Borohydride-mediated radical addition reactions of organic iodides to electron-deficient alkenes

Article abstract of DOI:10.1021/jo500464q

Cyanoborohydrides are efficient reagents in the reductive addition reactions of alkyl iodides and electron-deficient olefins. In contrast to using tin reagents, the reaction took place chemoselectively at the carbon-iodine bond but not at the carbon-bromine or carbon-chlorine bond. The reaction system was successfully applied to three-component reactions, including radical carbonylation. The rate constant for the hydrogen abstraction of a primary alkyl radical from tetrabutylammonium cyanoborohydride was estimated to be <1 × 10⁴ M^-1 s^-1 at 25 °C by a kinetic competition method. This value is 3 orders of magnitude smaller than that of tributyltin hydride.

Full text of DOI:10.1021/jo500464q

Article
pubs.acs.org/joc
Borohydride-Mediated Radical Addition Reactions of Organic Iodides
to Electron-Deficient Alkenes
Takuji Kawamoto, Shohei Uehara, Hidefumi Hirao, Takahide Fukuyama, Hiroshi Matsubara,
and Ilhyong Ryu*
Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan
S
* Supporting Information
ABSTRACT: Cyanoborohydrides are efficient reagents in the reductive addition
reactions of alkyl iodides and electron-deficient olefins. In contrast to using tin reagents,
the reaction took place chemoselectively at the carbon−iodine bond but not at the
carbon−bromine or carbon−chlorine bond. The reaction system was successfully
applied to three-component reactions, including radical carbonylation. The rate
constant for the hydrogen abstraction of a primary alkyl radical from
tetrabutylammonium cyanoborohydride was estimated to be <1 × 104 M−1 s−1 at 25
°C by a kinetic competition method. This value is 3 orders of magnitude smaller than
that of tributyltin hydride.
Scheme 1. Borohydride-Based Giese Reaction and the
Related Radical Carbonylation
INTRODUCTION
■
The tremendous development of radical chemistry during the
past three decades has led to some very efficient methods for
the synthesis of biologically active compounds.1 This develop-
ment could not have been attained without the use of tin
reagents that possess an impressively broad applicability.
Recently, hydrogen atom donors for carbon radical reductions,
silyl hydrides, germyl hydrides, thiols, and phosphite have been
employed in reductive chain reactions.2
HCHO.12 In this article, we provide the full scope and
limitations of reductive alkyl radical addition to electron-
deficient olefins in the presence of cyanoborohydride reagents.
It should be noted that recent work has shown that NHC−
boranes (N-heterocyclic carbene−boranes) can act as useful
radical mediators13 and trialkylborane (alkylcatecholborane)−
water (alcohol) can serve as hydrogen to carbon radicals.14
Whereas borohydrides are recognized as useful reagents for
hydride sources (H−), borohydrides are rarely used as radical
hydrogen donors (H•). In 1973, Barltrop and Bradbury
reported the photoreductions of iodobenzene, bromobenzene,
and chlorobenzene by sodium borohydride via radical chain
mechanisms to give benzene.3,4 In a similar case, but with
Bu3PBH2Ph, Roberts reported that the reaction of butyl iodide
with ethyl acrylate in the presence of a radical initiator afforded
the reductive addition product ethyl heptanoate in moderate
yield (50%).5,6 Later, Kurata and co-workers also reported the
reductive macrocyclization of ω-iodoacrylates using sodium
cyanoborohydride.7 The total chain mechanism was not clear at
that stage, but they advocated a radical mechanism in which
borohydride reagents served as the hydrogen donor to an
electrophilic radical. In pursuit of a potential substitute for tin
hydride, we envisioned that radical methodologies based on
borohydride as the hydrogen donor would have great potential
and would be quite useful. In our preliminary communication,8
we reported that the reductive addition of alkyl radicals to
electron-deficient olefins9,10 and the related carbonylation
reactions proceeded in the presence of cyanoborohydride
reagents as radical mediators (Scheme 1). We also reported the
radical hydroxymethylation of alkyl iodides with CO11 or
RESULTS AND DISCUSSION
■
We examined the reaction of 1-iodooctane (1a) with ethyl
acrylate (2a) as a model reaction under a variety of reaction
conditions (Table 1). When a mixture of 1a, 2a (1.5 equiv),
and NaBH4 in ethanol was irradiated with a 500 W xenon lamp
using a Pyrex flask for 3 h under argon, the expected addition
product 3aa was obtained in 10% yield, in which the simple
reduction of 1a became a predominant reaction course (entry
1). The reaction using Bu4NBH4 in benzene resulted in the
hydride reduction of 1a, and no Giese product was formed
(entry 2). Interestingly, however, the use of NaBH3CN and
Bu4NBH3CN increased the yield of 3aa (entries 3 and 4). In
Received: February 27, 2014
Published: April 9, 2014
© 2014 American Chemical Society
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a
Table 1. Optimization of Reaction Conditions
Scheme 2. Chemoselective Reactions
b
yield, %
1g, Bu4NBH3CN, which was soluble in several organic solvents,
and decane (internal standard) in benzene was irradiated with a
black light for 30 min. Then the yields of the nonane (5g;
6.6%) and 2-nonylthiopyridine (6g; 72.9%) were determined
by GC analysis of the crude product against an internal
standard (Scheme 3). To further validate the analysis, we
entry
1
1
borohydride
solvent
conditions
3aa
4aa
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
NaBH4
EtOH
C6H6
Xe, Pyrex
Xe, Pyrex
Xe, Pyrex
Xe, Pyrex
V-65, reflux
10
0
0
0
c
2
Bu4NBH4
3
NaBH3CN
Bu4NBH3CN
NaBH3CN
NaBH3CN
NaBH3CN
NaBH3CN
Bu4NBH3CN
Bu4NBH3CN
Bu4NBH3CN
NaBH3CN
NaBH3CN
MeOH
MeOH
MeOH
MeOH
EtOH
THP
75
66
72
74
75
60
69
59
51
0
9
4
16
14
10
12
2
5
6
AIBN, reflux
Scheme 3. Estimated Rate Constant for Hydrogen
Abstraction from Bu4NBH3CN
d
7
V-65, flow
8
V-65, reflux
Xe, Pyrex
Xe, Pyrex
Xe, Pyrex
Xe, Pyrex
Xe, Pyrex
9
i-PrOH
C6H6
15
16
18
0
10
11
12
13
MeCN
MeOH
MeOH
0
0
a
The reaction was conducted on a 1 mmol scale with [1a] = 0.5 M, 2a
b
(1.5 equiv), and borohydride reagent (5.0 equiv). Isolated yield after
c
flash chromatography on SiO2. Octane was formed quantitatively.
d
[1a] = 0.1 M, 2a (1.6 equiv), and NaBH3CN (3 equiv); residence
time 10 min. For details, see ref 8b.
this reaction, the 1:2 product 4aa was also formed as a
byproduct,15 but the formation of reduced product was
negligible. The thermal reaction conditions using a radical
initiator such as V-65 (2,2′-azobis(2,4-dimethylvaleronitrile))
and AIBN (2,2′-azobis(isobutyronitrile)) also gave 3aa in 72
and 74% yields, respectively (entries 5 and 6), whereas heating
to 80 °C without a radical initiator did not allow the reaction.
