Transition-metal-free transformation of aryl bromides into aromatic esters and amides via aryl trichloromethyl ketones

Article abstract of DOI:10.1002/ejoc.201301170

A variety of aryl bromides have been treated with Mg and then chloral, followed by tBuOCl and subsequently alcohols or amines to produce the corresponding aromatic esters or amides in good yields via the formation of aryl trichloromethyl ketones as intermediates. These reactions are examples of a transition-metal-free one-pot preparation of aromatic esters and amides from aryl bromides. Aryl bromides have been treated with Mg and then chloral, followed by tBuOCl or tBuOCl with I₂ as an additive, and subsequently alcohols or amines to form the corresponding aromatic esters and aromatic amides via aryl trichloromethyl ketones as intermediates. Copyright

Full text of DOI:10.1002/ejoc.201301170

FULL PAPER
DOI: 10.1002/ejoc.201301170
Transition-Metal-Free Transformation of Aryl Bromides into Aromatic Esters
and Amides via Aryl Trichloromethyl Ketones
Souya Dohi,[a] Katsuhiko Moriyama,[a] and Hideo Togo*[a]
Keywords: Synthetic methods / Grignard reagents / Esters / Amides / Ketones
A variety of aryl bromides have been treated with Mg and
then chloral, followed by tBuOCl and subsequently alcohols
or amines to produce the corresponding aromatic esters or
amides in good yields via the formation of aryl tri-
chloromethyl ketones as intermediates. These reactions are
examples of a transition-metal-free one-pot preparation of
aromatic esters and amides from aryl bromides.
Introduction
However, these reactions have several drawbacks, such as
the use of an expensive palladium catalyst, the requirement
Aromatic esters[1] and amides[2] are important and useful of a high temperature (over 100 °C), and the use of compli-
building blocks and structural elements of pharmaceuticals cated equipment and/or toxic CO gas. As alternative meth-
and agrochemicals. In general, aromatic esters are prepared ods, the halogen/metal exchange of aryl halides followed by
by the condensation of aromatic carboxylic acids and treatment with ethyl chloroformate,[7a] dimethyl carbonate
alcohols by the Fischer esterification[3a–3c] and Mitsunobu (the preparation of methyl 4-trimethylsilylbenzoate),[7b] di-
reaction.[3c–3e] The Favorskii rearrangement of α-halo tert-butyl dicarbonate,[7c] and ethyl cyanoformate[7d] have
ketones in the presence of a base,[3f] the Baeyer–Villiger oxi- been reported for the synthesis of aromatic esters, and the
dation of ketones with peroxides,[3g] and the Pinner reaction reactions of arylmagnesium reagents with chlorocarbamate
of nitriles with an alcohol[3h] can also be used.[3] Aromatic in the presence of [NiCl2(Ph3P)2],[7e] the reactions of aryl-
amides are prepared by the Schotten–Baumann reaction be- magnesium reagents with carbamoyltributylphosphonium
tween acyl chlorides and amines,[3c,4a,4b] the reaction of car- chloride,[7f] the reactions of chlorocarbamate with organo-
boxylic acids and amines in the presence of Ph3P/BrCCl3 cuprates,[7g] the reactions of arylmagnesium chlorides with
or Ph3P/(PyS)2,[3c] the Beckmann rearrangement of ox- chlorocarbamate,[7h] and the reactions of trichloroacetyl
imes,[4c] and the Ritter reaction of nitriles with an N-alkyl- isocyanate with organozinc halides and subsequent treat-
ated precursor.[4d] The preparation of aromatic esters and ment with alcohols[7i] have been reported for aromatic
amides from aromatic bromides by a carbonylation reaction amides. However, there are still shortcomings, such as the
is very attractive for synthetic organic chemists.
variable and low yields depending on the substrate, and the
Transition-metal-catalyzed preparations of aromatic es- troublesome preparation of the complexes. On the other
ters from aromatic halides have been well studied[5a] and hand, it is known that aryl trichloromethyl ketones, which
recently the Pd(OAc)2/dcpp·2HBF4-catalyzed carbonylation act as precursors of aromatic esters and amides, cannot be
of aromatic chlorides in the presence of alcohol under efficiently obtained by the reaction of phenylmagnesium
CO,[5b] the Pd(OAc)2/Xantphos-catalyzed carbonylation of bromide with ethyl trichloroacetate at low temperature.
aromatic bromides in the presence of methanol under Careful treatment of PhMgBr and ethyl trichloroacetate
CO,[5c] and related reactions with Pd complexes have been (1.0 equiv.) at –78 °C gives a trace amount of the desired
reported.[5d,5e] Aromatic amides can also be prepared by the phenyl trichloromethyl ketone and therefore the direct prep-
transition-metal-catalyzed amidation[2] of aryl bromides aration of aryl trichloromethyl ketones from aryl Grignard
with amines under CO in the presence of [PdBr2(Ph3P)2][6a] reagents and trichloroacetate esters is not practical.[7h]
and the amidation of aromatic bromides with carbamoyl-
silanes in the presence of [Pd(Ph3P)4],[6b] and related reac-
tions with Pd or Mo complexes have been reported.[6c–6h]
It would be useful to develop a transition-metal-free, less
toxic, inexpensive, and practical organic synthesis of aro-
matic esters and amides from readily available aromatic
bromides under mild conditions. Here, as part of our syn-
thetic study of molecular iodine,[8] we would like to report
the transition-metal-free transformation of aryl bromides
into aromatic esters and amides via the formation of aryl
trichloromethyl ketones. The oxidation of 1-aryl-2,2,2-tri-
chloroethanols and 1-alkyl-2,2,2-trichloroethanol into the
[a] Graduate School of Science, Chiba University,
Yayoi-cho 1-33, Japan
E-mail: togo@faculty.chiba-u.jp
http://reaction-2.chem.chiba-u.jp/index.html
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301170.
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corresponding trichloromethyl ketones with chromic ac- (NBS), N-chlorosuccinimide (NCS), and tert-butyl hypo-
id,[9a,9b] and the oxidation of 1-aryl-2,2,2-trifluoroethanols chlorite (tBuOCl), were investigated (Table 1).
and 1-alkyl-2,2,2-trifluoroethanols into the corresponding
The oxidation of adduct 2a derived from PhMgBr and
trifluoromethyl ketones with oxoammonium salt[9c] have chloral by tBuOCl (entry 6) or by tBuOCl with I2 as an
been reported. In addition, the reactions of aryl tri- additive (entry 7) proved to be the best choice. When
chloromethyl ketones with alcohols and amines have been PhMgCl was used instead of PhMgBr, tBuOCl alone was
reported to give the corresponding aromatic esters and not effective for the oxidation, but tBuOCl with KI or I2 as
amides, respectively.[10] In a related reaction, the prepara- an additive showed high reactivity to give the correspond-
tion of primary aromatic amides from the reactions of aryl ing trichloromethyl ketone in good yields (entries 8–11).
methyl ketones or 1-phenylethanols with molecular iodine The formation of ArMgBr from ArBr is more practical
and aqueous NH3 at 60 °C have recently been reported.[11] than that of ArMgCl from ArCl in terms of the ease of
Based on these reports and our previous study,[8] we have formation of Grignard reagents. On the basis of these re-
examined the one-pot preparation of aromatic esters and sults, the aryl bromides 4a–4j, that is, phenyl bromide, 4-
amides by the reaction of aryl bromides with Mg followed methylphenyl bromide, 3-methylphenyl bromide, 2-meth-
by treatment with chloral and oxidation to aryl tri- ylphenyl bromide, 4-methoxyphenyl bromide, 4-chlo-
chloromethyl ketones, and the subsequent reaction with rophenyl bromide, 4-(trifluoromethyl)phenyl bromide, 1-
alcohols and amines to provide the corresponding aromatic bromonaphthalene, 2-bromothiophene, and 3-bromobenzo-
esters and amides, respectively.
thiophene, were treated with Mg and then chloral followed
by the oxidation with tBuOCl to provide aryl tri-
Table 2. Formation of aryl trichloromethyl ketones by the reactions
of ArBr with Mg, chloral, and subsequent oxidation with tBuOCl.
