Efficient O-Acylation of Alcohols and Phenol Using Cp2TiCl as a Reaction Promoter

Article abstract of DOI:10.1002/ejoc.201600496

A method has been developed for the conversion of primary, secondary, and tertiary alcohols, and phenol, into the corresponding esters at room temperature. The method uses a titanium(III) species generated from a substoichiometric amount of titanocene dichloride together with manganese(0) as a reductant, as well as methylene diiodide. It involves a transesterification from an ethyl ester, or a reaction with an acyl chloride. A radical mechanism is proposed for these transformations.

Full text of DOI:10.1002/ejoc.201600496

DOI: 10.1002/ejoc.201600496
Full Paper
Acylation
Efficient O-Acylation of Alcohols and Phenol Using Cp2TiCl as a
Reaction Promoter
María Jesús Durán-Peña,[a] José Manuel Botubol-Ares,[a] James R. Hanson,[b]
Rosario Hernández-Galán,[a] and Isidro G. Collado*[a]
Abstract: A method has been developed for the conversion of as a reductant, as well as methylene diiodide. It involves a trans-
primary, secondary, and tertiary alcohols, and phenol, into the esterification from an ethyl ester, or a reaction with an acyl
corresponding esters at room temperature. The method uses a chloride. A radical mechanism is proposed for these transforma-
titanium(III) species generated from
a substoichiometric tions.
amount of titanocene dichloride together with manganese(0)
Introduction
tiary alcohols, and from phenol, under mild conditions at room
temperature.
Transesterification and acylation reactions are important trans-
formations in organic chemistry, and esters are widely found in
many naturally occurring compounds.[1] Although a number of
methods have been reported for the acylation of alcohols, some
of these use bases, elevated temperatures, or lengthy workup
procedures. In some instances, the methods are incompatible
with particular functional groups.[2]
Results and Discussion
Bis(cyclopentadienyl)titanium(III) chloride, Cp2TiIIICl,[5] has be-
come a very popular reagent in radical reactions because of its
soft one-electron-reductive character.[6] This complex is toler-
ated by a variety of functional groups.[7] In our previous work,
we prepared Cp2TiIIICl in situ by stirring a red solution of com-
mercially available Cp2TiCl2 (0.5 equiv.) with manganese dust
(12.8 equiv.) in dry and degassed tetrahydrofuran to give a
green solution of the TiIII complex.[8] A solution of the allylic
alcohol geraniol (1; 1 equiv.) together with CH2I2 (5 equiv.) was
then added, and the mixture was stirred for 2.5 h. The reaction
was quenched under an inert gas with ethyl acetate (2 equiv.)
to give acetates ( )-3a and 3b quantitatively (Scheme 1).[3]
We have recently developed new methods for the cycloprop-
anation of allylic alcohols[3] and for the tetrahydrofuranylation
and tetrahydropyranylation of alcohols,[4] catalysed by low-va-
lent titanium species. We obtained either the cyclopropanated
product or the THF/THP ether, depending on the alkyl halide
used. Furthermore, we observed that when the cyclopropan-
ation reaction of geraniol mediated by a TiIII species was
quenched by the addition of ethyl acetate, transesterification
occurred, giving the acetates of geraniol (3b) and its cyclo-
propyl derivative [( )-3a] rather than compounds [e.g., ( )-2]
retaining the free hydroxy group. This result shows that acti-
vated species derived from geraniol and cyclopropylgeraniol
were present in the solution. This unexpected observation has
led to a mild and efficient method for the esterification of a
wide variety of primary and secondary alcohols mediated by a
TiIII species. In this paper, we report our recent results on the
first transesterification and O-acylation of alcohols mediated by
Cp2TiCl in the presence of CH2I2 and an ester or an acyl chlor-
ide. This method gives esters from primary, secondary, and ter-
Scheme 1. Preparation of compounds ( )-2, ( )-3a, and 3b.
As part of our work on exploring the reactivity of TiIII species
and developing new titanium-catalysed reactions, we examined
the role of each reagent and the scope of the esterification
reaction. We evaluated the roles of titanium, manganese, and
diiodomethane in the reaction (see Table 1). We observed that
the transesterification did not proceed in the absence of CH2I2
(Entry 2, Table 1). Furthermore, the initial generation of a TiIII
species from TiIV and Mn0 was required. No reaction was ob-
served in the absence of either TiIV or manganese dust, indicat-
[a] Departamento de Química Orgánica, University of Cádiz,
Facultad de Ciencias,
Polígono Río San Pedro s/n, 11510 Puerto Real, Cádiz, Spain
E-mail: isidro.gonzalez@uca.es
http://www.isidrogcollado.es/
[b] Department of Organic Chemistry, University of Sussex,
Brighton, Sussex, BN1 9QJ, United Kingdom
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under http://dx.doi.org/10.1002/ejoc.201600496.