This strongly supported the hypothesis that a radical chain
mechanism is involved in this reaction. We found that with this
reaction it is possible to reduce the time and the amount of
cyanoborohydride under continuous microflow conditions
(entry 7).8b Some other solvents such as THP, i-PrOH,
C6H6, and MeCN also worked well (entries 8−11).
We also tested bromoalkanes and chloroalkanes as substrates.
Interestingly, no reaction took place when the corresponding 1-
bromooctane (1b) and 1-chlorooctane (1c) were used (entries
12 and 13). Thus, in the present Giese-type process
iodoalkanes appear to be crucial. To confirm this feature, a
mixture of 1-iodooctane (1a) and three types of alkyl bromides,
1d−f, were treated with ethyl acrylate (2a) (Scheme 2). As we
expected, only 1a gave the addition products, whereas three
bromides remained unchanged.
conduced the control experiment without cyanoborohydride.
The reduced product 5g was obtained in 3.8% yield. The nonyl
radical generated from PTOC ester has two competing
equations. It can react with the starting PTOC ester to provide
thio ether and another nonyl radical (self-trapping) or it can
react with cyanoborohydride to provide nonane and a borane
radical anion. The rate constant for H transfer (kH) is then
calculated in the usual way from the known rate constant for
self-trapping (kT)16 and the experimentally determined product
ratio, which was corrected for background reduction (3.8%). In
this way, the rate constant kH for the reaction of a primary alkyl
radical with Bu4NBH3CN was estimated to be <1 × 104 M−1
s−1. This is lower than the rate constants of tributyltin
hydride,17 tris(trimethylsilyl)silicon hydride,18 tributylgerma-
nium hydride,19 and an NHC−borane such as diMeImd-BH3
(1,3-dimethylimidazol-2-ylidene−borane) (Scheme 4).20
Having the identified optimal conditions in hand, we then
studied the generality of the borohydride-mediated Giese
reaction for a variety of alkyl iodides with electron-deficient
olefins (Figure 1). Primary alkyl iodides 1a,h,i,n,o reacted with
ethyl acrylate (2a) to give the corresponding esters in good
yields (Table 1, entries 1−3, 8, and 9). Under similar
conditions, secondary and tertiary iodoalkanes such as 1j−m
reacted with 2a to give the corresponding addition products in
good yields (entries 4−7). The reactions of alkyl iodides 1p,q
were chemoselective and gave the corresponding chlorine- and
Since the Giese reaction progressed even with a high
concentration of borohydride reagents, we expected that
cyanoborohydride would have a low level of ability for
hydrogen transfer to the alkyl radical. This led us to obtain
the rate constant for the reaction of a primary alkyl radical with
Bu4NBH3CN (kH) via a kinetic competition method. A
solution of the pyridine-2-thioneoxycarbonyl (PTOC) ester
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Scheme 4. Rate Constants for Hydrogen Abstraction from
Metal Hydrides
Table 2. Radical Addition Reactions of Alkyl Iodides with
Electron-Deficient Olefins using NaBH3CN
Figure 1. Electron-deficient olefins.
bromine-retaining products 3pa,qa, respectively (entries 10 and
11). These products can serve as the second radical precursors
when the ordinary tin hydride mediated system is applied. On
the other hand, aryl iodides such as iodobenzene (1r) and 1-
iodonaphthalene (1s) resulted in a lower yield, in which the
reduction course preceded the addition (entries 12 and 13).21
The reaction of 1a with methyl crotonate (2b) gave the
corresponding adduct 3ab in 67% yield (entry 14), whereas
methyl methacrylate (2c) gave a poor yield of adduct 3ac due
to the formation of significant amounts of 1:2 and 1:3 products
(entry 15). The procedure using sodium cyanoborohydride/
MeOH could be applied to the addition of 1a to acrylonitrile
(2d) and phenyl vinyl sulfone (2e) (entries 16 and 17) (Table
2).
Radical cascade reactions were examined by using hex-5-enyl
iodide (1t) and cyclopropylmethyl iodide (1u) as the substrates
(Scheme 5). When the reaction of 1u with 2a was carried out,
7ua, originating from one molecule of 1u and two molecules of
2a, was formed as the major product (66% yield, cis/trans =
67/33) (Scheme 5).22 The formation of 7ua was rationally
explained by the formation of cyclopropylcarbinyl radical A and
its rapid ring opening to give homoallyl radical B,23 which then
undergoes addition to 2a. The resulting radical C is ready to
undergo 5-exo cyclization to give D, which adds to a second
molecule of 2a and then abstracts hydrogen from cyanobor-
ohydride to give 7ua.
When the procedure was applied to a radical addition
reaction with α,β-unsaturated ketones, the reduction hampered
the desired radical addition course. To elucidate the extent of
the background reduction, we carried out a simple reduction of
octyl vinyl ketone (2f). Treating 2f with 1 equiv of NaBH3CN
in MeOH at room temperature for 6 h gave a mixture of 1-
undecen-3-ol (17%), 3-undecanone (31%), and 3-undecanol
(5%) (Scheme 6). In contrast, Bu4NBH3CN did not reduce 2f
effectively under the same conditions.
Thus, the problem surrounding the addition reaction across
α,β-unsaturated ketones was circumvented by the use of a
milder reagentBu4NBH3CN instead of NaBH3CN. The
results are summarized in Table 3. A variety of enones, 2f−i,
a
b
Isolated yield after flash chromatography on SiO2. Products
c
containing two and three molecules of 2c were also formed. 2d (3
equiv), 20 h.
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Scheme 5. Tandem Radical Processes
Table 3. Radical Addition Reactions of Alkyl Iodides with
Enones using Bu4NBH3CN
Scheme 6. Background Reduction
reacted with primary alkyl iodides 1a,h,p,v smoothly to form
the corresponding unsymmetrical ketones (entries 1−7). The
reaction of secondary and tertiary alkyl iodides 1j, k, and m
with 2h also worked well (entries 8−10).
a
b
Isolated yield after flash chromatography on SiO2. 2g (10 equiv),
Bu4NBH3CN (5 equiv).
