Organocatalytic oxidative dimerization of alcohols to esters

Article abstract of DOI:10.1055/s-0032-1317018

2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) catalyzes the direct oxidation of primary alkyl alcohols to symmetric esters at 1-2mol% loadings. These rapid reactions take place at room temperature to afford the products in yields of 55-99%. Georg Thieme Verlag Stuttgart ? New York.

Full text of DOI:10.1055/s-0032-1317018

LETTER
▌2261
letter
Organocatalytic Oxidative Dimerization of Alcohols to Esters
Organocatalytic Oxidative Dimerization of Alcohols to Esters
Adi Abramovich, Hila Toledo, Evgeni Pisarevsky, Alex M. Szpilman*
Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, 32000 Haifa, Israel
Fax +972(4)8295703; E-mail: szpilman@tx.technion.ac.il
Received: 15.06.2012; Accepted after revision: 10.07.2012
if the oxidant is added slowly to the reaction mixture con-
taining the alcohol, TEMPO, and a base.
Abstract: 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) cata-
lyzes the direct oxidation of primary alkyl alcohols to symmetric
esters at 1–2 mol% loadings. These rapid reactions take place at
room temperature to afford the products in yields of 55–99%.
Accordingly, we screened a variety of conditions in the
TEMPO-catalyzed dimerization of 3-phenylpropanol
(Table 1). In all the successful experiments, pyridine was
used as a base. Other bases, for example, potassium car-
bonate, triethylamine, or dimethylaniline inhibited the re-
action. The oxidant (2 equiv) was added over one hour as
a stock solution. Many standard oxidants including phe-
nyliodonium diacetate, and phenyliodonium dichloride,
either failed to give any reaction or afforded only alde-
hyde (entries 1 and 2). However, promising results were
achieved with TCCA (44% yield; Table 1, entry 4) as the
oxidant in acetonitrile. Due to the low cost and high ratio
of oxidant (Cl+) to weight in TCCA and its environmen-
tally friendly profile, it was chosen for further optimiza-
tion. Gratifyingly, reducing the amount of TCCA
(0.6 equiv) resulted in complete conversion of the sub-
strate into ester 3a in an excellent 94% isolated yield (en-
try 5). No difference in yield was observed using 1 or 2
mol% TEMPO or 2 or 4 equivalent of pyridine. Interest-
ingly, use of NCS (entry 3) afforded the product in lower
yield than structurally related TCCA. It should be noted
that TCCA is only sparingly soluble in most common or-
ganic solvents but dissolves readily in acetonitrile. The
solvent requirement is minimal because the reaction can
be run at an initial concentration of 1 M of alcohol and is
diluted to 0.5 M after complete addition of the oxidant
stock solution. The strict exclusion of water is essential to
Key words: catalysis, dimerization, alcohols, esters, oxidation
Acylations are one of the most ubiquitous and important
processes in organic chemistry,1 and the development of
more efficient ways of preparing esters and amides has
been identified as a high priority research goal.1 Symmet-
ric esters (RCO2CH2R) are of importance in, for example,
the food and fragrance industries, but commonly require
multiple synthetic steps. Oxidative dimerization is an at-
tractive solution to this problem. Although oxidative di-
merization has been achieved with stoichiometric
oxidants, these protocols often require the use of an excess
of expensive and toxic reagent, proceed in low yield, or
require unpractical long reaction times.2,3 Several groups
have reported efficient high-temperature transition-metal-
catalyzed oxidative dimerization of alcohols to give es-
ters.4 In contrast, and despite the potential advantages,
there are few examples of organocatalytic processes.5