Results and Discussion
First, the reactions of PhMgX [X = Br (1a), Cl (1b)] and
chloral (2,2,2-trichloroethanal), and the subsequent oxi-
dation to phenyl trichloromethyl ketone (3a) with less toxic
oxidants such as I2, 1,3-diiodo-5,5-dimethylhydantoin
(DIH), N-iodosuccinimide (NIS), N-bromosuccinimide
Table 1. Formation of phenyl trichloromethyl ketone by the reac-
tions of PhMgX with chloral and subsequent oxidation.
[a] The yields were determined based on the amount of chloral. [b]
I2 (10 mol-%) was added in the third step. [c] Et2O (4 mL) was
added to the THF solution in the first step, the second step was
carried out at –20 °C, and Et2O was removed before the third step.
[d] Conditions for the third step: tBuOCl (2.0 equiv.) and I2
(10 mol-%) were added and the mixture was stirred for 2 h at 0 °C.
[a] The yields were determined based on the amount of chloral.
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Transformation of Aryl Bromides into Aromatic Esters and Amides
chloromethyl ketones 3a–3j in good yields (Table 2, en- respectively, although the reaction time was 2 h for the last
tries 1–10). LiCl was added as it is known to be effective step (entries 5 and 10). Thus, the nucleophiles in the last
for the smooth formation of Grignard reagents from aryl step in these reactions can be reduced to 1.2 equiv. to pro-
bromides with Mg.[12] The yield of compound 3g was low vide the corresponding aromatic esters and amides in good
(60%) because the trichloromethyl ketone formed partly de- yields.
composed during purification by column chromatography
When chiral (S)-1-phenylethylamine (5i, 1.2 equiv.) was
due to its high sensitivity to nucleophiles. On the other used as the nucleophile, the corresponding amide 6bi was
hand, the reaction between 3-phenylpropylmagnesium obtained in good yield with high ee (Ͼ99%, entry 11).
bromide and chloral did not occur smoothly (entry 11) be- Based on these procedures and conditions, aryl bromides
cause the alkyl Grignard reagent reacts with one of the 4a–4j were treated with Mg in the presence of LiCl and then
chlorine atoms of chloral.
chloral, followed by tBuOCl and subsequently methanol to
Next, the one-pot transformation of 4-methylphenyl provide aromatic methyl esters 6aa–6da and 6ha–6ja in
bromide 4b with Mg in the presence of LiCl and then chlo- good yields (Table 4, entries 1–4 and 11–13). When 4-meth-
ral, followed by the treatment with tBuOCl and then vari- oxyphenyl bromide was used, it was necessary to use a mix-
ous nucleophiles (2 mL), such as methanol (5a), ethanol ture of THF and diethyl ether as the solvent and the reac-
(5b), 2-propanol (5c), benzyl alcohol (5d), aq. NH3 (5e), aq. tion with chloral was carried out at –20 °C to give amide
methylamine (5f), piperidine (5g), and benzylamine (5h),
was carried out to give the corresponding esters and amides
6ba–6bh in good yields, respectively (Table 3, entries 1–4
and 6–9). When the amount of benzyl alcohol (5d) and ben-
zylamine (5h) was reduced to 1.2 equiv., the corresponding
aromatic ester and amide were also obtained in good yields,
Table 4. Formation of aromatic methyl esters from the reactions of
ArBr with Mg, chloral, tBuOCl, and MeOH.
Table 3. Formation of esters and amides from the reactions of 4-
MeC6H4Br with Mg, chloral, tBuOCl, and nucleophiles.
[a] The yields were determined based on the amount of chloral. [b]
DMAP (10 mol-%) was used in the fourth step. [c] Conditions for
the fourth step: BnOH (1.2 equiv.) and Et3N (2.0 equiv.) were
added and the mixture was stirred for 2 h at room temp. [d] Condi-
tions for the fourth step: BnNH2 (1.2 equiv.) and Et3N (1.0 equiv.)
were added and the mixture was stirred for 2 h at room temp. [e]
Conditions for the fourth step: Amine (1.2 equiv.) and Et3N
(1.0 equiv.) were added and the mixture was stirred for 2 h at room
temp.
[a] The yields were determined based on the amount of chloral. [b]
I2 (10 mol-%) was added in the third step. [c] Yield of alcohol. [d]
Et2O (4 mL) was added to the THF solution in the first step, the
second step was carried out at –20 °C, Et2O was removed before
the third step. [e] Yield of tert-butyl ester. [f] The third step was
carried out at 0 °C. [g] Conditions for the third step: tBuOCl
(2.0 equiv.) and I2 (10 mol-%) were added and the mixture was
stirred for 2 h at 0 °C.
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6ea in good yield because the corresponding Grignard rea-
The reaction developed in this work proceeds by the ad-
gent was rather reactive (entries 5 and 6). Moreover, when dition of aryl Grignard reagents 1 to chloral, the oxidation
4-chlorophenyl bromide and 4-(trifluoromethyl)phenyl of the adducts 2 to aryl trichloromethyl ketones 3 by tBu-
bromide were used, tBuOCl and I2 were added in the third OCl via the formation of hypobromites I and its β-elimi-
step for effective oxidation to the trichloromethyl ketones at nation, and finally the nucleophilic substitution of aryl tri-
0 °C, and the high reactivity of the trichloromethyl ketones chloromethyl ketones 3 by alcohols or amines to provide
towards nucleophiles, such as tBuOH, furnished esters 6fa aromatic esters or amides 6 with the generation of chloro-
and 6ga in good yields (entries 7–10).
form (Scheme 1). The key point in this reaction is the oxi-
Similarly, aryl bromides 4a–4j were treated with Mg in dation of adducts 2 by tBuOCl with β-elimination of hypo-
the presence of LiCl and then chloral, followed by tBuOCl bromite I to generate aryl trichloromethyl ketones 3. When
and subsequently methylamine (2 mL) to provide the aro- I2 or KI is added to the solution of adducts 2 and tBuOCl,
matic N-methylamides 6af–6df and 6hf–6jf in good yields hypoiodite is formed and its β-elimination occurs smoothly
(Table 5, entries 1–4 and 8–10). When 4-methoxyphenyl to give aryl trichloromethyl ketones 3. Once the aryl tri-
bromide was used, it was necessary to use a mixture of THF chloromethyl ketones 3 have formed, they react smoothly
and diethyl ether as the solvent and the reaction with chlo- with alcohols and amines to give aromatic esters and
ral was again carried out at –20 °C to improve the yield of amides 6, respectively. The in situ formation of tBuOI from
amide 6ef (entry 5). Moreover, when 4-chlorophenyl brom- tBuOK and KI and its synthetic use have been reported
ide and 4-(trifluoromethyl)phenyl bromide were used, tBu- previously.[13] On the other hand, when ArMgCl instead of
OCl and I2 were again added in the third step for the effec- ArMgBr was used in the addition reaction with chloral,
tive oxidation to ketones at 0 °C to give amides 6ff and 6gf treatment of the reaction mixture with tBuOCl alone does
in good yields (entries 6 and 7).
not generate the trichloromethyl ketone effectively due to
the poor β-elimination ability of the formed hypochlorite.
