Palladium-catalyzed direct acylation of ketoximes and aldoximes from the alcohol oxidation level through C-H bond activation

Article abstract of DOI:10.1002/ejoc.201300649

A highly efficient palladium-catalyzed oxidative ortho-acylation of O-methyl ketoximes and O-methyl aldoximes with benzylic and aliphatic alcohols from the alcohol oxidation level is described. This protocol potentially provides new opportunities to use readily available alcohols as starting materials for catalytic reactions, and represents a catalytic alternative to transcend the barriers imposed by classical Friedel-Crafts acylation. A highly efficient palladium-catalyzed oxidative ortho-acylation of O-methyl ketoximes and O-methyl aldoximes with benzylic and aliphatic alcohols from the alcohol oxidation level is described. Copyright

Full text of DOI:10.1002/ejoc.201300649

FULL PAPER
DOI: 10.1002/ejoc.201300649
Palladium-Catalyzed Direct Acylation of Ketoximes and Aldoximes from the
Alcohol Oxidation Level through C–H Bond Activation
Satyasheel Sharma,[a] Minyoung Kim,[a] Jihye Park,[a] Mirim Kim,[a] Jong Hwan Kwak,[a]
Young Hoon Jung,[a] Joa Sub Oh,[b] Youngil Lee,[c] and In Su Kim*[a]
Keywords: Acylation / Alcohols / C–H Activation / Oximes / Palladium
A highly efficient palladium-catalyzed oxidative ortho-acyl-
ation of O-methyl ketoximes and O-methyl aldoximes with
benzylic and aliphatic alcohols from the alcohol oxidation
level is described. This protocol potentially provides new op-
portunities to use readily available alcohols as starting mate-
rials for catalytic reactions, and represents a catalytic alterna-
tive to transcend the barriers imposed by classical Friedel–
Crafts acylation.
transformation.[5] As a result of the pioneering efforts of
Murai and co-workers[6] on C–H bond activation, recent
Introduction
Aryl ketones are important structural motifs in natural progress has been made on dehydrogenative cross-coupling
products, pharmaceuticals, fragrances and functional mate- between sp2 or sp3 C–H bonds and sp2 C–H bonds of ar-
rials.[1] Friedel–Crafts acylation using preactivated acyl enes or alkenes.[7] Transition-metal-catalyzed acylation has
chlorides is a common tool for the preparation of aryl been well-documented.[8] Cheng et al. first described palla-
ketones.[2] An alternative pathway that can be used to di- dium-catalyzed ortho-acylation reaction of arenes contain-
rectly access this scaffold is coupling reactions between ar- ing a pyridine directing group with aryl aldehydes to afford
enes and benzonitriles promoted by stoichiometric amounts aryl ketones.[9] Later, palladium- or rhodium-catalyzed sp2
of Lewis acids.[3] However, all these reactions have inherent C–H bond acylations of 2-arylpyridines,[10] oximes,[11]
limitations. They usually suffer from a lack of atom effi- amides,[12] acetanilides,[13] indoles,[14] azobenzenes,[15] and
ciency due to the required preparation of stoichiometric benzothiazoles[16] with aldehydes were reported. Decarbox-
amounts of suitable cross-coupling partners. In addition, ylative acylations of acetanilides,[17] arylpyridines,[18] phen-
many of these reactions demand the use of toxic reagents oxypyridine,[19]
indole,[20]
enamides,[21]
oximes,[22]
and harsh conditions as well as the production of poten- amides,[23] and carbamates[24] using α-keto acids as acyl
tially hazardous byproducts. Therefore, the development of equivalents have also been demonstrated. Recently, a palla-
truly catalytic alternatives is highly desirable.
dium-catalyzed acylation through C–C, C–H and C–O
Transition-metal-catalyzed cross-coupling reactions have bond cleavage of α-diketones, toluenes and carboxylic acids,
emerged as a powerful tool that allows synthetic chemists respectively, was reported.[25] However, the use of transi-
to produce structurally diverse organic molecules.[4] In par- tion-metal-catalyzed oxidative acylation on aromatic sp2 C–
ticular, carbon–carbon cross-coupling reactions involving H bonds by employing alcohols as acyl surrogates is ex-
selective activation of carbon–hydrogen bonds has become tremely rare. In 2011, Li and co-workers described an ele-
an attractive alternative to traditional cross-coupling reac- gant study of palladium-catalyzed oxidative ortho-acylation
tions, because such methods avoid a multistep preparation of arylpyridines with benzylic and aliphatic alcohols as acyl
of preactivated starting materials and the production of sources through C–H bond activation.[26] Yuan et al. also
stoichiometric amounts of metallic waste. Thus, cross-cou- reported a palladium-catalyzed oxidative C–H bond acyl-
pling reactions that proceed through C–H bond activation ation of acetanilides with benzylic alcohols.[27] Recently, we
can lead to an improved overall efficiency of the desired demonstrated Pd-catalyzed oxidative sp2 C–H bond acyl-
ation of N-benzyltriflamides and 2-phenoxypyridines with
alcohols as coupling partners.[28]
[a] School of Pharmacy, Sungkyunkwan University,
Alcohols have long served as versatile connection points
in the construction of carbon frameworks. Notably,
alcohols are available at low cost in great structural diver-
sity, and are easy to store and handle. Thus, alcohols can
be reliable candidates for the acylation reaction because
they can be readily oxidized into aldehydes under metal ca-
talysis.[29]
Suwon 440-746, Republic of Korea
E-mail: insukim@skku.edu
http://pharm.skku.edu/
[b] College of Pharmacy, Dankook University,
Cheonan 330-714, Republic of Korea
[c] Department of Chemistry, University of Ulsan,
Ulsan 680-749, Republic of Korea
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300649.
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Direct Acylation of Ketoximes and Aldoximes
As part of an ongoing research program directed toward 4 equiv. TBHP, under otherwise identical conditions, the
the development of transition-metal-catalyzed oxidative formation of 3a was found to be improved in 58% yield
acylation reactions, we herein report the palladium-cata- (Table 1, entry 10). Further study revealed that AcOH addi-
lyzed ortho-acylation of O-methyl ketoximes and O-methyl tive is unique in its ability to facilitate high levels of conver-
aldoximes with benzylic alcohols and aliphatic alcohols, in sion (Table 1, entry 11). Furthermore, the combination of
the presence of tert-butyl hydroperoxide (TBHP) as a con- 3 equiv. TBHP and 3 equiv. AcOH was found to be effec-
venient oxidant, from the alcohol oxidation level.
tive, giving 3a in 75% yield. However, decreased loadings
of TBHP or AcOH were found to be less effective (Table 1,
entries 13 and 14). Finally, decreased loading of 2a, under
otherwise identical conditions, led to significantly decreased
formation of 3a (Table 1, entry 15).