Herein, we report an efficient direct 2,2,6,6-tetramethyl-
piperidine-1-oxyl (TEMPO; 1)6 catalyzed oxidative di-
merization of alcohols to esters. The reaction uses only 1–
2 mol% TEMPO, is complete within 0.5–2 hours, takes
place at room temperature, and uses trichloroisocyanuric
acid (7; TCCA), which is an inexpensive and environmen-
tally benign stoichiometric oxidant.7
Table 1 Optimization Study
A particular challenge was that TEMPO-catalyzed oxida-
tion of primary alcohols usually delivers the aldehyde as
the major product.8,9 Bobbitt and Brückner reported
that oxidative dimerization of alcohols with an activating
β-oxygen substituent could be achieved by using super-
stoichiometric amounts of 4-acetylamino-2,2,6,6-tetra-
(2 mol%)
OH
Me
Me
Me
Me
O
N
O
Ph
1
2a
+ oxidant
Ph
O
Ph
pyridine (4 equiv)
MeCN
3a
methylpiperidine-1-oxoammonium
tetrafluoroborate
Entry
Oxidant
Solvent
Yield of 3a (%)
(2.5 equiv), an oxidized analogue of TEMPO, in the pres-
ence of pyridine.3 We and others had observed in unrelat-
ed work that carboxylic acids are formed in preference to
aldehydes under Anneli’s conditions9 when the bleach is
added slowly to the reaction. Thus, we postulated that es-
ter formation should be favored over aldehyde formation
1
PhIOAc2 (4)
PhICl2 (5)
NCS (6)
CH2Cl2
CH2Cl2
MeCN
MeCN
MeCN
–
a
2
3
35
44
94
4
TCCA (7)
TCCA (7)
5b
a A 1:1 mixture of aldehyde and esters was formed.
SYNLETT 2012, 23, 2261–2265
Advanced online publication: 20.08.2012
DOI: 10.1055/s-0032-1317018; Art ID: ST-2012-B0515-L
© Georg Thieme Verlag Stuttgart · New York
b Reaction conditions: TEMPO (1 mol%), TCCA (0.6 equiv), pyridine
(2 equiv).
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6

2262
A. Abramovich et al.
LETTER
avoid formation of carboxylic acids as side products of the alcohols. Both unactivated alcohols (entries 9–11 and 13)
reaction.
and alcohols with an activating β-oxygen or nitrogen
function (entries 1–8) afforded the products in 55–99%
yield.
Next, we examined the scope of the optimized conditions
(Table 2). The method is applicable to a range of primary
Table 2 Direct Oxidative Dimerization of Alcoholsa
(0.6–1.3 equiv)
Me
Me
O
(1 or 2 mol%)
N
O
Me
Me
Cl
Cl
O
OH
1
O
N
N
+
R
2 or 4 equiv pyridine
MeCN
R
O
R
O
N
Cl
2
7
3
Entry
1
Id
Starting Material
Product(s)
Yield (%)
86
OH
O
O
O
b
O
O
O
O
O
O
2
3
c
64
99
OH
O
O
OH
d
Me
O
O
Me
Me
Me
O
O
Me
Me
Me
Me
Me
O
O
4
e
55b
O
O
O
O
O
OH
O
O
O
O
O
O
5
6
f
83c
75c
OH
O
O
O
O
O
g
OH
O
O
O
O
OH
N
7
h
82
N
N
O
O
O
O
O
O
O
HO
HO
OH
8
9
i
70–100
86
O
O
OH
OH
j
O
O
Me
Me
Me
10
11
12
k
l
68d
59
H11C5
O
O
O
C5H11
C9H19
O
O
OH
OH
H19C9
H19C9
l
75e
C9H19
Synlett 2012, 23, 2261–2265
© Georg Thieme Verlag Stuttgart · New York

LETTER
Organocatalytic Oxidative Dimerization of Alcohols to Esters
2263
Table 2 Direct Oxidative Dimerization of Alcoholsa (continued)
(0.6–1.3 equiv)
Me
Me
O
(1 or 2 mol%)
N
O
Me
Me
Cl
Cl
O
OH
1
O
N
N
+
R
2 or 4 equiv pyridine
MeCN
R
O
R
O
N
Cl
2
7
3
Entry
13
Id
Starting Material
Product(s)
Yield (%)
O
m
80
OH
O
O
O
not deter-
mined 2:1
mixture
O
H
14
15
n
a
OH
+
O
74e
O
OH
a See experimental sections for procedure. No difference in yield was observed using 1 or 2 mol% of TEMPO or 2 or 4 equiv of pyridine.
b No epimerization was observed.
c Mixture of diastereoisomers.
d Volatile.
e Using t-BuOCl (2 equiv) as oxidant.
yield of 80%. The method is versatile since it is compati-
ble with a range of functionalities such as acetals (entries
oxidant
OH
2
Me
Me
Me
Me
4–6), ethers (entries 1–3), imides (entry 7) and, of course,
esters. Of further importance, ester 3e (entry 4), which is
prone to epimerization, was obtained as a single diastereo-
isomer.