Table 5. Formation of aromatic N-methylamides by the the reac-
tions of ArBr with Mg, chloral, tBuOCl, and MeNH2.
Scheme 1. Reaction pathway.
Conclusions
A variety of aryl bromides have been treated with Mg in
the presence of LiCl and then chloral, followed by tBuOCl
or tBuOCl with I2 as an additive, and subsequently alcohols
or amines to form the corresponding aromatic esters and
amides, respectively, in good yields via the formation of aryl
trichloromethyl ketones under mild conditions. We believe
the present reactions are useful for the transition-metal-free
one-pot preparation of aromatic esters and amides from
aryl bromides.
[a] The yields were determined based on the amount of chloral. [b]
I2 (10 mol-%) was added in the third step. [c] Et2O (4 mL) was
added in the first step, the second step was carried out at –20 °C,
and Et2O was removed before the third step. [d] Conditions for the
third step: tBuOCl (2.0 equiv.) and I2 (10 mol-%) were added and
the mixture was stirred for 2 h at 0 °C.
Experimental Section
General: 1H and 13C NMR spectra were obtained with JEOL JNM-
ECX400, JNM-ECS400, and JNM-ECA500 spectrometers. Chemi-
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Transformation of Aryl Bromides into Aromatic Esters and Amides
cal shifts are expressed in ppm downfield from TMS in units of δ.
19F NMR spectra were recorded with a 471 MHz spectrometer.
High-resolution mass spectra (HRMS) were recorded with an Or-
bitrap mass spectrometer. Mass spectra were recorded with JMS-
T100GCV, JMS-HX110, and Thermo LTQ Orbitrap XL spectrom-
eters. IR spectra were recorded with a JASCO FT/IR-4100 spec-
trometer. Melting points were determined with a Yamato Melting
Point Apparatus Model MP-21. Silica gel 60F254 (Merck) was used
for TLC and silica gel 60 (Kanto Kagaku Co.) was used for short
column chromatography. tBuOCl was commercially available from
Tokyo Kasei Co, (purity over 98%) and was used without further
purification.
Typical Experimental Procedure for the One-Pot Transformation of
Aryl Bromides into Aromatic Esters 6 with Alcohol (1.2 equiv.):
Magnesium turnings (72.9 mg, 3.0 mmol) and LiCl (127 mg,
3.0 mmol) were dried with a heat gun for 10 min in vacuo. Under
argon, THF (1.0 mL) was added to a flask. Then a solution of 4-
bromotoluene (4b; 513 mg, 3.0 mmol) in dry THF (2.0 mL) was
added at room temp. and the mixture was stirred for 2 h at room
temp. Chloral (195 μL, 2.0 mmol) was slowly added at 0 °C and
the mixture stirred for 30 min at 0 °C. Then tBuOCl (452 μL,
4.0 mmol) was added and the reaction mixture was stirred for 2 h
at room temp. Benzyl alcohol (5d; 248 μL, 2.4 mmol) and triethyl-
amine (556 μL, 4 mmol) were added and the mixture was stirred
for 2 h at room temp. The reaction mixture was quenched with
NH4Cl (4 mL) and satd. Na2SO3 (1 mL), and then extracted with
EtOAc (3ϫ 15 mL). The organic layer was washed with brine and
dried with Na2SO4. Purification by short column chromatography
(silica gel, EtOAc/hexane = 0:1 to 1:10) yielded benzyl 4-methyl-
benzoate (6bd; 339 mg, 75%) as a white solid.
Typical Experimental Procedure for the One-Pot Transformation of
Aryl Bromides into Aryl Trichloromethyl Ketones 3: Magnesium
turnings (72.9 mg, 3.0 mmol) and LiCl (127 mg, 3.0 mmol) were
dried with a heat gun for 10 min in vacuo. Under argon, THF
(1.0 mL) was added to a flask. Then a solution of 4-bromotoluene
(4b; 513 mg, 3.0 mmol) in dry THF (2.0 mL) was added at room
temp. and the mixture was stirred for 2 h at room temp. Chloral
(195 μL, 2.0 mmol) was slowly added at 0 °C and the reaction mix-
ture was stirred for 30 min at 0 °C. Then tBuOCl (452 μL,
4.0 mmol) was added and the mixture was stirred for 2 h at room
temp. The reaction mixture was quenched with 1 m HCl (2 mL)
and a satd. Na2SO3 solution (1 mL), and then extracted with
EtOAc (3ϫ 15 mL). The organic layer was washed with brine and
dried with Na2SO4. Purification by short column chromatography
(silica gel, EtOAc/hexane = 0:1 to 1:50) yielded 4-methylphenyl tri-
chloromethyl ketone (3b; 428 mg, 90%) as a colorless oil.
Typical Experimental Procedure for the One-Pot Transformation of
Aryl Bromides into Aromatic Amides 6 with Amine (1.2 equiv.):
Magnesium turnings (72.9 mg, 3.0 mmol) and LiCl (127 mg,
3.0 mmol) were dried with a heat gun for 10 min in vacuo. Under
argon, THF (1.0 mL) was added to a flask. Then a solution of 4-
bromotoluene (4b; 513 mg, 3.0 mmol) in dry THF (2.0 mL) was
added at room temp. and the mixture was stirred for 2 h at room
temp. Chloral (195 μL, 2.0 mmol) was slowly added at 0 °C and
the mixture stirred for 30 min at 0 °C. Then tBuOCl (452 μL,
4.0 mmol) was added and the reaction mixture stirred for 2 h at
room temp. Benzylamine (5h; 262 μL, 2.4 mmol) and triethylamine
(278 μL, 2 mmol) were added and the mixture stirred for 2 h at
room temp. The reaction mixture was quenched with 1 m HCl
(3 mL) and satd. Na2SO3 (1 mL), and then extracted with EtOAc
(3ϫ 15 mL). The organic layer was washed with brine and dried
with Na2SO4. Purification by short column chromatography (silica
gel, EtOAc/hexane = 1:3 to 4:1) yielded N-benzyl-4-methylbenz-
amide (6bh; 356 mg, 79%) as a white solid.
