Efficient solvent- And temperature-tuned access to aldoxime ethers and phenolic functions by Pd-catalyzed C-O cross-coupling of aldoximes with aryl bromides and bromo-chalcones

Article abstract of DOI:10.1039/c9nj05124d

A single method with a functionality switching option was developed for the first time for the Pd-catalyzed C-O cross-coupling of aryl bromides and bromo-chalcones with aldoximes. The ligand tBuXPhos (L2) was found to be an effective supporting ligand for the Pd-catalyzed coupling of aldoximes with bromo coupling partners. The functionality switching from oxime ethers to a phenolic or hydroxy group was driven by solvent or temperature. This method offers the products in good to excellent yields in short reaction times.

Full text of DOI:10.1039/c9nj05124d

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Efficient solvent- and temperature-tuned access
to aldoxime ethers and phenolic functions by
Pd-catalyzed C–O cross-coupling of aldoximes
with aryl bromides and bromo-chalcones†
a
Cite this:DOI: 10.1039/c9nj05124d
Reeta,ab T. M. Rangarajan, *c Kumar Kaushik,
and Raj Pal Singh*a
Rishi Pal Singh,c Manjula Singhd
A single method with a functionality switching option was developed for the first time for the Pd-catalyzed
C–O cross-coupling of aryl bromides and bromo-chalcones with aldoximes. The ligand tBuXPhos (L2) was
found to be an effective supporting ligand for the Pd-catalyzed coupling of aldoximes with bromo coupling
partners. The functionality switching from oxime ethers to a phenolic or hydroxy group was driven by
solvent or temperature. This method offers the products in good to excellent yields in short reaction times.
Received 11th October 2019,
Accepted 15th December 2019
DOI: 10.1039/c9nj05124d
rsc.li/njc
with electron-deficient aryl systems, in the presence of a strong
base via an SNAr-type process, and subsequent hydrolysis with
Introduction
Oxime ethers are not only the fundamental constituents of acid. Recently, several other improved methods have been
pharmaceutical, bioactive (Fig. 1) and agricultural chemicals,1 as developed for the synthesis of aryloxyamines.1g,3f,g,m,n,9,10
the potent inhibitors of transthyretin amyloid fibril formation,1a
Unfortunately, the synthesis of O-aryl oxime ethers by direct
antibiotic (cefmenoxime),1b antifungal1c (oxiconazole), antihist- coupling of aryl halides and oximes is not well explored;11a
amine (1a),1d therapeutic agent for insomnia (eplivanserin however, several other methods are available for the coupling of
(1b)),1e,f melanin-concentrating hormone 1 receptor antagonist ketoximes with arylboronic acids by copper catalysts11b–f and
(1c),1g antiplasmodial,1h monoamine oxidase, and acetyl cholines- diaryliodonium salts,3f,g,12 which are obtained from aryl halides,
terase inhibitor (1d),1i insecticidal,1j fungicidal,1k herbicidal agents,1l but commercially, these starting materials are relatively more
etc., but also important and versatile precursors in the synthesis of expensive than aryl halides.
various structural motifs.2
Moreover, similarly to oximes,2c,14 O-arylaldoxime ethers are
O-Aryl oxime ethers have received special attention due to also important starting materials for the synthesis of biologically
their accessibility to numerous medicinally and synthetically active nitriles,2a benzoxazoles,3b,c and phenols.3i Although aldoxime
important organic compounds2 such as benzoxazole,3a–c dihydro- ethers have received considerable interest, no efficient methods
benzofuran,3d,e benzofurans,3e–i phenols,3j quinolines,3k 3-amino- have been reported thus far for their synthesis. Aldoxime ethers
benzisoxazoles,3l and pyrroles.3m Conventionally, the synthesis synthesized via the copper-mediated direct coupling of aryl coupling
of O-aryl oxime ethers is achieved via (i) the condensation of partners with aldoximes suffer from harsh reaction conditions and
O-aryloxyamines with carbonyl compounds1a,3e,f,4 and (ii) O-arylation poor yields.11a,b,d,e T. Punniyamurthy et al. reported the efficient
of oximes with activated nitro- or fluoroarene derivatives in the copper triflate-mediated synthesis of benzoxazoles from aldoxime
presence of a strong base via an SNAr-type process.1a,3e,4a,5 The ethers, which were synthesized from the condensation of aryloxy-
former can be achieved via the amine exchange reaction of amines and benzaldehydes. The synthesis of aryloxyamines is
2,4-dinitrophenoxyamine with phenols3f,6 and O-arylation of slightly cumbersome, and hence has limited substrate scope
ethyl acetohyroxamate,1a,4d,7 or N-protected hydroxylamine8 (Scheme 1).3b Therefore, the synthesis of benzoxazoles through
this method is likely to be less striking.
a Centre for Fire, Explosive and Environment Safety, DRDO, Delhi, India.