We also applied a radical reaction system using
Bu4NBH3CN−AIBN for the corresponding three-component
coupling reaction with the incorporation of CO, for which
tributyltin hydride or TTMSS was used in the original
processes.24 When a mixture of 1-iodooctane (1a), CO, and
methyl acrylate (2a′) (2 equiv) with Bu4NBH3CN was
subjected to the radical reaction conditions, 1,4-dicarbonyl
compound 8aa′ was obtained in 62% yield (Table 4, entry 1).
Similarly, the reaction of secondary and tertiary alkyl iodides,
CO, and acrylate gave the corresponding three-component
coupling product. The reaction using ethyl vinyl ketone (2h)
with 1-iodoheptane (1w) took place to give 1,4-diketone 8wh
in 51% yield.
Mechanistic Insight. Corey employed sodium borohydride
in the catalytic tin hydride reduction of various alkyl halides,25
and Stork employed sodium cyanoborohydride as a milder
reagent.26 The role of borohydride reagent in these studies is
the conversion of tributyltin halides, formed during the course
of the reaction, to tributyltin hydride. In the present
borohydride-mediated Giese reaction system, the generated
nucleophilic alkyl radical smoothly adds to an electron-deficient
olefin, such as methyl acrylate, to give an α-carbonyl radical,27
which would abstract hydrogen directly from a cyanoborohy-
dride anion to give the product and a cyanoborane radical
anion (BH2CN•−). In the photoreaction system using the
PTOC ester 1g and acrylonitrile in the presence of
Bu4NBH3CN, the Giese addition product 3gd was obtained
in 9% yield along with group transfer product 9gd (14%). As a
control reaction, we tried the reduction of 9gd in the presence
of Bu4NBH3CN, but after 12 h, no reduction product was
observed (Scheme 7). These results supported that the
mechanism involves a direct hydrogen transfer to adduct
radical rather than an indirect mechanism via an initially formed
atom or group transfer adduct.
To gain further insight into the hydrogen delivery step, we
carried out theoretical calculations using the Gaussian program.
All calculations were performed at the BHandHLYP/6-
311+G** level (Figure 2).28 After complexation hydrogen
•
abstraction of the α-ester radical (CH3OCOCH2 ) from
cyanoborohydride is quite smooth (activation energy 29.1 kJ
mol−1). On the other hand, the activation energy for hydrogen
abstraction of ethyl radical from cyanoborohydride (60.7 kJ
mol−1) is twice that of the α-ester radical. This would be
rationalized by the polar effect29 that the nucleophilic
cyanoborohydride anion would react with electrophilic α-
ester radical more favorably. It is known that the resulting
cyanoborane radical anion exhibits a nucleophilic character
(Figure 3).30
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delivery from cyanoborohydride anion, preventing radical
polymerization.
Table 4. Three-Component Coupling Reactions
EXPERIMENTAL SECTION
■
Instrumentation and Chemicals. 1H NMR spectra were
recorded at 500 or 400 MHz. 13C NMR spectra were recorded at
125 or 100 MHz and referenced to the solvent peak at 77.00 ppm.
Melting points were measured in capillaries. HRMS data were
obtained by EI using a double-focusing mass spectrometer. Photolysis
was carried out using a Pyrex round-bottomed flask and using a 500 W
xenon short arc lamp. Thin-layer chromatography (TLC) was
performed and visualized by fluorescence quenching under UV light
or by staining with p-anisaldeyde/AcOH/H2SO4/EtOH or 12MoO3·
H3PO4/EtOH. The products were purified by flash chromatography
on silica gel and, if necessary, were further purified by recycling
preparative HPLC equipped with GPC columns (JAIGEL-1H +
JAIGEL-2H columns) using CHCl3 as eluent. EtOH, MeOH, and
PhH were dried and purified by standard distillation techniques. Alkyl
iodides 1h,i,k,l,p,u were prepared from the corresponding alcohol.
1o,t,v were prepared from the corresponding bromides with sodium
iodide in dry acetone. 1q was prepared from 4-bromobenzyl alcohol
and 1,5-diiodopentane by the Williamson method using sodium
hydride. 2f was prepared via 1-undecen-3-ol, which was obtained by a
Grignard reaction of n-octylmagnesium bromide with acrolein,
followed by Jones oxidation. Alkenes 2a−e,g−i were distilled prior
to use. Other reagents were commercially available and were used
without further purification.
a
Isolated yield after flash chromatography on SiO2.
Scheme 7. Control Experiment
Typical Procedure A (Table 2, Entry 1). Using a magnetic
stirring bar, 1-iodooctane (1a; 239.5 mg, 1.0 mmol), ethyl acrylate (2a;
150.0 mg, 1.5 mmol), NaBH3CN (311.7 mg, 5.0 mmol), and methanol
(2.0 mL) were mixed in a Pyrex 10 mL round-bottomed flask, and
then the mixture was irradiated by a xenon arc lamp (500 W) with
stirring for 3 h under argon. A saturated ammonium chloride aqueous
solution (1 mL) was added to the reaction mixture. The mixture was
poured into water (20 mL) and extracted with Et2O (20 mL × 3). The
organic layer was washed with brine and dried over Na2SO4 and then
filtered and concentrated in vacuo. The residue was purified by flash
chromatography on silica gel (gradient from hexane/Et2O 20/1 to
hexane/Et2O 10/1) to give 3aa (160.7 mg, 75%).
Typical Procedure B (Table 3, Entry 1). Using a magnetic
stirring bar, Bu4NBH3CN (311.7 mg, 1.5 mmol), 1a (118.6 mg, 0.49
mmol), 2h (127.1 mg, 1.5 mmol), and methanol (1.0 mL) were mixed
in a Pyrex 10 mL round-bottomed flask, and then the mixture was
irradiated by a xenon arc lamp (500 W) with stirring for 6 h under
argon. The solvent was removed under reduced pressure. The residue
was purified by flash chromatography on silica gel (hexane/Et2O 20/
1) to give 3ah (64.9 mg, 67%).
Taking these results into consideration, we proposed a
reaction mechanism for the cyanoborohydride-mediated Giese
reaction (Scheme 8). Radical initiation generates the alkyl
radical A, which adds to the electron-deficient alkene to give
radical B. B abstracts hydrogen from cyanoborohydride to give
the product.31 The resulting cyanoborane radical anion C
abstracts iodine atom to give an alkyl radical.32 Although we do
not yet know the rate constants of iodine abstraction from alkyl
iodides with BH2CN radical anion, alkyl radical formation from
alkyl bromides with BH3 radical anion is known to proceed
with rate constants on the order of 108.33
Typical Procedure C (Table 4, Entry 1). Using a magnetic
stirring bar, AIBN (8.7 mg, 0.053 mmol), Bu4NBH3CN (721.5 mg,
2.56 mmol), 1a (120.1 mg, 0.5 mmol), 2a′ (170.1 mg, 1.98 mmol),
and methanol (30 mL) were mixed in a 100 mL stainless steel
autoclave. The autoclave was closed, purged three times with carbon
monoxide, pressurized with 90 atm of CO, and then heated at 80 °C
for 19 h. Excess CO was discharged at room temperature. A saturated
ammonium chloride aqueous solution (10 mL) was added to the
reaction mixture. The mixture was poured into water (50 mL) and
extracted with Et2O (3 × 50 mL). The organic layer was washed with
brine and dried over Na2SO4 and then filtered and concentrated in
vacuo. The residue was purified by flash chromatography on silica gel
(hexane/AcOEt 30/1) to give 8aa′ (70.3 mg, 62%).
