 2H,
H2OSiTBDMS), 1.84 (ddt, = 13.6, 8.1, 5.5 Hz, 1H,
HaCHbCH2OSiTBDMS), 1.79 1.71 (m, 1H,
= 6.4 Hz, 3H, CH3CH),
C
5.20 – 5.12 (m, 1H, C
C
C
H
- 1.71 (m, 3H CH3C(CH3)=CH), 1.71 - 1.67 (m, 3H,
CH3C(CH3)=CH), 1.61 (s, 3H, CH2C(CH3)=CH). 13C NMR
(75 MHz, CDCl3) δ 161.1, 143.2, 131.9, 123.6, 117.6, 60.8,
39.5, 26.2, 25.7, 17.7, 16.5. Analytical data in accordance
with literature.18
J
–
CHaCHbCH2OSiTBDMS), 1.30 (d,
J
0.88 (s, 9H, Si(CH3)2C(CH3)3), 0.04 (s, 6H,
Si(CH3)2C(CH3)3). 13C NMR (126 MHz, CDCl3) δ 160.9,
68.7, 59.3, 38.9, 26.0, 20.4, 18.4, -5.27, -5.29. IR (thin film)
ν
max (cm-1): 1725 (C=O); HRMS (ESI): m/z calculated for
4-Methoxyphenol formate 11g
General procedure A was followed to afford the title
C11H24O3Si: requires: 255.1392 for [M+Na]+; found:
255.1399.
compound (0.114 g, 0.75 mmol) as an orange oil in 75%
1
yield. H NMR (300MHz, CDCl3) δ 8.30 (s, 1H, (C=O)
H
),
), 3.82 (s,
3H, CH3). 13C NMR (75MHz, CDCl3) δ 159.7, 157.6, 143.3,
7.12 - 7.01 (m, 2H, Ar
H
), 6.96 - 6.87 (m, 2H, Ar
H
(2,2-dimethyl-1,3-dioxolan-4-yl)methyl formate 11l

7
General procedure A was followed to afford the title
Hz, 1H, Ar
H
), 7.70 (td,
J
= 7.7, 1.8 Hz, 1H, Ar
H
), 7.35 (d,
ACCEPTED MANUSCRIPT
compound (0.139 g, 0.87 mmol) as a yellow oil in 87%
J
= 7.8 Hz, 1H, Ar
H), 7.26 (s, 1H, Ar
H
), 5.22 (s, 2H, CH2),
1
yield. H NMR (500 MHz, CDCl3) δ 8.09 (s, 1H, C(O)
H),
2.16 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3) δ 170.8,
155.8, 149.7, 136.9, 123.0, 122.0, 67.0, 21.1. Analytical data
in accordance with literature.22
4.35 (qd, = 6.2, 4.6 Hz, 1H, CH2C CH2OC(O)), 4.26
J
H
(ddd,
(ddd,
J
J
= 11.5, 4.6, 0.9 Hz, 1H, CH2CHCHaHbOC(O)), 4.17
= 11.5, 6.2, 0.8 Hz, 1H, CH2CHCHaHbOC(O)), 4.10
(dd,
J
= 8.5, 6.5 Hz, 1H, CHaCHbCHCH2OC(O)), 3.76 (dd,
J
Cinnamyl acetate 12f
= 8.6, 6.0 Hz, 1H, CHaCHbCHCH2OC(O)), 1.44 (s, 3H,
General procedure B was followed to afford the title
compound (0.146 g, 0.83 mmol) as a clear oil in 83% yield.
CH3), 1.37 (s, 3H, CH3). 13C NMR (126 MHz, CDCl3) δ
1H NMR (300 MHz, CDCl3) δ 7.26 (s, 5H, Ar
H
), 6.66 (dt,
= 15.9, 6.5 Hz,
J = 6.5, 1.4 Hz, 2H,
J
160.7, 110.2, 73.4, 66.4, 64.3, 26.8, 25.4. IR (thin film)
ν
max (cm-1): 1722 (C=O); HRMS (ESI): m/z calculated for
C7H12O4: requires: 183.0628 for [M+Na]; found: 183.0631.
= 15.9, 1.4 Hz, 1H, CH=C
HCH2), 6.29 (dt, J
1H, C =CHCH2), 4.73 (dd,
H
CH=CHCH2), 2.11 (s, 3H, CH3). 13C NMR (75 MHz,
CDCl3) δ 171.0, 136.3, 134.4, 128.7, 128.2, 126.7, 123.3,
65.2, 21.2. Analytical data in accordance with literature.24
Benzyl acetate 12a
General procedure B was followed to afford the title
compound (0.135 g, 0.90 mmol) as a clear oil in 90% yield.
1H NMR (300 MHz, CDCl3) δ 7.48 – 7.29 (m, 5H, Ar
H),
(E)-3,7-dimethylocta-2,6-dien-1-yl acetate 12g
5.11 (s, 2H, CH2Ph), 2.11 (s, 3H, CH3). 13C NMR (75 MHz,
CDCl3) δ 171.1, 136.0, 128.7, 128.4, 66.5, 21.2. Analytical
data in accordance with literature.20
General procedure B was followed to afford the title
compound (0.174 g, 0.89 mmol) as a waxy white solid in
89% yield.1H NMR (300 MHz, CDCl3) δ 5.34 (tq,
J
= 7.2,
= 5.5, 1.5 Hz, 1H,
= 7.1 Hz, 2H, CH2OAc), 2.16 – 1.99
(m, 7H, 2 x CH2 and (C=O)CH3), 1.69 (dd, = 5.9, 1.3 Hz,
= 1.4 Hz, 3H, CH2C(CH3)=CH).
1.3 Hz, 1H, C=C
HCH2O), 5.08 (tq, J
2-Bromophenethyl acetate 12b
C=C CH2), 4.58 (d,
H
J
General procedure B was followed to afford the title
compound (0.184 g, 0.76 mmol) as a clear oil in 76% yield.