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ing that both titanium and manganese participated in the reac- 8, Table 3). It is worth noting that each of the allylic alcohols
tion (Entries 3–6, Table 1).
reacted to give a mixture of the corresponding acetate and the
Table 1. Acetylation of geraniol (1) using different reaction conditions under
base-free conditions.
Table 3. Cp2TiIIICl-catalysed acetylation of alcohols by ethyl acetate under
base-free conditions.
Entry
TiIV
Mn
CH2I2
Product (yield)[a]
[equiv.]
[equiv.]
[equiv.]
1
2
3
4
5
6
0.5
0.5
0
0
0.5
0.5
12.8
12.8
12.8
12.8
0
5
0
0
5
0
5
( )-3a/3b (1:2; >99 %)
n.r.[b]
n.r.[b]
n.r.[b]
n.r.[b]
n.r.[b]
0
[a] Determined by GC analysis of the crude mixture. [b] n.r. = no reaction.
We went on to study the reaction conditions and the nature
of the alkyl halide (Table 2). The reaction of a THF solution of
geraniol (1) in the presence of Cp2TiIIICl was examined with a
series of alkyl bromides and iodides at room temperature. We
observed that the transesterification reaction did not proceed
when alkyl bromides such as CH2Br2 and CHBr3 were used (En-
tries 1, 2, and 4, Table 2).
Table 2. Acetylation of geraniol (1) using different alkyl halides under base-
free conditions.
Entry
TiIV
Mn
Alkyl halide
Product (yield)[a]
[equiv.]
[equiv.]
1
2
3
4
5
6
7
0.2
0.2
0.2
0.5
0.5
0.5
0.5
8
8
8
12.8
12.8
12.8
12.8
CH2Br2 (5.0 equiv.)
CHBr3 (5.0 equiv.)
CH2I2 (5.0 equiv.)
CHBr3 (5.0 equiv.)
CH2I2 (5.0 equiv.)
CHI3 (5.0 equiv.)
I2 (5.0 equiv.)
n.r.[b]
( )-4 (96 %)
( )-4 (3 %)
( )-4 (98 %)
( )-3a/3b (1:2; >99 %)
( )-4 (99 %)
complex mixture
[a] Determined by GC analysis of the crude mixture. [b] n.r. = no reaction.
The results showed not only that the use of CH2I2 was essen-
tial for a successful reaction, but also that the number of equiv-
alents of both the titanium complex and manganese (compare
Entries 3 and 5, Table 2) was crucial. The esterification reaction
did not proceed with 0.2 equiv. of titanocene and 8.0 equiv. of
manganese (Entry 3, Table 2). The use of different iodide sour-
ces such as CHI3 or I2 resulted in the formation of ( )-4 or a
complex mixture (Entries 6 and 7, Table 2).
To examine the generality of the procedure, the acetylation
conditions were applied to a variety of primary, secondary, and
tertiary alcohols, and to phenol, at room temperature. The reac-
tion proceeded quantitatively with aliphatic, benzylic, and
allylic primary and secondary alcohols (1 and 5–11; Entries 1–
[a] Determined by GC analysis of the crude mixture. [b] n.r. = no reaction.
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acetate of the corresponding cyclopropyl derivative (Entries 1, with the primary alcohol (i.e., 6), giving 26 in low yield (2 %;
2, and 8, Table 3). Furthermore, when the reaction was Entry 3, Table 4). The tertiary alcohol (i.e., 14) and phenol (15)
quenched with ethyl acetate under an inert gas after a longer did not react with any of the ethyl esters that were tested (En-
overnight reaction, the acetylated cyclopropyl derivatives [( )- tries 7 and 8, Table 4). In order to improve the O-acylation of
3a, ( )-16a, 22a] were formed in good yields in a simple one- tertiary alcohols and phenol, and to extend the reaction to
pot reaction (see Supporting Information, S3). Phenol (15) and other acyl chains, we then decided to quench the reaction with
aliphatic tertiary alcohols did not react (Entries 10–12, Table 3), acyl chlorides.
and benzylic tertiary alcohol 12 was converted into the corre-
sponding acetylated product (i.e., 23a) in low yield, together
with its corresponding THF ether ( )-23b (15 %; Entry 9,
Table 3).