Results and Discussion
We commenced our investigation by exploring the cou-
pling of acetophenone O-methyl oxime (1a) with benzyl
alcohol (2a); selected results are summarized in Table 1. To
our delight, the combination of Pd(OAc)2 and TBHP in
1,2-dichloroethane (DCE) solvent at 80 °C catalyzed the
coupling of 1a and 2a to provide the desired product 3a in
48% yield (Table 1, entry 1). In the absence of Pd(OAc)2 or
TBHP, under otherwise identical conditions, no formation
of 3a was observed. Screening of solvents showed that DCE
was superior to other solvents such as toluene, tetra-
hydrofuran (THF) and N,N-dimethylformamide (DMF)
(Table 1, entries 2–4). Further investigation of the effect of
palladium catalysts were undertaken, and Pd(OAc)2 was
found to be most effective in this coupling reaction (Table 1,
entries 5 and 6). Other oxidants including (NH4)2S2O8,
Ag2CO3 and benzoquinone failed to effect any significant
product formation (Table 1, entries 7–9). Logically, it was
thought that formation of 3a could be controlled by the
amount of TBHP included. Indeed, through the use of
To evaluate the substrate scope and limitations of this
process, a broad range of O-methyl ketoximes were sub-
jected to the optimal reaction conditions (Table 2). Cou-
pling of benzyl alcohol (2a) and O-methyl ketoximes 1b–d
with an electron-donating group (OMe) and halogen groups
(F and Cl) at the para-position were found to be favored in
the acylation reaction, affording the corresponding prod-
ucts 3b–d in high yields, whereas the reaction of 1e, with
Table 2. Scope of O-methyl ketoximes.[a,b]
Table 1. Selected optimization of reaction conditions.[a]
Entry Oxidant (equiv.)
Additive
(equiv.)
Solvent
Yield
(%)[b]
1
2
3
4
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)
(NH4)2S2O8 (3)
Ag2CO3 (3)
benzoquinone (3)
TBHP (4)
TBHP (4)
TBHP (3)
TBHP (2)
TBHP (3)
TBHP (3)
DCE
toluene
THF
DMF
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
48
43
5
trace
24
trace
n.r.
n.r.
trace
58
76
75
46
64
41
5[c]
6[d]
7
8
9
10
11
12
13
14
15[e]
AcOH (3)
AcOH (3)
AcOH (3)
AcOH (1)
AcOH (3)
[a] Reaction conditions: 1a (0.3 mmol), 2a (0.9 mmol), Pd(OAc)2
(5 mol-%), oxidant, additive, solvent (1 mL), 80 °C, 4 h in pressure
tubes. [b] Isolated yield after flash column chromatography.
[c] Pd(TFA)2 (5 mol-%) was used. [d] PdCl2 (5 mol-%) was used.
[e] 2a (2 equiv.) was used.
[a] Isolated yield by flash column chromatography. [b] Reaction
time in hours. [c] Regioisomers at C-6 and C-2 were obtained with
3:1 ratio.
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FULL PAPER
electron-withdrawing group (CF3) at the para-position, was reactions proceeded smoothly in high yields. This transfor-
found to be relatively less reactive under these reaction con- mation also showed good tolerance toward halogen groups.
ditions. The acylation of meta-substituted O-methyl ketox- Notably, the chloro and bromo moieties offer the opportu-
imes 1f and 1g preferentially occurred at the less sterically nity for further transformations of the products by using
hindered ortho-position, to afford the corresponding prod- other traditional cross-coupling reactions. In addition, 1-
uct 3f and 3g as single regioisomers. However, meta-fluoro- naphthalenemethanol (2k) and 2-naphthalenemethanol (2l)
acetophenone O-methyl oxime (1h) afforded a mixture of were found to be favored in the reaction under these reac-
regioisomers at C-6 and C-2 with 3:1 ratio. These results tion conditions, affording the desired products 4k and 4l.
suggest steric effects of the substrate strongly interfere with Aliphatic alcohols 2m and 2n displayed relatively poor reac-
the formation of the cyclopalladated intermediate. Notably, tivity in the present catalytic system compared with benzylic
in the case of benzophenone O-methyl oxime (1i), with four alcohols. However, allylic alcohols failed to deliver the de-
ortho-C–H bonds, only monoacylation took place to pro- sired acylation products.
vide the corresponding product 3i in 80% yield. Finally,
ortho-substituted O-methyl ketoximes 1j–l were found to be ketoximes to aldoximes (Table 4). To our delight, benz-
good substrates in this catalytic transformation. aldehyde O-methyl oxime (5a) coupled with benzylic
We then sought to expand the substrate scope from
To further evaluate the substrate scope and limitations alcohols 2a–c with electron-neutral, -donating, and -with-
of the reaction, a range of benzylic alcohols and aliphatic drawing substituents under the same optimal reaction con-
alcohols were coupled with chroman-4-one O-methyl oxime ditions used in the coupling reaction between O-methyl ke-
(1j) under the optimal reaction conditions, as shown in toximes and alcohols, albeit with slightly decreased reactiv-
Table 3. With either electron-rich or electron-deficient ity. Furthermore, ortho-substituted O-methyl aldoxime 5b
groups, for example p-MeO (2b), m-Me (2g), o-MeO (2i), p- and naphthalene-derived O-methyl aldoxime 5c also partici-
CO2Me (2c), and p-CF3 (2d) groups, the oxidative coupling pated in this catalytic acylation reaction to furnish the cor-
responding products 6d and 6e, respectively. To the best of
our knowledge, this is the first report of a catalytic acyl-
ation reaction of aldoximes from the alcohol oxidation
level.
Table 3. Scope of the reaction with alcohols.[a,b]
Table 4. Expansion of substrate scope to O-methyl aldoximes.[a,b]
[a] Isolated yield by flash column chromatography. [b] Reaction
time in hours.
To gain some mechanistic insight, a series of experiments
were conducted (Schemes 1, 2, and 3). First, a crossover
experiment between alcohols and aldehydes was performed
under the optimal reaction conditions (Scheme 1). Expo-
sure of O-methyl ketoxime 1j to equimolar quantities of
alcohol 2a and aldehyde 7b provided a mixture of 3j and
4b, respectively, in 67% combined yield in a 1:2.7 ratio
[a] Isolated yield by flash column chromatography. [b] Reaction
time in hours.
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Direct Acylation of Ketoximes and Aldoximes
Scheme 1. Intermolecular competition experiments.
Scheme 2. Intramolecular competition experiments.
Scheme 3. Unexpected acylation through the formation of benzylic radicals.
[Scheme 1, Equation (1)]. Exposure of 1j to equimolar competition experiment between alcohols 2a and 2b re-
quantities of 7a and 2b under otherwise identical conditions sulted in a 1:1.3 ratio of products [Scheme 1, Equation (3)].
provided a mixture of 3j and 4b, respectively, in 74% yield
Intramolecular competition experiments with benzophen-
in a 1.7:1 ratio [Scheme 1, Equation (2)]. In addition, a one O-methyl ketoxime 8a and electronically different ar-
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Scheme 4. Plausible reaction mechanism.
ene moieties was performed to illustrate the chemoselectiv- quent directed cyclopalladation provides five-membered
ity of this method (Scheme 2). Interestingly, no significant palladacycle I.[32] At the same time, the alcohol was oxid-
distinction of product distribution between 9a and 9b was ized to aldehyde by TBHP and the tBuO· radical reacts with
observed.