Therefore, efficient methods for the synthesis of aldoxime
ethers from aryl bromides and aldoximes are in demand and
need to be urgently developed.
Additionally, the introduction of phenolic function(s) in
organic compounds is one of the essential synthetic tasks in
organic chemistry since phenols are important synthetic inter-
mediates of a myriad of useful compounds and constituents of
E-mail: rajcfees@gmail.com
b Department of Chemistry, University of Delhi, Delhi, India
c Department of Chemistry, Sri Venkateswara College, University of Delhi,
New Delhi, India. E-mail: rangarajan93150@gmail.com
d Department of Chemistry, Shivaji College, University of Delhi, New Delhi, India
† Electronic supplementary information (ESI) available: Detailed procedures,
characterization data, and spectra. See DOI: 10.1039/c9nj05124d
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Fig. 1 Oxime ether-containing molecules with therapeutic properties.
Scheme 1 Synthesis of aldoxime ethers and subsequent cyclization.
Fig. 2 Structure of natural chalcones containing hydroxyl groups.
over 200 approved drugs and 100 000 natural products.3i Chalcones and phosphine ligands, and the Cu-catalyzed method requires
are a group of natural products with widespread medicinal the multi-step synthesis of oxalamide ligands, which starts with
properties. Many natural and synthetic chalcones containing the expensive starting material 3-methylisatoic anhydride ($55/1 g or
hydroxyl groups are biologically active13 (Fig. 1 and 2). However, $514/25 g)15 and also a ligand that may not be commercially
the synthesis of hydroxy chalcones through the classical Claisen– available.3j
Schmidt condensation of benzaldehydes with acetophenones in
Herein, we report the relatively inexpensive tBuXPhos ligand-
the presence of aqueous alkaline bases is not effective due to the supported Pd-catalyzed coupling of aldoximes with aryl bromides
fact that the presence of hydroxyl substituents in the aromatic and bromo-chalcones as coupling partners under mild reaction
rings decreases the reactivity of the carbonyl compounds through conditions with solvent- and temperature-facilitated functionality
delocalization of the negative charge on oxygen, which is generated switching from aldoxime ethers to phenolic functions.
by the action of a base. Therefore, the acid-catalyzed Aldol reaction
is considered to be the preferred method of interest.13a,b
Recently, Fier and Maloney revealed aldoximes as hydroxide
surrogates in the Pd- and Cu-catalyzed conversion of aryl bromides
Results and discussion
and aldoximes to phenols. The advantage of this method is the First, we examined different phosphine ligands (L1–L12) (Fig. 3)
late stage hydroxylation of drug-like molecules.3j However, the for the Pd-catalyzed coupling of 40-bromoacetophenone 1, with
Pd-catalyzed method requires expensive palladacycle catalysts 4-methylbenzaldoxime i, under the conditions of [(p-allylPdCl)2]
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Fig. 3 Structure of the phosphine ligands used for screening.
(1.0 mol%), Cs2CO3 (1.5 eq.), in toluene at 90 1C (Table 1). the oxime-coupled product 1c in 90% yield (entry 24), which is
Among the twelve ligands examined, only five ligands (L2, L5–L7, quite good compared to the reaction yield in toluene. This result
and L9) were found to be promising in the coupling reaction to reveals that the solvent THF can promote the coupling at both
afford the desired product 1c in 83%, 75%, 83%, 78%, and 82% low and high temperature; however, at high temperature THF
yield, respectively, with complete conversion (entries 1–12). also promoted the oxime–imine proton-abstraction, which led
Additionally, the ligand tBuXPhos (L2) facilitated the coupling to the formation of phenol. This result and the reaction in DMF
in a shorter reaction time (1.5 h) compared to the others (entry 15) clearly imply that the formation of phenol occurs only
(entry 2).
