Hydroesterification of alkenes with sodium formate and alcohols promoted by cooperative catalysis of Ru3(CO)12 and 2-pyridinemethanol

Article abstract of DOI:10.1021/jo501828j

(Figure Presented) A chelation-assisted hydroesterification reaction of alkenes with sodium formate and alcohols that involves cooperative catalysis by Ru₃(CO)₁₂ and 2-pyridinemethanol is described. In this three-component coupling reaction, sodium formate serves as the carbon monoxide source.

Full text of DOI:10.1021/jo501828j

Note
pubs.acs.org/joc
Hydroesterification of Alkenes with Sodium Formate and Alcohols
Promoted by Cooperative Catalysis of Ru3(CO)12 and
2‑Pyridinemethanol
Dong-Su Kim, Woo-Jin Park, Chang-Hee Lee, and Chul-Ho Jun*
Department of Chemistry, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea
S
* Supporting Information
ABSTRACT: A chelation-assisted hydroesterification reaction of alkenes with sodium formate and alcohols that involves
cooperative catalysis by Ru3(CO)12 and 2-pyridinemethanol is described. In this three-component coupling reaction, sodium
formate serves as the carbon monoxide source.
ransition-metal-catalyzed carbonylative esterification re-
actions are of current interest in organic synthesis because
Rh(I)/2-aminopicoline system.5 In this process, 2-amino-3-
picoline serves as a chelation assistant that aids temporary
installation of the metal onto the substrate during the C−H
bond activation reaction and removal from the product after
the reaction. We envisaged that 2-pyridinemethanol would also
act as a chelation assistant in a new hydroesterification reaction
depicted in eq 2. In studies probing this proposal, we also
observed that sodium formate can be used as a carbonyl source.
Herein we describe the results of an effort that has led to
development of the new chelation-assisted strategy for the one-
pot preparation of esters from alkenes, sodium formate, and
alcohols promoted by the cooperative catalyst system
comprising Ru3(CO)12 and 2-pyridinemethanol.
T
the resulting esters are important substances in the chemical,
pharmaceutical, and perfume industries.1 Among the various
synthetic protocols to carry out these processes, chelation-
assisted ruthenium-catalyzed hydroesterification reactions of
alkenes with 2-pyridinemethyl formate is perhaps the best
method (eq 1).2 This reaction is facile because the 2-pyridyl
In studies aimed at determining the feasibility and optimal
conditions for the new hydroesterification process, reactions of
cyclohexene (2a) with 2-phenylethyl alcohol (3a) and sodium
formate (1) were carried out at 170 °C for 4 h in the presence
of Ru3(CO)12 (4a) (5 mol %) and 2-pyridinemethanol (5a)
(20 mol %). This reaction produced 2-phenylethyl cyclo-
hexanecarboxylate (6a) in 97% yield (Table 1, entry 1). We
observed that the chelation auxiliary 5a is indispensable for this
process, as the reaction does not take place in its absence (entry
2). In addition, we found that the length of the linker between
the 2-pyridyl and alcohol moieties in the cocatalyst is
important, as 2-pyridone (5b) and 2-pyridineethanol (5c) are
much less effective than 5a in promoting the reaction (entries 3
and 4). The presence of pyridine-2,6-dimethanol (5d) and
imidazolylmethanol 5e (entries 5 and 6) as well as the addition
of tetrabutylammonium iodide (TBAI) (entry 7)2d did not
improve the efficiency of the reaction. Finally, a reaction carried
group acts as a chelating auxiliary for the cyclometalation step
that generates CO and Ru(II) hydride, the latter of which is an
important intermediate in the process. In addition, a rhodium-
catalyzed hydroesterification reaction of alkenes with CO gas
and stoichiometric amounts of 2-pyridinemethanol has also
been devised.3
Studies carried out in recent years have shown that aryl or
alkyl formates can be utilized in place of 2-pyridinemethyl
formate for these processes.4 All of these reactions utilize
formate ester to generate the corresponding ester in which the
2-pyridinemethoxy or alkoxy group of the ester remains at its
original position in the resulting ester. As a result, in order to
utilize this procedure to prepare specific alkyl esters, a separate
transesterification step with a desired alcohol is required. In a
previous investigation, we developed a chelation-assisted