Typical Experimental Procedure for the One-Pot Transformation of
Aryl Bromides into Aromatic Methyl Esters 6: Magnesium turnings
(72.9 mg, 3.0 mmol) and LiCl (127 mg, 3.0 mmol) were dried with
a heat gun for 10 min in vacuo. Under argon, THF (1.0 mL) was
added to a flask. Then a solution of 4-bromotoluene (4b; 513 mg,
3.0 mmol) in dry THF (2.0 mL) was added at room temp. and the
mixture was stirred for 2 h at room temp. Chloral (195 μL,
2.0 mmol) was slowly added at 0 °C and the mixture was stirred
for 30 min at 0 °C. Then tBuOCl (452 μL, 4.0 mmol) was added
and the reaction mixture was stirred for 2 h at room temp. Meth-
anol (5a; 2 mL) and triethylamine (556 μL, 4 mmol) were added
and the mixture was stirred for 1 h at room temp. The reaction
mixture was quenched with NH4Cl (4 mL) and satd. Na2SO3
(1 mL), and then extracted with EtOAc (3ϫ 15 mL). The organic
layer was washed with brine and dried with Na2SO4. Purification
by short column chromatography (silica gel, EtOAc/hexane = 0:1
to 1:10) yielded methyl 4-methylbenzoate (6ba; 228 mg, 76%) as a
white solid.
Compounds 3h, 3i, 3j, 6ja, and 6jf are new compounds and com-
pounds 3b, 3c, 3d, 3e, 3f, 3g, 6bc, 6bd, 6bg, 6bi, 6gf, and 6if are
known. The other aromatic esters and amides were commercially
available and were identified by comparison with authentic com-
pounds.
2,2,2-Trichloroacetophenone (3a) (commercially available): Color-
less oil (367 mg, 82% yield). IR (neat): ν = 1710 cm–1. 1H NMR
˜
(500 MHz, CDCl3): δ = 7.50 (t, J = 7.5 Hz, 2 H), 7.64 (t, J =
7.5 Hz, 1 H), 8.27 (d, J = 7.5 Hz, 2 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 95.4, 128.4, 129.0, 131.5, 134.3, 181.2 ppm.
Typical Experimental Procedure for the One-Pot Transformation of
Aryl Bromides into Aromatic N-Methyl Amides 6: Magnesium turn-
ings (72.9 mg, 3.0 mmol) and LiCl (127 mg, 3.0 mmol) were dried
with a heat gun for 10 min in vacuo. Under argon, THF (1.0 mL)
was added to a flask. Then a solution of 4-bromotoluene (4b;
513 mg, 3.0 mmol) in dry THF (2.0 mL) was added at room temp.
and the mixture was stirred for 2 h at room temp. Chloral (195 μL,
2.0 mmol) was slowly added at 0 °C and the mixture was stirred
for 30 min at 0 °C. Then tBuOCl (452 μL, 4.0 mmol) was added
and the reaction mixture was stirred for 2 h at room temp. Methyl-
amine (5f; 40% in water, 2 mL) was added and the mixture was
stirred for 1 h at room temp. The reaction mixture was quenched
with 1 m HCl (until neutrality) and satd. Na2SO3 (1 mL), and then
extracted with EtOAc (3ϫ 15 mL). The organic layer was washed
with brine and dried with Na2SO4. Purification by short column
chromatography (silica gel, EtOAc/hexane = 1:3 to 4:1) yielded N,4-
dimethylbenzamide (5bf; 263 mg, 88%) as a white solid.
2,2,2-Trichloro-4Ј-methylacetophenone (3b):[9a] Colorless oil
(428 mg, 90% yield). IR (neat):
ν =
˜
1711 cm–1. 1H NMR
(500 MHz, CDCl3): δ = 2.45 (s, 3 H), 7.30 (d, J = 8.6 Hz, 2 H),
8.17 (d, J = 8.6 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
21.8, 95.6, 126.3, 129.1, 131.7, 145.6, 180.9 ppm.
2,2,2-Trichloro-3Ј-methylacetophenone (3c):[9a] Colorless oil
(423 mg, 89% yield). IR (neat):
ν =
˜
1710 cm–1. 1H NMR
(500 MHz, CDCl3): δ = 2.44 (s, 3 H), 7.38 (t, J = 7.7 Hz, 1 H),
7.45 (d, J = 7.7 Hz, 1 H), 8.04 (s, 1 H), 8.07 (d, J = 7.7 Hz, 1
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 21.4, 95.5, 128.2, 128.6,
129.1, 131.9, 135.1, 138.4, 181.5 ppm.
2,2,2-Trichloro-2Ј-methylacetophenone (3d):[9a] Colorless oil
(409 mg, 86% yield). IR (neat):
ν =
˜
1730 cm–1. 1H NMR
(500 MHz, CDCl3): δ = 2.42 (s, 3 H), 7.26 (t, J = 7.7 Hz, 1 H),
7.32 (d, J = 7.7 Hz, 1 H), 7.43 (t, J = 7.7 Hz, 1 H), 7.91 (d, J =
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7.7 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 20.7, 96.0,
125.0, 128.3, 131.5, 131.7, 132.1, 138.7, 186.1 ppm.
Benzyl 4-Methylbenzoate (6bd):[15] White solid (371 mg, 82% yield);
m.p. 44–45 °C (ref.[14] 45–46 °C). IR (neat): ν = 1612 cm–1. 1H
˜
NMR (500 MHz, CDCl3): δ = 2.40 (s, 3 H), 5.35 (s, 2 H), 7.32 (d,
J = 8.0 Hz, 2 H), 7.33 (t, J = 7.5 Hz, 1 H), 7.38 (t, J = 7.5 Hz, 2
H), 7.44 (d, J = 7.5 Hz, 2 H), 7.97 (d, J = 8.0 Hz, 2 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 21.6, 66.5, 127.3, 128.08, 128.14,
128.5, 129.1, 129.7, 136.2, 143.7, 166.5 ppm.
2,2,2-Trichloro-4Ј-methoxyacetophenone (3e):[9a] White solid
(431 mg, 85% yield); m.p. 33–34 °C (ref.[9a] 33–34 °C). IR (neat): ν
˜
1
= 1697 cm–1. H NMR (500 MHz, CDCl3): δ = 3.91 (s, 3 H), 6.97
(d, J = 8.9 Hz, 2 H), 8.28 (d, J = 8.9 Hz, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 55.6, 95.7, 113.7, 121.1, 134.2, 164.3,
179.8 ppm.
4-Methylbenzamide (6be) (commercially available): White solid
(203 mg, 75% yield); m.p. 158–159 °C. IR (neat): ν = 3340, 3158,
˜
2,2,2-Trichloro-4Ј-chloroacetophenone (3f):[9a] White solid (495 mg,
1667 cm–1. 1H NMR (500 MHz, [D6]DMSO): δ = 2.32 (s, 3 H),
7.28 (d, J = 8.3 Hz, 2 H), 7.28 (br. s, 1 H), 7.77 (d, J = 8.3 Hz, 2
96% yield); m.p. 27–28 °C (ref.[9a] oil). IR (neat): ν = 1713 cm–1.
˜
1H NMR (500 MHz, CDCl3): δ = 7.48 (d, J = 8.9 Hz, 2 H), 8.21
(d, J = 8.9 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 95.1,
127.3, 128.8, 132.9, 141.0, 180.2 ppm.