after the formation of the coupled product, which immediately
Under the same conditions with L2, the base KOH was also undergoes base-promoted imine proton abstraction,3j as shown
found to be as effective as Cs2CO3 to give the desired product 1c in Scheme 2.
in the good yield of 81% (entry 13). Further, with a change in
Further Pd source optimization (see ESI†) for the coupling
the reaction solvent from toluene (non-polar) to DMF (polar) reaction in toluene showed that [(p-allylPdCl)2] is an excellent
under the conditions with L2 at 90 1C, surprisingly, the reaction catalyst for the coupling of oxime. With these promising
afforded the product phenol 1p in 92% yield (entry 14),3j and the ligands and optimized reaction conditions, we again aimed to
same at a lower temperature of 40 1C (entry 15) was unsuccessful find the best conditions for the coupling of oxime with the
and even no coupled product 1c was formed, and therefore no neutral aryl bromide, 30-bromoacetophenone (Table 2). Among
phenol. With this interesting result, we further investigated the the 5 ligands examined (entries 1–5) for the coupling of oxime
same phenolic product (1p) with ligands L3–L7 in DMF solvent in toluene, only two ligands tBuBrettPhos, L6, and RockPhos,
at 90 1C. Besides L3 and L4, the other ligands L5–L7 gave the L7, were effective towards the coupling reaction with 2.0 mol%
desired product 1p in good to excellent yields (entries 18–20, Pd-catalyst loading, affording the coupling product 11c in good
respectively). The effect of the base KOH was also checked for yields (entries 3, and 4, respectively). The ligand tBuXPhos (L2)
the formation of 1p in DMF solvent, which was successful with a gave the coupled product 11c with the conversion of 90% and
reduced yield of only 59% (entry 21). The moderately polar yield of 70% over 4.0 h (entry 1). The promising ligands L6 and
solvent THF was chosen to carry out the reaction using L2 at L7 in toluene were also checked for the coupling reaction in
75 1C, and the phenolic product 1p was obtained in excellent DMF, which gave the phenolic product 11p in excellent yields
yield of 93% (entry 22), while the same using L6 afforded the (entries 6, and 7, respectively). The solvent THF was inefficient
product 1p in only 85% yield (entry 22). It was very surprising for substrate 7 with a different electronic nature using the
that the reaction in THF solvent at even 40 1C using L2 afforded promising ligand L7 at 40 1C (entry 8). This result reveals that
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Table 1 Optimization of the reaction conditions for the Pd-catalyzed cross-coupling of 40-bromoacetophenone with 4-methylbenzaldoximea
Yieldc (%)
Entry
Ligand
Base
Solvent
Reaction timeb (h)
Conv. (%)
1a
1b
1
2
3
4
5
6
7
8
L1
L2
L3
L4
L5
L6
L7
L8
L9
L10
L11
L12
L2
L2
L2
L3
L4
L5
L6
L7
L2
L2
L6
L2
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
KOH
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
KOH
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
THF
12.0
1.5
16.0
16.0
2.0
2.0
2.0
12.0
2.0
15.0
12.0
12.0
1.0
1.0
23
ND
100
ND
ND
100
100
100
ND
100
ND
ND
ND
100
100
ND
ND
ND
100
100
100
100
100
100
100
NR
83
NR
NR
75
83
78
NR
82
NR
NR
NR
81
—
NR
NR
NR
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
—
92
NRd
NR
NR
85
92
91
59
93e
85e
—
22
24
2.0
1.0
1.5
3.0
2.0
2.0
5.0
—
6
Cs2CO3
Cs2CO3
Cs2CO3
THF
THF
5
90d
a
Reaction conditions: 40-bromoacetophenone (0.5 mmol, 1.0 eq.), 4-methylbenzaldoxime (0.55 mmol, 1.1 eq.), base (0.75 mmol, 1.5 eq.),
b
c
d
[(p-allylPdCl)2] (1.0 mol%), ligand, L1–L12 (2.5 mol%), solvent (2.0 mL), 90 1C, Ar atm. Reaction time optimized by TLC. Isolated yield. 40 1C.
e
75 1C; NR = no reaction; ND = not determined.