hydroacylation reaction of alkenes with aldehydes that produces
alkyl ketones and occurs under cooperative catalysis by a
Special Issue: Mechanisms in Metal-Based Organic Chemistry
Received: August 8, 2014
© XXXX American Chemical Society
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Table 1. Optimization of the Reaction Conditions
Scheme 1. Proposed Mechanism for the Hydroesterification
Reaction of Alkenes with Sodium Formate and Alcohols
under Cooperative Catalysis by Ru(0) and 2-
Pyridinemethanol
Evidence exists for the proposal that CO and NaOH are
formed from 1 at high temperatures (>150 °C). For example,
the results of IR spectroscopic studies showed that 1 at high
temperature generates CO gas, which is trapped by Rh(I) to
form (CO)Rh(I) (IR peak at 2357 cm−1).8 Also, the generation
of NaOH in this thermal process was confirmed by the
observation of pH changes.9
In the mechanistic pathway, transesterification of the
resulting 2-pyridylmethyl ester 7a with 2-phenylethyl alcohol
(3a) gives ester 6a along with the starting material 5a. Sodium
formate-derived NaOH plays an important role in this
transesterification process by serving as a base catalyst in the
transesterification step.10 This effect is seen in the hydro-
esterification reaction of 2-(4-aminophenyl)ethanol (3b),
which possesses both an amino group and an alcohol group
(Table 2, entry 2). Specifically, the reaction of 3b with sodium
formate and cyclohexene carried out under the standard
conditions was observed to generate ester 6b exclusively in 54%
yield and none of the corresponding amide (Scheme 2). Thus,
it appears that under the basic conditions, the alcohol moiety in
3b is more nucleophilic than the aniline-type amine group.
out at 150 °C took place much more slowly (entry 8). Other
Ru(II) species including 4b, 4c, and Rh4(CO)12 (4d) did not
show catalytic activity in this hydroesterification process
(entries 9−11).
To determine the source of the carbonyl group in the ester
product 6a, 13C-enriched sodium formate (1*) was employed
for the hydroesterification reaction (eq 3). The results of 13C
Scheme 2. NaOH-Catalyzed Transesterification of 7a to 6b
NMR spectroscopic analysis showed that the carbonyl carbon
in 6a* is 26% enriched with 13C, demonstrating that the
carbonyl group of the ester product is derived from sodium
formate (see the Supporting Information).6 The findings
suggest that the new hydroesterification reaction operates by
the mechanistic pathway shown in Scheme 1. In this route,
initial chelation-assisted O−H bond cleavage of 2-pyridineme-
thanol (5a) with Ru3(CO)12 (4a) generates the five-membered
ruthenacyclic complex 8.7 Hydride insertion into cyclohexene
(2a) then gives the cyclohexyl−Ru(II) intermediate 9, which
undergoes migratory insertion of the cyclohexyl group into
coordinated CO in 9 to generate acyl−Ru(II) complex 10.
Reductive elimination in 10 produces ester 7a along with Ru(0)
intermediate 4d, which regenerates catalyst 4a by addition of
CO formed by decomposition of sodium formate (1).
The alcohol scope of the new catalytic hydroesterification
reaction of cyclohexene was explored next. While benzyl
alcohol (3c) is transformed into ester 6c in 85% yield under the
optimal conditions (Table 2, entry 3), phenol (3d) reacts to
produce the corresponding ester 6d in a much lower yield of
38% (entry 4). The source of this efficiency difference is likely
to be the difference in the nucleophilicities of the alcohol and
phenol. 2-Phenylethanols containing electron-donating and
-withdrawing substituents at the para position on the aryl ring,
such as methoxy (3e) and fluorine (3f), display similar
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Note
12).11 Thus, it appears that steric hindrance effects the
nucleophilicity of the alcohol in the anticipated manner.
Finally, cycloalkylmethanols such as cyclohexylmethanol (3l)
and cyclobutylmethanol (3m) also react efficiently under the
optimal conditions (entries 13 and 14).
Table 2. Catalytic Hydroesterification Reactions of Various
Alcohols with Sodium Formate
Reactions of various alkenes with 2-phenylethanol were
examined (Table 3). Simple cycloalkenes 2a and 2b were
observed to react to form the corresponding ester products 6a
and 6n in yields of 97% and 64% (entries 1 and 2).