CONCLUSION
■
In conclusion we have demonstrated that the Giese reaction
using alkyl iodides as starting materials and cyanoborohydrides
as a hydrogen source proceeds well without the use of tin
hydride or its precursors. The process can be applied to
carbonylative three-component coupling reactions. We have
determined the rate constant of H abstraction by primary alkyl
radical from tetrabutylammonium cyanoborohydride to be <1
× 104 M−1 s−1 at 25 °C, by the pyridine-2-thioneoxycarbonyl
(PTOC) competition kinetic method at a single concentration
point. DFT calculations predicted that cyanoborohydride reacts
more smoothly with an electrophilic radical than with an
ordinary alkyl radical, which is in good agreement with the
observation that the adduct radical undergoes quick hydrogen
Spectral Data for Compounds. Ethyl Undecanoate (3aa).22
Yield: 161 mg (75%). 1H NMR (CDCl3, 500 MHz): δ 0.88 (t, J = 6.9
Hz, 3H), 1.16−1.38 (m, 17H), 1.55−1.68 (m, 2H), 2.29 (t, J = 7.6 Hz,
2H), 4.12 (q, J = 7.2 Hz, 2H). 13C NMR (CDCl3, 125 MHz): δ 14.1,
14.2, 22.6, 25.0, 29.1, 29.2, 29.3, 29.4, 29.5, 31.9, 34.4, 60.1, 173.9. IR
(neat): 1739 cm−1. MS (EI; m/z (relative intensity)): 214 (M+, 9),
169 (24), 101 (69), 88 (100), 73 (51), 70(49), 61 (37), 60 (35), 57
(33), 55 (48).
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Figure 2. Optimized structures and energy barriers for hydrogen abstraction of α-carbonyl and ethyl radical from cyanoborohydride.
Scheme 8. Possible Radical Chain Mechanism
Figure 3. Polar effect for hydrogen abstraction.
Ethyl 5-Ethylheptanoate (3ha). Yield: 94 mg (51%). 1H NMR
(CDCl3, 500 MHz): δ 0.84 (t, J = 7.6 Hz, 6H), 1.18 (sext, J = 6.1 Hz,
1H), 1.22−1.34 (m, 9H), 1.55−1.64 (m, 2H), 2.28 (t, J = 7.6 Hz, 2H),
4.13 (q, J = 7.0 Hz, 2H). 13C NMR (CDCl3, 125 MHz): δ 10.8, 14.2,
22.2, 25.2, 32.1, 34.7, 40.1, 60.0, 173.7. IR (neat): 1739 cm−1. MS (EI;
m/z (relative intensity)): 186 (M+, 0.3), 157 (12), 123 (13), 111(14),
101(15), 88 (100), 83 (40), 73 (18), 70 (33), 60 (21), 55 (47).
HRMS (EI): calcd for C11H22O2 (M+) 186.1620, found 186.1612.
142.3, 173.50. IR (neat): 1737 cm−1. MS (EI; m/z (relative
intensity)): 175 (M+−OEt, 14), 174 (29), 130 (59), 105 (13), 101
(13), 91 (100), 88 (35), 77 (21), 65 (17).
Ethyl 6-Phenylhexanoate (3la).34 Yield: 146 mg (71%). H NMR
Ethyl 3-Cyclohexylpropionate (3ja).35 Yield: 130 mg (70%). H
1
1
(CDCl3, 500 MHz): δ 1.25 (t, J = 7.1 Hz, 3H), 1.33−1.42 (m, 2H),
1.60−1.68 (m, 4H), 2.29 (t, J = 7.6 Hz, 2H), 2.61 (t, J = 7.8 Hz, 2H),
4.12 (q, J = 7.0 Hz, 2H), 7.15−7.31 (m, 5H). 13C NMR (CDCl3, 125
MHz): δ 14.1, 24.7, 28.6, 31.0, 34.1, 35.6, 60.0, 125.5, 128.08, 128.14,
NMR (CDCl3, 500 MHz): δ 0.81−0.91 (m, 2H), 1.05−1.29 (m, 7H),
1.48−1.55 (m, 2H), 1.60−1.74 (m, 5H), 2.30 (t, J = 8.0 Hz, 2H), 4.12
(q, J = 7.0 Hz, 2H). 13C NMR (CDCl3, 125 MHz): δ 14.0, 26.0, 26.3,
31.7, 32.2, 32.8, 37.0, 59.8, 173.8. IR (neat): 1735 cm−1. MS (EI; m/z
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(relative intensity)): 184 (M+, 1), 139 (14), 121 (20), 101 (100), 88
(81), 73 (42), 55 (95).
Methyl 2-Methylundecanoate (3ac).22 Yield: 44 mg (21%).1H
NMR (CDCl3, 500 MHz): δ 0.88 (t, J = 7.1 Hz, 3H), 1.14 (d, J = 6.9
Hz, 3H), 1.20−1.33 (m, 14H), 1.34−1.45 (m, 1H), 1.59−1.70 (m,
1H), 2.43 (sext, J = 7.0, 7.0 Hz, 1H), 3.67 (s, 3H). 13C NMR (CDCl3,
125 MHz): δ 14.1, 17.0, 22.7, 27.2, 29.3, 29.47, 29.49, 29.53, 31.9,
33.8, 39.4, 51.4, 177.4. IR (neat): 1741 cm−1. MS (EI; m/z (relative
intensity)): 214 (M+, 5), 157 (17), 143 (13), 101 (57), 89 (13), 88
(100), 71 (12), 69 (23), 59 (23), 57 (48), 55 (40).
Ethyl 4-Butyloctanoate (3ka). Yield: 171 mg (71%). 1H NMR
(CDCl3, 500 MHz): δ 0.89 (t, J = 7.1 Hz, 6H), 1.12−1.32 (m, 16H),
1.55−1.62 (m, 2H), 2.24−2.30 (m, 2H), 4.12 (q, J = 7.2 Hz, 2H). 13C
NMR (CDCl3, 125 MHz): δ 14.0, 14.2, 23.0, 28.6, 28.7, 31.7, 32.9,
36.8, 60.0, 174.0. IR (neat): 1739 cm−1. MS (EI; m/z (relative
intensity)): 228 (M+, 2), 183 (16), 141 (55), 129 (57), 101 (100), 88
(81), 85 (63), 83 (62), 73 (69), 71 (69), 70 (59), 57 (75), 55 (85).