J
6H, CH3(C)CH3), 1.60 (d,
J
1H NMR (300 MHz, CDCl3) δ 7.55 (dt,
J
= 7.9, 0.9 Hz, 1H,
), 7.11 (ddd, = 7.9, 5.1, 4.1
= 7.0 Hz, 2H, CH2OC(O)CH3), 3.09
= 7.0 Hz, 2H, ArCH2), 2.04 (s, 3H, CH3). 13C NMR (75
13C NMR (75 MHz, CDCl3) δ 171.3, 142.5, 132.0, 123.9,
118.3, 61.6, 39.7, 26.4, 25.8, 21.2, 17.8, 16.6. Analytical
data in accordance with literature.22
Ar
Hz, 1H, Ar
(t,
H), 7.29 – 7.22 (m, 2H, Ar
H
J
H), 4.30 (t,
J
J
MHz, CDCl3) δ 171.1, 137.3, 133.1, 131.2, 128.5, 127.6,
124.8, 63.5, 35.4, 21.1. Analytical data in accordance with
literature.21
(S)-(4-(prop-1-en-2-yl)cyclohex-1-en-1-yl)methyl acetate 12h
General procedure B was followed to afford the title
compound as a clear oil in 85% yield (0.165 g, 0.85 mmol).
1
[α]D20 = -65.5 in CHCl3. H NMR (300 MHz, CDCl3) δ 5.76
3,7-Dimethyloct-6-en-1-yl acetate 12c
(dd,
C=CH2), 4.45 (d,
7H, 2 x CH2 and (C=O)CH3), 2.03 – 1.80 (m, 2H, CH2), 1.74
J
= 4.6, 2.4 Hz, 1H, CH2C=C
H), 4.80 – 4.66 (m, 2H,
General procedure B was followed to afford the title
compound (0.178 g, 0.90 mmol) as a clear oil in 92% yield.
J
= 1.7 Hz, 2H, CH2OAc), 2.23 – 2.04 (m,
1H NMR (300 MHz, CDCl3) δ 5.08 (tdt,
J
= 5.8, 3.0, 1.5 Hz,
), 4.17 – 4.01 (m, 2H, CH2OAc), 2.04 (s, 3H,
(C=O)CH3), 1.95 (dt, = 15.0, 7.7 Hz, 2H, CH2), 1.72 –
1.62 (m, 4H, CH2), 1.60 (d, = 1.4 Hz, 3H,CH3(C)CH3),
1.56 – 1.27 (m, 3H, CH3(C)CH3), 1.18 (dddd, = 13.5, 9.1,
= 6.4 Hz, 3H, CHCH3).
(t, J = 1.1 Hz, 3H, CH3C=CH2), 1.54 – 1.41 (m, 1H, CH).
1H, C=C
H
13C NMR (75 MHz, CDCl3) δ 171.2, 149.8, 132.7, 126.0,
108.9, 68.7, 40.9, 30.6, 27.4, 26.5, 21.2, 20.9. Analytical
data in accordance with literature.25
J
J
J
7.5, 6.2 Hz, 1H, (C
HCH3), 0.91 (d,
J
(rac)-1-phenylethyl acetate 12i
13C NMR (75 MHz, CDCl3) δ 171.4, 131.5, 124.7, 63.2,
37.1, 35.5, 29.6, 25.9, 25.5, 21.2, 19.5, 17.8. Analytical data
in accordance with literature.22
General procedure B was followed to afford the title
compound (0.126 g, 0.77 mmol) as a pale yellow oil in 77%
1
yield. H NMR (300 MHz, CDCl3) δ 7.40 – 7.26 (m, 5H,
Ar
1.54 (d,
H
), 5.88 (q,
J = 6.6 Hz, 1H, CH), 2.08 (s, 3H, C(O)CH3),
= 6.6 Hz, 3H, CHCH3). 13C NMR (75 MHz,
[1,1'-biphenyl]-4-ylmethyl acetate 12d
J
General procedure B was followed to afford the title
compound (0.153 g, 0.68 mmol) as a white solid in 68%
yield. H NMR (300 MHz, CDCl3) δ 7.63 – 7.55 (m, 4H,
CDCl3) δ 170.5, 141.8, 128.6, 128.0, 126.2, 72.5, 22.4, 21.5.
Analytical data in accordance with literature.26
1
Ar
H
), 7.49 – 7.41 (m, 4H, Ar
H
), 7.40 – 7.32 (m, 1H, Ar
H),
2-Methyl-5-(prop-1-en-2-yl)cyclohex-2-en-1-yl acetate (mix of
isomers) 12j
5.15 (s, 2H, CH2), 2.13 (s, 3H, CH3). 13C NMR (75 MHz,
CDCl3) δ 171.1, 141.4, 140.8, 135.0, 128.9, 127.6, 127.5,
127.3, 66.2, 21.2. Analytical data in accordance with
literature.23
General procedure B was followed to afford the title
compound (0.132 g, 0.68 mmol) as a clear oil in 68% yield.
1H NMR (300 MHz, CDCl3) δ 5.74 (dt,
J
= 5.3, 1.8 Hz, 1H),
5.60 (dq, J = 5.5, 1.8 Hz, 1H), 5.45 (d, J = 1.5 Hz, 1H), 5.30
– 5.22 (m, 1H), 4.77 – 4.68 (m, 4H), 2.37 – 2.15 (m, 4H),
Pyridin-2-ylmethyl acetate 12e
General procedure B was followed to afford the title
compound (0.105 g, 0.70 mmol) as a clear oil in 70% yield.
2.08 (d,
4.4, 1.1 Hz, 5H), 1.69 (dd,
2.5, 1.3 Hz, 3H), 1.61 – 1.54 (m, 1H), 1.53 – 1.41 (m, 1H).