Interestingly, norbornene (2c) reacts under the optimal
conditions to form only the exo ester 6o in 88% yield (entry
3).12 Sterically hindered alkenes such as 3,3-dimethylbut-1-ene
(2d) and α-methylstyrene (2e) serve as suitable substrates for
the hydroesterification reaction. These alkenes regioselectively
produce ester products 6p and 6q (94% and 87%, respectively;
entries 4 and 5), wihich arise by addition to the terminal alkene
carbons. These outcomes suggest that steric factors are
important in forming the intermediate Ru complex 9 (Scheme
1). In this regard, it is interesting that the reaction of 1-hexene
(2f) affords an 87% yield of a mixture of linear ester 6r and
branched ester 6s in a 68/32 ratio (entry 6). Styrene (2g) also
gives a product mixture of 6t and 6u in a 64/36 ratio in 66%
yield (entry 7).
In the investigation described herein, we developed a new
three-component hydroesterification reaction of alkenes with
alcohols in the presence of sodium formate and the cooperative
catalytic system comprising Ru3(CO)12 and 2-pyridinemetha-
nol. The reaction follows a mechanistic route that consists of
chelation-assisted hydroesterification and transesterification
processes. In the reaction, sodium formate undergoes
decomposition to form NaOH and carbon monoxide, the
latter of which serves as the carbonyl source and the former
promotes the transesterification step.
EXPERIMENTAL SECTION
■
General. Flash column chromatography was performed using 230−
400 mesh silica gel, and column chromatography was monitored by
analytical thin-layer chromatography (TLC) carried out on silica gel
plates using UV light as a visualizing agent, p-anisaldehyde, ninhydrin,
and KMnO4 solution as staining solutions, and heat as a developing
agent. pH values were recorded using a pH meter at room
tempreature. Gas chromatographic analyses were performed on an
Agilent 7890A instrument with an FID detector and an Agilent HP-5
capillary column. Mass chromatography analyses were performed
using an HP-5MS column. IR spectra were recorded using an FT-IR
spectrometer. 1H NMR (400 MHz) and 13C NMR (100 MHz) spectra
were recorded with chemical shifts reported relative to residual
1
deuterated solvent peaks. H NMR spectra were referenced to CDCl3
1
(δ 7.26 for H) as an internal standard and are reported as follows:
chemical shift (multiplicity, coupling constant, integration). Multi-
plicities are abbreviated as follows: br = broad, s = singlet, d = doublet,
t = triplet, q = quartet, m = multiplet. 13C NMR spectra were
referenced to residual CDCl3 (δ 77.26 for 13C) as an internal standard.
The analyzer type for high-resolution mass spectra was an ion-trap
(orbitrap).
Materials. Commercially available reagent-grade chemicals and
complexes 1, 2a−g, 3a−l, 4a−b, and 5a−d were purchased and used
as received, unless otherwise stated. Reagents 4c13 and 5e14 were
prepared using literature procedures. 13C-enriched sodium formate
(1*) was prepared by treatment of 13C-enriched formic acid with
NaOH in H2O followed by removal of solvent. Cyclobutylmethanol
(3m) was prepared by reduction of cyclobutanecarboxylic acid using
LiAlH4.
reactivities. The reaction of thiophenyl-substituted alcohol 3g
takes place in a moderate 65% yield to produce the
corresponding ester 6g, while the 4-pyridyl analogue 3h reacts
to form ester 6f in only 22% yield. It is likely that the strongly
coordinating pyridyl substituent in 3h retards the complexation
of Ru catalyst 4a with 5a that is required for chelation-assisted
O−H bond cleavage. However, when 5a is used as the starting
alcohol, a 72% yield of the corresponding ester 7a is generated.
Steric factors also influence the efficiency and regioselectivity
(see below) of the transesterification reaction. This is
exemplified by reactions with the 1° (3i), 2° (3j), and 3°
(3k) alcohols, which form the corresponding esters in
respective yields of 90%, 14%, and 4% (Table 2, entries 10−
Typical Procedure: Preparation of 2-Phenylethyl Cyclo-
hexanecarboxylate (6a) (Table 1). To a 1 mL pressure vial were
added sodium formate (1) (16.8 mg, 0.2 mmol), cyclohexene (2a)
C
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Table 3. Catalytic Hydroesterification of Various Alkenes with Sodium Formate
(61.4 μL, 0.6 mmol), phenethyl alcohol (3a) (121 μL, 1.0 mmol),
Ru3(CO)12 (4a) (6.4 mg, 0.01 mmol), and 2-pyridinemethanol (5a)
(3.9 μL, 0.04 mmol). The mixture was stirred at 170 °C for 4 h. After
cooling, the mixture was subjected to column chromatography (n-
hexane/ethyl acetate = 10:1) on silica gel to give 6a (45.0 mg, 97%) as
a colorless oil.