TBHP to generate the tBuOO· radical,[33] which can ab-
The reaction between O-methyl ketoxime 1j and benzyl stract a hydrogen atom from the aldehyde to give a reactive
alcohol (2a) in the presence of radical scavenger ascorbic acyl radical.[34] Palladacycle I can react with a benzoyl radi-
acid resulted in drastically reduced formation of the acyl- cal to afford dimeric PdIII or PdIV intermediate II,[35] which
ated product 3j (Ͻ 5% yield).[11a,30] This result indicates can undergo reductive elimination to afford the desired
that the reaction proceeds through a possible radical path- product 3a, and regenerate the PdII catalyst.
way. To further support the mechanistic pathway for this
reaction, some related experiments were undertaken. Benzyl
alcohol (2a) was converted into the corresponding benz-
aldehyde (7a) in the presence of TBHP, irrespective of
whether palladium acetate was present or not. However, no
acylation reaction between O-methyl ketoxime 1j and benz-
aldehyde (7a) was detected in the absence of TBHP, even
when palladium acetate was used in a stoichiometric
amount. Interestingly, we found that 3-phenyl propan-1-ol
(2o) gave a mixture of the desired product 4o and the unex-
pected compound 3j. Furthermore, aliphatic alcohol 2p
provided unexpected compound 3j as a major compound
without any of the desired product (Scheme 3). These re-
sults can be rationalized by considering that the radical ini-
tiator TBHP can generate the benzylic radicals by C–C or
C–O bond cleavage, which may be trapped by a palladacy-
cle intermediate to give the corresponding benzylated prod-
uct or rapidly oxidized to provide the benzoyl radical in the
catalytic cycle. However, all attempts to trap the benzylated
product failed, presumably due to the fast oxidation kinet-
ics of the benzylic C–H bonds.[31]
Conclusions
We have described a highly efficient method for palla-
dium-catalyzed oxidative ortho-acylation of O-methyl ket-
oximes and O-methyl aldoximes with benzylic alcohols and
aliphatic alcohols from the alcohol oxidation level. These
transformations have been applied to a wide range of sub-
strates, and typically proceed with excellent levels of regio-
and chemoselectivity as well as with high functional group
tolerance. Furthermore, this protocol allows the generation
of an array of 1,2-diacylbenzenes, which are known to be
crucial synthetic precursors of biologically active com-
pounds, in a simple procedure while removing the O-methyl
oxime group from O-methyl ketoximes and O-methyl aldox-
imes. Further applications of this method to the synthesis
of biologically active compounds and a more detailed
mechanistic investigation are in progress.
Experimental Section
The mechanism presented in Scheme 4 for palladium-cat-
alyzed oxidative acylation from the alcohol oxidation level
appears plausible based upon the collected data. First, co-
General Methods: Commercially available reagents were used with-
out additional purification, unless otherwise stated. Sealed tubes
ordination of the nitrogen atom of 1a to PdII and subse- (13ϫ100 mm2) were purchased from Fischer Scientific, oven-dried
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Direct Acylation of Ketoximes and Aldoximes
overnight, and cooled under a stream of nitrogen prior to use.
Thin-layer chromatography was carried out by using plates coated
with Kieselgel 60F254 (Merck). For flash column chromatography,
E. Merck Kieselgel 60 (230–400 mesh) was used. NMR spectra (1H
and 13C NMR) were recorded with a Bruker Unity 400 MHz spec-
trometer for CDCl3 solutions and chemical shifts are reported as
parts per million (ppm) relative to, respectively, residual CHCl3 (δH
= 7.24 ppm) and CDCl3 (δC = 77.2 ppm) as internal standards.
Resonance patterns are reported as: s (singlet), d (doublet), t (trip-
let), q (quartet), sept (septet), and m (multiplet). In addition, the
notation br. is used to indicate a broad signal. Coupling constants
(J) are reported in Hertz [Hz]. IR spectra were recorded with a
Varian 2000 Infrared spectrophotometer and are reported as cm–1.
High-resolution mass spectra (HRMS) were recorded with a JEOL
JMS-600 spectrometer.
JC,F = 249.5 Hz), 152.9, 140.9 (d, JC,F = 6.4 Hz), 137.5, 132.8, 132.4
(d, JC,F = 3.9 Hz), 129.6 (d, JC,F = 8.0 Hz), 129.2, 128.4, 117.0 (d,
JC,F = 21.5 Hz), 116.1 (d, JC,F = 22.4 Hz), 61.7, 14.3 ppm. IR
(KBr): ν = 2937, 1671, 1600, 1578, 1492, 1408, 1369, 1318, 1274,
˜
1177, 1069, 976, 828 cm–1. HRMS (EI): calcd. for C16H14FNO2
[M]+ 271.1009; found 271.1011.
{5-Chloro-2-[1-(methoxyimino)ethyl]phenyl}(phenyl)methanone (3d):
1
Rf = 0.50 (n-hexane/EtOAc, 6:1). H NMR (400 MHz, CDCl3): δ
= 7.67 (d, J = 7.7 Hz, 2 H), 7.52–7.46 (m, 2 H), 7.43–7.37 (m, 4
H), 3.62 (s, 3 H), 1.98 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 196.0, 152.8, 140.3, 137.5, 134.8, 134.6, 132.9, 130.1, 129.3,
128.9, 128.8, 128.4, 61.8, 14.1 ppm. IR (KBr): ν = 2936, 1671, 1594,
˜
1479, 1449, 1369, 1315, 1283, 1179, 1105, 1048, 827 cm–1. HRMS
(EI): calcd. for C16H14ClNO2 [M]+ 287.0713; found 287.0713.
{2-[1-(Methoxyimino)ethyl]-5-(trifluoromethyl)phenyl}(phenyl)meth-
Synthesis of O-Methyl Ketoximes. General Procedure: O-Methyl
ketoximes were prepared from the corresponding methyl ketones
and methoxylamine hydrochloride according to the reported pro-
cedure.[36]
1
anone (3e): Rf = 0.44 (n-hexane/EtOAc, 6:1). H NMR (400 MHz,
CDCl3): δ = 7.76 (d, J = 8.2 Hz, 1 H), 7.71–7.66 (m, 3 H), 7.61 (d,
J = 8.2 Hz, 1 H), 7.53 (t, J = 7.2 Hz, 1 H), 7.40 (t, J = 7.7 Hz, 2
H), 3.65 (s, 3 H), 2.03 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 196.1, 152.7, 139.5 (d, JC,F = 10.2 Hz), 137.4, 133.0, 130.5 (q,
Synthesis of O-Methyl Aldoximes. General Procedure: A solution
of methoxylamine hydrochloride (1.34 g, 0.016 mol) in a mixture
of water (15 mL) and THF (5 mL) was treated with sodium acetate
JC,F = 33.1 Hz), 129.3, 129.2, 128.4, 128.1, 127.6, 126.8 (q, JC,F
=
3.6 Hz), 125.7 (q, JC,F = 3.6 Hz), 124.9, 122.2, 61.9, 14.1 ppm. IR
(1.12 g, 0.014 mol) followed by the aldehyde (9.32 mmol, 1 equiv.) (KBr): ν = 2939, 1673, 1450, 1338, 1268, 1175, 1130, 1092, 1048,
˜
and the resulting mixture was stirred at room temperature for 4 h.