HRMS (EI): calcd for C14H28O2 (M+) 228.2089, found 228.2083.
Ethyl 4-Methyl-6-phenylhexanoate (3la). Yield: 169 mg (68%).
1H NMR (CDCl3, 500 MHz): δ 0.95 (d, J = 5.5 Hz, 3H), 1.25 (t, J =
5.5 Hz, 3H), 1.42−1.54 (m, 3H), 1.59−1.67 (m, 1H), 1.68−1.78 (m,
1H), 2.21−2.38 (m, 2H), 2.54−2.70 (m, 2H) 4.12 (q, J = 7.2 Hz, 2H),
7.14−7.20 (m, 3H), 7.24−7.30 (m, 2H). 13C NMR (CDCl3, 125
MHz): δ 14.2, 19.2, 31.8, 32.0, 32.1, 33.3, 38.5, 60.2, 125.6, 128.3,
128.3, 142.7, 174.0. IR (neat): 1736 cm−1. MS (EI; m/z (relative
intensity)): 234 (M+, 3), 144 (20), 105 (22), 101 (24), 91 (100), 88
(50), 73 (29). HRMS (EI): calcd for C15H22O2 (M+) 234.1620, found
234.1624.
Undecanenitrile (3ad).38 Yield: 95 mg (69%). H NMR (CDCl3,
1
500 MHz): δ 0.89 (t, J = 6.9 Hz, 3H), 1.21−1.37 (m, 12H), 1.38−1.48
(m, 2H), 1.66 (quint, J = 7.5 Hz, 2H), 2.33 (t, J = 7.3 Hz, 2H). 13C
NMR (CDCl3, 125 MHz): δ 14.0, 17.0, 22.6, 25.3, 28.6, 28.7, 29.1,
29.2, 29.4, 31.8, 119.7. IR (neat): 2926, 2247 cm−1. MS (EI; m/z
(relative intensity)): 152 (M+ − CH3, 4), 138 (21), 124 (53), 110
(78), 96 (94), 82 (100), 69 (82), 57 (89), 55 (97).
(Decane-1-sulfonyl)benzene (3ae).36 Yield: 196 mg (69%). 1H
NMR (CDCl3, 500 MHz): δ 0.87 (t, J = 6.9 Hz, 3H), 1.20−1.38 (m,
14H), 1.66−1.75 (m, 2H), 3.06−3.11 (m, 2H), 7.54−7.59 (m, 2H),
7.63−7.68 (m, 1H), 7.89−7.93 (m, 2H). 13C NMR (CDCl3, 125
MHz): δ 13.9, 22.5, 28.1, 28.8, 29.0, 29.2, 31.7, 56.08, 56.13, 127.9,
129.06, 129.08, 133.5, 139.1.
Ethyl 3-(Adamantan-1-yl)propionate (3ma).36 Yield: 173 mg
1
1
(73%). H NMR (CDCl3, 500 MHz): δ 1.26 (t, J = 7.1 Hz, 3H),
Ethyl 4-Cyclopentylbutyrate (3ta). Yield: 54 mg (56%). H NMR
1.37−1.49 (m, 7H), 1.58−1.65 (m, 3H), 1.66−1.74 (m, 3H), 1.95 (m,
3H), 2.22−2.28 (m, 2H) 4.12 (q, J = 7.2 Hz, 2H). 13C NMR (CDCl3,
125 MHz): δ 14.1, 28.1, 28.4, 31.8, 37.0, 38.9, 41.9, 60.1, 174.6. IR
(neat): 1738 cm−1. MS (EI; m/z (relative intensity)): 236 (M+, 34),
191 (33), 135 (100), 107 (39), 93 (51), 91 (40), 79 (54), 67 (31).
(CDCl3, 500 MHz): δ 1.01−1.13 (m, 2H), 1.26 (t, J = 7.1 Hz, 3H),
1.29−1.35 (m, 2H), 1.44−1.67 (m, 6H), 1.68−1.80 (m, 3H), 2.29 (t, J
= 7.6 Hz, 2H), 4.13 (q, J = 7.2 Hz, 2H). 13C NMR (CDCl3, 125
MHz): δ 14.2, 24.2, 25.1, 32.6, 34.6, 35.6, 39.8, 60.1, 173.9. IR (neat):
1738 cm−1. MS (EI; m/z (relative intensity)): 184 (M+, 1), 141 (33),
121 (35), 101 (45), 88 (100), 70 (55), 60 (52), 55 (52). HRMS (EI):
calcd for C11H20O2 (M+) 184.1463, found 184.1457.
1
Ethyl 4-(Trimethylsilyl)butanoate (3na). Yield: 76 mg (41%). H
NMR (CDCl3, 500 MHz): δ −0.01 (s, 9H), 0.48−0.54 (m, 2H), 1.26
(t, J = 7.1 Hz, 3H), 1.59−1.67 (m, 2H), 2.31 (t, J = 7.3 Hz, 2H), 4.13
(q, J = 7.2 Hz, 2H). 13C NMR (CDCl3, 125 MHz): δ −1.8, 14.2, 16.4,
19.8, 38.0, 60.1, 173.7. IR (neat): 1738 cm−1. MS (EI; m/z (relative
intensity)): 143 (M+−OEt, 4), 117 (45), 101 (11), 73 (100), 59 (11).
HRMS (EI): calcd for C9H20O2Si (M+) 188.1233, found 188.1232.
2-(3-(Ethoxycarbonyl)propyl)cyclopentanecarboxylic Acid Ethyl
Ester (7ua). Obtained as a cis/trans isomer mixture in a 67/33 ratio, as
determined by GC analysis of the crude reaction mixture before being
submitted to chromatographic separation. Yield: 87 mg (66%). The cis
and trans isomers of 7ua were separated using a preparative HPLC.