Scheme 2 Mechanism of the base-promoted in situ oxime imine proton abstraction and subsequent phenol formation.
the solvent, for a given catalyst system, also plays a key role in (entries 8, and 9, respectively) rather than 20p. However, the
facilitating the coupling with product selectivity.
reaction in THF at 40 1C was incomplete over a 20 h reaction time,
Moreover, the promising ligands were also examined again although product 20c was obtained in 72% yield (entry 10). This
for their suitability for the coupling of oxime i, with the substrate result reveals that the electronic nature of 3-substituted simple aryl
(E)-3-(3-bromophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one, 16 bromides and bromo-chalcones is different and they react differently
(Table 3). The reaction required 3.0 mol% Pd-catalyst loading under the given conditions. The selectivity of the products for
for this substrate and was carried out in toluene at 75 1C. Only the 3-substituted bromo coupling partners was caused by the
ligands L2 and L7 were found to be better supporting ligands in solvent rather than temperature. None of the ligands supported
producing product 20c in good yields (entries 1 and 4) while the the Pd-catalyzed coupling of the electron-rich aryl bromides
reaction in DMF produced product 20p in good yields (entries 4-bromotoluene and 4-bromoanisole with oxime under the reaction
6, and 7), respectively. The promising ligand L6 (Table 2, entry conditions. Therefore, the catalyst system and ligand did not
3) was unsuccessful for this substrate (Table 3, entry 3). In facilitate the coupling of aldoxime with electron-rich aryl bromides.
contrast to aryl bromides, the reaction in THF at 75 1C using
With the optimized reaction conditions in hand, we then
ligands L2 and L7 gave the coupled product 20c in good yields explored the applicability of the method in the coupling of
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Table 2 Optimization of the reaction conditions for the Pd-catalyzed cross-coupling of 30-bromoacetophenone with 4-methylbenzaldoximea
Yieldb (%)
Entry
Ligand
Base
Solvent
Reaction time (h)
Conv. (%)
2a
2b
1
2
3
4
5
6
7
8
L2
L5
L6
L7
L9
L6
L7
L7
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Toluene
Toluene
Toluene
Toluene
Toluene
DMF
4.0
23.0
3.0
2.0
7.0
6.0
5.0
9.0
90
70
NR
88
87
42
—
—
—
—
—
—
92
90
—
ND
100
100
60
98
98
DMF
THF
—
60
53c
a
Reaction conditions: 30-bromoacetophenone (0.5 mmol, 1.0 eq.), 4-methylbenzaldoxime (0.55 mmol, 1.1 eq.), Cs2CO3 (0.75 mmol, 1.5 eq.),
b
c
[(p-allylPdCl)2] (2.0 mol%), ligand, (5.0 mol%), solvent (2.0 mL), Ar atm. 90 1C. Isolated yield. 40 1C, NR = no reaction. ND = not determined.
Table 3 Optimization of the reaction conditions for the Pd-catalyzed cross-coupling of (E)-3-(3-bromophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one
with 4-methylbenzaldoximea
Yieldb (%)
Reaction time
(h)
Conv.
(%)
Entry
Ligand
Base
Solvent
3a
3b
1
2
3
4
L2
L5
L6
L7
L9
L2
L7
L2
L7
L2
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Toluene
Toluene
Toluene
Toluene
Toluene
DMF
DMF
THF
THF
THF
3.0
22.0
22.0
6.0
22.0
2.0
2.0
3.0
6.0
20.0
97
ND
60
78
NR
42
78
NR
—
—
—
—
—
—
80
79
—
—
—
97
5
ND
100
100
100
98
6c
7c
8
—
81
79
72
9
10d
80
a
Reaction conditions: (E)-3-(3-bromophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one (0.5 mmol, 1.0 eq.), 4-methylbenzaldoxime (0.55 mmol, 1.1 eq.),
b
c
d
Cs2CO3 (0.75 mmol, 1.5 eq.), [(p-allylPdCl)2] (3.0 mol%), ligand (7.5 mol%), solvent (2.0 mL), 75 1C, Ar atm. Isolated yield. 90 1C. 40 1C,
NR = no reaction. ND = not determined.