H
R
Me
Me
Me
Me
8
N
O
H
N
O
1
– H+
We proceeded to investigate the mechanism. No ester for-
mation was observed in the absence of TEMPO (1). The
reaction takes place through formation of aldehydes,
which could be observed by NMR spectroscopic analysis
when the reaction was quenched at low conversions. No-
tably, despite the presence of pyridine, no aldol condensa-
tion product could be observed at the short reaction time
required for oxidation.
OH
R
– H+
11
H
O
R
Me
Me
Me
Me
Me
Me
Me
Me
R
OH
2
N
N
O
O
R
O
O
9
12
H
H
O
R
R
O
oxidant
H
R
Two possibilities presented themselves; (1) a Tishchenko
type mechanism, and (2) attack by another molecule of al-
cohol 2 on the incipient aldehyde 10 to form a hemiacetal
11 followed by oxidation to the ester 3 (Scheme 1).10 In
addition, a case could be made for attack by either a deriv-
ative of the oxidant, or pyridine upon aldehyde 10 to give
a hemi-acetal-like species.11 If such an intermediate
would be oxidized, a reactive acylating reagent would be
formed in each case which, upon reaction with a molecule
of alcohol 2, would lead to formation of the observed
product 3.
10
O
Me
Me
Me
Me
R
O
R
N
3
13
OH
Scheme 1 Plausible mechanism for the oxidative dimerization of
primary alcohols
In the case of hindered unactivated cyclohexylmethanol,
both the ester and aldehyde was present in the isolated ma-
terial (Table 2, entry 14). In contrast, similarly hindered
but activated 2-tetrahydropyryl- and 2-tetrahydrofuryl-
methanol afforded the esters in high yield (entries 5 and
6). Furthermore, the sensitive and only slightly less hin-
dered cyclobutylmethanol reacted to give the product in a
The possibility that the nucleophile was derived from
the oxidant was tested first. It was found that the use of
t-BuOCl as an alternative oxidant afforded the esters 3 in
high yield (compare Table 1, entry 5 and Table 2, entry
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 2261–2265

2264
A. Abramovich et al.
LETTER
Dunn, P. J.; Hayler, J. D.; Humphrey, G. R.; Leazer, J. L Jr.;
Linderman, R. J.; Lorenz, K.; Manley, J.; Pearlman, B. A.;
Wells, A.; Zaks, A.; Zhang, T. Y. Green Chem. 2007, 9, 411.
(2) (a) Yunker, M. B.; Fraser-Reid, B. J. Chem. Soc., Chem.
Commun. 1975, 61. (b) Kajigaeshi, S.; Kawamukai, H.;
Fujisaki, S. Bull. Chem. Soc. Jpn. 1989, 62, 2585.
(c) Morimoto, T.; Hirano, M.; Hamaguchi, T.; Shimoyama,
M.; Zhuang, X. Bull. Chem. Soc. Jpn. 1992, 65, 703.
(d) Takase, K.; Masuda, H.; Kai, O.; Nishiyama, Y.;
Sakagushi, S.; Ishii, Y. Chem. Lett. 1995, 871. (e) Moria, N.;
Togo, H. Tetrahedron 2005, 61, 5915. (f) Tumkevicius, S.;
Navickas, V.; Dailide, M. Pol. J. Chem. 2006, 80, 1377.
(g) Nikishin, G. I.; Sokova, L. L.; Kapustina, N. I.
Russ. Chem. Bull., Int. Ed. 2011, 60, 310.