Alcohols and amines react with acyl chlorides to give esters
and amides, respectively, in a reaction known as the Schotten–
Baumann reaction.[9] This reaction requires a nonnucleophilic
base, such as pyridine, to be present to obtain high yields. ( )-
Having made this observation, we examined the scope of 1-Phenylethanol [( )-9] was chosen as a model substrate, and
the transesterification reaction with other ethyl esters. For this subjected to our reaction conditions. Then, the reaction was
purpose, we chose as model substrates a group of primary, sec- quenched under an inert gas with valeroyl chloride to give ester
ondary, and tertiary alcohols, and phenol [6, ( )-9, 14, and 15]. ( )-29 in 99 % yield, together with 1,4-iodohydrin 30 (96 %
These were subjected to our reaction conditions using ethyl yield based on the acyl chloride; Entry 1, Table 5). In order to
propionate, ethyl butyrate, and ethyl benzoate. Our results explore the O-acylation reaction using an acyl chloride, the role
showed that 2-phenylethanol (6) was converted into the corre- of each reagent was studied. Firstly, we carried out a control
sponding propionate (24; 99 % yield) and butyrate (25; 64 % reaction between compound ( )-9 and valeroyl chloride in THF
yield) derivatives in good yields (Entries 1 and 2, Table 4), in the absence of any other reagent (Entry 2, Table 5). Ester ( )-
whereas ( )-1-phenylethanol [( )-9] gave the propionate [( )- 29 was only obtained in 50 % yield, in contrast to the 99 %
27; 56 % yield] and butyrate [( )-28; 45 % yield] in moderate yield obtained when the reaction was carried out under our
yields (Entries 4 and 5, Table 4). Ethyl benzoate only reacted reaction conditions (Entry 1, Table 5). Similar lower yields were
also obtained in the absence of CH2I2, Ti, or Mn (Entries 3–5,
Table 5). Finally, compound ( )-29 was obtained in 64 % yield
together with 1,4-halohydrin 30 when the reaction was carried
out with Mn (12.8 equiv.) and CH2I2 (5 equiv.; Entry 6, Table 5).
Table 4. Cp2TiIIICl-catalysed transesterification of alcohols under base-free
conditions.
Table 5. O-Acylation of ( )-9 with valeroyl chloride under different reaction
conditions.
Entry
TiIV
Mn
CH2I2
Product (yield)[a]
[equiv.]
[equiv.]
[equiv.]
1
2
3
4
5
6
0.5
0
0.5
0
0.5
0
12.8
0
12.8
12.8
0
5
0
0
0
5
5
( )-29 (99 %) + 30 (96 %)[b]
( )-29 (50 %)
( )-29 (53 %)
( )-29 (55 %)
( )-29 (50 %)
12.8
( )-29 (64 %) + 30 (95 %)[b]
[a] Determined by GC analysis of the crude mixture. [b] Yield based on acyl
chloride.
Compounds 6, ( )-9, 12, 14, and 15 were again chosen as
model substrates. These compounds were subjected to our re-
action conditions, and the reactions were quenched under an
inert gas with valeroyl, pivaloyl, and benzoyl chlorides. Valeroyl
chloride reacted with all the tested substrates in excellent yields
(84–99 %; Entries 1, 4, 7, and 11, Table 6). Benzoyl chloride re-
acted with 2-phenylethanol (6), ( )-1-phenylethanol [( )-9], ter-
tiary alcohol 14, and phenol (15) to give esters 26, ( )-34, 38,
and 41, respectively, in good yields (78–99 %); ester 37 was
obtained from 2-phenylpropan-2-ol (12) in moderate yield (En-
tries 3, 6, 9, 10, and 13, Table 6). Similar results were achieved
with pivaloyl chloride, which gave esters 32 and 40 in excellent
yields (99 and 91 %) from 6 and 15, respectively; ester ( )-33
[a] Determined by GC analysis of the crude mixture. [b] n.r. = no reaction.
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was obtained in moderate yield (61 %) from ( )-1-phenyl- Figure 1) were obtained in high yields (>90 %),[10] together with
ethanol [( )-9] (Entries 2, 5, and 12, Table 6). Reaction of the O-acylation products of the relevant alcohols. This shows
pivaloyl chloride with 2-phenylpropan-2-ol (12) gave hindered that the excess acyl chloride was reacting with a product from
ester 36 in only 20 % yield, together with THF ether ( )-23b.