The reaction mixture was diluted with EtOAc, washed with brine,
dried with Mg2SO4 and concentrated in vacuo. The residue was
purified by flash column chromatography (n-hexane/EtOAc) to af-
ford the corresponding O-methyl aldoximes.
840 cm–1. HRMS (EI): calcd. for C17H14F3NO2 [M]+ 321.0977;
found 321.0972.
{3-[1-(Methoxyimino)ethyl]naphthalen-2-yl}(phenyl)methanone (3f):
1
Rf = 0.40 (n-hexane/EtOAc, 6:1). H NMR (400 MHz, CDCl3): δ
= 7.95 (s, 1 H), 7.93 (s, 1 H), 7.90 (d, J = 7.8 Hz, 1 H), 7.85 (d, J
Acylation of O-Methyl Ketoximes or O-Methyl Aldoximes. Typical = 7.8 Hz, 1 H), 7.74 (d, J = 7.9 Hz, 2 H), 7.60–7.49 (m, 3 H), 7.39
Procedure: To an oven-dried sealed tube charged with acetophen-
one O-methyl oxime (1a; 44.8 mg, 0.3 mmol, 1.0 equiv.), Pd(OAc)2
(t, J = 7.6 Hz, 2 H), 3.69 (s, 3 H), 2.13 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 197.3, 153.8, 138.4, 136.6, 133.6, 132.5,
(3.4 mg, 0.015 mmol, 5 mol-%), TBHP (0.16 mL, 0.9 mmol, 132.4, 129.5, 129.4, 128.5, 128.4, 128.3, 128.2, 127.8, 127.6, 127.4,
3.0 equiv.), and AcOH (45 μL, 0.9 mmol, 3.0 equiv.) in anhydrous
DCE (1 mL, 0.3 m), was added benzyl alcohol (2a; 97.3 mg,
0.9 mmol, 3 equiv.). The reaction mixture was stirred at 80 °C for
4 h. After cooling to room temperature, the reaction mixture was
evaporated onto silica gel. Purification of the product by column
chromatography (SiO2; n-hexane/EtOAc, 15:1) provided 3a
(57.2 mg, 75%).
61.7, 14.2 ppm. IR (KBr): ν = 2935, 1742, 1681, 1597, 1451, 1365,
˜
1282, 1193, 1053, 872 cm–1. HRMS (EI): calcd. for C20H17NO2
[M]+ 303.1259; found 303.1261.
{4-Methoxy-2-[1-(methoxyimino)ethyl]phenyl}(phenyl)methanone
(3g): Rf = 0.32 (n-hexane/EtOAc, 4:1). 1H NMR (400 MHz,
CDCl3): δ = 7.67 (d, J = 7.8 Hz, 2 H), 7.50–7.45 (m, 2 H), 7.37 (t,
J = 7.4 Hz, 2 H), 6.96–6.91 (m, 2 H), 3.86 (s, 3 H), 3.71 (s, 3 H),
1.97 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 196.9, 161.3,
154.8, 139.3, 138.7, 132.3, 131.7, 131.1, 129.4, 128.2, 114.0, 113.4,
{2-[1-(Methoxyimino)ethyl]phenyl}(phenyl)methanone (3a): Rf
=
0.44 (n-hexane/EtOAc, 6:1). 1H NMR (400 MHz, CDCl3): δ = 7.68
(d, J = 7.6 Hz, 2 H), 7.52–7.44 (m, 5 H), 7.37 (t, J = 7.6 Hz, 2 H), 61.7, 55.6, 15.2 ppm. IR (KBr): ν = 2938, 2817, 1662, 1600, 1563,
˜
3.65 (s, 3 H), 2.00 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 197.6, 154.0, 138.8, 138.2, 136.4, 132.6, 130.2, 129.3, 129.0, 128.6,
1489, 1448, 1420, 1367, 1314, 1284, 1256, 1231, 1177, 1155, 1067,
1046, 938, 916, 864 cm–1. HRMS (EI): calcd. for C17H17NO3 [M]+
283.1208; found 283.1208.
128.3, 127.7, 61.7, 14.4 ppm. IR (KBr): ν = 2935, 1668, 1597, 1449,
˜
1367, 1314, 1286, 1154, 1048, 928 cm–1. HRMS (EI): calcd. for
C16H15NO2 [M]+ 253.1103; found 253.1103.
{4-Fluoro-2-[1-(methoxyimino)ethyl]phenyl}(phenyl)methanone (3h):
Rf = 0.50 (n-hexane/EtOAc, 6:1). H NMR (400 MHz, CDCl3): δ
1
{5-Methoxy-2-[1-(methoxyimino)ethyl]phenyl}(phenyl)methanone
(3b): Rf = 0.30 (n-hexane/EtOAc, 6:1). 1H NMR (400 MHz,
CDCl3): δ = 7.68 (d, J = 7.6 Hz, 2 H), 7.48 (t, J = 7.2 Hz, 1 H),
= 7.66 (d, J = 7.9 Hz, 2 H), 7.53–7.44 (m, 2 H), 7.38 (t, J = 7.6 Hz,
2 H), 7.19–7.11 (m, 2 H), 3.67 (s, 3 H), 1.98 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 196.6, 163.5 (d, JC,F = 249.3 Hz),
7.42–7.35 (m, 3 H), 7.04–6.96 (m, 2 H), 3.82 (s, 3 H), 3.61 (s, 3 H), 153.1 (d, JC,F = 2.2 Hz), 139.2 (d, JC,F = 7.9 Hz), 138.1, 134.8 (d,
1.96 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 197.3, 159.8, JC,F = 3.4 Hz), 132.7, 131.3 (d, JC,F = 8.8 Hz), 129.3, 128.3, 115.4
153.3, 140.2, 138.1, 132.5, 129.2, 128.9, 128.6, 128.2, 115.9, 114.0,
61.5, 55.6, 14.2 ppm. IR (KBr): ν = 2937, 1669, 1601, 1497, 1414,
(d, JC,F = 21.3 Hz), 114.9 (d, JC,F = 23.0 Hz), 61.9, 14.4 ppm. IR
(KBr): ν = 2937, 1669, 1604, 1448, 1369, 1283, 1203, 1148, 1047,
˜
˜
1367, 1288, 1177, 1122, 1040, 896 cm–1. HRMS (EI): calcd. for 874 cm–1. HRMS (EI): calcd. for C16H14FO2 [M]+ 271.1009; found
C17H17NO3 [M]+ 283.1208; found 283.1212.
271.1002.