15) under otherwise identical conditions. Since t-butanol
is an exceedingly poor nucleophile, this ruled out the oxi-
dant as the source of a nucleophile. In certain cases, the
use of t-BuOCl may be preferable to TCCA in the reac-
tion. Indeed, the oxidation of long chain aliphatic alcohol
2l proceeded in higher yield with t-BuOCl than with
TCCA (compare Table 2, entry 11 and 12).
Replacing pyridine with the poorer nucleophile 2,6-luti-
dine resulted only in the formation of aldehyde. In con-
trast, when 3-phenylpropanal rather than 3-phenyl-1-
propanol (2a) was used as the starting material with pyri-
dine as the base, no reaction took place. This experiment also
rules out a Tishchenko type mechanism. When 2-propanol
was added to this reaction mixture, very slow conversion
could be observed. These facts point to the primary alco-
hol as the nucleophile and indicate a different role for pyr-
idine. In further support, exchanging pyridine for a more
nucleophilic reagent i.e., 4-(N,N-dimethylamino)pyridine
(DMAP) or its N-oxide derivative DMAPO inhibited the
reaction. Examining the decanal and pyridine mixture in
detail by NMR spectroscopic analysis did not indicate the
formation of any adducts.
(3) Merbouh, N.; Bobbitt, J. M.; Brückner, C. J. Org. Chem.
2004, 69, 5116.
(4) For transition-metal catalysis protocols, see: (a) Tamaru, Y.;
Yamada, Y.; Inoue, K.; Yamamoto, Y.; Yoshida, Z. J. Org.
Chem. 1983, 48, 1286. (b) Murahashi, S.-I.; Naota, T.; Ito,
K.; Maeda, Y.; Taki, H. J. Org. Chem. 1987, 52, 4319.
(c) Suzuki, T.; Matsuo, T.; Watanabe, K.; Katoh, T. Synlett
2005, 1453. (d) Zhang, J.; Leitus, G.; Ben-David, Y.;
Milstein, D. J. Am. Chem. Soc. 2005, 127, 10840. (e) Izumi,
A.; Obora, Y.; Sakaguchi, S.; Ishii, Y. Tetrahedron Lett.
2006, 47, 9199. (f) Arita, S.; Koike, T.; Kayaki, Y.; Ikariya,
T. Chem. Asian J. 2008, 3, 1479. (g) Musa, S.;
Shaposhnikov, I.; Cohen, S.; Gelman, D. Angew. Chem. Int.
Ed. 2011, 50, 3533. (h) Spasyuk, D.; Smith, S.; Gusev, D. G.
Angew. Chem. Int. Ed. 2012, 51, 2772.
Thus, the most plausible mechanism is that shown in
Scheme 1. This mechanism is also analogous to the mech-
anism postulated for the TEMPO-catalyzed oxidation of
aldehydes to carboxylic acids,12 which is believed to pro-
ceed via the hydrated aldehyde. Indeed, benzylic alcohol
and sterically encumbered neopentyl alcohol were oxi-
dized to the corresponding aldehydes without any ester
formation. These aldehydes form hydrates relatively
slowly.12
(5) (a) Sheng, X.; Ma, H.; Gao, J.; Du, Z.; Xu, J. Oxid. Commun.
2010, 33, 274. (b) Liu, X.; Wu, J.; Shang, Z. Synth.
Commun. 2012, 42, 75. (c) For an example of NHC-
catalyzed synthesis of esters from allylic and benzylic
alcohols, see: Maki, B. E.; Chan, A.; Phillips, E. M.; Scheidt,
K. A. Org. Lett. 2007, 9, 371.
(6) General references for TEMPO: (a) Bobbitt, J. M.;
Brückner, C.; Merbouh, N. Org. React. (NY) 2010, 74, 103.
(b) Tebben, L.; Studer, A. Angew. Chem. Int. Ed. 2011, 50,
5034.
(7) For a review on the use of TCCA in organic synthesis, see:
Tilstam, U.; Weinmann, H. Org. Process. Res. Dev. 2002, 6,
384.
(8) Luca, L. D.; Giacomelli, G.; Porcheddu, A. Org. Lett. 2001,
3, 304.