Cis isomer: 1H NMR (CDCl3, 500 MHz) δ 1.19−1.28 (m, 7H), 1.33−
1.49 (m, 2H), 1.50−1.74 (m, 3H), 1.75−1.98 (m, 4H), 2.02−2.12 (m,
1H), 2.21−2.34 (m, 2H), 2.78−2.85 (m, 1H), 4.06−4.17 (m, 4H); 13C
NMR (CDCl3, 125 MHz) δ 14.2, 14.3, 23.8, 24.0, 28.4, 30.6, 31.0,
34.5, 43.4, 47.5, 59.8, 60.2, 173.6, 175.4; IR (neat) 1733 cm−1; MS (EI;
m/z (relative intensity)) 211 (M+ − OEt, 50), 183 (30), 169 (69), 136
(55), 119 (42), 114 (53), 95 (100), 73 (41), 67 (67), 55 (51); HRMS
(EI): calcd for C14H24O4 (M+) 256.1675, found 256.1683. Trans
Ethyl 5,5-Diethoxypentanoate (3oa).37 Yield: 153 mg (70%). H
1
NMR (CDCl3, 500 MHz): δ 1.20 (t, J = 7.1 Hz, 6H), 1.25 (t, J = 7.1
Hz, 3H), 1.61−1.74 (m, 4H), 2.33 (t, J = 7.3 Hz, 2H), 3.45−3.53 (m,
2H), 3.61−3.68 (m, 2H), 4.13 (q, J = 7.2 Hz, 2H), 4.49 (t, J = 5.5 Hz,
1H). 13C NMR (CDCl3, 125 MHz): δ 14.1, 15.1, 20.1, 32.8, 33.8, 60.0,
60.6, 102.4, 173.3. IR (neat): 1737 cm−1. MS (EI; m/z (relative
intensity)): 173 (M+ − OEt, 6), 127 (11), 103 (11), 99 (16), 97 (32),
85 (100), 75 (11), 73 (13), 70 (22), 57 (46).
Ethyl 11-Chloroundecanoate (3pa). Yield: 163 mg (67%). 1H
NMR (CDCl3, 500 MHz): δ 1.20−1.34 (m, 10 H), 1.25 (t, J = 7.1 Hz,
3H), 1.36−1.46 (m, 2H), 1.56−1.66 (m, 2H), 1.76 (quint, J = 7.1 Hz,
2H), 2.28 (t, J = 7.6 Hz, 2H), 3.52 (t, J = 6.7 Hz, 2H), 4.12 (q, J = 7.0
Hz, 2H); 13C NMR (CDCl3, 125 MHz): δ 14.2, 24.9, 26.8, 28.8, 29.0,
29.1, 29.2, 29.3, 32.5, 34.2, 45.0, 60.0, 173.7. IR (neat): 1737 cm−1. MS
(EI; m/z (relative intensity)): 248 (M+, 1), 205 (12), 203 (21), 115
(14), 101 (64), 88 (100), 83 (22), 73 (41), 70 (47), 60 (45), 57 (27),
55 (68). HRMS (EI): calcd for C13H2535ClO2 (M+) 248.1543, found
248.1546.
1
isomer: H NMR (CDCl3, 500 MHz) δ 1.16−1.35 (m, 8H), 1.47−
1.74 (m, 5H), 1.78−1.97 (m, 3H), 2.05−2.15 (m, 1H), 2.23−2.35 (m,
3H), 4.09−4.18 (m, 4H); 13C NMR (CDCl3, 125 MHz) δ 14.2, 14.3,
23.6, 24.7, 30.3, 32.5, 34.5, 34.8, 44.0, 50.4, 60.18, 60.20, 173.6, 176.6;
IR (neat) 1732 cm−1; MS (EI; m/z (relative intensity)) 211 (M+ −
OEt, 57), 182 (58), 169 (61), 136 (100), 95 (97), 67 (72), 55 (48);
HRMS (EI) calcd for C14H24O4 (M+) 256.1675, found 256.1669.
2-Dodecanone (3ag).40 Yield: 65 mg (67%). H NMR (CDCl3,
1
500 MHz): δ 0.88 (t, J = 6.9 Hz, 3H), 1.25−1.38 (m, 14H), 1.50−1.62
(m, 2H), 2.13 (s, 3H), 2.41 (t, J = 7.6 Hz, 2H). 13C NMR (CDCl3,
125 MHz): δ 14.1, 22.6, 23.8, 29.1, 29.3, 29.36, 29.43, 29.5, 29.8, 31.9,
43.8, 209.3. IR (neat): 1719 cm−1. MS (EI; m/z (relative intensity)):
184 (M+, 8), 85 (20), 82 (12), 71 (44), 58 (100), 55 (24).
Ethyl 8-((4-Bromobenzyl)oxy)octanoate (3qa). Yield: 149 mg
1
(67%). H NMR (CDCl3, 500 MHz): δ 1.25 (t, J = 7.1 Hz, 3H),
1.28−1.40 (m, 6H), 1.55−1.66 (m, 4H), 2.28 (t, J = 7.6 Hz, 2H), 3.44
(t, J = 6.6 Hz, 2H), 4.12 (q, J = 7.2, 2H), 4.43 (s, 2H), 7.16−7.24 (m,
2H), 7.42−7.48 (m, 2H). 13C NMR (CDCl3, 125 MHz): δ 14.4, 24.8,
25.9, 28.9, 29.0, 29.5, 34.2, 60.0, 70.4, 71.9, 121.1, 129.10, 131.3, 137.6,
173.6. IR (neat): 1735 cm−1. MS (EI; m/z (relative intensity)): 356
(M+, 2), 277 (18), 207 (15), 185 (13), 171 (100), 169 (74), 125 (42),
101 (58), 97 (34), 90 (31), 88 (38), 55 (50). HRMS (EI): calcd for
C17H2579BrO3 (M+) 356.0987, found 356.0991.
3-Tridecanone (3ah).39 Yield: 53 mg (56%). H NMR (CDCl3,
1
500 MHz): δ 0.88 (t, J = 6.9 Hz, 3H), 1.05 (t, J = 7.3 Hz, 3H), 1.20−
1.34 (m, 14H), 1.52−1.61 (m, 2H), 2.39 (t, J = 7.3 Hz, 2H), 2.42 (q, J
= 7.3, 2H). 13C NMR (CDCl3, 125 MHz): δ 7.8, 14.1, 22.7, 24.0,
29.27, 29.29, 29.4, 29.5, 29.6, 31.9, 35.8, 42.4, 212.0. IR (neat): 1718
cm−1. MS (EI; m/z (relative intensity)): 198 (M+, 2), 169 (47), 95
(17), 85 (45), 72 (100), 57 (97), 55 (27).
Methyl 3-Methylundecanoate (3ab).22 Yield: 151 mg (67%).1H
NMR (CDCl3, 500 MHz): δ 0.88 (t, J = 6.9 Hz, 3H), 0.93 (d, J = 6.4
Hz, 3H), 1.13−1.35 (m, 14H), 1.88−1.99 (m, 1H), 2.10 (dd, J = 14.7,
7.8 Hz, 1H), 2.30 (dd, J = 14.7, 6.0 Hz, 1H), 3.66 (s, 3H). 13C NMR
(CDCl3, 125 MHz): δ 14.1, 19.7, 22.7, 26.9, 29.3, 29.6, 29.7, 30.3,
31.9, 36.7, 41.7, 51.3, 173.8. IR (neat): 1742 cm−1. MS (EI; m/z
(relative intensity)): 214 (M+, 6), 183 (14), 157 (11), 101 (47), 74
(100), 69 (28), 59 (26).