H), 7.90 (br. s,
1
H) ppm. 13C NMR (125 MHz, [D6]-
DMSO): δ = 21.0, 127.5, 128.8, 131.5, 141.1, 167.9 ppm.
N,4-Dimethylbenzamide (6bf) (commercially available): White solid
2,2,2-Trichloro-4Ј-(trifluoromethyl)acetophenone (3g):[14] Colorless
(263 mg, 88% yield); m.p. 144–145 °C. IR (neat): ν = 3334,
˜
oil (350 mg, 60% yield). IR (neat): ν = 1719 cm–1. 1H NMR
˜
1628 cm–1. 1H NMR (500 MHz, CDCl3): δ = 2.38 (s, 3 H), 2.97(I)/
2.98(II) (s, 3 H), 6.48 (br. s, 1 H), 7.20 (d, J = 8.0 Hz, 2 H), 7.67
(d, J = 8.0 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 21.4,
26.7, 126.8, 129.1, 131.7, 141.6, 168.2 ppm.
(500 MHz, CDCl3): δ = 7.78 (d, J = 8.3 Hz, 2 H), 8.37 (d, J =
8.3 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 94.8, 123.2
(q, JC,F = 273.5 Hz), 125.5 (q, JC,F = 3.6 Hz), 131.8, 132.3, 135.3
(q, JC,F = 32.4 Hz), 180.5 ppm. 19F NMR (471 MHz, CDCl3): δ
= –63.3 ppm.
N-(4-Methylbenzoyl)piperidine (6bg):[16] White solid (366 mg, 90%
yield); m.p. 53–54 °C (ref.[16] 53.5–54.0 °C). IR (neat):
ν =
˜
2,2,2-Trichloro-1Ј-acetonaphthone (3h): White solid (493 mg, 90%
1610 cm–1. 1H NMR (500 MHz, CDCl3): δ = 1.51 (br. s, 2 H), 1.67
(br. s, 4 H), 2.37 (s, 3 H), 3.36(I)/3.70(II) (br. s, 4 H), 7.19 (d, J =
8.0 Hz, 2 H), 7.29 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 21.3, 24.6, 25.6, 26.5, 43.1, 48.8, 126.8, 128.9, 133.5,
139.3, 170.4 ppm.
yield); m.p. 40–41 °C. IR (neat): ν = 1716 cm–1. 1H NMR
˜
(500 MHz, CDCl3): δ = 7.51 (t, J = 7.7 Hz, 1 H), 7.56 (t, J =
7.7 Hz, 1 H), 7.61 (t, J = 7.7 Hz, 1 H), 7.91 (d, J = 7.7 Hz, 1 H),
7.97 (d, J = 7.7 Hz, 1 H), 8.03 (d, J = 7.7 Hz, 1 H), 8.16 (d, J =
7.7 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 96.2, 123.8,
125.1, 126.8, 127.3, 128.0, 128.7, 130.0, 131.0, 132.6, 133.6,
186.0 ppm. C12H7Cl3O (273.54): C 52.69, H 2.58; found C 52.83,
H 2.58.
N-Benzyl-4-methylbenzamide (6bh) (commercially available): White
solid (329 mg, 73% yield); m.p. 133–134 °C. IR (neat): ν = 3308,
˜
1638 cm–1. 1H NMR (500 MHz, CDCl3): δ = 2.38 (s, 3 H), 4.62 (d,
J = 5.7 Hz, 2 H), 6.52 (br. s, 1 H), 7.20 (d, J = 8.3 Hz, 2 H), 7.26–
7.31 (m, 1 H), 7.32–7.36 (m, 4 H), 7.68 (d, J = 8.3 Hz, 2 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 21.4, 44.0, 126.9, 127.6, 127.9,
128.7, 129.2, 131.5, 138.3, 141.9, 167.2 ppm.
2-(2,2,2-Trichloroacetyl)thiophene (3i): Colorless oil (358 mg, 78%
yield). IR (neat): ν = 1683 cm–1. 1H NMR (500 MHz, CDCl ): δ =
˜
3
7.20 (dd, J = 4.9, 4.0 Hz, 1 H), 7.81 (dd, J = 4.9, 0.9 Hz, 1 H), 8.18
(dd, J = 4.0, 0.9 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
95.0, 128.4, 134.0, 136.7, 137.1, 175.1 ppm. C6H3Cl3OS (229.50): C
31.40, H 1.32; found C 31.49, H 1.31.
(S)-4-Methyl-N-(1-phenylethyl)benzamide (6bi):[17] White solid
(335 mg, 73% yield, Ͼ99% ee); m.p. 135–136 °C (ref.[17] 127–
1
128 °C, rac). IR (neat): ν = 3341, 1633 cm–1. H NMR (500 MHz,
˜
3-(2,2,2-Trichloroacetyl)benzo[b]thiophene
(3j):
White
solid
CDCl3): δ = 1.60 (d, J = 6.9 Hz, 3 H), 2.38 (s, 3 H), 5.33 (quint.,
J = 6.9 Hz, 1 H), 6.34 (br. s, 1 H), 7.21 (d, J = 8.0 Hz, 2 H), 7.27
(t, J = 7.5 Hz, 1 H), 7.35 (t, J = 7.5 Hz, 2 H), 7.39 (d, J = 7.5 Hz,
2 H), 7.67 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 21.4, 21.7, 49.1, 126.2, 126.9, 127.4, 128.7, 129.2, 131.7, 141.8,
143.2, 166.4 ppm. HPLC analysis (Chiralcel OD-H, 1.0 mL/min,
230 nm, hexane/iPrOH = 9:1): tR = 11.0 (minor, R), 13.2 min
(major, S).
1
(475 mg, 85% yield); m.p. 65–66 °C. IR (neat): ν = 1684 cm–1. H
˜
NMR (500 MHz, CDCl3): δ = 7.48 (t, J = 8.0 Hz, 1 H), 7.56 (t, J
= 8.0 Hz, 1 H), 7.91 (d, J = 8.0 Hz, 1 H), 8.70 (d, J = 8.0 Hz, 1
H), 8.92 (s, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 96.0,
122.4, 124.0, 125.4, 125.9, 126.4, 137.9, 138.7, 141.1, 176.0 ppm.
C10H5Cl3OS (279.56): C 42.96, H 1.80; found C 43.00, H 1.75.
Methyl 4-Methylbenzoate (6ba, commercially available): White solid
1
(228 mg, 76% yield); m.p. 33–34 °C. IR (neat): ν = 1704 cm–1. H
˜
Methyl Benzoate (6aa) (commercially available): Colorless oil
1719 cm–1. 1H NMR
NMR (500 MHz, CDCl3): δ = 2.38 (s, 3 H), 3.88 (s, 3 H), 7.21 (d,
J = 8.0 Hz, 2 H), 7.91 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 21.6, 51.8, 127.4, 129.0, 129.5, 143.5,
167.1 ppm.
(196 mg, 72% yield). IR (neat):
ν =
˜
(500 MHz, CDCl3): δ = 3.92 (s, 3 H), 7.44 (t, J = 7.5 Hz, 2 H),
7.56 (t, J = 7.5 Hz, 1 H), 8.04 (d, J = 7.5 Hz, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 52.1, 128.3, 129.5, 130.1, 132.9, 167.1 ppm.