When the acyl chlorides used in Tables 5 and 6 were present
in excess, the corresponding 1,4-iodohydrins (i.e., 30, 42, 43;
the opening of the tetrahydrofuran ring.[11]
Table 6. Cp2TiIIICl-catalysed O-acylation of alcohols and phenol by acyl chlor-
ides under base-free conditions.
Figure 1. 1,4-Halohydrins as by-products in the O-acylation reaction.
In the context of our interest in the study of TiIII-catalysed
reactions, we then explored the role of the solvent with the aim
of avoiding the formation of the 1,4-halohydrin or cyclopropyl
products in the O-acylation reaction. Thus, the Cp2TiIIICl reagent
was generated in dry degassed 1,4-dioxane and tested against
a number of alcohols, quenching the reaction under an inert
gas with ethyl acetate or acyl chlorides. A solution of 1 together
with CH2I2 (5 equiv.) was added to the TiIII reagent generated
under our reaction conditions in 1,4-dioxane, and the mixture
was stirred for 2.5 h.
Surprisingly, when the reaction was quenched with ethyl
acetate, geranyl acetate (3b) was obtained in a poor 8 % yield.
The same experiment was carried out using cinnamyl alcohol
(5), and cinnamyl acetate (16b) was formed in only 9 % yield.
None of the cyclopropanation product was observed in either
reaction. However, when the reaction of 1 was quenched with
pivaloyl, valeroyl, and benzoyl chlorides, the corresponding O-
acylation products 44–46 (Entries 1–3, Table 7) were obtained
quantitatively, and again the corresponding cyclopropyl deriva-
tives were not detected. These results confirm the key role of
the solvent in the TiIII-mediated cyclopropanation.[3]
In order to extend the scope of the O-acylation in 1,4-diox-
ane, model substrates 6, ( )-9, 12, and 15 were tested under
our reaction conditions. Benzoyl, valeroyl, and pivaloyl deriva-
tives 26, 31, and 32, were obtained quantitatively from primary
alcohol 6 (Entries 4–6, Table 7) when 1,4-dioxane was used as
a solvent. This was comparable to the result when the reaction
was carried out in THF. A comparable yield was also obtained
when secondary alcohol ( )-9 was quenched with pivaloyl
chloride (Entry 8, Table 7). In contrast, valeroyl and benzoyl de-
rivatives ( )-29 and ( )-34 were obtained in lower yields than
when THF was used as solvent (Entries 7 and 9, Table 7). Lower
yields were also observed for the formation of valeroyl, pivaloyl,
and benzoyl derivatives from tertiary alcohol 12 and phenol
(15) (Entries 10–15, Table 7).
A plausible reaction mechanism is shown in Scheme 2, in
which the TiIII species is regenerated at various stages by the
excess Mn. The mechanism is similar to that described by us for
the cyclopropanation reaction of allylic alcohols.[3] In the light
of our results, a related mechanism for the transesterification
and O-acylation reactions is proposed, in which an activated
alkyl/aryloxytitanium species is formed prior to the reaction
with esters or acyl chlorides. Coordination of the alcohol to a
TiIII species generates complex A. A methylene iodide radical
generated from methylene diiodide then reacts with complex
A to give complex B. This complex is then reduced by the Mn to
give a TiIII-carbenoid species C. A direct hydrogen-atom transfer
[a] Determined by GC analysis of the crude mixture.
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Table 7. Cp2TiIIICl-catalysed O-acylation using 1,4-dioxane as solvent.
[a] Determined by GC analysis of the crude mixture.
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(HAT) from alcohol–Ti complex C to the iodomethylene radical due to the higher reactivity of the carbonyl carbon atom in
generates an activated alkyl/aryloxytitanium species.[12] these reagents.
Quenching of the reaction under an inert gas with either an
ester or an acyl chloride then gives the product of transesterifi-
cation or O-acylation, together with species D. Coordination of
a new alcohol molecule to species D then regenerates complex
C (Scheme 2).
Experimental Section
General Methods: Unless otherwise noted, materials and reagents
were obtained from commercial suppliers and used without further
purification. Tetrahydrofuran and 1,4-dioxane were freshly distilled
from Na and strictly deoxygenated under argon for 30 min before
use. Ethyl esters and acyl chlorides were not degassed or dried
before use. Air- and moisture-sensitive reactions were carried out
under argon. Purification by semipreparative and analytical HPLC
was carried out with a Hitachi/Merck L-6270 apparatus equipped
with a differential refractometer detector (RI-7490). A LiChrospher®
Si 60 (5 μm) LiChroCart® (250 mm × 4 mm) column and a LiChros-
pher® Si 60 (10 μm) LiChroCart® (250 mm × 10 mm) were used in
isolation experiments. Silica gel (Merck) was used for column chro-
matography. TLC was carried out on Merck Kiesegel 60 F254
(0.25 mm thick plates). Reaction yields were determined by GC us-
ing a Cyclosil B chiral column. Optical rotations were determined
with a digital polarimeter. Infrared spectra were recorded with an
FTIR spectrophotometer and are reported as wavenumbers (cm–1).