J
= 1.0 Hz, 6H), 2.02 – 1.79 (m, 3H), 1.72 (dt,
= 2.7, 1.4 Hz, 3H), 1.64 (dp,
J
J
=
=
J
1H NMR (300 MHz, CDCl3) δ 8.60 (ddd,
J
= 4.9, 1.9, 0.9

8
Tetrahedron
13C NMR (75 MHz, CDCl ) δ 171.1, 171.1, 148.9, 148.4,
170.9, 170.3, 170.3, 169.8, 96.9, 70.9, 70.2, 68.6, 67.2, 62.0,
ACCEPTED MANUSCRIPT
3
133.0, 131.1, 128.1, 126.1, 109.5, 109.3, 73.4, 70.8, 40.4,
35.9, 34.1, 33.7, 31.0, 30.9, 21.6, 21.4, 21.0, 20.8, 20.6,
19.0. Analytical data in accordance with literature.27
55.6, 20.90, 20.85, 20.8. Analytical data in accordance with
literature.8d
Phenylmethylene dipropionate 3b
General procedure C was followed to afford the title
compound (2.15 g, 9.12 mmol) as a clear oil in 97% yield.1H
(3aR,5R,6S,6aR)-5-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2,2-
dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl acetate 12k
NMR (300 MHz, CDCl3) δ 7.71 (s, 1H, C
(qd, = 3.8, 1.5 Hz, 2H, Ar ), 7.41 (ddt,
Hz, 3H, Ar ), 2.40 (tt, = 7.4, 3.6 Hz, 4H, 2 x CH2CH3),
1.16 (t,
= 7.5 Hz, 6H, 2 x CH2CH3). 13C NMR (75 MHz,
CDCl3) δ 172.47, 135.81, 129.80, 128.72, 126.78, 89.72,
27.55, 8.89. IR (thin film)
max (cm-1): 2983 (ArC-H),
H(OCOEt)2), 7.51
General procedure B was followed for 24 h to afford the title
compound (0.21 g, 0.69 mmol) as a white solid in 70%
J
H
J = 4.3, 3.1, 1.6
H
J
20
1
yield. [α]D = -32 in CHCl3. H NMR (300 MHz, CDCl3) δ
5.88 (d, = 3.7 Hz, 1H, OC O), 5.24 (d, = 2.4 Hz, 1H,
CHOC(O)CH3), 4.50 (d, 3.7 Hz, 1H,
C(O)CH2), 4.25 (m, 2H,
J
J
H
J
OC
OC
H
H
J
=
4.17
ν
–
1756 (C=O); HRMS (ESI): m/z calculated for C13H12O4:
requires: 259.0946 for [M+Na]+; found: 259.0995.
Analytical data in accordance with literature.30
OCH(CHOCH2O)C(O)CH3 and CHC(O)CH3), 4.05 (tdd, J =
10.7, 7.0, 3.3 Hz, 2H, OCH2CHO), 2.10 (s, 3H,
CHC(O)CH3), 1.52 (s, 3H, OCO(CH3aCH3b)), 1.41 (s, 3H,
OCO(CH3aCH3b)), 1.32 (s, 3H, OCO(CH3aCH3b)), 1.30 (s,
Phenylmethylene dibenzoate 3c
13
3H, OCO(CH3aCH3b)). C NMR (75 MHz, CDCl3) δ 169.8,
General procedure C was followed to afford the title
compound (3.09 g, 9.30 mmol) as a clear oil in 99% yield.
112.4, 109.5, 105.1, 83.4, 79.8, 76.3, 72.5, 67.3, 27.0, 26.8,
26.3, 25.4, 21.1. Analytical data in accordance with
literature.28
1H NMR (300 MHz, CDCl3) δ 8.25 – 8.06 (m, 5H, C
H
and
), 7.62 – 7.50 (m, 4H, Ar ),
). 13C NMR (75 MHz, CDCl3) δ
164.6, 162.5, 134.7, 133.7, 130.7, 130.2, 129.9, 129.2,
129.0, 128.9, 128.6, 126.9, 90.8. IR (thin film)
max (cm-1):
Ar
H
), 7.75 – 7.64 (m, 3H, Ar
H
H
7.49 – 7.40 (m, 4H, Ar
H
(4aR,6S,7S,8R,8aS)-6-Methoxy-2-
phenylhexahydropyrano[3,2-d][1,3]dioxine-7,8-diyl diacetate
12l
ν
3064 (ArC-H), 1722 (C=O); HRMS (ESI): m/z calculated
for C21H16O4: requires: 355.0946 for [M+Na]+; found:
355.0929. Analytical data in accordance with literature.30
(4aR,6S,7S,8S,8aR)-6-Methoxy-2-
phenylhexahydropyrano[3,2-d][1,3]dioxine-7,8-diol (0.282
g, 1.0 mmol) was added to phenylmethylene diacetate (0.582
g, 3.0 mmol) and K2CO3 (0.270 g, 2.0 mmol) and the
reaction mixture stirred at 90 °C for 16 h. The crude reaction
mixture was then purified by column chromatography to
give the title compound (0.238 g, 0.65 mmol) as a white
Phenylmethylene diacrylate 3d
General procedure C was followed to afford the title
compound (2.12 g, 9.12 mmol) as a clear oil in 97% yield.
1H NMR (300 MHz, CDCl3) δ 7.87 (s, 1H, C
H
Ph), 7.65 –
), 6.52 (dd,
17.3, 1.4 Hz, 2H, CHaHb=CH), 6.27 – 6.03 (m, 2H,
CHaHb=C ), 5.93 (dd, = 10.5, 1.3 Hz, 2H, CHaHb=CH).
13C NMR (75 MHz, CDCl3) δ 164.0, 134.8, 132.8, 129.9,
128.8, 127.6, 126.8, 90.1. IR (thin film)
max (cm-1): 3040
1
solid in 65% yield. H NMR (300 MHz, CDCl3) δ 7.44 (qd,
7.48 (m, 2H, Ar
H
), 7.51 – 7.36 (m, 3H, Ar
H
J =
J
= 5.4, 4.5, 1.9 Hz, 2H, Ar
Ar ), 5.58 (t, = 9.6 Hz, 1H, C
PhC ), 4.95 – 4.88 (m, 2H, 2 x C C(O)CH3), 4.31 (dd,
10.1, 4.7 Hz, 1H, CH2CH(O)C (O)), 3.93 (td, = 9.9, 4.7
Hz, 1H, CH2C (O)CH(O)), 3.77 (t, = 10.2 Hz, 1H,
OCHaHbCHO), 3.65 (t, = 9.6 Hz, 1H, OCHaHbCHO), 3.41
H
), 7.36 (dt,
J = 4.6, 2.8 Hz, 3H,
H
H
J
H
OCH3), 5.51 (s, 1H,
H
J
H
J =
H
J
ν
H
J
(ArC-H), 1732 (C=O); HRMS (ESI): m/z calculated for
J
C13H12O4: requires: 255.0633 for [M+Na]+; found: 255.0667.
(s, 3H, OCH3), 2.10 (s, 3H, C(O)CH3), 2.05 (s, 3H,
C(O)CH3). 13C NMR (75 MHz, CDCl3) δ 170.6, 169.9,
137.0, 129.2, 128.4, 126.3, 101.7, 97.7, 79.3, 71.7, 69.1,
69.0, 62.4, 55.5, 21.0, 20.9. Analytical data in accordance
with literature.29
Phenylmethylene dihexanoate 3e
General procedure C was followed to afford the title
compound (2.89 g, 9.02 mmol) as a clear oil in 96% yield.