{5-Fluoro-2-[1-(methoxyimino)ethyl]phenyl}(phenyl)methanone (3c):
{2-Fluoro-6-[1-(methoxyimino)ethyl]phenyl}(phenyl)methanone
1
Rf = 0.43 (n-hexane/EtOAc, 6:1). H NMR (400 MHz, CDCl3): δ (3hh): Rf = 0.37 (n-hexane/EtOAc, 6:1). 1H NMR (400 MHz,
= 7.68 (d, J = 7.6 Hz, 2 H), 7.54–7.44 (m, 2 H), 7.38 (t, J = 7.6 Hz,
2 H), 7.23–7.14 (m, 2 H), 3.62 (s, 3 H), 1.98 (s, 3 H) ppm. 13C 7.47–7.38 (m, 3 H), 7.29 (d, J = 7.8 Hz, 1 H), 7.14 (t, J = 8.6 Hz,
NMR (100 MHz, CDCl3): δ = 196.0 (d, JC,F = 1.2 Hz), 162.5 (d,
1 H), 3.54 (s, 3 H), 2.06 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 7.78 (d, J = 7.7 Hz, 2 H), 7.52 (t, J = 7.2 Hz, 1 H),
Eur. J. Org. Chem. 2013, 6656–6665
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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6661

I. S. Kim et al.
CDCl3): δ = 193.1, 160.9, 158.4 (d, JC,F = 246.4 Hz), 138.0, 137.5, H) ppm. 13C NMR (100 MHz, CDCl3): δ = 196.4, 166.4, 156.9,
FULL PAPER
137.4 (d, JC,F = 4.1 Hz), 133.0, 132.9 (d, JC,F = 2.8 Hz), 130.7,
130.6 (d, JC,F = 8.5 Hz), 130.2, 129.0, 128.4, 123.3, 123.2 (d, JC,F
= 3.1 Hz), 116.3, 116.1 (d, JC,F = 22.0 Hz), 61.6, 13.6 ppm. IR
146.0, 141.4, 138.2, 133.1, 130.6, 129.5, 128.8, 121.0, 119.2, 116.2,
64.9, 61.7, 52.4, 24.0 ppm. IR (KBr): ν = 2938, 1724, 1678, 1619,
˜
1571, 1502, 1443, 1406, 1319, 1278, 1190, 1106, 1078, 1051, 944,
(KBr): ν = 2937, 1677, 1605, 1567, 1448, 1369, 1317, 1268, 1144, 872 cm–1. HRMS (EI): calcd. for C19H17NO5 [M]+ 339.1107; found
˜
1049, 945, 877 cm–1. HRMS (EI): calcd. for C16H14FO2 [M]+
271.1009; found 271.1008.
339.1117.
[4-(Methoxyimino)chroman-5-yl][4-(trifluoromethyl)phenyl]meth-
1
{2-[(Methoxyimino)(phenyl)methyl]phenyl}(phenyl)methanone (3i):
anone (4d): Rf = 0.47 (n-hexane/EtOAc, 4:1). H NMR (400 MHz,
1
Rf = 0.38 (n-hexane/EtOAc, 4:1). H NMR (400 MHz, CDCl3): δ
CDCl3): δ = 7.83 (d, J = 8.2 Hz, 2 H), 7.63 (d, J = 8.2 Hz, 2 H),
7.34 (t, J = 7.7 Hz, 1 H), 7.03 (d, J = 8.3 Hz, 1 H), 6.87 (d, J =
7.4 Hz, 1 H), 4.20 (t, J = 6.2 Hz, 2 H), 3.48 (s, 3 H), 2.78 (t, J =
6.2 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 196.0, 157.0,
146.0, 140.7 (d, JC,F = 9.6 Hz), 133.6 (q, JC,F = 32.1 Hz), 130.6,
129.1 (d, JC,F = 5.7 Hz), 125.3 (q, JC,F = 3.6 Hz), 125.1, 122.4,
= 7.77–7.74 (m, 2 H), 7.51–7.27 (m, 12 H), 3.72 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 197.6, 155.0, 140.3, 138.2, 136.1,
132.9, 132.8, 130.4, 130.0, 129.8, 129.7, 129.4, 129.1, 129.0, 128.4,
128.1, 62.4 ppm. IR (KBr): ν = 2935, 2897, 2816, 1590, 1484, 1444,
˜
1326, 1165, 1054, 1031, 982, 919, 878 cm–1. HRMS (EI): calcd. for
C21H17NO2 [M]+ 315.1259; found 315.1257.
120.9, 119.3, 116.1, 64.9, 61.8, 23.9 ppm. IR (KBr): ν = 2939, 1681,
˜
1620, 1571, 1511, 1470, 1446, 1410, 1326, 1278, 1246, 1170, 1129,
1066, 1052, 1017, 945, 894 cm–1. HRMS (EI): calcd. for
C18H14F3NO3 [M]+ 349.0926; found 349.0927.
[4-(Methoxyimino)chroman-5-yl](phenyl)methanone (3j): Rf = 0.39
(n-hexane/EtOAc, 6:1). H NMR (400 MHz, CDCl3): δ = 7.73 (d,
1
J = 7.8 Hz, 2 H), 7.47 (t, J = 7.1 Hz, 1 H), 7.36 (t, J = 7.8 Hz, 2
H), 7.30 (t, J = 7.6 Hz, 1 H), 6.99 (d, J = 8.2 Hz, 1 H), 6.87 (d, J
= 7.4 Hz, 1 H), 4.19 (t, J = 6.2 Hz, 2 H), 3.49 (s, 3 H), 2.77 (t, J =
6.2 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 197.3, 156.9,
146.0, 138.8, 137.9, 132.4, 130.4, 129.0, 128.2, 120.9, 118.8, 116.2,
(4-Fluorophenyl)[4-(methoxyimino)chroman-5-yl]methanone (4e): Rf
= 0.37 (n-hexane/EtOAc, 4:1). 1H NMR (400 MHz, CDCl3): δ =
7.76–7.72 (m, 2 H), 7.30 (t, J = 7.8 Hz, 1 H), 7.06–6.98 (m, 3 H),
6.84 (d, J = 7.4 Hz, 1 H), 4.19 (t, J = 6.2 Hz, 2 H), 3.49 (s, 3 H),
2.77 (t, J = 6.2 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
195.8, 165.0 (d, JC,F = 252.2 Hz), 165.9, 146.0, 138.5, 134.3 (d, JC,F
= 3.0 Hz), 131.4 (d, JC,F = 9.0 Hz), 130.4, 120.8, 118.9, 116.1, 115.3
64.9, 61.7, 24.0 ppm. IR (KBr): ν = 2937, 1673, 1595, 1469, 1318,
˜
1279, 1145, 1079, 945, 850 cm–1. HRMS (EI): calcd. for
C17H15NO3 [M]+ 281.1052; found 281.1049.
(d, JC,F = 21.8 Hz), 64.9, 61.8, 24.0 ppm. IR (KBr): ν = 2938, 2900,
˜
[8-(Methoxyimino)-5,6,7,8-tetrahydronaphthalen-1-yl](phenyl)meth-
anone (3k): Rf = 0.61 (n-hexane/EtOAc, 6:1). H NMR (400 MHz,
1
2819, 1674, 1620, 1597, 1570, 1504, 1469, 1445, 1409, 1320, 1279,
1244, 1190, 1151, 1079, 1051, 1012, 945, 893 cm–1. HRMS (EI):
calcd. for C17H14FNO3 [M]+ 299.0958; found 299.0956.