2-Phenylethyl Cyclohexanecarboxylate (6a). [CAS no. 37139-88-
1]; 1H NMR (400 MHz, CDCl3) δ 7.32−7.29 (m, 2H), 7.24−7.21 (m,
3H), 4.28 (t, J = 7.0 Hz, 2H), 2.93 (t, J = 7.0 Hz, 2H), 2.27 (tt, J =
11.1, 3.5 Hz, 1H), 1.89−1.85 (m, 2H), 1.75−1.71 (m, 2H), 1.65−1.63
(m, 1H), 1.45−1.36 (m, 2H), 1.31−1.18 (m, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 176.2, 138.1, 129.1, 128.6, 126.6, 64.7, 43.3,
35.3, 29.1, 25.9, 25.6.
4-Methoxyphenethyl Cyclohexanecarboxylate (6e). (39.3 mg,
75%); H NMR (400 MHz, CDCl3) δ 7.13 (d, J = 8.5 Hz, 2H), 6.84
1
(d, J = 8.6 Hz, 2H), 4.23 (t, J = 7.0 Hz, 2H), 3.78 (s, 3H), 2.86 (t, J =
7.0 Hz, 2H), 2.27 (tt, J = 11.1, 3.5 Hz, 1H), 1.88−1.85 (m, 2H), 1.74−
1.72 (m, 2H), 1.64−1.62 (m, 1H), 1.44−1.36 (m, 2H), 1.31−1.21 (m,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 176.2, 158.4, 130.1, 130.0,
114.0, 65.0, 55.4, 43.3, 34.4, 29.1, 25.9, 25.6; IR (CDCl3) 2931, 2855,
727, 1612, 1512, 1450, 1300, 1244, 1165, 1131, 1033, 982, 822, 753,
562, 518 cm−1; HR-MS(ESI+) calcd for C16H22O3Na+ [M + Na]+
285.1461, found 285.1456.
4-Fluorophenethyl Cyclohexanecarboxylate (6f). (38.5 mg, 77%);
1H NMR (400 MHz, CDCl3) δ 7.16 (dd, J = 8.4, 5.4 Hz, 2H), 6.98 (t,
J = 8.6 Hz, 2H), 4.24 (t, J = 6.8 Hz, 2H), 2.89 (t, J = 6.8 Hz, 2H), 2.26
(tt, J = 11.1, 3.5 Hz, 1H), 1.86−1.83 (m, 2H), 1.74−1.70 (m, 2H),
1.64−1.61 (m, 1H), 1.43−1.37 (m, 2H), 1.30−1.20 (m, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 176.2, 161.8 (d, J = 242.8 Hz), 133.8 (d, J
= 3.3 Hz), 130.5 (d, J = 7.8 Hz), 115.4 (d, J = 21.1 Hz), 64.7, 43.3,
34.5, 29.1, 25.9, 25.6; IR (CDCl3) 2932, 2856, 1728, 1601, 1509, 1450,
1388, 1312, 1274, 1245, 1221, 1167, 1157, 1131, 1022, 824, 756, 555,
4-Aminophenethyl Cyclohexanecarboxylate (6b). (26.7 mg,
1
54%); H NMR (400 MHz, CDCl3) δ 7.00 (d, J = 8.1 Hz, 2H),
6.64 (d, J = 8.1 Hz, 2H), 4.20 (t, J = 7.0 Hz, 2H), 3.56 (br s, 2H), 2.81
(t, J = 7.0 Hz, 2H), 2.26 (tt, J = 11.1, 3.4 Hz, 1H), 1.88−1.85 (m, 2H),
1.74−1.71 (m, 2H), 1.63−1.62 (m, 1H), 1.45−1.36 (m, 2H), 1.30−
1.18 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 176.3, 144.7,
129.9, 128.1, 115.5, 65.2, 43.3, 34.4, 29.1, 25.9, 25.6; IR (CDCl3) 3373,
2931, 2855, 1728, 1626, 1518, 1450, 1388, 1312, 1276, 1247, 1170,
1023, 823, 557, 513 cm−1; HR-MS(ESI+) calcd for C15H21NO2Na+
[M + Na]+ 270.1465, found 270.1455.