1
7-(1,3-Dioxan-2-yl)-3-heptanone (3vh). Yield: 76 mg (73%). H
NMR (CDCl3, 500 MHz): δ 1.04 (t, J = 7.4 Hz, 3H), 1.30−1.43 (m,
3H), 1.55−1.63 (m, 4H), 2.01−2.12 (m, 1H), 2.37−2.44 (m, 4H),
3.71−3.79 (m, 2H), 4.06−4.12 (m, 2H), 4.5 (t, J = 5.0 Hz, 1H). 13C
NMR (CDCl3, 125 MHz): δ 7.7, 23.5, 23.6, 25.7, 34.8, 35.7, 42.1, 66.8,
102.0, 211.5 (two signals are accidentally superimposed on each
other). IR (neat): 1714 cm−1. MS (EI; m/z (relative intensity)): 200
4005
dx.doi.org/10.1021/jo500464q | J. Org. Chem. 2014, 79, 3999−4007

The Journal of Organic Chemistry
Article
(M+, 4), 128 (44), 113 (15), 87 (100), 67 (42), 57 (60). HRMS (EI):
calcd for C11H20O3 (M+) 200.1412, found 200.1404.
1-(1,3-Dioxan-2-yl)-5-tridecanone (3vf). Yield: 95 mg (67%). H
13C NMR (CDCl3, 125 MHz): δ 25.5, 25.8, 27.6, 28.4, 34.9, 50.6,
51.6, 173.3, 211.9.
1
Ethyl 4-Oxo-4-(1-adamantyl)butanoate (8ma).42 Yield: 71 mg
1
NMR (CDCl3, 500 MHz): δ 0.88 (t, J = 7.1 Hz, 3H), 1.20−1.43 (m,
(54%). H NMR (CDCl3, 500 MHz): δ 1.25 (t, J = 7.1 Hz, 3H),
13H), 1.51−1.63 (m, 6H), 2.00−2.12 (m, 1H), 2.34−2.42 (m, 4H),
1.64−1.72 (m, 3H), 1.72−1.78 (m, 3H), 1.82−1.86 (m, 6H), 2.01−
2.08 (m, 3H), 2.55 (t, J = 6.7 Hz, 2H), 2.77 (t, J = 6.3 Hz, 2H), 4.12
(q, J = 7.2 Hz, 2H). 13C NMR (CDCl3, 125 MHz): δ 14.1, 27.9, 28.5,
31.0, 36.5, 38.2, 46.1, 60.4, 173.0, 213.7.
3.71−3.79 (m, 2H), 4.05−4.12 (m, 2H), 4.51 (t, J = 5.3 Hz, 1H). 13
C
NMR (CDCl3, 125 MHz): δ 14.0, 22.6, 23.5, 23.6, 23.8, 25.8, 29.1,
29.2, 29.3, 31.8, 34.9, 42.6, 42.8, 66.8, 102.0, 211.3. IR (KBr): 1705
cm−1. MS (EI; m/z (relative intensity)): 284 (M+, 1), 128 (49), 110
(12), 87 (100), 57 (21). HRMS (EI): calcd for C17H32O3 (M+)
284.2351, found 284.2350.
3,6-Tridecanedione (8wh).43 Yield: 54 mg (51%). 1H NMR
(CDCl3, 500 MHz): δ 0.88 (t, J = 7.1 Hz, 3H), 1.06 (t, J = 7.3 Hz,
3H), 1.27 (br, 8H), 1.56 (br, 2H), 2.45 (t, J = 7.4 Hz, 2H), 2.49 (q, J =
7.9 Hz, 2H), 2.68 (s, 4H). 13C NMR (CDCl3, 125 MHz): δ 7.8, 14.0,
22.6, 23.8, 29.0, 29.1, 31.6, 35.6, 35.9, 36.0, 42.9, 209.8, 210.1.
5-Methyl-3-tridecanone (3ai).41 Yield: 70 mg (66%). 1H NMR
(CDCl3, 500 MHz): δ 0.83−0.92 (m, 6H), 1.05 (t, J = 7.3 Hz, 3H),
1.10−1.35 (m, 14H), 1.94−2.06 (m, 1H), 2.20 (dd, J = 15.6, 7.8 Hz,
1H), 2.34−2.48 (m, 3H). 13C NMR (CDCl3, 125 MHz): δ 7.8, 14.1,
19.9, 22.6, 27.0, 29.27, 29.30, 29.6, 29.8, 31.9, 36.4, 37.0, 49.9, 211.7.
IR (neat): 1716 cm−1. MS (EI; m/z (relative intensity)): 212 (M+, 1),
183 (19), 99 (28), 86 (48), 72 (47), 57 (100), 55(21).
ASSOCIATED CONTENT
* Supporting Information
Text and figures giving kinetic experiments and calculations,
■
S
1
deuterium labeling experiments, DFT calculations, and H and
7-Phenyl-2-heptanone (3hh). Yield: 69 mg (69%). 1H NMR
(CDCl3, 500 MHz): δ 1.03 (t, J = 7.3 Hz, 3H), 1.27−1.36 (m, 2H),
1.55−1.66 (m, 4H), 2.34−2.42 (m, 4H), 2.59 (t, J = 7.8 Hz, 2H),
7.12−7.19 (m, 3H), 7.22−7.29 (m, 2H). 13C NMR (CDCl3, 125
MHz): δ 7.8, 23.6, 28.8, 31.2, 35.7, 35.8, 42.2, 125.6, 128.2, 128.3,
142.4, 211.6. IR (neat): 3027, 2934, 1714 cm−1. MS (EI; m/z (relative
intensity)): 204 (M+, 1), 186 (23), 175 (19), 130 (23), 91 (100), 85
(26), 71 (18), 57 (76). HRMS (EI): calcd for C14H20O (M+)
204.1514, found 204.1513.
13C NMR spectra for all products. This material is available free
of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail for I.R.: ryu@c.s.osakafu-u.ac.jp.
■
Notes
13-Chloro-3-tridecanone (3ph). Yield: 74 mg (65%). 1H NMR
(CDCl3, 500 MHz): δ 1.05 (t, J = 7.3 Hz, 3H), 1.20−1.36 (m, 10H),
1.37−1.47 (m, 2H), 1.51−1.62 (m, 2H), 1.76 (quint, J = 7.1 Hz, 2H)
2.36−2.45 (m, 4H), 3.53 (t, J = 6.9 Hz, 2H). 13C NMR (CDCl3, 125
MHz): δ 7.8, 23.9, 26.8, 28.8, 29.2, 29.29, 29.31, 29.33, 32.6, 35.8, 42.4,
45.1, 211.9. IR (neat): 1715 cm−1. MS (EI; m/z (relative intensity)):
232 (M+, 2), 203 (35), 85 (36), 73 (100), 69 (29), 57 (68), 55 (49).