CDCl3): δ = 7.67 (d, J = 7.8 Hz, 2 H), 7.43 (t, J = 7.1 Hz, 1 H),
7.42–7.28 (m, 3 H), 7.23 (d, J = 7.4 Hz, 1 H), 7.16 (d, J = 7.4 Hz,
1 H), 3.50 (s, 3 H), 2.75 (t, J = 5.9 Hz, 2 H), 2.52 (t, J = 6.9 Hz, 2
H), 1.84–1.77 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
197.9, 151.7, 140.6, 138.6, 138.3, 132.1, 129.6, 128.9, 128.8, 128.5,
(4-Bromophenyl)[4-(methoxyimino)chroman-5-yl]methanone (4f): Rf
= 0.63 (n-hexane/EtOAc, 4:1). 1H NMR (400 MHz, CDCl3): δ =
7.63 (d, J = 8.3 Hz, 2 H), 7.54 (d, J = 7.5 Hz, 2 H), 7.35 (t, J =
7.6 Hz, 1 H), 7.04 (d, J = 8.3 Hz, 1 H), 6.88 (d, J = 7.4 Hz, 1 H),
4.23 (t, J = 6.2 Hz, 2 H), 3.55 (s, 3 H), 2.82 (t, J = 6.2 Hz, 2
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 196.2, 156.9, 146.0,
138.2, 136.8, 131.6, 130.5, 127.4, 120.8, 119.0, 116.1, 64.9, 61.8,
128.2, 128.1, 126.4, 61.6, 30.4, 24.2, 21.1 ppm. IR (KBr): ν = 2932,
˜
1666, 1596, 1446, 1313, 1280, 1166, 1040, 933, 808 cm–1. HRMS
(EI): calcd. for C18H17NO2 [M]+ 279.1259; found 279.1257.
[3-Methoxy-8-(methoxyimino)-5,6,7,8-tetrahydronaphthalen-1-yl]-
(phenyl)methanone (3l): Rf = 0.34 (n-hexane/EtOAc, 6:1). 1H NMR
(400 MHz, CDCl3): δ = 7.70 (d, J = 7.8 Hz, 2 H), 7.46 (t, J =
7.6 Hz, 1 H), 7.35 (t, J = 7.7 Hz, 2 H), 6.77 (d, J = 2.3 Hz, 1 H),
6.72 (d, J = 2.5 Hz, 1 H), 3.79 (s, 3 H), 3.48 (s, 3 H), 2.73 (t, J =
6.0 Hz, 2 H), 2.52 (t, J = 6.7 Hz, 2 H), 1.83–1.79 (m, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 197.5, 159.6, 151.4, 142.4, 140.2,
138.1, 132.2, 128.9, 128.1, 121.5, 114.7, 112.1, 61.4, 55.5, 30.6, 24.1,
24.0 ppm. IR (KBr): ν = 2936, 2817, 1676, 1619, 1586, 1469, 1445,
˜
1396, 1319, 1278, 1245, 1190, 1172, 1154, 1068, 1051, 1008, 945,
893 cm–1. HRMS (EI): calcd. for C17H14BrNO3 [M]+ 359.0157;
found 359.0155.
[4-(Methoxyimino)chroman-5-yl](m-tolyl)methanone (4g): Rf = 0.62
1
(n-hexane/EtOAc, 4:1). H NMR (400 MHz, CDCl3): δ = 7.62 (s,
1 H), 7.52 (d, J = 7.5 Hz, 1 H), 7.36–7.28 (m, 3 H), 7.03 (d, J =
8.3 Hz, 1 H), 6.90 (d, J = 7.4 Hz, 1 H), 4.23 (t, J = 6.2 Hz, 2 H),
3.56 (s, 3 H), 2.82 (t, J = 6.1 Hz, 2 H), 2.38 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 197.6, 156.9, 146.0, 139.0, 137.9, 133.2,
130.3, 129.4, 128.1, 126.4, 120.9, 118.7, 116.2, 64.9, 61.7, 24.0,
21.1 ppm. IR (KBr): ν = 2936, 1671, 1595, 1470, 1354, 1289, 1214,
˜
1175, 1087, 1013, 879 cm–1. HRMS (EI): calcd. for C19H19NO3
[M]+ 309.1365; found 309.1370.
[4-(Methoxyimino)chroman-5-yl](4-methoxyphenyl)methanone (4b):
1
21.4 ppm. IR (KBr): ν = 2936, 2818, 1673, 1619, 1589, 1468, 1445,
˜
Rf = 0.24 (n-hexane/EtOAc, 4:1). H NMR (400 MHz, CDCl3): δ
1319, 1282, 1245, 1172, 1142, 1079, 1052, 954, 885 cm–1. HRMS
(EI): calcd. for C18H17NO3 [M]+ 295.1208; found 295.1204.
= 7.69 (d, J = 8.6 Hz, 2 H), 7.29 (t, J = 7.8 Hz, 1 H), 6.97 (d, J =
8.3 Hz, 1 H), 6.87–6.83 (m, 3 H), 4.21 (t, J = 6.2 Hz, 2 H), 3.82 (s,
3 H), 3.52 (s, 3 H), 2.79 (t, J = 6.0 Hz, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 196.2, 163.0, 157.9, 146.0, 139.2, 131.0,
130.3, 120.8, 118.5, 116.1, 113.4, 64.9, 61.8, 55.4, 24.0 ppm. IR
(3-Chlorophenyl)[4-(methoxyimino)chroman-5-yl]methanone (4h): Rf
= 0.53 (n-hexane/EtOAc, 4:1). 1H NMR (400 MHz, CDCl3): δ =
7.75 (s, 1 H), 7.62 (d, J = 7.7 Hz, 1 H), 7.49 (d, J = 7.9 Hz, 1 H),
7.39–7.33 (m, 2 H), 7.06 (d, J = 8.3 Hz, 1 H), 6.90 (d, J = 7.4 Hz,
1 H), 4.25 (t, J = 6.2 Hz, 2 H), 3.57 (s, 3 H), 2.83 (t, J = 6.2 Hz, 2
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 195.9, 156.9, 146.0,
139.7, 138.0, 134.5, 132.3, 130.5, 129.6, 128.9, 127.1, 120.9, 119.2,
(KBr): ν = 2936, 1666, 1600, 1575, 1509, 1467, 1444, 1419, 1318,
˜
1280, 1257, 1169, 1153, 1079, 1050, 944, 872 cm–1. HRMS (EI):
calcd. for C18H17NO4 [M]+ 311.1158; found 311.1159.
Methyl 4-[4-(Methoxyimino)chroman-5-carbonyl]benzoate (4c): Rf =
0.56 (n-hexane/EtOAc, 4:1). 1H NMR (400 MHz, CDCl3): δ = 8.01
116.1, 64.9, 61.8, 24.0 ppm. IR (KBr): ν = 2936, 2818, 1678, 1619,
˜
(d, J = 8.2 Hz, 2 H), 7.76 (d, J = 8.2 Hz, 2 H), 7.32 (t, J = 7.7 Hz, 1571, 1468, 1445, 1423, 1320, 1279, 1245, 1188, 1155, 1078, 1051,
1 H), 7.00 (d, J = 8.3 Hz, 1 H), 6.87 (d, J = 7.4 Hz, 1 H), 4.18 (t,
J = 6.2 Hz, 2 H), 3.89 (s, 3 H), 3.46 (s, 3 H), 2.74 (t, J = 6.2 Hz, 2
952, 893 cm–1. HRMS (EI): calcd. for C17H14ClNO3 [M]+
315.0662; found 315.0660.