1H NMR (300 MHz, CDCl3) δ 7.71 (s, 1H, C
H
Ph), 7.51 (qd,
= 4.2, 3.1, 1.6 Hz,
= 7.4, 2.3 Hz, 4H, 2 x (C=O)CH2CH2),
1.70 – 1.58 (m, 4H, 2 x (C=O)CH2CH2), 1.30 (dq, = 7.2,
(2R,3S,4R,5S,6S)-2-(acetoxymethyl)-6-methoxytetrahydro-
2H-pyran-3,4,5-triyl triacetate 12m
J
= 3.7, 1.5 Hz, 2H, Ar
H), 7.40 (ddt, J
3H, Ar ), 2.37 (td,
H
J
J
Methyl α-D-glucopyranoside (0.194 g, 1.0 mmol) was added
to phenylmethylene diacetate (1.16 g, 6.0 mmol) and K2CO3
(1.10 g, 8.0 mmol) the reaction was stirred at 90 °C for 16 h.
The crude reaction mixture was then purified by column
chromatography to give the title compound (0.230 g, 0.63
3.7, 3.3 Hz, 8H, 2 x (C=O)CH2CH2), 0.94 – 0.82 (m, 6H, 2 x
CH2CH2CH3). 13C NMR (75 MHz, CDCl3) δ 171.8, 135.9,
129.8, 128.7, 126.8, 89.6, 34.2, 31.3, 24.5, 22.4, 14.0. IR
(thin film)
ν
max (cm-1): 2956 (ArC-H), 1752 (C=O);
1
HRMS (ESI): m/z calculated for C19H28O4: requires:
343.1885 for [M+Na]+; found: 343.1898. Analytical data in
accordance with literature.31
mmol) as a white solid in 63% yield. H NMR (300 MHz,
CDCl3) δ 5.48 (dd,
9.3 Hz, 1H), 4.98 – 4.84 (m, 2H), 4.26 (dd,
1H), 4.10 (dd, = 12.3, 2.4 Hz, 1H), 3.98 (ddd,
J
= 10.1, 9.4 Hz, 1H), 5.07 (dd,
= 12.3, 4.6 Hz,
= 10.2,
J = 10.2,
J
J
J
Phenylmethylene bis(2-phenylacetate) 3f
4.6, 2.3 Hz, 1H), 3.41 (s, 3H), 2.10 (s, 3H), 2.08 (s, 3H),
2.03 (s, 3H), 2.01 (s, 3H). 13C NMR (75 MHz, CDCl3) δ

9
General procedure C was followed to afford the title
173.8, 136.3, 128.7, 128.3, 126.8, 66.2, 34.4, 31.4, 24.8,
ACCEPTED MANUSCRIPT
compound (3.18 g, 8.84 mmol) as a clear oil in a 94% yield.
22.4, 14.0. Analytical data in accordance with literature.33
1H NMR (250 MHz, CDCl3) δ 7.69 (s, 1H, C
H
Ph), 7.43 –
13
7.16 (m, 15H, Ar
MHz, CDCl3) δ 169.5, 135.3, 133.2, 129.9, 129.5, 129.4,
128.7, 127.4, 126.7, 90.3, 41.1. IR (thin film)
max (cm-1):
H), 3.64 (s, 4H, 2 x CH2Ph). C NMR (75
Benzyl 2-phenylacetate 13e
General procedure D was followed to afford the title
compound (0.140 g, 0.62 mmol) as a clear oil in 62% yield.
ν
1H NMR (300 MHz, CDCl3) δ 7.40 – 7.28 (m, 10H, Ar
H),
3032, 2981 (ArC-H), 1759 (C=O); HRMS (ESI): m/z
calculated for C23H20O4: requires: 383.1259 for [M+Na]+;
found: 383.1259.
5.15 (s, 2H, PhCH2O), 3.68 (s, 2H, (C=O)CH2Ph). 13C NMR
(75 MHz, CDCl3) δ 171.5, 136.0, 134.0, 129.4, 128.7, 128.7,
128.3, 128.2, 127.2, 66.7, 41.5. Analytical data in
accordance with literature.33
Phenylmethylene bis(2,2,2-trifluoroacetate) 3g
Trifluoroacetic acid (0.035 mL, 0.47 mmol) was added in a
dropwise manner to a solution of benzaldehyde (0.50 g, 4.7
mmol) and trifluoroacetic anhydride (0.98 mL, 7.08 mmol)
at rt. After 2 h the reaction was concentrated in vacuo to
afford the title compound (1.4 g, 4.5 mmol) as a yellow oil
Benzyl 2,2,2-trifluoroacetate 13f
Benzyl alcohol (0.108 g, 1.0 mmol) was added to
phenylmethylene bis(2,2,2-trifluoroacetate) (0.474 g, 1.5
mmol) and K2CO3 (2.0 mmol, 0.270 g) and the reaction
stirred at rt for 1 h. The crude reaction mixture was then
purified by column chromatography to give the title
compound (0.181 g, 0.89 mmol) as a clear oil in 89% yield;
1H NMR (300 MHz, CDCl3) δ 7.40 (s, 5H), 5.36 (s, 2H). 13C
1
in 95% yield. H NMR (300 MHz, CDCl3) δ 7.79 (s, 1H,
ArH), 7.62 – 7.45 (m, 5H, ArH
). 13C NMR (75 MHz,
CDCl3) δ 155.3 (q, 2JC-F = 44.7 Hz), 134.4, 131.8, 129.4,
127.0, 114.1 (q, 1JC-F = 285.5 Hz), 93.8. IR (thin film)
ν
max (cm-1): 1809 (C=O).
NMR (75 MHz, CDCl3) δ 157.5 (q, 2
JC-F = 42.5 Hz), 133.4,
129.4, 129.0, 128.8, 114.6 (q, 1JC-F = 285.8 Hz), 69.7.
Analytical data in accordance with literature.34
Benzyl propionate 13a
General procedure D was followed to afford the title
compound (0.154 g, 0.94 mmol) as a clear oil in 94% yield.
Acetoxy(phenyl)methyl pivalate 4a
1H NMR (300 MHz, CDCl3) δ 7.37 – 7.32 (m, 5H, Ar
H
),
= 7.6 Hz, 2H, CH2CH3), 1.17
= 7.6 Hz, 3H, CH2CH3). C NMR (75 MHz, CDCl3) δ
General procedure E was followed to afford the title
compound (0.82 g, 3.30 mmol) as a clear oil in 75% yield.