1H and 13C NMR spectroscopic measurements were recorded with
Varian Unity 400 MHz and Agilent 500 MHz spectrometers using
SiMe4 as the internal reference. Chemical shifts were referenced to
CDCl3 (δH = 7.25 ppm; δC = 77.0 ppm). Signals in NMR spectra were
assigned using a combination of 1D and 2D techniques. Multiplici-
ties are described using the following abbreviations: s = singlet, d =
doublet, t = triplet, q = quadruplet; quint = quintuplet; sext = sextu-
plet; m = multiplet, br. = broad. High-resolution mass spectrometry
(HRMS) was carried out with a double-focussing magnetic sector
mass spectrometer in positive-ion mode, or with a QTOF mass spec-
trometer in positive-ion APCI mode or in positive-ion electrospray
mode at a 20 V cone voltage.
General Procedure for the Preparation of Esters Mediated by
TiIII: A mixture of bis(cyclopentadienyl)titanium dichloride (81.5 mg,
0.32 mmol) and Mn dust (434 mg, 8.19 mmol) in strictly deoxygen-
ated THF or 1,4-dioxane (12.7 mL) under Ar was stirred at room
temperature for 15 min. The solution turned green. Then, a solution
of the corresponding alcohol (0.64 mmol) and CH2I2 (3.2 mmol) in
strictly deoxygenated THF or 1,4-dioxane (1.3 mL) was added, and
the mixture was stirred for 2.5 h. Then, the corresponding ester or
Scheme 2. Proposed mechanism for the formation of the products of trans-
esterification and O-acylation.
acyl chloride (1.28 mmol) was added under an inert gas, and the
reaction mixture was stirred for 1.5 h. The reaction mixture was
then filtered through a Celite pad, and the solvent was evaporated
under reduced pressure. The resulting crude product was purified
by column chromatography on silica gel using mixtures of hexanes
and ethyl acetate as eluent to give the corresponding esters.
Conclusions
We have developed a new method for the transesterification
( )-(1R*,2R*)-2-Methyl-2-(4-methylpent-3-enyl)cyclopropyl-
and O-acylation of alcohols. The method uses substoichiometric
methyl Acetate [( )-3a]: Spectroscopic data for compound ( )-3a
amounts of Cp2TiIIICl with manganese(0) as a reductant to-
gether with methylene diiodide in THF, and uses an ethyl ester
are identical to those described in the literature.[3]
(E)-3,7-Dimethylocta-2,6-dienyl Acetate (3b): Spectroscopic data
for compound 3b are identical to those described in the litera-
ture.[13]
or acyl chloride as the source of the ester group. Each of these
components has been shown to play a key role in the success
of the reaction. Esters of primary, secondary, and benzylic alco-
hols have been obtained under mild conditions in good to ex-
cellent yields, both with ethyl esters and with acyl chlorides.
The sterically more congested tertiary alcohols gave lower reac-
tion yields. Esters were not obtained from phenol using ethyl
esters, due to the delocalization of the phenoxy radical. How-
( )-(E)-2-[(3,7-Dimethylocta-2,6-dien-1-yl)oxy]tetrahydrofuran
[( )-4]: Spectroscopic data for compound ( )-4 are identical to
those described in the literature.[4]
( )-(1R*,2R*)-(2-Phenylcyclopropyl)methyl Acetate [( )-16a]:
Spectroscopic data for compound ( )-16a are identical to those
ever, they could be obtained in good yields using acyl chlorides, described in the literature.[14]
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Cinnamyl Acetate (16b): Spectroscopic data for compound 16b
2.31 (t, J = 7.4 Hz, 2 H), 1.65 (sext, J = 7.4 Hz, 2 H), 1.52 (d, J =
6.6 Hz, 3 H), 0.93 (t, J = 7.4 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 172.9, 141.8, 128.4 (2 C), 127.8, 126.0 (2 C), 72.0, 36.5, 22.3, 18.4,
13.7 ppm. HRMS (ESI+): calcd. for C12H16O2Na [M + Na]+ 215.1048;
found 215.1038.
are identical to those described in the literature.[15]
Phenethyl Acetate (17): Spectroscopic data for compound 17 are
identical to those described in the literature.[16]
Benzyl Acetate (18): Yellow amorphous solid. IR (film): ν = 3034,
˜
( )-1-Phenethyl Pentanoate [( )-29]: Spectroscopic data for com-
pound ( )-29 are identical to those described in the literature.[23]
2940, 1740, 1722, 1454, 1374, 1230, 714, 698 cm–1
.