+
425 cm−1; HR-MS(ESI+) calcd for C15H20FO2 [M + H]+ 251.1442,
found 251.1425.
2-(Thiophen-2-yl)ethyl Cyclohexanecarboxylate (6g). (31.0 mg,
1
65%); H NMR (400 MHz, CDCl3) δ 7.15 (dd, J = 5.1, 1.1 Hz, 1H),
6.94 (dd, J = 5.0, 3.4 Hz, 1H), 6.86−6.85 (m, 1H), 4.28 (t, J = 6.6 Hz,
2H), 3.14 (t, J = 6.6 Hz, 2H), 2.29 (tt, J = 11.2, 3.6 Hz, 1H), 1.91−
1.87 (m, 2H), 1.76−1.72 (m, 2H), 1.65−1.58 (m, 1H), 1.47−1.38 (m,
2H), 1.32−1.19 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 176.2,
140.3, 127.0, 125.7, 124.2, 64.5, 43.3, 29.5, 29.1, 25.9, 25.6; IR
(CDCl3) 2930, 2854, 1728, 1450, 1311, 1245, 1165, 1038, 848, 691,
503 cm−1; HR-MS(ESI+) calcd for C13H18O2SNa+ [M + Na]+
261.0920, found 261.0913.
Benzyl Cyclohexanecarboxylate (6c). [CAS no. 22733-94-4] (37.1
1
mg, 85%); H NMR (400 MHz, CDCl3) δ 7.38−7.31 (m, 5H), 5.11
(s, 2H), 2.36 (tt, J = 11.2, 3.6 Hz, 1H), 1.96−1.92 (m, 2H), 1.78−1.74
(m, 2H), 1.67−1.62 (m, 1H), 1.52−1.42 (m, 2H), 1.33−1.20 (m, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 176.1, 136.5, 128.7, 128.2, 128.1,
66.0, 43.4, 29.2, 25.9, 25.6.
Phenyl Cyclohexanecarboxylate (6d). [CAS no. 3954-12-9] (15.5
1
mg, 38%); H NMR (400 MHz, CDCl3) δ 7.39−7.35 (m, 2H), 7.21
3-(Pyridin-4-yl)propyl Cyclohexanecarboxylate (6h). (10.9 mg,
1
(t, J = 7.4 Hz, 1H), 7.07−7.05 (m, 2H), 2.56 (tt, J = 11.2, 3.6 Hz, 1H),
2.09−2.05 (m, 2H), 1.85−1.80 (m, 2H), 1.71−1.66 (m, 1H), 1.64−
1.54 (m, 2H), 1.41−1.26 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3)
δ 174.8, 151.0, 129.5, 125.8, 121.7, 43.4, 29.1, 25.9, 25.5.
22%); H NMR (400 MHz, CDCl3) δ 8.47 (d, J = 6.0 Hz, 2H), 7.09
(d, J = 5.9 Hz, 2H), 4.05 (t, J = 6.4 Hz, 2H), 2.66 (t, J = 7.5 Hz, 2H),
2.26 (tt, J = 11.2, 3.6 Hz, 1H), 1.97−1.90 (m, 2H), 1.89−1.85 (m,
2H), 1.75−1.71 (m, 2H), 1.63−1.60 (m, 1H), 1.45−1.36 (m, 2H),
D
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Note
1.31−1.22 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 176.2,
150.3, 149.9, 124.0, 63.1, 43.3, 31.7, 29.3, 29.2, 25.9, 25.5; IR (CDCl3)
2931, 2855, 1728, 1601, 1509, 1450, 1388, 1312, 1245, 1221, 1167,
1157, 1131, 1022, 895, 824, 756, 555, 504, 469 cm−1; HR-MS(ESI+)
calcd for C15H21NO2Na+ [M + Na]+ 270.1465, found 270.1455.
Heptyl Cyclohexanecarboxylate (6i). [CAS no. 92319-47-6] (40.7
13C{1H} NMR (100 MHz, CDCl3) δ 173.9, 138.1, 129.1, 128.6, 126.7,
64.8, 35.3, 34.5, 31.6, 28.9, 25.1, 22.6, 14.2.