5.12 (s, 2H, CH2Ph), 2.39 (q,
(t,
J
1H NMR (300 MHz, CDCl3)) δ 7.66 (s, 1H, OC
H
O), 7.53 –
J
174.5, 136.3, 128.7, 128.3, 126.8, 66.3, 27.8, 9.3. Analytical
7.49 (m, 2H, ArH), 7.42 – 7.39 (m, 3H, ArH), 2.12 (s, 3H,
data in accordance with literature.32
C(O)CH3), 1.23 (s, 9H, C(O)C(CH3)3). 13C NMR (75 MHz,
CDCl3)) δ 176.4, 169.1, 135.8, 129.7, 128.7, 126.7, 89.9,
39.0, 27.0, 21.1.
Benzyl benzoate 13b
General procedure D was followed to afford the title
compound (0.166 g, 0.78 mmol) as a clear oil in 78% yield.
Phenyl(2-phenylacetoxy)methyl pivalate 4b
1H NMR (300 MHz, CDCl3) δ 8.11 – 8.07 (m, 2H, Ar
H),
General procedure E was followed to afford the title
compound (1.20 g, 3.69 mmol) as a clear oil in 84% yield.
7.60 – 7.48 (m, 1H, ArH), 7.54 – 7.35 (m, 7H, ArH), 5.38 (s,
2H, CH2Ph). 13C NMR (75 MHz, CDCl3) δ 166.6, 136.2,
133.2, 130.3, 129.8, 128.7, 128.5, 128.4, 128.3, 66.8.
Analytical data in accordance with literature.32
1H NMR (300 MHz, CDCl3) δ 7.68 (s, 1H, OC
HO), 7.47 –
7.43 (m, 2H, ArH), 7.41 – 7.38 (m, 3H, ArH), 7.31 – 7.26
(m, 5H, ArH), 3.68 (s, 2H, CH2Ph), 1.17 (s, 9H, C(CH3)3).
13C NMR (75 MHz, CDCl3) δ 176.3, 169.6, 135.7, 133.4,
Benzyl acrylate 13c
129.7, 129.4, 128.7, 128.7, 127.4, 126.6, 90.0, 41.3, 38.9,
General procedure D was followed to afford the title
compound (0.131 g, 0.81 mmol) as a clear oil in 81% yield.
27.0. I R (thin film) ν
max (cm-1): 2995, 2983 (ArC-H),
1769, 1756 (C=O); HRMS (ESI): m/z calculated for
1H NMR (300 MHz, CDCl3) δ 7.39 – 7.32 (m, 5H, Ar
H),
C20H22O4: requires: 349.1410 for [M+Na]+; found: 349.1473.
6.45 (dd,
J = 17.3, 1.4 Hz, 1H, CH=CHaHb), 6.17 (dd, J
=
17.3, 10.4 Hz, 1H, CH=CHaHb), 5.85 (dd,
J
= 10.4, 1.4 Hz,
Phenyl(propionyloxy)methyl pivalate 4c
1H, CH=CHaHb), 5.21 (s, 2H, CH2Ph). 13C NMR (75 MHz,
CDCl3) δ 166.2, 136.0, 131.2, 128.7, 128.5, 128.4, 128.4,
66.5. Analytical data in accordance with literature.32
General procedure E was followed to afford the title
compound (0.95 g, 3.62 mmol) as a clear oil in 82% yield.1H
NMR (300 MHz, CDCl3) δ 7.68 (s, 1H, OC
HO), 7.53 – 7.49
(m, 2H, Ar ), 7.42 – 7.38 (m, 3H, Ar ), 2.40 (qd,
H
H
J
= 7.5,
Benzyl hexanoate 13d
3.0 Hz, 2H, CH2CH3), 1.23 (s, 9H, C(CH3)3), 1.16 (t,
J = 7.5
General procedure D was followed to afford the title
compound (0.144 g, 0.70 mmol) as a clear oil in 70% yield.
Hz, 3H, CH2CH3). 13C NMR (75 MHz, CDCl3) δ 176.4,
172.5, 135.9, 129.7, 128.7, 126.7, 89.8, 39.0, 27.6, 27.0, 9.0.
1H NMR (300 MHz, CDCl3) δ 7.37 – 7.32 (m, 5H, Ar
H),
IR (thin film) ν
max (cm-1): 2978 (ArC-H), 1754, 1750
5.12 (s, 2H, CH2Ph), 2.37 (t,
(C=O)CH2CH2CH2CH2CH3), 1.71
J
–
= 7.5 Hz, 2H,
1.61 (m, 2H,
(C=O); HRMS (ESI): m/z calculated for C15H20O4: requires:
287.1254 for [M+Na]+; found: 287.1268.
(C=O)CH2CH2CH2CH2CH3), 1.31 (dq,
4H, (C=O)CH2CH2CH2
(C=O)CH2CH2CH2CH2CH3). 13C NMR (75 MHz, CDCl3) δ
J = 7.5, 3.8, 3.2 Hz,
H2CH3), 0.91 – 0.87 (m, 3H,
C
Phenyl(pivaloyloxy)methyl acrylate 4d

10
Tetrahedron
General procedure E was followed to afford the title
6.50 (dd,
J
= 3.5, 1.7 Hz, 1H, C(=O)CCHC
H
), 5.44 (tq,
= 5.0, 2.8 Hz, 1H,
H=), 4.87 – 4.78 (m, 2H, -OCH2), 2.16 – 1.99 (m,
J =
ACCEPTED MANUSCRIPT
compound (0.92 g, 3.52 mmol) as a clear oil in 80% yield.