1H NMR
(400 MHz, CDCl3): δ = 7.37–7.25 (m, 5 H), 5.10 (s, 2 H), 2.10 (s, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 170.9, 135.9, 128.5 (2 C), 128.24
(2 C), 128.22, 66.3, 21.0 ppm. HRMS (APCI+): calcd. for C9H11O2 [M
+ H]+ 151.0759; found 151.0767.
4-Iodobutyl Pentanoate (30): Spectroscopic data for compound
30 are identical to those described in the literature.[24]
Phenethyl Pentanoate (31): Colourless amorphous solid. tR
=
12.3 min, petroleum ether/ethyl acetate (95:5), flow = 3.0 mL/min.
4-Fluorobenzyl Acetate (19): Yellow oil. IR (film): ν = 2953, 1742,
˜
1
1606, 1513, 1231 cm–1. H NMR (400 MHz, CDCl3): δ = 7.33 (dd, J =
IR (film): ν = 2959, 2934, 2873, 1737, 1455, 1251, 1172, 749, 699
˜
1
cm–1. H NMR (400 MHz, CDCl3): δ = 7.31–7.20 (m, 5 H), 4.28 (t, J =
8.7, 5.4 Hz, 2 H), 7.03 (t, J = 8.7 Hz, 2 H), 5.06 (s, 2 H), 2.08 (s, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 170.8, 162.6 (d, JC,F = 248 Hz),
7.1 Hz, 2 H), 2.93 (t, J = 7.1 Hz, 2 H), 2.28 (t, J = 7.6 Hz, 2 H), 1.60–
1.53 (m, 2 H), 1.35–1.26 (m, 2 H), 0.88 (t, J = 7.1 Hz, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 173.8, 137.9, 128.9 (2 C), 128.4 (2 C),
126.5, 64.7, 35.1, 34.0, 27.0, 22.2, 13.7 ppm. HRMS (ESI+): calcd. for
C13H18O2Na [M + Na]+ 229.1204; found 229.1193.
131.8 (d, JC,F = 3.2 Hz), 130.2 (d, JC,F = 8.3 Hz, 2 C), 115.5 (d, JC,F
=
21.6 Hz, 2 C), 65.6, 21.0 ppm. HRMS (APCI+): calcd. for C9H10O2F [M
+ H]+ 169.0665; found 169.0653.
( )-1-Phenethyl Acetate [( )-20]: Spectroscopic data for com-
pound ( )-20 are identical to those described in the literature.[16,17]
Phenethyl Pivalate (32): Spectroscopic data for compound 32 are
identical to those described in the literature.[25]
(R)-Octan-2-yl Acetate (21): Spectroscopic data for compound 21
( )-1-Phenethyl Pivalate [( )-33]: Spectroscopic data for com-
pound ( )-33 are identical to those described in the literature.[26]
are identical to those described in the literature.[18]
(1S,2R,4R,6R)-1-Methyl-4-(prop-1-en-2-yl)bicyclo[4.1.0]heptan-
2-yl Acetate (22a): Colourless amorphous solid. tR = 24.6 min, pe-
troleum ether/ethyl acetate (99:1), flow = 1.0 mL/min. [α]2D0 = –45.0
( )-1-Phenethyl Benzoate [( )-34]: Spectroscopic data for com-
pound ( )-34 are identical to those described in the literature.[27]
2-Phenylpropan-2-yl Pentanoate (35): Colourless oil. tR = 9 min,
(c = 0.1, CHCl3). IR (film): ν = 2943, 1731, 1372, 1242, 1025, 966,
˜
1
890 cm–1. H NMR (400 MHz, CDCl3): δ = 5.21 (dd, J = 11.0, 5.8 Hz,
petroleum ether/ethyl acetate (95:5), flow = 3.0 mL/min. IR (film):
ν = 2959, 2934, 2873, 1737, 1455, 1251, 1172, 749, 699 cm–1 1H
.