HRMS (EI): calcd for C13H2535ClO (M+) 232.1594, found 232.1601.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by a Grant-in-Aid for Scientific
Research from the MEXT and the JSPS. T.K. acknowledges the
Research Fellowship of the JSPS for Young Scientists.
1-Cyclohexyl-3-pentanone (3jh).22 Yield: 40 mg (48%). H NMR
1
REFERENCES
■
(CDCl3, 500 MHz): δ 0.82−0.95 (m, 2H), 1.05 (t, J = 7.3 Hz, 3H),
1.08−1.26 (m, 4H), 1.42−1.50 (m, 2H), 1.60−1.73 (m, 5H), 2.37−
2.46 (m, 4H). 13C NMR (CDCl3, 125 MHz): δ 7.9, 26.2, 26.5, 31.3,
33.1, 35.8, 37.3, 40.0, 212.1. IR (neat): 1717 cm−1. MS (EI; m/z
(relative intensity)): 168 (M+, 9), 139 (52), 121 (94), 96 (87), 85
(56), 81 (67), 72 (93), 57 (99), 55 (100).
(1) Radicals in Organic Synthesis; Renaud, P., Sibi, M. P., Eds.; Wiley-
VCH: Weinheim, Germany, 2001.
(2) For a review of tin-free reductive radical reactions, see: Studer, A.;
Amrein, S. Synthesis 2002, 835−849.
(3) Barltrop, J. A.; Bradbury, D. J. Am. Chem. Soc. 1973, 95, 5085−
5086.
6-Butyl-3-decanone (3kh). Yield: 70 mg (66%). 1H NMR (CDCl3,
500 MHz): δ 0.89 (t, J = 6.9 Hz, 6H), 1.05 (t, J = 7.3 Hz, 3H), 1.16−
1.40 (m, 14H), 1.49−1.56 (m, 2H), 2.34−2.39 (m, 2H), 2.40 (q, J =
7.3 Hz, 2H). 13C NMR (CDCl3, 125 MHz): δ 7.9, 14.1, 23.1, 27.6,
28.81, 33.1, 35.8, 37.0, 39.8, 212.2. IR (neat): 1717 cm−1. MS (EI; m/z
(relative intensity)): 183 (M+ − Et, 32), 165 (14), 140 (33), 109 (26),
85 (89), 72 (64), 57 (100). HRMS (EI): calcd for C14H28O (M+)
212.2140, found 212.2142.
(4) (a) Groves, J. T.; Ma, K. W. J. Am. Chem. Soc. 1974, 96, 6527−
6529. (b) Groves, J. T.; Kittisopikul, S. Tetrahedron Lett. 1977, 18,
4291−4294. (c) Abeywickrema, A. N.; Beckwith, A. L. J. Tetrahedron
Lett. 1986, 27, 109−112. (d) Kropp, M.; Schuster, G. B. Tetrahedron
Lett. 1987, 28, 5295−5298. (e) Liu, Q.; Han, B.; Zhang, W.; Yang, L.;
Liu, Z.-L.; Yu, W. Synlett 2005, 2248−2250.
(5) Baban, J. A.; Roberts, B. P. J. Chem. Soc., Perkin Trans. 2 1988,
1195−1200.
1-(Adamantan-1-yl)-3-pentanone (3mh). Yield: 62 mg (55%). 1H
NMR (CDCl3, 500 MHz): δ 1.04 (t, J = 7.4 Hz, 3H), 1.30−1.37 (m,
2H), 1.41−1.48 (m, 6H), 1.57−1.64 (m, 3H), 1.66−1.74 (m, 3H),
1.90−1.97 (m, 3H), 2.31−2.37 (m, 2H), 2.42 (q, J = 7.3 Hz, 2H). 13C
NMR (CDCl3, 125 MHz): δ 8.0, 28.6, 31.8, 35.8, 36.0, 37.1, 38.0, 42.2,
212.6. IR (neat): 1715 cm−1. MS (EI; m/z (relative intensity)): 220
(M+, 3), 202 (28), 191 (67), 173 (37), 135 (100), 107 (21), 93 (39),
91 (30), 79 (48), 67 (25), 57 (41). HRMS (EI): calcd for C15H24O
(M+) 220.1827, found 220.1830.
(6) Barton, D. H. R.; Jacob, M. Tetrahedron Lett. 1998, 39, 1331−
1334.
(7) (a) Abe, M.; Hayashikoshi, T.; Kurata, T. Chem. Lett. 1994, 23,
1789−1792. (b) Kurata, T.; Kinoshita, R. J. Oleo Sci. 2001, 50, 759−
762.
(8) (a) Ryu, I.; Uehara, S.; Hirao, H.; Fukuyama, T. Org. Lett. 2008,
10, 1005−1008. (b) Fukuyama, T.; Kawamoto, T.; Kobayashi, M.;
Ryu, I. Beilstein J. Org. Chem. 2013, 9, 1791−1796.
(9) (a) Burke, S. D.; Fobare, W. F.; Armistead, D. M. J. Org. Chem.
1982, 47, 3348−3350. (b) Giese, B.; Dupuis, J. Angew. Chem., Int. Ed.
Methyl 4-Oxododecanoate (8aa′).24c Yield: 70 mg (62%). 1H
NMR (CDCl3, 500 MHz): δ 0.88 (t, J = 6.9 Hz, 3H), 1.19−1.33 (m,
10H), 1.53−1.63 (m, 2H), 2.44 (t, J = 7.6 Hz, 2H), 2.59 (t, J = 6.7 Hz,
2H), 2.72 (t, J = 6.7, 2H), 3.68 (s, 3H). 13C NMR (CDCl3, 125 MHz):
δ 14.0, 22.6, 23.8, 27.7, 29.06, 29.14, 29.3, 31.8, 37.0, 42.8, 51.7, 173.2,
209.0.
́ ́
1983, 22, 622−623. (c) Giese, B.; Gonzalez-Gomez, J. A.; Witzel, T.
Angew. Chem., Int. Ed. 1984, 23, 69−70. Also see the fluorous tin
hydride version: (d) Curran, D. P.; Hadida, S.; Kim, S.; Luo, Z. J. Am.
Chem. Soc. 1999, 121, 6607−6615.
(10) For different approaches of alkyl radical addition reactions to
electron-deficient olefins using organoboron compounds, see:
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Methyl 4-Oxo-4-cyclohexylbutanoate (8ja′).24a Yield: 59 mg
1
(60%). H NMR (CDCl3, 500 MHz): δ 1.10−1.42 (m, 5H), 1.60−
1.70 (m, 1H), 1.72−1.81 (m, 2H), 1.82−1.92 (m, 2H), 2.34−2.42 (m,
1H), 2.58 (t, J = 6.6 Hz, 2H), 2.76 (t, J = 6.4 Hz, 2H), 3.67 (s, 3H).
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