Presently, the role of pyridine in the reaction remains un-
clear. We believe that, in addition to acting as a base, it
may act as a shuttle for chlorine between TCCA and the
reduced form of TEMPO (13).13 Mixing two equivalents
of pyridine and one equivalent of TCCA in acetonitrile-d3
led to the rapid formation of an unidentified precipitate.
However, the pyridine species remaining in solution had
only the characteristic NMR signals of pyridine.
(9) Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. J. Org.
Chem. 1987, 52, 2559.
(10) The mechanism is consistent with the generally accepted
mechanism for TEMPO oxidations under basic conditions,
see: Bailey, W. F.; Bobbitt, J. M.; Wiberg, K. B. J. Org.
Chem. 2007, 72, 4504.
(11) It has been reported that aldehydes are oxidized by 4-
acetylamino-2,2,6,6-tetramethylpiperidine-1-
The present method allows for the rapid and convenient
synthesis of esters through the dimerization of primary al-
cohols.14 Many of the esters prepared in this study are of
interest for the chemical industry. We believe that this
method is a valuable alternative for the preparation of
these compounds.
oxoammonium tetrafluoroborate and pyridine via acyl-
pyridinium salts, see: Bartelson, A. L.; Bobbitt, J. M.;
Bailey, W. F. Chem. Abstr. 2009, 985377.
Acknowledgment
(12) Qiu, J. C.; Pradhan, P. P.; Blanck, N. B.; Bobbitt, J. M.;
Bailey, W. F. Org. Lett. 2012, 14, 350; and references
therein.
This research was supported in part by a German-Israeli Foundation
(GIF) Young Investigator Grant (Grant No. I-2234-2067/2009) and
was supported in part by the Israel Science Foundation (Grant No.
1419/10). Alex M. Szpilman is the incumbent of the Chaya Career
Development Chair.
(13) Oxidation shuttles in TEMPO-mediated chemistry have
been reported by others see ref. 9 and see also: Rychnovsky,
S. D.; Vaidyanathan, R. J. Org. Chem. 1999, 64, 310.
(14) All reactions were carried out using oven-dried (120 °C)
glassware. Acetonitrile was dried by passage over activated
alumina under a nitrogen atmosphere (water content
<20 ppm, Karl–Fischer titration). Pyridine was distilled
from calcium hydride. All other commercially available
reagents were used without further purification.
References
(1) (a) Carey, J. S.; Laffan, D.; Thomson, C.; Williams, M. T.
Org. Biomol. Chem. 2006, 4, 2337. (b) Constable, D. J. C.;
Synlett 2012, 23, 2261–2265
© Georg Thieme Verlag Stuttgart · New York

LETTER
Chromatographic purification of products (flash
Organocatalytic Oxidative Dimerization of Alcohols to Esters
2265
(Tetrahydrofuran-2-yl)methyl Tetrahydrofuran-2-
chromatography) was performed on silica 32–63, 60 Å.
NMR spectra were recorded with a Bruker Avance I 300
spectrometer operating at 300 MHz and 75 MHz for 1H and
13C acquisitions, respectively, or with Bruker Avance III 400
spectrometers operating at 400 MHz (1H) and 101 MHz
(13C) or with a Bruker DPX200 spectrometer operating at
200 MHz (1H) and 50 MHz (13C). Chemical shifts (δ) are
reported in ppm with the solvent resonance as the internal
standard relative to chloroform (δ = 7.26 ppm for 1H, and δ
= 77.0 ppm for 13C). IR spectra were recorded with a Bruker
FTIR. High-resolution mass spectra APCI were recorded
with a Waters Micromass LCT premier instrument operating
at 70 eV (acetonitrile–water, 70%; flowrate 0.2 mL). All
known pure compounds showed NMR spectra consistent
with those reported in the literature.
General Procedure: The alcohol (2 mmol), TEMPO
(3.1 mg, 0.02 mmol, 1 mol%) and pyridine (0.322 mL,
4.0 mmol, 2 equiv) were dissolved in acetonitrile (2 mL).