1H NMR (300 MHz, CDCl3) δ 7.75 (s, 1H, OC
O), 7.56 –
7.51 (m, 2H, Ar ), 7.45 – 7.40 (m, 3H, Ar ), 6.50 (dd,
17.3, 1.4 Hz, 1H, C =CHaHb), 6.15 (dd, = 17.3, 10.4 Hz,
= 10.4, 1.4 Hz, 1H,
7.1, 1.3 Hz, 1H, -OCH2C
CH2CH2C
4H, H2
H=), 5.09 (tt, J
H
H
H
J
=
C
C
H2CH=), 1.75 (d,
J
=
1.3 Hz, 3H,
1.3 Hz, 3H,
1.3 Hz, 3H,
H
J
CH=C(CH3aCH3b)), 1.67 (d,
OCH2CH=C(CH3), 1.60 (d,
J
=
1H, CH=CHaHb), 5.92 (dd,
J
J
=
CH=CHaHb), 1.23 (s, 9H, C(CH3)3). 13C NMR (75 MHz,
CDCl3) δ 176.4, 164.1, 135.8, 132.6, 129.8, 128.7, 127.7,
CH=C(CH3aCH3b)). 13C NMR (75 MHz, CDCl3) δ 158.8,
146.2, 142.9, 131.9, 123.7, 117.9, 117.8, 111.8, 61.9, 60.4,
39.6, 26.3, 25.7, 17.7, 16.6. IR (thin film) νmax (cm-1: 2916
(ArC-H), 1716 (C=O); HRMS (ESI): m/z calculated for
C15H20O3: requires: 271.1305 for [M+Na]+; found: 271.1302.
126.7, 90.0, 39.0, 27.0. IR (thin film)
ν
max (cm-1): 2975,
2875 (ArC-H), 1744 (C=O); HRMS (ESI): m/z calculated
for C15H18O4: requires: 285.1097 for [M+Na]+; found:
285.1149
Phenyl(2-phenylacetoxy)methyl furanoate 4e
Perillyl propanoate 13i
General procedure E was followed to afford the title
compound (1.00 g, 3.31 mmol) as a clear oil in 74% yield.
General procedure D was followed to afford the title
compound (0.098g, 0.47 mmol) as a clear oil in 94% yield.
1H NMR (300 MHz, CDCl3) δ 5.80 – 5.67 (m, 1H,
1H NMR (300 MHz, CDCl3) δ 7.88 (s, 1H, C
H
Ph), 7.61 (dd,
J
= 1.8, 0.8 Hz, 1H, C(=O)COC
2H, Ar ), 7.49 – 7.37 (m, 3H, Ar
C(=O)COCHC CH), 6.52 (dd,
C(=O)COCHCHC
H
CHCH), 7.60 – 7.55 (m,
OCH2C=C
4.45 (d,
C(=O)CH2), 2.22 – 2.02 (m, 4H, CH2C(CH2)=CCH2), 2.01 –
1.77 (m, 1H, CH2=C(CH3)C ), 1.72 (s, 3H, CH2=C(CH3)),
1.47 (ddt, = 12.7, 11.3, 8.5 Hz, 2H, CH2=C(CH3)CHCH2),
1.13 (t,
= 7.6 Hz, 3H, C(=O)CH2CH3). 13C NMR (75 MHz,
CDCl3) δ 174.4, 149.6, 132.7, 125.6, 108.8, 68.3, 40.8, 30.5,
27.6, 27.3, 26.4, 20.7, 9.2. IR (thin film) νmax (cm-1: 2921
(ArC-H), 1736 (C=O); HRMS (ESI): m/z calculated for
C13H18O2: requires: 231.1398 for [M+Na]+; found: 231.1348.
H
), 4.70 (dp,
J
= 3.0, 1.3 Hz, 2H, C(CH3)=CH2),
H
H
), 7.29 – 7.22 (m, 1H,
J
= 1.7 Hz, 2H, OCH2), 2.34 (q,
J
= 7.6 Hz, 2H,
H
J = 3.5, 1.7 Hz, 1H,
H
), 1.25 (s, 9H, C(CH3)3). 13C NMR (75
H
MHz, CDCl3) δ 176.3, 156.5, 147.1, 143.7 135.5, 129.7,
128.7, 126.6, 119.3, 112.0, 90.0, 38.9, 26.9. IR (thin film)
νmax (cm-1): 2976, 2875 (ArC-H), 1769, 1741 (C=O); HRMS
(ESI): m/z calculated for C17H18O5: requires: 325.1046 for
[M+Na]+; found: 325.1099.
J
J
Benzyl acetate 12a
Perillyl furanoate 13j
General procedure D was followed to afford the title
compound (0.135 g, 0.90 mmol) as a clear oil in 90% yield.
Analytical data was in accordance with 12a synthesized
using general procedure B.
General procedure D was followed to afford the title
compound (0.1021g, 0.42 mmol) as a clear oil in 83% yield.
1H NMR (300 MHz, CDCl3) δ 7.58 (dd,
J = 1.7, 0.9 Hz, 1H,
C(=O)COC
6.51 (dd,
= 5.1, 2.8, 1.4 Hz, 1H, OCH2C=C
C(CH3)=CH2), 4.71 – 4.69 (m, 2H, OCH2), 2.25 – 2.09 (m,
4H, CH2C(CH2)=CCH2), 2.08 1.96 (m, 1H,
CH2=C(CH3)C ), 1.74 (t, = 1.1 Hz, 3H, CH2=C(CH3)),),
H
), 7.19 (dd,
J
= 3.5, 0.8 Hz, 1H, C(=O)CC
H
),
J
Benzyl propionate 13a
J
= 3.5, 1.8 Hz, 1H, C(=O)CCHC
H), 5.84 (ddd,
H), 4.75 – 4.71 (m, 2H,
General procedure D was followed to afford the title
compound (0.154 g, 0.94 mmol) as a clear oil in 94% yield.
Analytical data was in accordance with 13a synthesized
using general procedure B.
–
H
J
1.62 – 1.19 (m, 2H, CH2=C(CH3)CHCH2). 13C NMR (75
MHz, CDCl3) δ 158.7, 149.6, 146.3, 144.7, 132.3, 126.3,
117.9, 111.8, 108.8, 68.8, 40.8, 30.5, 27.3, 26.4, 20.8. IR
(thin film) νmax (cm-1: 2922 (ArC-H), 1716 (C=O); HRMS
(ESI): m/z calculated for C15H18O3: requires: 269.1148 for
[M+Na]+; found: 269.1145.
Geraniol propanoate 13g
General procedure D was followed to afford the title
compound (0.091g, 0.43 mmol) as a clear oil in 86% yield.
1H NMR (300 MHz, CDCl3) δ 5.45 – 5.22 (m, 1H, -
Citronellyl acrylate 13k
OCH2C
4.60 (d, 2H, -OCH2C=), 2.33 (q,
C(=O)CH2CH3), 2.17 – 1.97 (m, 4H. CH2
1.72 – 1.69 (m, 3H, CH=C(CH3aCH3b)2), 1.68 (d,
H=), 5.08 (q,
J
= 1.4 Hz, 1H, CH2C
= 7.6 Hz, 2H,
H2 =C(CH3)2),
= 1.3 Hz,
= 5.2, 0.9 Hz, 3H,
7.6 Hz, 3H,
H=C(CH3)2),
General procedure D was followed to afford the title
compound (0.0772g, 0.37 mmol) as a clear oil in 73% yield.