Phenethyl 2-Methylhexanoate (6s). (13 mg, 28%); 1H NMR (400
MHz, CDCl3) δ 7.32−7.29 (m, 2H), 7.25−7.21 (m, 3H), 4.30 (td, J =
7.0, 1.3 Hz, 2H), 2.95 (t, J = 7.0 Hz, 2H), 2.45−2.37 (m, 1H), 1.67−
1.58 (m, 1H), 1.43−1.34 (m, 1H), 1.31−1.19 (m, 4H), 1.12 (d, J = 6.9
Hz, 3H), 0.88 (t, J = 6.9 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3)
δ 177.0, 138.1, 129.1, 128.6, 126.6, 64.7, 39.7, 35.3, 33.6, 29.5, 22.7,
17.2, 14.1; IR (CDCl3) 3030, 2860, 1729, 1455, 1381, 1170, 697, 571
cm−1; HR-MS(ESI+) calcd for C15H22O2Na+ [M + Na]+ 257.1512,
found 257.1505.
1
mg, 90%); H NMR (400 MHz, CDCl3) δ 4.04 (t, J = 6.7 Hz, 2H),
2.26 (tt, J = 11.2, 3.6 Hz, 1H), 1.90−1.87 (m, 2H), 1.76−1.72 (m,
2H), 1.64−1.57 (m, 3H), 1.47−1.38 (m, 2H), 1.32−1.25 (m, 11H),
0.89−0.86 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 176.5, 64.5,
43.5, 31.9, 29.2, 29.1, 28.9, 26.1, 26.0, 25.7, 22.8, 14.3.
Isopropyl Cyclohexanecarboxylate (6j). [CAS no. 6553-80-6] (4.8
mg, 14%); 1H NMR (400 MHz, CDCl3) δ 5.00−4.94 (m, 1H), 2.24−
2.19 (m, 1H), 1.88−1.85 (m, 2H), 1.74−1.71 (m, 2H), 1.63−1.61 (m,
1H), 1.44−1.36 (m, 2H), 1.27−1.23 (m, 3H), 1.19 (d, J = 6.2 Hz,
6H); 13C{1H} NMR (100 MHz, CDCl3) δ 175.9, 67.2, 43.6, 29.2,
26.0, 25.6, 22.0.
Phenethyl 3-Phenylpropanoate (6t). [CAS no. 28049-10-7] (21.5
1
mg, 42%); H NMR (400 MHz, CDCl3) δ 7.32−7.17 (m, 10H), 4.30
(t, J = 7.2 Hz, 2H), 2.95−2.90 (m, 4H), 2.63 (t, J = 8.0 Hz, 2H);
13C{1H} NMR (100 MHz, CDCl3) δ 173.0, 140.7, 138.0, 129.1, 128.7,
128.5, 126.7, 126.4, 65.1, 36.1, 35.3, 31.1.
Phenethyl 2-Phenylpropanoate (6u). [CAS no. 66256-02-8] (12.1
mg, 24%); 1H NMR (400 MHz, CDCl3) δ 7.34−7.19 (m, 8H), 7.11−
7.09 (m, 2H), 4.34−4.23 (m, 2H), 7.40 (q, J = 7.2 Hz, 1H), 2.87 (td, J
= 6.8, 1.6 Hz, 2H), 1.48 (d, J = 7.2 Hz, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 174.6, 140.7, 138.0, 129.1, 128.8, 128.6, 127.7, 127.3,
126.6, 65.4, 45.7, 35.2, 18.6.
tert-Butyl Cyclohexanecarboxylate (6k). [CAS no. 16537-05-6]
1
(1.5 mg, 4%); H NMR (400 MHz, CDCl3) δ 2.16 (tt, J = 11.2, 3.6
Hz, 1H), 1.87−1.83 (m, 2H), 1.74−1.70 (m, 2H), 1.63−1.58 (m, 1H),
1.42 (s, 9H), 1.42−1.36 (m, 3H), 1.27−1.20 (m, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 175.9, 79.8, 44.3, 29.3, 28.3, 26.0, 25.7.
Cyclohexylmethyl Cyclohexanecarboxylate (6l). [CAS no. 2611-
02-1] (30.1 mg, 67%); 1H NMR (400 MHz, CDCl3) δ 3.85 (d, J = 6.5
Hz, 2H), 2.28 (tt, J = 11.2, 3.6 Hz, 1H), 1.91−1.87 (m, 2H), 1.72−
1.60 (m, 9H), 1.47−1.38 (m, 2H), 1.31−1.16 (m, 6H), 0.99−0.90 (m,
2H); 13C{1H} NMR (100 MHz, CDCl3) δ 176.4, 69.5, 43.5, 37.4,
29.9, 29.3, 26.6, 26.0, 25.9, 25.7.