Ethyl 4-Methylbenzoate (6bb) (commercially available): Colorless
Methyl 3-Methylbenzoate (6ca) (commercially available): Colorless
oil (259 mg, 79% yield). IR (neat): ν = 1714 cm–1. 1H NMR
oil (264 mg, 88% yield). IR (neat): ν = 1718 cm–1. 1H NMR
˜
˜
(500 MHz, CDCl3): δ = 1.39 (t, J = 7.2 Hz, 3 H), 2.41 (s, 3 H),
4.36 (q, J = 7.2 Hz, 2 H), 7.23 (d, J = 8.0 Hz, 2 H), 7.94 (d, J =
8.0 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.3, 21.6,
60.7, 127.7, 129.0, 129.5, 143.4, 166.7 ppm.
(500 MHz, CDCl3): δ = 2.40 (s, 3 H), 3.91 (s, 3 H), 7.32 (m, 1 H),
7.37 (d, J = 7.7 Hz, 1 H), 7.84 (d, J = 7.5 Hz, 1 H), 7.86 (s, 1
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 21.2, 52.0, 126.7, 128.2,
130.0, 130.1, 133.7, 138.1, 167.3 ppm.
Isopropyl 4-Methylbenzoate (6bc):[15] Colorless oil (264 mg, 74% Methyl 2-Methylbenzoate (6da) (commercially available): Colorless
yield). IR (neat): ν = 1711 cm–1. 1H NMR (500 MHz, CDCl ): δ = oil (255 mg, 85% yield). IR (neat): ν = 1719 cm–1. 1H NMR
˜
˜
3
1.36 (d, J = 6.3 Hz, 6 H), 2.40 (s, 3 H), 5.24 (sept, J = 6.3 Hz, 1
H), 7.23 (d, J = 8.3 Hz, 2 H), 7.93 (d, J = 8.3 Hz, 2 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 21.6, 21.9, 68.1, 128.1, 128.9, 129.5,
143.3, 166.2 ppm.
(500 MHz, CDCl3): δ = 2.60 (s, 3 H), 3.89 (s, 3 H), 7.21–7.27 (m,
2 H), 7.40 (dt, J = 7.7, 1.4 Hz, 1 H), 7.91 (dd, J = 7.4, 1.4 Hz, 1
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 21.7, 51.8, 125.7, 129.5,
130.5, 131.7, 131.9, 140.2, 168.1 ppm.
7820
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 7815–7822

Transformation of Aryl Bromides into Aromatic Esters and Amides
Methyl 4-Methoxybenzoate (6ea) (commercially available): White
H), 3.83 (s, 3 H), 6.46 (br. s, 1 H), 6.89 (d, J = 8.9 Hz, 2 H), 7.74
(d, J = 8.9 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 26.7,
55.3, 113.6, 126.8, 128.6, 161.9, 167.9 ppm.
solid (266 mg, 80% yield); m.p. 48–49 °C. IR (neat): ν = 1705 cm–1.
˜
1H NMR (500 MHz, CDCl3): δ = 3.84 (s, 3 H), 3.89 (s, 3 H), 6.91
(d, J = 8.9 Hz, 2 H), 7.99 (d, J = 8.9 Hz, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 51.8, 55.3, 113.5, 122.5, 131.5, 163.2,
166.8 ppm.
4-Chloro-N-methylbenzamide (6ff) (commercially available): White
solid (315 mg, 93% yield); m.p. 157–158 °C. IR (neat): ν = 3334,
˜
1
1633 cm–1. H NMR (500 MHz, CDCl3): δ = 3.00(I)/3.01(II) (s, 3
Methyl 4-Chlorobenzoate (6fa) (commercially available): White solid
H), 6.27 (br. s, 1 H), 7.39 (d, J = 8.6 Hz, 2 H), 7.70 (d, J = 8.6 Hz,
2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 26.9, 128.3, 128.8,
132.9, 137.5, 167.2 ppm.
1
(328 mg, 96% yield); m.p. 44–45 °C. IR (neat): ν = 1718 cm–1. H
˜
NMR (500 MHz, CDCl3): δ = 3.91 (s, 3 H), 7.41 (d, J = 8.6 Hz, 2
H), 7.97 (d, J = 8.6 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 52.2, 128.5, 128.7, 130.9, 139.3, 166.2 ppm.
N-Methyl-4-(trifluoromethyl)benzamide (6gf):[18] White solid
(354 mg, 87% yield); m.p. 155–156 °C. IR (neat): ν = 3301,
˜
1
1647 cm–1. H NMR (500 MHz, CDCl3): δ = 3.02(I)/3.03(II) (s, 3
Methyl 4-(Trifluoromethyl)benzoate (6ga) (commercially available):
Colorless oil (355 mg, 87% yield). IR (neat): ν = 1726 cm–1. 1H
˜
H), 6.47 (br. s, 1 H), 7.68 (d, J = 8.3 Hz, 2 H), 7.87 (d, J = 8.3 Hz,
2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 26.9, 123.6 (q, JC,F
NMR (500 MHz, CDCl3): δ = 3.96 (s, 3 H), 7.71 (d, J = 8.3 Hz, 2
H), 8.18 (d, J = 8.3 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 52.5, 123.6 (q, JC,F = 273.3 Hz), 125.4 (q, JC,F = 3.6 Hz), 130.0,
133.3, 134.4 (q, JC,F = 32.4 Hz), 165.9 ppm. 19F NMR (471 MHz,
CDCl3): δ = –63.0 ppm.
= 272.3 Hz), 125.6 (q, JC,F = 3.6 Hz), 127.3, 133.1 (q, JC,F
=
32.4 Hz), 137.8, 167.0 ppm. 19F NMR (471 MHz, CDCl3): δ =
–62.8 ppm.
N-Methyl-1-naphthamide (6hf) (commercially available): White solid
Methyl 1-Naphthoate (6ha) (commercially available): Colorless oil
(307 mg, 83% yield); m.p. 160–161 °C. IR (neat): ν = 3675, 3271,
˜
1712 cm–1. 1H NMR
1
1632 cm–1. H NMR (500 MHz, CDCl3): δ = 2.97(I)/2.98(II) (s, 3
(335 mg, 90% yield). IR (neat):
ν =
˜
(500 MHz, CDCl3): δ = 4.00 (s, 3 H), 7.50 (dd, J = 8.0, 7.5 Hz, 1
H), 7.53 (dd, J = 8.3, 6.9 Hz, 1 H), 7.62 (dd, J = 8.6, 6.9 Hz, 1 H),
7.88 (d, J = 8.3 Hz, 1 H), 8.02 (d, J = 8.0 Hz, 1 H), 8.19 (d, J =
7.5 Hz, 1 H), 8.91 (d, J = 8.6 Hz, 1 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 52.2, 124.5, 125.8, 126.2, 127.0, 127.7, 128.5, 130.2,
131.3, 133.4, 133.8, 168.0 ppm.
H), 6.23 (br. s, 1 H), 7.35 (dd, J = 8.0, 7.0 Hz, 1 H), 7.44–7.52
(m, 3 H), 7.79–7.87 (m, 2 H), 8.20–8.26 (m, 1 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 26.7, 124.6, 124.8, 125.4, 126.3, 126.9,
128.2, 130.0, 130.3, 133.5, 134.4, 170.2 ppm.