J
C
CH
1H NMR (300 MHz, CDCl3) δ 6.40 (dd,
J
= 17.3, 1.6 Hz,
= 17.3, 10.4 Hz, 1H,
= 10.4, 1.6 Hz, 1H,
= 7.1, 5.7, 2.9, 1.4 Hz, 1H,
J
1H, C(=O)CH=CHaHb), 6.12 (dd,
C(=O)C =CHaHb), 5.82 (dd,
C(=O)CH=CHaHb), 5.09 (dddd,
-OCH2CH2CH(CH3)CH2CH2C
2H, -OCH2), 1.99 (td,
H2CH=C(CH3)2), 1.68 (q,
CH=C(CH3aCH3b), 1.60 (d,
J
3H, -OCH2CHC(CH3)), 1.59 (dd,
CH=C(CH3aCH3b)2), 1.14 (t,
J
H
J
J
=
C(=O)CH2CH3). 13C NMR (75 MHz, CDCl3) δ 174.6, 142.2,
131.9, 123.8, 118.3, 61.3, 39.6, 27.6, 26.3, 25.7, 17.7, 16.5,
9.2. Analytical data in accordance with literature.35
J
H=C(CH3)2), 4.32 – 3.99 (m,
J
= 15.2, 13.5, 6.0 Hz, 2H,
C
J
J
=
=
1.4 Hz, 3H,
1.3 Hz, 3H,
Geranyl furanoate 13h
CH=C(CH3aCH3b), 1.53 – 1.08 (m, 5H, CH2
0.93 (d,
= 6.4 Hz, 3H, CHCH3). 13C NMR (75 MHz,
CDCl3) δ 166.4, 131.4, 130.5, 128.6, 124.6, 63.1, 36.9, 35.4,
CH(CH3)CH2),
General procedure D was followed to afford the title
compound (0.1195g, 0.48 mmol) as a clear oil in 96% yield.
J
1H NMR (300 MHz, CDCl3) δ 7.57 (dd,
J
= 1.8, 0.9 Hz, 1H,
C(=O)COC
H
), 7.18 (dd,
J
= 3.5, 0.9 Hz, 1H, C(=O)CC ),
H

11
29.5, 25.8, 25.4, 19.4, 17.7. Analytical data in accordance
with literature.36
5. Conflicts of interest
The authors declare no conflicts of interest.
ACCEPTED MANUSCRIPT
6. Acknowledgements
Citronellyl furanoate 13l
We thank the EPSRC and the Centre for Doctoral Training
in Sustainable Chemical Technologies (EP/L016354/1) for
funding.
General procedure D was followed to afford the title
compound (0.075g, 0.41 mmol) as a clear oil in 90% yield.
1H NMR (300 MHz, CDCl3) δ 7.58 (dd,
J = 1.7, 0.9 Hz, 1H,
C(=O)COC
6.51 (dd,
7.1, 1.5 Hz, 1H, CH2C
C(=O)COCH2), 2.08 – 1.90 (m, 2H, CH2CH=C(CH3)2), 1.67
(q, = 1.3 Hz, 3H, CH=C(CH3aCH3b)), 1.60 (d, = 1.2 Hz,
3H, CH=C(CH3aCH3b)), 1.56 (s, 2H, C(=O)COCH2CH2),
1.46 – 1.31 (m, 2H, CH2CH2CH=C(CH3)2), 1.30 – 1.14 (m,
1H, -OCH2CH2CH(CH3)), 0.95 (d, J = 6.4 Hz, 3H, -
H
), 7.16 (dd,
J
= 3.5, 0.9 Hz, 1H, C(=O)CC
H
),
=
7. References and Notes
J
= 3.5, 1.8 Hz, 1H, C(=O)CCHC
H), 5.09 (tt,
J
H
=C(CH3)2), 4.45 – 4.24 (m, 2H,
1.
(a) Otera, J.; Nishikido, J. Esterification: Methods,
and Application (2nd Ed.), Wiley-
Reactions
J
J
VCH, Weinheim (2010); (b) Carey, J. S.; Laffan D.; Thomson C.;
Williams, M. T. Org. Biomol. Chem. 2006, 2337-2347; (c)
Dugger, R. W.; Ragan, J. A.; Ripin, D. H. B. Org. Proc. Res. Dev.
2005, 9, 253-258; (d) Melero, J. A.; Iglesias, J.; Morales, G.
Green Chem. 2009, 11, 1285-1308.
OCH2CH2CH(CH3),). 13C NMR (75 MHz, CDCl3) δ 158.9,
146.2, 144.9, 131.4, 124.5, 117.7, 111.8, 63.6, 36.9, 35.5,
29.5, 25.7, 25.4, 19.5, 17.7. IR (thin film) νmax (cm-1): 2970,
2926 (ArC-H), 1736 (C=O); HRMS (ESI): m/z calculated
for C15H22O3: requires: 273.1461 for [M+Na]+; found:
273.1459.
2.
(a) Wuts, P. G. M.; Greene, T. W. Protection for the
Hydroxyl Group, Including 1,2- and 1,3-Diols. In Greene's
Protective Groups in Organic Synthesis, John Wiley & Sons,
Inc.: 2006; pp 16-366; (b) Hagiwara, H.; Morohashi, K.; Sakai,
H.; Suzuki, T.; Ando, M. Tetrahedron 1998, 54, 5845-5852.
3.
See (a) Otera, J. Chem. Rev. 1993, 93, 1449-1470; (b)
Paravidino, M.; Hanefeld, U. Green Chem. 2011, 13, 2651-2657;
(c) Hanefeld, U. Org. Biomol. Chem. 2003, 2405-2415; (d)
Mohammadpoor-Baltork, I.; Aliyan, H.; Khosropour, A. R.
Tetrahedron 2001, 57, 5851-5854; (e) Zolfigol, M. A.;
Chehardoli, G.; Dehghanian, M.; Niknam, K.; Shirini, F.;
Khoramabadi-Zad, A. J. Chin. Chem. Soc. 2008, 55, 885-889; (f)
Habibi, M. H.; Tangestaninejad, S.; Mirkhani, V.; Yadollahi, B.