Pyridin-2-ylmethyl Cyclohexanecarboxylate (7a). [CAS no.
1
401516-10-7] (31.6 mg, 72%); H NMR (400 MHz, CDCl3) δ 8.56
(d, J = 4.3 Hz, 1H), 7.67 (td, J = 7.7, 1.7 Hz, 1H), 7.31 (d, J = 7.8 Hz,
1H), 7.21−7.18 (m, 1H), 5.20 (s, 2H), 2.40 (tt, J = 11.3, 3.6 Hz, 1H),
1.97−1.93 (m, 2H), 1.77−1.73 (m, 2H), 1.64−1.61 (m, 1H), 1.51−
1.42 (m, 2H), 1.32−1.21 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3)
δ 175.8, 156.3, 149.5, 136.9, 122.9, 121.7, 66.6, 43.3, 29.2, 25.9, 25.6.
Cyclobutylmethyl Cyclohexanecarboxylate (6m). (33.0 mg, 84%);
1H NMR (400 MHz, CDCl3) δ 4.00 (d, J = 6.6 Hz, 2H), 2.64−2.52
(m, 1H), 2.27 (tt, J = 11.2, 3.6 Hz, 1H), 2.06−1.98 (m, 2H), 1.92−
1.78 (m, 4H), 1.76−1.70 (m, 4H), 1.62−1.59 (m, 1H), 1.47−1.37 (m,
2H), 1.31−1.17 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 176.5,
67.9, 43.4, 34.3, 29.2, 25.9, 25.6, 24.8, 18.6; IR (CDCl3) 2931, 2856,
1730, 1450, 1246, 1132, 1035, 979, 913, 750 cm−1; HR-MS(ESI+)
calcd for C12H20O2Na+ [M + Na]+ 219.1356, found 219.1346.
Phenethyl Cyclopentanecarboxylate (6n). [CAS no. 959061-87-1]
ASSOCIATED CONTENT
■
S
* Supporting Information
Determination of pH changes, FT-IR spectra, and H and 13C
1
NMR spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
1
(27.9 mg, 64%); H NMR (400 MHz, CDCl3) δ 7.32−7.29 (m, 2H),
AUTHOR INFORMATION
Corresponding Author
*E-mail: junch@yonsei.ac.kr.
■
7.26−7.22 (m, 3H), 4.29 (t, J = 7.0 Hz, 2H), 2.94 (t, J = 7.0 Hz, 2H),
2.73−2.69 (m, 1H), 1.88−1.66 (m, 6H), 1.59−1.54 (m, 2H); 13C{1H}
NMR (100 MHz, CDCl3) δ 176.9, 138.1, 129.1, 128.6, 126.7, 64.9,
44.0, 35.3, 30.1, 25.9.
Notes
exo-Phenethyl Bicyclo[2.2.1]heptane-2-carboxylate (6o). (43.0
mg, 88%); 1H NMR (400 MHz, CDCl3) δ 7.34−7.31 (m, 2H), 7.28−
7.24 (m, 3H), 4.35−4.25 (m, 2H), 2.96 (t, J = 7.0 Hz, 2H), 2.47 (br s,
1H), 2.33−2.30 (m, 2H), 1.85−1.79 (m, 1H), 1.56−1.51 (m, 2H),
1.50−1.46 (m, 1H), 1.44−1.41 (m, 1H), 1.27−1.22 (m, 1H), 1.21−
1.14 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 176.2, 138.1,
129.1, 128.6, 126.7, 64.9, 46.6, 41.0, 36.6, 36.1, 35.3, 34.2, 29.6, 28.8;
IR (CDCl3) 3028, 2953, 2871, 1727, 1604, 1497, 1454, 1386, 1349,
1311, 1269, 1215, 1169, 1064, 745, 697, 569, 494 cm−1; HR-MS(ESI
+) calcd for C16H20O2Na+ [M + Na]+ 267.1351, found 267.1351.
Phenethyl 4,4-Dimethylpentanoate (6p). [CAS no. 213748-75-5]
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This study was supported by a grant from the Defense
Acquisition Program Administration (Grant UD120056GD)
through the Agency for Defense Development.