N-Methylthiophene-2-carboxamide (6if):[18] White solid (217 mg,
77% yield); m.p. 111–112 °C. IR (neat): ν = 3285, 1613 cm–1. 1H
˜
Methyl Thiophene-2-carboxylate (3ia) (commercially available):
NMR (500 MHz, CDCl3): δ = 2.99(I)/2.30(II) (s, 3 H), 6.27 (br. s,
1 H), 7.06 (dd, J = 4.9, 3.7 Hz, 1 H), 7.45 (dd, J = 4.9, 1.2 Hz, 1
H), 7.52 (dd, J = 3.7, 1.2 Hz, 1 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 26.7, 127.6, 127.9, 129.6, 138.9, 162.6 ppm.
Colorless oil (199 mg, 70% yield). IR (neat): ν = 1706 cm–1. 1H
˜
NMR (500 MHz, CDCl3): δ = 3.89 (s, 3 H), 7.10 (dd, J = 4.6,
4.1 Hz, 1 H), 7.55 (dd, J = 4.6, 0.6 Hz, 1 H), 7.81 (dd, J = 4.1,
0.6 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 52.1, 127.7,
132.3, 133.4, 133.5, 162.7 ppm.
N-Methylbenzo[b]thiophene-3-carboxamide (6jf): White solid
(325 mg, 85% yield); m.p. 131–132 °C. IR (neat): ν = 3300,
˜
1
1633 cm–1. H NMR (500 MHz, CDCl3): δ = 2.95(I)/2.96(II) (s, 3
Methyl Benzo[b]thiophene-3-carboxylate (6ja): Colorless oil
(319 mg, 83% yield). IR (neat):
ν =
˜
1707 cm–1. 1H NMR
H), 7.33–7.42 (m, 2 H), 7.80–7.84 (m, 2 H), 8.35 (d, J = 7.7 Hz, 1
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 26.4, 122.4, 124.2,
124.9, 124.9, 128.9, 131.9, 136.7, 140.0, 164.9 ppm. HRMS (APCI):
calcd. for C10H10ONS [M]+ 192.0478; found 192.0474.
(500 MHz, CDCl3): δ = 3.96 (s, 3 H), 7.40–7.44 (m, 1 H), 7.47–
7.52 (m, 1 H), 7.88 (d, J = 8.0 Hz, 1 H), 8.38 (s, 1 H), 8.60 (d, J =
8.0 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 51.7, 122.5,
124.7, 125.0, 125.4, 127.0, 136.6, 136.7, 140.0, 163.2 ppm. HRMS
(APCI): calcd. for C10H9O2S [M]+ 193.0318; found 193.0316.
Supporting Information (see footnote on the first page of this arti-
1
cle): H, 13C, and 19F NMR spectra of all esters and amides, and
N-Methylbenzamide (6af) (commercially available): White solid
a chiral HPLC chart.
(205 mg, 76% yield); m.p. 78–79 °C. IR (neat): ν = 3675, 3327,
˜
1
1636 cm–1. H NMR (500 MHz, CDCl3): δ = 3.00(I)/3.01(II) (s, 3
Acknowledgments
H), 6.30 (br. s, 1 H), 7.42 (t, J = 7.2 Hz, 2 H), 7.48 (t, J = 7.2 Hz,
1 H), 7.76 (d, J = 7.2 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 26.8, 126.8, 128.5, 131.3, 134.6, 168.2 ppm.
Financial support from the Japanese Ministry of Education, Cul-
ture, Sports, Science, and Technology (MEXT) in the form of a
Grant-in-Aid for Scientific Research (grant number 25105710) and
the Iodine Research Project of Chiba University is gratefully ac-
knowledged.
N,3-Dimethylbenzamide (6cf) (commercially available): White solid
(272 mg, 91% yield); m.p. 45–46 °C. IR (neat): ν = 3257, 1632 cm–1.
˜
1H NMR (500 MHz, CDCl3): δ = 2.38 (s, 3 H), 2.99(I)/3.00(II) (s,
3 H), 6.32 (br. s, 1 H), 7.28–7.32 (m, 2 H), 7.51–7.56 (m, 1 H), 7.59
(s, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 21.3, 26.8, 123.7,
127.6, 128.3, 132.0, 134.5, 138.3, 168.4 ppm.
[1] a) D. S. Johnson, J. J. Li, (Eds.), The Art of Drug Synthesis
Wiley, Hoboken, NJ, 2007; b) A. Zapf, M. Beller, Top. Catal.
2002, 19, 101–109; c) J. Stetter, F. Lieb, Angew. Chem. 2000,
112, 1792; Angew. Chem. Int. Ed. 2000, 39, 1724–1744.
[2] For recent reviews, see: a) A. Roy, S. Roy, G. W. Gribble, Tetra-
hedron 2012, 68, 9867–9923; b) L. R. Odell, F. Russo, M.
Larhed, Synlett 2012, 23, 685–698, and references cited therein.
[3] For the Fischer ester Synthesis see: a) E. Fischer, A. Speier,
Ber. Dtsch. Chem. Ges. 1895, 28, 3252–3258; b) S. P. Bew, D. L.
Hughs, S. V. Sharma, J. Org. Chem. 2006, 71, 7881–7884; c)
R. C. Larock, Comprehensive Organic Transformations, 2nd ed.,
Wiley, New York, 1999, p. 1625–1993; for the Mitsunobu reac-
N,2-Dimethylbenzamide (6df) (commercially available): White solid
(257 mg, 86% yield); m.p. 76–77 °C. IR (neat): ν = 3675, 3291,
˜
1633 cm–1. 1H NMR (500 MHz, CDCl3): δ = 2.39 (s, 3 H), 2.92(I)/
2.93(II) (s, 3 H), 5.99 (br. s, 1 H), 7.11–7.20 (m, 2 H), 7.24–7.31
(m, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 19.7, 26.5, 125.6,
126.6, 129.7, 130.8, 135.9, 136.4, 170.8 ppm.
N-Methyl-4-methoxybenzamide (6ef, commercially available): White
solid (271 mg, 82% yield); m.p. 118–119 °C. IR (neat): ν = 3351,
˜
1
1628 cm–1. H NMR (500 MHz, CDCl3): δ = 2.96(I)/2.97(II) (s, 3
Eur. J. Org. Chem. 2013, 7815–7822
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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7821

S. Dohi, K. Moriyama, H. Togo
FULL PAPER
tion, see: d) O. Mitsunobu, Synthesis 1981, 1–28; e) M. P. Watt-
erson, G. W. J. Fleet, Tetrahedron Lett. 2003, 44, 5853–5857;
f) A. E. Favorskii, J. Prakt. Chem. 1895, 51, 533–563; A. E.
Favorskii, J. Prakt. Chem. 1913, 88, 641–698; g) A. Baeyer, V.
Villiger, Ber. Dtsch. Chem. Ges. 1899, 32, 3625–3633; h) A.
Pinner, F. Klein, Ber. Dtsch. Chem. Ges. 1883, 16, 352; i) A.