6662
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 6656–6665

Direct Acylation of Ketoximes and Aldoximes
[4-(Methoxyimino)chroman-5-yl](2-methoxyphenyl)methanone (4i):
Rf = 0.15 (n-hexane/EtOAc, 4:1). H NMR (400 MHz, CDCl3): δ (t, J = 7.6 Hz, 2 H), 1.70–1.67 (m, 2 H), 1.32–1.30 (m, 4 H), 0.89–
= 7.68 (d, J = 7.7 Hz, 1 H), 7.41 (t, J = 7.7 Hz, 1 H), 7.28–7.24
(m, 1 H), 6.94–6.85 (m, 4 H), 4.17 (t, J = 6.2 Hz, 2 H), 3.64 (s, 3
H), 3.56 (s, 3 H), 2.77 (t, J = 6.2 Hz, 2 H) ppm. 13C NMR
(t, J = 6.3 Hz, 2 H), 3.89 (s, 3 H), 2.89 (t, J = 6.2 Hz, 2 H), 2.70
1
0.85 (m, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 207.5, 157.1,
147.2, 141.6, 130.5, 119.3, 118.5, 114.8, 64.8, 62.2, 43.5, 31.5, 24.4,
24.2, 22.6, 14.0 ppm. IR (KBr): ν = 2956, 2935, 2872, 2818, 1702,
˜
(100 MHz, CDCl3): δ = 195.6, 159.3, 156.6, 149.5, 142.9, 133.6, 1616, 1592, 1569, 1467, 1444, 1319, 1260, 1245, 1165, 1121, 1080,
131.9, 130.1, 127.4, 120.7, 120.0, 118.1, 116.0, 112.0, 65.0, 61.7,
1050, 962, 877 cm–1. HRMS (EI): calcd. for C16H21NO3 [M]+
275.1521; found 275.1522.
55.6, 24.3 ppm. IR (KBr): ν = 2938, 2837, 1647, 1620, 1594, 1488,
˜
1463, 1300, 1244, 1181, 1157, 1112, 1079, 1048, 1026, 941,
892 cm–1. HRMS (EI): calcd. for C18H17NO4 [M]+ 311.1158; found
311.1164.
1-[4-(Methoxyimino)chroman-5-yl]-3-phenylpropan-1-one (4o): Rf =
0.52 (n-hexane/EtOAc, 4:1). 1H NMR (400 MHz, CDCl3): δ =
7.31–7.22 (m, 6 H), 6.96 (d, J = 8.2 Hz, 1 H), 6.76 (d, J = 7.4 Hz,
1 H), 4.25 (t, J = 6.2 Hz, 2 H), 3.98 (s, 3 H), 3.09 (s, 4 H), 2.95 (t,
J = 6.2 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 206.2,
157.1, 147.4, 141.3, 141.1, 130.6, 128.5, 128.3, 126.1, 119.3, 118.7,
(2-Fluorophenyl)[4-(methoxyimino)chroman-5-yl]methanone (4j): Rf
= 0.34 (n-hexane/EtOAc, 4:1). 1H NMR (400 MHz, CDCl3): δ =
7.66 (t, J = 7.7 Hz, 1 H), 7.40–7.36 (m, 1 H), 7.25 (t, J = 7.7 Hz,
1 H), 7.08 (t, J = 7.6 Hz, 1 H), 6.97–6.84 (m, 3 H), 4.13 (t, J =
6.2 Hz, 2 H), 3.51 (s, 3 H), 2.73 (t, J = 6.2 Hz, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 193.5, 161.0 (d, JC,F = 256.7 Hz), 156.9,
146.5, 140.4, 133.9 (d, JC,F = 9.0 Hz), 131.2, 130.4, 126.5 (d, JC,F
114.8, 64.8, 62.3, 45.0, 30.7, 24.5 ppm. IR (KBr): ν = 2936, 2817,
˜
1701, 1615, 1568, 1496, 1469, 1445, 1360, 1319, 1291, 1245, 1165,
1089, 1047, 964, 884 cm–1. HRMS (EI): calcd. for C19H19NO3
[M]+ 309.1365; found 309.1370.
= 9.4 Hz), 123.7 (d, JC,F = 3.7 Hz), 120.6, 119.0, 116.5 (d, JC,F
22.4 Hz), 116.0 (d, JC,F = 2.2 Hz), 64.9, 61.7, 24.2 ppm. IR (KBr):
=
2-Benzoylbenzaldehyde O-Methyl Oxime (6a): Rf = 0.41 (n-hexane/
EtOAc, 6:1). H NMR (400 MHz, CDCl3): δ = 8.13 (s, 1 H), 7.88
(d, J = 7.8 Hz, 1 H), 7.76 (d, J = 7.9 Hz, 2 H), 7.58–7.38 (m, 6 H),
3.83 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 197.1, 146.4,
138.3, 137.5, 133.3, 131.0, 130.6, 130.1, 129.1, 129.0, 128.5, 127.2,
1
ν = 2938, 2900, 2819, 1675, 1610, 1573, 1481, 1448, 1320, 1296,
˜
1273, 1244, 1186, 1150, 1100, 1078, 1051, 1010, 944, 892 cm–1.
HRMS (EI): calcd. for C17H14FNO3 [M]+ 299.0958; found
299.0961.
62.1 ppm. IR (KBr): ν = 2937, 1663, 1597, 1448, 1315, 1268, 1180,
˜
1054, 1001, 846 cm–1. HRMS (EI): calcd. for C15H13NO2 [M]+
239.0946; found 239.0943.
[4-(Methoxyimino)chroman-5-yl](naphthalen-1-yl)methanone (4k):
1
Rf = 0.41 (n-hexane/EtOAc, 4:1). H NMR (400 MHz, CDCl3): δ
= 9.23 (d, J = 8.6 Hz, 1 H), 7.93 (d, J = 8.1 Hz, 1 H), 7.85 (d, J =
8.1 Hz, 1 H), 7.65 (t, J = 7.4 Hz, 1 H), 7.53 (t, J = 7.5 Hz, 1 H),
7.42–7.24 (m, 3 H), 7.09–7.03 (m, 2 H), 4.16 (t, J = 6.2 Hz, 2 H),
3.23 (s, 3 H), 2.72 (t, J = 6.2 Hz, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 198.8, 157.2, 146.8, 140.3, 134.7, 133.9, 133.2, 131.5,
130.4, 130.2, 128.3, 127.9, 127.2, 126.4, 124.1, 122.3, 119.0, 116.8,
2-(4-Methoxybenzoyl)benzaldehyde O-Methyl Oxime (6b): Rf = 0.41
(n-hexane/EtOAc, 4:1). H NMR (400 MHz, CDCl3): δ = 8.09 (s,
1 H), 7.90 (d, J = 7.8 Hz, 1 H), 7.74 (d, J = 7.8 Hz, 2 H), 7.49–
7.35 (m, 3 H), 6.89 (d, J = 8.7 Hz, 2 H), 3.85 (s, 6 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 195.7, 163.9, 146.4, 139.0, 132.6,
130.7, 130.4, 130.2, 129.4, 129.0, 126.8, 113.8, 62.1, 55.6 ppm. IR
1
65.0, 61.8, 24.4 ppm. IR (KBr): ν = 2936, 2818, 1663, 1614, 1591,
˜
(KBr): ν = 2924, 2853, 1665, 1599, 1511, 1461, 1421, 1304, 1259,
˜
1209, 1177, 1150, 1054, 930, 843 cm–1. HRMS (EI): calcd. for
C16H15NO3 [M]+ 269.1052; found 269.1051.