A stock solution of TCCA (156 mg/mL, 0.32 mmol/mL,
0.32 equiv/mL) in acetonitrile (3 mL) is added dropwise
over 0.5–1 h until no more starting material was observed by
TLC (usually 2–3 mL stock solution, 0.65–1.3 equiv of
TCCA). Sat. NaHCO3 (25 mL) was added and the reaction
was extracted with diethyl ether (4 × 20 mL). The combined
extracts were dried over Na2SO4 and the product was
purified by flash chromatography (EtOAc–hexane).
3-Phenylpropyl 3-Phenylpropanoate (3a):15 The product
was purified by flash chromatography (EtOAc–hexane,
14%) as an oil (252 mg, 94%). Rf = 0.57 (EtOAc–hexane,
20%). 1H NMR (200 MHz, CDCl3): δ = 7.23 (m, 10 H), 4.09
(t, J = 6.5 Hz, 2 H), 2.96 (t, J = 7.6 Hz, 2 H), 2.63 (t,
J = 7.6 Hz, 4 H), 1.93 (dt, J = 13.2, 6.5 Hz, 2 H).
carboxylate (3f):3 The product was purified by flash
chromatography (EtOAc–hexane, 80%) as an oil (166 mg,
83%). 1H NMR (400 MHz, CDCl3): δ = 4.47 (m, 1 H), 4.17
(m, 1 H), 4.05 (m, 3 H), 3.86 (m, 2 H), 3.76 (dd, J = 14.3,
7.2 Hz, 1 H), 2.22 (m, 1 H), 1.92 (m, 6 H), 1.58 (m, 2 H).
(Tetrahydro-2H-pyran-2-yl)methyl Tetrahydro-2H-
pyran-2-carboxylate (3g):3 The product was purified by
flash chromatography (EtOAc–hexane, 80%) as an oil
(171 mg, 75%). 1H NMR (400 MHz, CDCl3): δ = 4.09 (m,
1 H), 3.48 (m, 1 H), 1.96 (m, J = 11.6 Hz, 1 H), 1.87 (m,
J = 7.4 Hz, 1 H), 1.56 (m, 2 H), 1.32 (m, 1 H).
2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl (1,3-
Dioxo-1,3-dihydro-2H-isoindol-2-yl) Acetate (3h): The
product was purified by flash chromatography (EtOAc–
hexane, 50%) as a solid (310 mg, 82%). Rf = 0.49 (EtOAc–
hexane, 50%). 1H NMR (400 MHz, CDCl3): δ = 7.89–7.80
(m, J = 6.3, 3.1 Hz, 4 H), 7.77–7.70 (m, 4 H), 4.44–4.38 (m,
4 H), 3.98 (t, J = 5.3 Hz, 2 H). 13C NMR (101 MHz, CDCl3):
δ = 167.99, 167.29, 167.16, 134.16, 134.07, 132.08, 131.96,
123.60, 123.47, 62.96, 38.80, 36.65. IR (thin film): 3024,
1763, 1722, 1633, 1520, 1404, 1215, 1014 cm–1. HRMS
(APCI): m/z [M + 1] calcd for C19H12N2O6: 379.0930; found:
379.0929.