Pinner, F. Klein, Ber. Dtsch. Chem. Ges. 1883, 16, 1643–1655.
[4] a) C. Schotten, Ber. Dtsch. Chem. Ges. 1884, 17, 2544–2547; b)
E. Baumann, Ber. Dtsch. Chem. Ges. 1886, 19, 3218–3222; c)
E. Beckmann, Ber. Dtsch. Chem. Ges. 1886, 19, 988–993; d)
J. J. Ritter, P. P. Minieri, J. Am. Chem. Soc. 1948, 70, 4045–
4048.
[5] a) A. Schoenberg, I. Bartoletti, R. F. Heck, J. Org. Chem. 1974,
39, 3318–3326; for recent papers, see: b) D. A. Watson, X. Fan,
S. L. Buchwald, J. Org. Chem. 2008, 73, 7096–7101; c) J. R.
Martinelli, D. A. Watson, D. M. M. Freckmann, T. E. Barder,
S. L. Buchwald, J. Org. Chem. 2008, 73, 7102–7107; d) R. H.
Munday, J. R. Martinelli, S. L. Buchwald, J. Am. Chem. Soc.
2008, 130, 2754–2755; e) R. Shang, Y. Fu, J. Li, S. Zhang, Q.
Guo, L. Liu, J. Am. Chem. Soc. 2009, 131, 5738–5739.
[6] a) A. Schoenberg, R. F. Heck, J. Org. Chem. 1974, 39, 3327–
3331; for recent papers, see: b) R. F. Cunico, B. Maity, Org.
papers, see: c) S. Ushijima, S. Dohi, K. Moriyama, H. Togo,
Tetrahedron 2012, 68, 1436–1442; d) H. Baba, K. Moriyama,
H. Togo, Synlett 2012, 23, 1175–1180; e) S. Ushijima, K. Mori-
yama, H. Togo, Tetrahedron 2012, 68, 4701–4709; f) S. Ushi-
jima, K. Moriyama, H. Togo, Tetrahedron 2012, 68, 4588–4595;
g) S. Dohi, K. Moriyama, H. Togo, Tetrahedron 2012, 68,
6557–6564.
a) C. Gallina, C. Giordano, Synthesis 1989, 466–468; b) E. J.
Corey, J. O. Link, Y. Shao, Tetrahedron Lett. 1992, 33, 3435–
3438; c) C. B. Kelly, M. A. Mercadante, T. A. Hamlin, M. H.
Fletcher, J. Org. Chem. 2012, 77, 8131–8141.
a) R. A. Rebelo, M. C. Rezende, F. Nome, C. Zucco, Synth.
Commun. 1987, 17, 1741–1748; b) S. C. Hess, F. Nome, C.
Zucco, M. C. Rezende, Synth. Commun. 1989, 19, 3037–3045;
c) R. N. Ram, V. K. Soni, D. K. Gupta, Tetrahedron 2012, 68,
9068–9075.
L. Cao, J. Ding, M. Gao, Z. Wang, J. Li, A. Wu, Org. Lett.
2009, 11, 3810–3813.
[9]
[10]
[11]
[12]
F. M. Piller, P. Appokkuttan, A. Gavryushin, M. Helm, P.
Knochel, Angew. Chem. 2008, 120, 6907; Angew. Chem. Int.
Ed. 2008, 47, 6802–6806.
Lett. 2002, 4, 4357–4359; c) J. Ju, M. Jeong, J. Moon, H. M. [13]
Jung, S. Lee, Org. Lett. 2007, 9, 4615–4618; d) X. Wu, H. Neu-
mann, M. Beller, Chem. Asian J. 2010, 5, 2168–2172; e) X. Wu,
H. Neumann, M. Beller, Chem. Eur. J. 2010, 16, 9750–9753; f)
B. Roberts, D. Liptrot, L. Alcaraz, T. Luker, M. J. Stocks, Org.
Lett. 2010, 12, 4280–4283; g) D. N. Sawant, Y. S. Wagh, K. D.
Bhatte, B. M. Bhanage, J. Org. Chem. 2011, 76, 5489–5494; h)
T. T. Dang, Y. Zhu, S. C. Ghosh, A. Chen, C. L. L. Chai, A. M.
Seayad, Chem. Commun. 2012, 48, 1805–1807.
a) Y. Takeda, S. Okumura, S. Minakata, Synthesis 2013, 45,
1029–1033; b) S. Minakata, S. Okumura, T. Nagamachi, Y.
Takeda, Org. Lett. 2011, 13, 2966–2969; c) S. Minakata, I. Sa-
saki, T. Ide, Angew. Chem. 2010, 122, 1331; Angew. Chem. Int.
Ed. 2010, 49, 1309–1311; d) Y. Takeda, S. Okumura, S. Minak-
ata, Angew. Chem. 2012, 124, 7924; Angew. Chem. Int. Ed.
2012, 51, 7804–7808; e) Y. Takeda, S. Enokijima, T. Nagama-
chi, K. Nakayama, S. Minakata, Asian J. Org. Chem. 2013, 2,
91–97.
[7] a) L. D. Bratton, H. Huh, R. A. Bartsch, J. Heterocycl. Chem.
2000, 37, 815–819; b) J. C. J. Amedio, G. T. Lee, K. Prasad, O.
Repic, Synth. Commun. 1995, 25, 2599–2612; c) H. Li, J. Bal-
sells, Tetrahedron Lett. 2008, 49, 2034–2037; d) M. Mosrin, N.
Boudet, P. Knochel, Org. Biomol. Chem. 2008, 6, 3237–3239;
e) L. Lemoucheux, J. Rouden, M. Lasne, Tetrahedron Lett.
2000, 41, 9997–10001; f) L. Lemoucheux, T. Seitz, J. Rouden,
M. Lasne, Org. Lett. 2004, 6, 3703–3706; g) C. Dunst, P. Kno-
chel, Synlett 2011, 2064–2068; h) T. Yamazaki, T. Terajima, T.
Kawasaki-Taskasuka, Tetrahedron 2008, 64, 2419–2424; i)
M. A. Schade, G. Manolikakes, P. Knochel, Org. Lett. 2010,
12, 3648–3650.
[14] T. Imanishi, Y. Fujiwara, Y. Sawama, Y. Monguchi, H. Sajiki,
Adv. Synth. Catal. 2012, 354, 771–776.
[15] X. Jia, H. Wang, Q. Huang, L. Kong, W. Zhang, J. Chem. Res.
2006, 135–138.
[16] Y. Otani, O. Nagae, Y. Naruse, S. Inagaki, M. Ohno, K. Yama-
guchi, G. Yamamoto, M. Uchiyama, T. Ohwada, J. Am. Chem.
Soc. 2003, 125, 15191–15199.
[17] W. Songa, L. Maa, L. Huab, Synth. Commun. 2011, 41, 3186–
3196.
[18] T. K. Hyster, T. Rovis, J. Am. Chem. Soc. 2010, 132, 10565–
10569.
Received: August 2, 2013
[8] For reviews, see: a) H. Togo, S. Iida, Synlett 2006, 2159–2175;
Published Online: October 9, 2013
b) H. Togo, J. Synth. Org. Chem. 2008, 66, 652–663; for recent
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