1570, 1508, 1467, 1444, 1319, 1282, 1257, 1214, 1176, 1156, 1090,
1046, 989, 934, 875 cm–1. HRMS (EI): calcd. for C21H17NO3 [M]+
331.1208; found 331.1194.
Methyl 4-{2-[(Methoxyimino)methyl]benzoyl}benzoate (6c): Rf
=
0.39 (n-hexane/EtOAc, 4:1). 1H NMR (400 MHz, CDCl3): δ =
8.10–8.07 (m, 3 H), 7.83–7.78 (m, 3 H), 7.55–7.38 (m, 3 H), 3.93
(s, 3 H), 3.78 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
196.5, 166.2, 146.2, 141.0, 137.6, 133.8, 131.1, 130.9, 129.7, 129.2,
[4-(Methoxyimino)chroman-5-yl](naphthalen-2-yl)methanone (4l): Rf
= 0.55 (n-hexane/EtOAc, 4:1). 1H NMR (400 MHz, CDCl3): δ =
8.08–8.05 (m, 2 H), 7.92–7.84 (m, 3 H), 7.59 (t, J = 7.2 Hz, 1 H),
7.51 (t, J = 7.7 Hz, 1 H), 7.40 (t, J = 7.8 Hz, 1 H), 7.10 (d, J =
8.3 Hz, 1 H), 7.00 (d, J = 7.4 Hz, 1 H), 4.24 (t, J = 6.1 Hz, 2 H),
3.53 (s, 3 H), 2.81 (t, J = 6.1 Hz, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 197.4, 156.9, 146.0, 138.5, 135.5, 135.3, 132.5, 130.6,
130.4, 129.5, 128.2, 128.1, 127.8, 126.5, 124.9, 121.1, 118.9, 116.3,
127.8, 62.1, 52.5 ppm. IR (KBr): ν = 2936, 1725, 1667, 1565, 1502,
˜
1437, 1405, 1180, 1192, 1107, 1054, 1018, 932, 872 cm–1. HRMS
(EI): calcd. for C17H15NO4 [M]+ 297.1001; found 297.1001.
2-Benzoyl-6-methoxybenzaldehyde O-Methyl Oxime (6d): Rf = 0.36
64.9, 61.8, 24.0 ppm. IR (KBr): ν = 2935, 2817, 1736, 1669, 1623,
˜
1
(n-hexane/EtOAc, 4:1). H NMR (400 MHz, CDCl3): δ = 8.23 (s,
1593, 1571, 1467, 1444, 1352, 1319, 1289, 1244, 1177, 1152, 1122,
1077, 1050, 963, 934, 881 cm–1. HRMS (EI): calcd. for C21H17NO3
[M]+ 331.1208; found 331.1208.
1 H), 7.70 (d, J = 7.8 Hz, 2 H), 7.50–7.34 (m, 4 H), 7.00 (d, J =
8.4 Hz, 1 H), 6.95 (d, J = 7.6 Hz, 1 H), 3.86 (s, 3 H), 3.54 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 197.4, 157.6, 142.6,
140.2, 137.8, 132.6, 130.6, 129.3, 128.2, 120.5, 118.7, 112.0, 61.8,
1-[4-(Methoxyimino)chroman-5-yl]butan-1-one (4m): Rf = 0.56 (n-
hexane/EtOAc, 4:1). 1H NMR (400 MHz, CDCl3): δ = 7.25–7.21
(m, 1 H), 6.90 (d, J = 8.4 Hz, 1 H), 6.71 (d, J = 7.4 Hz, 1 H), 4.19
(t, J = 6.2 Hz, 2 H), 3.89 (s, 3 H), 2.89 (t, J = 6.3 Hz, 2 H), 2.69
(t, J = 6.2 Hz, 2 H), 1.73–1.68 (m, 2 H), 0.96 (t, J = 7.4 Hz, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 207.3, 157.1, 147.2,
141.5, 130.5, 119.3, 118.5, 114.8, 64.8, 62.2, 45.5, 24.4, 18.0,
55.9 ppm. IR (KBr): ν = 2938, 2900, 2841, 2817, 1673, 1591, 1570,
˜
1458, 1338, 1315, 1279, 1218, 1185, 1070, 1048, 1001, 975, 920,
852 cm–1. HRMS (EI): calcd. for C16H15NO3 [M]+ 269.1052; found
269.1050.
3-Benzoyl-2-naphthaldehyde O-Methyl Oxime (6e): Rf = 0.50 (n-
1
hexane/EtOAc, 4:1). H NMR (400 MHz, CDCl3): δ = 8.26 (d, J
13.9 ppm. IR (KBr): ν = 2962, 2937, 2875, 2818, 1701, 1616, 1592,
˜
= 10.7 Hz, 2 H), 7.93–7.80 (m, 5 H), 7.59–7.55 (m, 3 H), 7.43 (t, J
= 7.5 Hz, 2 H), 3.83 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 197.0, 146.9, 137.9, 135.5, 133.7, 133.1, 132.5, 130.1, 129.9,
128.5, 128.4, 128.3, 128.2, 128.1, 127.9, 127.7, 62.1 ppm. IR (KBr):
1568, 1468, 1445, 1363, 1319, 1300, 1246, 1166, 1119, 1055, 967,
879 cm–1. HRMS (EI): calcd. for C14H17NO3 [M]+ 247.1208; found
247.1208.
1-[4-(Methoxyimino)chroman-5-yl]hexan-1-one (4n): Rf = 0.58 (n- ν = 2936, 2898, 2817, 1662, 1596, 1450, 1315, 1283, 1209, 1178,
˜
hexane/EtOAc, 4:1). 1H NMR (400 MHz, CDCl3): δ = 7.25–7.21
(m, 1 H), 6.89 (d, J = 8.3 Hz, 1 H), 6.70 (d, J = 7.4 Hz, 1 H), 4.19
1145, 1095, 1048, 943, 889 cm–1. HRMS (EI): calcd. for
C19H15NO2 [M]+ 289.1103; found 289.1105.
Eur. J. Org. Chem. 2013, 6656–6665
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6663

I. S. Kim et al.
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Supporting Information (see footnote on the first page of this arti-
1
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Received: May 3, 2013
Published Online: September 3, 2013
Eur. J. Org. Chem. 2013, 6656–6665
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6665