Tetrahedron 2001, 57, 8333-8337; (g) Firouzabadi, H.; Iranpoor,
N.; Farahi, S. J. Mol. Catal. A: Chem. 2008, 289, 61-68; Taylor,
J. E.; Williams, J. M. J.; Bull, S. D. Tetrahedron Lett. 2012, 53,
4074-4076, and references contained therein.
(S)-methyl 2-acetamido-3-hydroxypropanoate 16
Et3N (0.42 mL, 3.21 mmol) was added in a dropwise manner
to (S)-Serine methyl ester hydrochloride salt (0.5 g, 3.21
mmol) suspended in acetone (3 mL). The reaction mixture
was stirred for 10 min and then filtered through a Celite®
pad. The filtrate was concentrated in vacuo to give (S)-serine
methyl ester which was used without further purification.
(S)-Serine methyl ester (1.0 mmol) was added to
phenylmethylene diacetate 3a (0.291 g, 1.5 mmol) and
NaHCO3 (0.168 g, 2.0 mmol) and EtOAc (2 mL) and the
reaction was stirred at 60 °C for 16 h, followed by
chromatographic purification to afford the title compound
(0.428 g, 2.56 mmol) as a brown oil in 83% yield. [α]D20 = -
4.
Katritzky, A. R.; He, H. Y.; Suzuki, K. J. Org. Chem.
2000, 65, 8210-8213.
5.
Grasa, G. A.; Singh, R.; Nolan, S. P. Synthesis, 2004,
971-985.
6.
See: (a) Samanta, R. C.; De Sarkar, S.; Frohlich, R.;
9.5, c = 2.0, MeOH (Lit14a [α]D25 -10.1 (c 1.9, MeOH)); H
1
Grimme, S.; Studer, A. Chem. Sci. 2013, 4, 2177-2184; (b)
Prajapti, S. K.; Nagarsenkar, A.; Babu, B. N. Tetrahedron Lett.
2014, 55, 1784-1787; (c) Prasad, A. K.; Kumar, V.; Malhotra, S.;
Ravikumar, V. T.; Sanghvi, Y. S.; Parmar, V. S. Bioorg. Med.
Chem. 2005, 13, 4467-4472; (d) Wakasugi, K.; Nakamura, A.;
Tanabe, Y. Tetrahedron Lett. 2001, 42, 7427-7430; (e) Reddy, T.
S.; Narasimhulu, M.; Suryakiran, N.; Mahesh, K. C.; Ashalatha,
K.; Venkateswarlu, Y. Tetrahedron Lett. 2006, 47, 6825-6829; (f)
Alleti, R.; Oh, W. S.; Perambuduru, M.; Afrasiabi, Z.; Sinn, E.;
Reddy, V. P. Green Chem. 2005, 7, 203-206; (g) Mohan, K. V. V.
K.; Narender, N. and Kulkarni, S. J. Green Chem. 2006, 8, 368-
372; (h) Chauhan, K. K.; Frost, C. G.; Love, I.; Waite, D. Synlett
1999, 1743-1744; (i) Iranpoor, N.; Shekarriz, M. Bull. Chem.
Soc. Jpn. 1999, 72, 455-458.
NMR (500 MHz, CDCl3) δ 6.52 (s, 1H, N
7.3, 3.6 Hz, 1H, C NH), 4.01 – 3.89 (m, 2H, CH2OH), 3.79
(s, 3H, OCH3), 2.81 (s, 1H, O ), 2.07 (s, 3H, (C=O)CH3),
13C NMR (126 MHz, CDCl3) δ 171.1, 170.8, 63.6, 54.9,
52.9, 23.3. IR (thin film)
max (cm-1): 3291 ((C=O)NH and
OH), 1738 (C=O ester), 1648 (C=O amide); HRMS (ESI):
m/z calculated for C6H11NO4: requires: 162.0766 for
[M+H]+; found: 162.0788. Analytical data in accordance
with literature.14
H), 4.67 (dt, J =
H
H
ν
(S)-methyl 2-acetamido-3-(formyloxy)propanoate 17
General procedure A was followed to afford the title
compound (0.377 g, 2.0 mmol) as a white solid in 78%
7.
(a) Hill, D. R.; Hsiao, C. -N.; Kurukulasuriya, R.;
1
yield. m.p. 95-97 °C, [α]D20 = -56.0, c 1.0, CHCl3. H NMR
Wittenberger, S. J. Org. Lett. 2002, 4, 111-113; (b) Mirkhani, V.;
Tangestaninejad, S.; Moghadam, M.; Yadollahi, B.; Alipanah, L.
Monatsh. Fur Chemie 2004, 135, 1257-1263; (c) Niknam, K.;
Saberi, D. Tetrahedron Lett. 2009, 50, 5210-5214; (d) Niknam,
K.; Saberi, D. Appl. Catal. A-Gen. 2009, 366, 220-225; (e)
Barluenga, J.; Campos, P. J.; Gonzalez-Nunez, E.; Asensio, G.
Synthesis 1985, 426-428; (f) Deutsch, J.; Niclas, H. J. Synth.
Commun. 1993, 23, 1561-1568; (g) Fernando, J. E. M.; Levens,
A.; Moock, D.; Lupton, D. W. Synthesis 2017, 49, 3505-3510; (h)
De Luca, L.; Giacomelli, G.; Porcheddu, A. J. Org. Chem. 2002,
67, 5152-5155; (i) Katritsky, A. R.; Chang, H. X.; Yang, B.
Synthesis 1995, 503-505; (j) Iranpoor, N.; Firouzabadi, H.;
(300 MHz, CDCl3) δ 8.03 (q,
J
= 0.9 Hz, 1H, (C=O)
H), 6.28
(s, 1H, N ), 4.90 (dt, = 7.1, 3.3 Hz, 1H, CH
H
J
NH), 4.60 –
4.45 (m, 2H, CH2O(C=O)H), 3.80 (s, 3H, OCH3), 2.06 (s,
3H, (C=O)CH3). 13C NMR (75 MHz, CDCl3) δ 170.0, 169.9,
160.3, 63.6, 53.2, 51.6, 23.2. IR (thin film)
ν
max (cm-1):
3292 ((C=O)NH), 1727, 1713, 1703 (C=O); HRMS (ESI):
m/z calculated for C7H11NO5: requires: 190.0715 for
[M+H]+; found: 190.0739.

12
Tetrahedron
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,
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