various aryl bromides and bromo-chalcones with benzaldoximes. solvent promotes the functionality switching at different tem-
The aryl bromide substrates required 1.0 or 2.0 mol% catalyst perature extremes and more precisely, the oxime proton was
loading for the coupling reaction to be effective, and those not labile to be abstracted by base at 40 1C, whereas it was
bearing an electron-withdrawing group at p-position seemed to promoted at 75 1C. The catalyst system could also effectively
be more labile with temperature in THF solvent (Table 4). The couple the activated aryl bromides with various oximes at 40 1C
catalyst system Pd/tBuXPhos (L2) was effective towards the to afford the coupled products 7c–10c in good to excellent yields
coupling of activated aryl bromides with 4-methylbenzaldoxime (entries 7–10). The ligands tBuBrettPhos (L6) and RockPhos (L7)
in THF solvent, interestingly, even at 40 1C and afforded the were found to be good supporting ligands for the [(p-allyl)PdCl]2
coupled products 1c–6c in good to excellent yields (entries 1–6). catalyst in the coupling of aryl bromides bearing an electron-
On the contrary, when the same reaction was carried out at 75 1C, withdrawing group at the m-position with various oximes
the phenolic products, 1p–6p, were obtained in good to excellent (Table 2). The reaction for these substrates required relatively
yields (entries 1–6) except 4p. Unfortunately, 1-bromo-4-nitrobenzene higher catalyst loadings (2.0 mol%) and the product selectivity
4 failed to give the phenolic product 4p at 75 1C, whereas it gave the towards oxime ethers and phenols was achieved using the
coupled product 4c successfully at 40 1C in 97% yield. Thus, the THF solvents toluene and DMF, respectively, rather than temperature.
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Table 4 Pd-Catalyzed C–O cross-coupling of aryl bromides with aldoximes with functionality switching by temperature and solvent
Product, L (yielda % & time)
Entry
1
Ar–Br
Oxime
THFb (40 1C)
THFb (75 1C)
2
3
4
5
6
7
NC
NC
8
9
NC
NC
10
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Table 4 (continued)
Product, L (yielda % & time)
Toluenec (90 1C)
DMFd (90 1C)
11
12
13
14
15
Reaction conditions: a Isolated yield. b Aryl bromides (1.0 mmol, 1.0 eq.), aldoximes (1.05 mmol, 1.05 eq.), Cs2CO3 (1.5 mmol, 1.5 eq.), [(p-allyl)PdCl]2
(1.0 mol%), tBuXPhos (L2) (2.5 mol%), Ar atm. c Aryl bromides (1.0 mmol, 1.0 eq.), aldoximes (1.05 mmol, 1.05 eq.), Cs2CO3 (1.5 mmol, 1.5 eq.),
[(p-allyl)PdCl]2 (2.0 mol%), tBuBrettPhos (L6) (or) RockPhos (L7) (5.0 mol%), toluene (3.0 mL), 90 1C, Ar atm. d Aryl bromides (1.0 mmol, 1.0 eq.), aldoximes
(1.05 mmol, 1.05 eq.), Cs2CO3 (1.5 mmol, 1.5 eq.), [(p-allyl)PdCl]2 (2.0 mol%), tBuBrettPhos (L6) (or) RockPhos (L7) (5.0 mol%), DMF (2.5 mL), 90 1C, Ar atm.
The product oxime ethers 11c–13c and phenols 11p–13p with 4-methylbenzaldoxime i to afford the coupled products
were obtained in good to excellent yields in toluene and DMF 24c–29c in good to excellent yields. The other oximes such as
(entries 11–13), respectively. However, the catalyst system did 4-methoxybenzaldoxime, iv, and 3,4-dimethoxybenzaldoxime,
not facilitate the coupling of oximes with substrates such as v, and 4-benzyloxybenzaldoxime, iii, were coupled with bromo-
20-bromoacetophenone and bromobenzene.
Next, we turned out our attention to bromo-chalcones as a excellent yields, respectively.