1,4-Dioxan-2-one (3i):4g The product was purified by flash
chromatography (EtOAc–hexane, 80%) as an oil (103 mg,
100%). Yields varied from 70 to 100% due to the inherent
instability of the product. 1H NMR (400 MHz, CDCl3): δ =
4.50 (t, J = 4.7 Hz, 2 H), 4.38 (s, 2 H), 3.87 (t, J = 4.7 Hz,
2 H).
Tetrahydro-2H-pyran-2-one (3j):4b The product was
purified by flash chromatography (EtOAc–hexane, 80%) as
an oil (86 mg, 86%). 1H NMR (400 MHz, CDCl3): δ = 4.34
(t, J = 5.5 Hz, 2 H), 2.56 (t, J = 6.9 Hz, 2 H), 2.01–1.79 (m,
4 H).
2-(Benzyloxy)ethyl 2-(Benzyloxy)acetate (3b):3 The
product was purified by flash chromatography (EtOAc–
hexane, 30%) as an oil (191 mg, 64%). Rf = 0.83 (EtOAc–
hexane, 50%). 1H NMR (300 MHz, CDCl3): δ = 7.44–7.27
(m, 10 H), 4.66 (s, 2 H), 4.56 (s, 2 H), 4.35 (t, J = 4.7 Hz,
2 H), 4.14 (s, 2 H), 3.69 (t, J = 9.5 Hz, 2 H).
Hexyl Hexanoate (3k):2d The product was purified by flash
chromatography (EtOAc–hexane, 20%) as an oil (137 mg,
68%). Rf = 0.5 (EtOAc–hexane, 20%). 1H NMR (200 MHz,
CDCl3): δ = 4.03 (t, J = 6.7 Hz, 2 H), 2.26 (t, J = 7.5 Hz,
2 H), 1.68–1.49 (m, 4 H), 1.37–1.18 (m, 10 H), 0.86 (t,
J = 6.6 Hz, 6 H).
2-Phenoxyethyl 2-Phenoxyacetate (3c):3 The product was
purified by flash chromatography (EtOAc–hexane, 30%) as
an oil (234 mg, 86%). Rf = 0.82 (EtOAc–hexane, 80%).
1H NMR (200 MHz, CDCl3): δ = 7.33–7.13 (m, 5 H), 6.90–
6.74 (m, 5 H), 4.65 (s, 2 H), 4.56 (t, J = 4.8 Hz, 2 H), 4.20–
4.12 (t, J = 4.5 Hz, 2 H).
Decyl Decanoate (3l):2d The reaction was carried out using
t-BuOCl (2 equiv) as the oxidant instead of TCCA. The
product was purified by flash chromatography (EtOAc–
hexane, 10%) as an oil (234 mg, 75%). 1H NMR (400 MHz,
CDCl3): δ = 4.05 (t, J = 6.7 Hz, 2 H), 2.29 (t, J = 7.5 Hz,
2 H), 1.68–1.55 (m, 4 H), 1.40–1.16 (m, J = 13.6 Hz, 26 H),
0.88 (t, J = 6.6 Hz, 6 H).
2-Butoxyethyl 2-Butoxyacetate (3d):3 The product was
purified by flash chromatography (EtOAc–hexane, 18%) as
an oil (250.7 mg, 99%). Rf = 0.51 (EtOAc–hexane, 20%). 1H
NMR (200 MHz, CDCl3): δ = 4.25 (t, J = 4.5 Hz, 2 H), 4.05
(s, 2 H), 3.59 (t, J = 4.9 Hz, 2 H), 3.54–3.36 (m, 4 H), 1.66–
1.21 (m, 8 H), 0.87 (td, J = 7.1, 1.6 Hz, 6 H).
(S)-[(S)-2,2-Dimethyl-1,3-dioxolan-4-yl]methyl 2,2-
Dimethyl-1,3-dioxolane-4-carboxylate (3e):3 The product
was purified by flash chromatography (EtOAc–hexane,
30%) as an oil (143 mg, 55%). Rf = 0.95 (EtOAc–hexane,
50%). 1H NMR (400 MHz, CDCl3): δ = 4.56 (t, J = 7.0 Hz,
1 H), 4.31–3.97 (m, 6 H), 3.69 (dd, J = 8.4, 5.9 Hz, 1 H),
1.44 (s, 3 H), 1.37 (s, 3 H), 1.34 (s, 3 H), 1.29 (s, 3 H).
Cyclobutylmethyl Cyclobutanecarboxylate (3m):16 The
product was purified by flash chromatography (Et2O–
pentane, 8%) as an oil (135 mg, 80%). Rf = 0.5 (Et2O–
pentane, 20%). 1H NMR (400 MHz, CDCl3): δ = 3.99 (d,
J = 6.7 Hz, 2 H), 3.07 (pent., J = 8.5 Hz, 1 H), 2.55 (sept.,
1 H), 2.17 (m, 4 H), 1.98 (m, 2 H), 1.84 (m, 4 H), 1.71 (m,
2 H).
(15) Kim, S.; Bae, S. B.; Lee, J. S.; Park, P. Tetrahedron 2009,
65, 1461.
(16) Roberts, J. D.; Simmons, H. E. Jr. J. Am. Chem. Soc. 1951,
73, 5487.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 2261–2265

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