REFERENCES
■
(1) (a) Transition Metals for Organic Synthesis, 2nd ed.; Beller, M.,
Bolm, C., Eds.; Wiley-VCH: Weinheim, Germany, 2004. (b) Ogliaruso,
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(44.1 mg, 94%); H NMR (400 MHz, CDCl3) δ 7.33−7.29 (m, 2H),
7.25−7.22 (m, 3H), 4.29 (t, J = 7.0 Hz, 2H), 2.95 (t, J = 7.0 Hz, 2H),
2.29−2.25 (m, 2H), 1.55−1.51 (m, 2H), 0.89 (s, 9H); 13C{1H} NMR
(100 MHz, CDCl3) δ 174.5, 138.0, 129.1, 128.6, 126.7, 65.0, 38.7,
35.3, 30.3, 30.2, 29.2.
Phenethyl 3-Phenylbutanoate (6q). (46.7 mg, 87%); 1H NMR
(400 MHz, CDCl3) δ 7.33−7.29 (m, 4H), 7.27−7.19 (m, 6H), 4.26
(td, J = 7.1, 2.4 Hz, 2H), 3.27 (q, J = 7.5 Hz, 1H), 2.88 (t, J = 7.0 Hz,
2H), 2.66−2.53 (m, 2H), 1.29 (d, J = 6.9 Hz, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 172.5, 145.8, 138.0, 129.0, 128.68, 128.67, 126.9,
126.7, 126.6, 64.9, 43.1, 36.6, 35.2, 22.0; IR (CDCl3) 3063, 2934,
1731, 1603, 1495, 1455, 1161, 750, 697, 495 cm−1; HR-MS(ESI+)
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̈
+
calcd for C18H21O2 [M + H]+ 269.1536, found 269.1531.
Phenethyl Heptanoate (6r). [CAS no. 5454-11-5] (27.7 mg, 59%);
1H NMR (400 MHz, CDCl3) δ 7.32−7.29 (m, 2H), 7.25−7.21 (m,
3H), 4.30 (t, J = 7.0 Hz, 2H), 2.94 (t, J = 7.0 Hz, 2H), 2.29 (t, J = 7.4
Hz, 2H), 1.66−1.56 (m, 2H), 1.31−1.28 (m, 6H), 0.91−0.87 (m, 3H);
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dx.doi.org/10.1021/jo501828j | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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(6) For comparison, when the reaction was carried out without
sodium formate, a 15% yield of 6a was obtained (based on presumed
1). This result implies that a part of the carbonyl in 6a comes from 4a.
(7) The reaction of sodium formate (1) with 2-pyridinemethanol
(5a) under Ru3(CO)12 catalyst did not take place at all. On the basis of
this result, it can be concluded that the mechanism does not involve
the formation of 2-pyridinylmethyl formate.
(8) (a) Liberation of CO from sodium formate (1) was identified by
trapping with an Rh(I) complex. For example, a mixture of
bis(cyclooctene)rhodium(I) chloride dimer and 1 was heated for 1
h at 170 °C to give a [(CO)Rh(I)] complex in which the IR peak of
CO coordinated to Rh(I) appears at 2357 cm−1. (b) For an example
of a metal formate used as a carbonyl source, see: Pri-Bar, I.;
Buchman, O. J. Org. Chem. 1988, 53, 624.
(9) (a) Sodium hydroxide generated from 1 was determined by
measuring the pH of the aqueous solution before and after heating at
170 °C for 1 h; the initial pH of 6.9 increased to 9.1 after the reaction.
(b) The pH of the reaction mixture was measured during the reaction;
the pH of 6.52 at the initial stage gradually increased to 10.74 after 4 h.
(10) Otera, J. Chem. Rev. 1993, 93, 1449.
(11) When excess amounts (10 equiv) of isopropyl alcohol (3j) and
tert-butyl alcohol (3k) were used in this hydroesterification, the yields
of 6j and 6k were only marginally increased to 15% and 7%,
respectively.
(12) The stereochemistry of ester 6o was determined after
conversion to the corresponding benzyl ester by comparison with
known data in ref 4c.
(13) Abdur-Rashid, K.; Amoroso, D.; Guo, R.; Chen, X.; Sui-Seng,
C.; Tsang, C.-W.; Jia, W. Cationic transition metal catalysts.
WO2009055912, May 07, 2009.
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F
dx.doi.org/10.1021/jo501828j | J. Org. Chem. XXXX, XXX, XXX−XXX