chalcones to give the coupled products 30c–33c in good to
coupling partner to access novel chalcones. The oximes could
Since synthetic and natural chalcones with hydroxyl groups
successfully couple with either of the phenyl rings of bromo- have received considerable interest due to their significant
chalcones. The tBuXPhos ligand was promising to support the biological activity, we were interested in the incorporation of
Pd-catalyzed coupling of oximes, unlike with 3-bromo-1-substituted a hydroxyl group3j in chalcones using 4-methylbenzaldoxime
benzene, and with 3-bromo-chalcones as well. The reaction of as a hydroxide surrogate. Switching the reaction solvent from
bromo-chalcones, (E)-3-(4-bromophenyl)-1-(substituted phenyl)- THF to DMF under the optimized reaction conditions led to
prop-2-en-1-ones, with 4-methylbenzaldoxime was driven by the switching of the functionality from oxime ethers to phenolic
Pd/tBuXPhos system in THF solvent at 75 1C to give the C–O compounds (Table 5). With 3.0 mol% Pd catalyst loading and
coupled products 16c–19c in good yields (Table 5). The 3-bromo- tBuXPhos (L2), both types of bromo-chalcones smoothly
chalcone, (E)-3-(3-bromophenyl)-1-(4-methoxyphenyl)prop-2-en- reacted with 4-methylbenzaldoxime, i, in DMF solvent to afford
1-one, 16, was also effectively coupled by the catalyst system to the hydroxyl chalcones in short reaction times. The bromo-
afford the coupled product 20c in 81% yield. The other oximes, chalcones (E)-3-(4-bromophenyl)-1-(substituted phenyl)prop-2-
such as 4-methoxybenzaldoxime iv, and 4-benzyloxybenzald- en-1-ones were reacted with the hydroxide surrogate 4-methyl-
oxime iii, were also successfully coupled with bromo-chalcones 13 benzaldoxime to form hydroxychalcones 16p–20p in good to
and 15 to afford the desired products 21c–23c, respectively, in good excellent yields. Similarly, (E)-1-(4-bromophenyl)-3-(substituted
yields and the reactions were completed within 3–4 h. Similarly, phenyl)prop-2-en-1-ones were well tolerant under the reaction
the other bromo-chalcones, (E)-1-(4-bromophenyl)-3-(substituted conditions to afford the hydroxylated products 24p–34p in
phenyl)prop-2-en-1-ones, nicely coupled using the catalyst system more than 95% yield.
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Table 5 Pd-Catalyzed C–O cross-coupling of bromo-chalcones with aldoximes in different solvents
Product, L (yielda % & time)
Entry
1
Ar–Br
Oxime
THFb (75 1C)
DMFb (90 1C)
2
3
4
5
6
7
NC
NC
NC
8
9
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Table 5 (continued)
10
11
12
13
14
15
16
17
18
19
NC
NC
NC
NC
NC
a
Reaction conditions: Bromo-chalcones (0.5 mmol, 1.0 eq.), aldoximes (0.525 mmol, 1.05 eq.), Cs2CO3 (0.75 mmol, 1.5 eq.), [(p-allyl)PdCl]2
b
(3.0 mol%), tBuXPhos (L2) (7.5 mol%), Ar atm. Isolated yield.
C–O cross-coupling reaction. We demonstrated the role of solvent
Conclusions
and temperature towards the selectivity of the products, oxime or
In conclusion, we developed a convenient methodology for the phenols, in the Pd-catalyzed C–O cross-coupling reaction for the
coupling of aldoximes with aryl bromides and bromo-chalcones first time. The catalyst system was highly efficient for activated
using an inexpensive tBuXPhos ligand (L2)-supported Pd-catalyzed aryl bromides in THF solvent and gave the coupled products
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even at 40 1C, whereas the hydroxylated products at 75 1C. The
catalyst system Pd/L2 could effectively facilitate the coupling of
bromo-chalcones with aldoximes in THF to give the coupled
products in good to excellent yields, whereas in DMF the
hydroxylated products were obtained in good to excellent
yields. For bromo-chalcones, and the temperature did not
result in selectivity for phenols. The catalyst system Pd/L2 could
not facilitate the reaction with less activated (m-substituted)
aryl bromides, while the other ligands tBuBrettPhos (L6) or
RockPhos (L7) could facilitate the coupling in toluene at 90 1C
to afford the coupled products, whereas in DMF at 90 1C
afforded the hydroxylated products. None of the catalyst systems
resulted in the coupling of neutral and deactivated aryl bromides
with aldoxime. This method offers the functionality switching
option, and consequently direct access to a wide range of
aldoxime ethers of synthetic importance and novel chalcones
for various biological screening studies.
Conflicts of interest
There are no conflicts to declare.
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Acknowledgements
Authors are grateful to Defence R & D Organization (DRDO) for
financial assistance. Authors also acknowledge Director, CFEES,
DRDO and Principal, Sri Venkateswara College, University of
Delhi, for their encouraging support throughout this work. We
thank Head, Department of Chemistry and USIC, University of
Delhi for providing analytical and other technical supports.
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