1 H), 4.62 (m, 2 H), 2.11–2.03 (m, 1 H), 2.07 (s, 3 H), 1.99–1.91 (m, 1
H), 1.83 (ddt, J = 12.2, 5.8, 2.0 Hz, 1 H), 1.64 (s, 3 H), 1.24–1.16 (m,
1 H), 1.07 (s, 3 H), 0.98–0.87 (m, 2 H), 0.54–0.48 (m, 2 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 171.3, 148.4, 109.1, 77.2, 41.7, 31.3,
29.9, 24.0, 21.4, 21.2, 20.6, 19.4, 17.9 ppm. HRMS (APCI+): calcd. for
˜
NMR (400 MHz, CDCl3): δ = 7.36–7.20 (m, 5 H), 2.28 (t, J = 7.5 Hz, 2
H), 1.75 (s, 6 H), 1.62–1.53 (m, 2 H), 1.37–1.28 (m, 2 H), 0.90 (t, J =
7.5 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 172.5, 146.0, 128.2
(2 C), 126.9, 124.2 (2 C), 81.2, 35.1, 28.6 (2 C), 27.1, 22.2, 13.7 ppm.
HRMS (APCI+): calcd. for C14H19O2 [M – H]+ 219.1385; found
219.1382.
C
13H21O2 [M + H]+ 209.1542; found 209.1541.
(1R,5R)-2-Methyl-5-(prop-1-en-2-yl)cyclohex-2-enyl Acetate
(22b): Colourless amorphous solid. tR = 19.6 min, petroleum ether/
2-Phenylpropan-2-yl Pivalate (36): Yellow oil. tR = 7.7 min, petro-
leum ether/ethyl acetate (95:5), flow = 3.0 mL/min. IR (film): ν =
˜
ethyl acetate (99:1), flow = 1.0 mL/min. IR (film): ν = 2943, 1731,
˜
1
2958, 2870, 1726, 1273, 1134 cm–1. H NMR (500 MHz, CDCl3): δ =
1372, 1242, 1025, 966, 890 cm–1
.
1H NMR (400 MHz, CDCl3): δ =
7.36–7.23 (m, 5 H), 1.75 (s, 6 H), 1.19 (s, 9 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 176.9, 146.2, 128.2 (2 C), 126.8, 124.1 (2 C),
80.8, 32.9, 28.4 (2 C), 27.1 (3 C) ppm. HRMS (APCI+): calcd. for
C14H21O2 [M + H]+ 221.1545; found 221.1542.
5.59 (m, 1 H), 5.44 (m, 1 H), 4.71 (m, 2 H), 2.34–2.26 (m, 1 H), 2.21–
2.15 (m, 1 H), 2.12–2.04 (m, 1 H), 2.07 (s, 3 H), 2.00–1.90 (m, 2 H),
1.71 (m, 3 H), 1.63 (m, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
171.0, 148.3, 132.8, 125.9, 109.3, 73.2, 40.3, 34.0, 30.8, 21.2, 20.5,
18.8 ppm. HRMS (APCI+): calcd. for C12H19O2 [M + H]+ 195.1385;
found 195.1377.
2-Phenylpropan-2-yl Benzoate (37): Yellow oil. tR = 11.2 min, pe-
troleum ether/ethyl acetate (95:5), flow = 3.0 mL/min. IR (film): ν =
˜
2981, 1720, 1450, 1314, 1282, 1112, 1098, 712, 699 cm–1
.
1H NMR
2-Phenylpropan-2-yl Acetate (23a): Spectroscopic data for com-
pound 23a were identical to those described in the literature.[19]
(500 MHz, CDCl3): δ = 8.04 (m, 2 H), 7.54 (m, 1 H), 7.43 (m, 4 H),
7.33 (m, 2 H), 7.26 (m, 1 H), 1.92 (s, 6 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 165.1, 145.8, 132.7, 131.5, 129.5 (2 C), 128.33 (2 C),
128.26 (2 C), 127.0, 124.3 (2 C), 82.2, 28.8 (2 C) ppm. HRMS (APCI+):
calcd. for C16H15O2 [M – H]+ 239.1072; found 239.1069.
( )-2-[(2-Phenylpropan-2-yl)oxy]tetrahydrofuran
[( )-23b]:
Spectroscopic data for compound ( )-23b are identical to those
described in the literature.[4]
Phenethyl Propionate (24): Spectroscopic data for compound 24
2,4,6-Trimethylhepta-1,6-dien-4-yl Benzoate (38): Colourless oil.
tR = 6.5 min, petroleum ether/ethyl acetate (97:3), flow = 3.0 mL/
weare identical to those described in the literature.[20]
min. IR (film): ν = 2969, 2946, 1714, 1644, 1450, 1375, 1314, 1278,
Phenethyl Butyrate (25): Spectroscopic data for compound 25 are
˜
1244, 1115, 1082, 710 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.99–
identical to those described in the literature.[21]
7.97 (dd, J = 8.0, 1.0 Hz, 2 H), 7.54–7.51 (t, J = 8.0 Hz, 1 H), 7.41 (t,
J = 8.0 Hz, 2 H), 4.88 (s, 2 H), 4.76 (s, 2 H), 2.84 (d, J = 14.5 Hz, 2 H),
2.61 (d, J = 14.5 Hz, 2 H), 1.78 (s, 6 H), 1.57 (s, 3 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 165.9, 141.8 (2 C), 132.5, 131.9, 129.4 (2 C),
128.3 (2 C), 115.5 (2 C), 84.7, 46.7 (2 C), 24.2 (3 C) ppm. HRMS
(APCI+): calcd. for C17H21O2 [M – H]+ 257.1542; found 257.1534.
Phenethyl Benzoate (26): Spectroscopic data for compound 26
are identical to those described in the literature.[16]
( )-1-Phenethyl Propionate [( )-27]: Spectroscopic data for com-
pound ( )-27 are identical to those described in the literature.[22]
( )-1-Phenethyl Butyrate [( )-28]: Colourless amorphous solid. IR
(film): ν = 2966, 2931, 1736, 1453, 1179, 760, 699 cm–1
(400 MHz, CDCl3): δ = 7.35–7.26 (m, 5 H), 5.89 (q, J = 6.6 Hz, 2 H),
.
1H NMR
Phenyl Pentanoate (39): Spectroscopic data for compound 39 are
˜
identical to those described in the literature.[28]
Eur. J. Org. Chem. 2016, 3584–3591
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3590
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
254–259; b) J. M. Cuerva, A. G. Campana, J. Justicia, A. Rosales, J. L. Oller-
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[10] Yields based on the amount of acyl chloride added.
[11] Work is in progress to study the scope and limitations of this method
for the synthesis of 1,4-halohydrins and their derivatives.
[12] M. Paradas, A. G. Campaña, T. Jiménez, R. Robles, J. E. Oltra, E. Buñuel, J.
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Phenyl Pivalate (40): Spectroscopic data for compound 40 are
identical to those described in the literature.[28]
Phenyl Benzoate (41): Spectroscopic data for compound 41 are
identical to those described in the literature.[28,29]
4-Iodobutyl Pivalate (42): Spectroscopic data for compound 42
are identical to those described in the literature.[24]
4-Iodobutyl Benzoate (43): Spectroscopic data for compound 43
are identical to those described in the literature.[30]
(E)-3,7-Dimethylocta-2,6-dienyl Pentanoate (44): Yellow oil. tR
=
6 min, petroleum ether/ethyl acetate (95:5), flow = 3.0 mL/min. IR
1
(film): ν = 2962, 2931, 2874, 1736, 1450, 1380, 1171 cm–1. H NMR
˜
(500 MHz, CDCl3): δ = 5.34 (t, J = 7.0 Hz, 1 H), 5.08 (t, J = 7.0 Hz, 1
H), 4.58 (d, J = 7.0 Hz, 2 H), 2.30 (t, J = 7.0 Hz, 2 H), 2.11–2.02 (m, 4
H), 1.70 (s, 3 H), 1.68 (s, 3 H), 1.64–1.58 (m, 2 H), 1.60 (s, 3 H), 1.35
(sept, J = 7.5 Hz, 2 H), 0.91 (t, J = 7.5 Hz, 3 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 173.9, 142.1, 131.8, 123.8, 118.4, 61.2, 39.5,
34.1, 27.1, 26.3, 25.7, 22.3, 17.7, 16.4, 13.7 ppm. HRMS (APCI+): calcd.
for C15H27O2 [M + H]+ 239.2011; found 239.2018.
(E)-3,7-Dimethylocta-2,6-dienyl Pivalate (45): Spectroscopic data
for compound 45 are identical to those described in the litera-
ture.[31]
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(E)-3,7-Dimethylocta-2,6-dienyl Benzoate (46): Spectroscopic
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ture.[32]
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Economía
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Competitividad (AGL2015-65684-C2-1-R and
BFU2015-68652-R) (MINECO-FEDER). M. J. D.-P. acknowledges
the award of a Contrato Puente para Doctores supported by
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Received: April 20, 2016
Published Online: July 4, 2016
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www.eurjoc.org
3591
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim