Stable and Reusable Palladium Nanoparticles-Catalyzed Conjugate Addition of Aryl Iodides to Enones: Route to Reductive Heck Products

Article abstract of DOI:10.1002/adsc.201700823

An efficient, binaphthyl-backbone-stabilized palladium nanoparticles (Pd-BNP) catalyst for the 1,4-addition of aryl halides to enones has been developed. The scope of the reaction has been studied with various substituted and sterically hindered aryl hali

Full text of DOI:10.1002/adsc.201700823

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DOI: 10.1002/adsc.201700823
Stable and Reusable Palladium Nanoparticles-Catalyzed
Conjugate Addition of Aryl Iodides to Enones: Route to
Reductive Heck Products
Naziya Parveen,a Rajib Saha,a and Govindasamy Sekara,*
a
Department of Chemistry, Indian Institute of Technology Madras, Chennai – 600036, India
E-mail: gsekar@iitm.ac.in
Received: June 27, 2017; Revised: August 29, 2017; Published online: && &&, 0000
Supporting information for this article is available under https://doi.org/10.1002/adsc.201700823.
Abstract: An efficient, binaphthyl-backbone-stabi- has been recovered and reused up to five times with-
lized palladium nanoparticles (Pd-BNP) catalyst for out any appreciable change in particle size or reac-
the 1,4-addition of aryl halides to enones has been tivity.
developed. The scope of the reaction has been stud-
ied with various substituted and sterically hindered Keywords: conjugate addition; palladium nanocata-
aryl halides and enones to afford the conjugate addi- lyst; reductive Heck reaction; reusable catalysts; b-
tion products in good to excellent yields. The catalyst substituted carbonyl compounds
Introduction
using alkylamines and formates as hydride source. In
comparison, similar conjugate adducts were also af-
Conjugate addition of aryl halides to a,b-unsaturated forded by metal-catalyzed conjugate additions of or-
carbonyl compounds has been proven as a useful tool ganometallic reagents such as organoboron,[4] organo-
for the construction of b-substituted saturated carbon- zinc,[5] organocopper,[6] organoaluminum,[7] organosili-
yl compounds, which are found to be versatile inter- con,[8] and organomagnesium reagents,[9] which are
mediates in the synthesis of valuable organic chemi- generally synthesized from aryl halides. However,
cals[1] and bioactive molecules (Figure 1).[2]
these strategies fail due to their sensitivity to the car-
In early 1980s, Cacchi et al.[3] reported the reaction bonyl functional groups for conjugate 1,4-addition of
between aryl halides and enones or enals to form con- a,b-unsaturated carbonyl compounds.
jugate adducts in the presence of a palladium catalyst
In 1997, Miyaura et al. reported a Rh-catalyzed 1,4-
addition reaction of organoboron reagents to a,b-un-
saturated carbonyl compounds[10] having broad func-
tional group tolerance that worked under mild reac-
tion conditions. Even after the enormous success and
promising enantioselectivity of the above-mentioned
catalysts, most of them are expensive and require
moisture-free environments for the desired reactivity.
These organometallic reagents need to be substitut-
ed with suitable aryl halides to avoid the additional
steps for the synthesis of the organometallic reagents
and simplify the methodologies to explore new scopes
for synthetic and industrial applications.
Since the 1970s, from Mizorokiꢀs[11] and Heckꢀs[12]
development of palladium[0]-catalyzed cross-coupling
between olefins and organic halides to form a,b-unsa-
turated carbonyl compounds,[13] extensive catalytic
protocols were designed using a class of phosphine-li-
gated palladium complexes as pre-catalyst to achieve
high reactivities and selectivities. However, the air-
Figure 1. Selected bioactive molecules bearing b-alkyl-sub-
stituted carbonyl derivatives.
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sensitive nature and high oxidation potential of such reported binaphthyl-stabilized palladium nanoparti-
trisubstituted phosphine ligands in the palladium cles (Pd-BNP) as a catalyst with high catalytic activity,
complexes,[14] together with high reaction temperature stability, recyclability and reusability without metal
and limited substrate scope are the major drawbacks. leaching.[19] Herein we report the Pd-BNP-catalyzed
Recently Minnard et al. reported the palladium(II) reductive Heck reactions of aryl halides to a,b-unsa-
acetate-catalyzed reductive Heck reaction of aryl io- turated carbonyl compounds (Scheme 1).
dides with electron deficient a,b-unsaturated olefins
in the presence of diisopropyl(ethyl)amine (DIPEA)
and NMP (N-methyl-2-pyrrolidone) as solvents at Results and Discussion
808C.[15] However, electron-deficient aryl iodides and
bromides were unable to produce the corresponding During the initial pursuit towards 1,4-conjugate addi-
reductive Heck products. Moreover, the homogene- tion to chalcone 1a using 4-iodoanisole 2a as model
ous catalytic systems thus far developed often suffer substrates with DIPEA (2 equiv.) in the presence of
from various drawbacks such as use of toxic and ex- Pd-BNP (2 mol%) catalyst in DMF solvent at 1008C,
pensive phosphine ligands and tedious work-up proce- the reaction gave the corresponding reductive Heck
dures.[16]
product 3a in 80% yield along with the Heck coupling
The aesthetic simplicity and well defined surface product 4a in 15% yield (Table 1, entry 1).
active sites of nanostructured metal catalysts[17] used
To improve the selectivity and yield of product 3a,
in organic synthesis not only enable facile recovery our effort was initiated with the screening of bases as
but also recycling of the expensive transition metals reductants for the conjugate addition of aryl iodides
and this inspired us to explore the potential for Pd- with chalcones under inert conditions and the results
nanoparticle as catalyst in highly efficient organic are compiled in Table 1. After a wide screening of
transformations.[18] Thus, it was highly significant to bases, we concluded that a bulky organic base such as
explore the scope of the reaction using Pd-BNP as a DBU was ineffective for the conjugate addition
stable, efficient and recoverable palladium nanocata- (entry 3). DABCO gave the reductive Heck product
lyst in the reductive Heck reaction. Recently, we have 3a in 9% yield along with 4a in 53% yield (entry 2).
In the case of triethylamine, 3a was obtained in
31% along with 45% of 4a (entry 5). In the cases of
inorganic base like NaHCO3, 3a was obtained in 7%
yield along with 80% of the Heck product (entry 7).
Within a short period of optimization, it was under-
stood that amines are the crucial bases for higher se-
lectivity of the reductive Heck product 3a that was
found to be congruent with the pioneering work of
Cacchi et al. who observed higher selectivity (4:1)
ratio of reductive Heck and Heck product with
Pd(OAc)2 as catalyst and tributylamine as reductant
in DMF.[20] Furthermore, according to McAlees et al.,
during the optimization study using PdCl2·2PhCN as
catalyst DIPEA as base was found to afford for
better selectivity and reactivity.[21]
In support of the results of McAlees et al., Peters
et al. during a mechanistic study found that[22] the
ethyl substituent in DIPEA was exclusively reactive
and underwent selective oxidation at the ethyl sub-
stituent when DIPEA was treated with a zwitterionic
palladium complex. To further understand the effect
of the ethyl substituent in DIPEA for enhancements
in selectivity and yield of the reaction, a test reaction
using N,N-diisopropylmethylamine (DIPMA, Table 1,
entry 8), gave a mixture of 3a and 4a in 62% and
20% yield, respectively. This observation of poor se-
lectivity along with lower reaction rate further sup-
ports that probably the ethyl moiety in DIPEA has a
significant effect on selectivity and reaction rate and
the resulting oxidized species; bis(isopropylamino)-
Scheme 1. Reductive Heck reaction to construct C C bonds.
ethene apparently inhibits the Heck reaction.[15]
ACHTUNGTRENNUNG
À
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Table 1. Optimization study for the synthesis of 3-(4-me-
thoxyphenyl)-1,3-diphenylpropan-1-one 3a
and the results obtained are compiled in Table 1. It
has been found that THF is a suitable substitute for
DMF as solvent and a drastic improvement in selec-
tivity and yield of 3a has been observed (entry 14).
Other than THF, solvents such as DMSO, CH3CN,
toluene, 1,4-dioxane and xylene failed to improve the
selectivity and yield of product 3a (entries 9–14).
Further effects of temperature and catalyst loading
were investigated to improve the yield of 3a. It has
been observed that the fluctuation from an optimum
temperature of 808C results in decreases in the yield
of product (entry 16), whereas upon decreasing the
catalyst loading from 2 mol% to 1 mol%, the yield of
product 3a was increased to 93% (entry 17). But on a
further decrease in catalyst loading to 0.5 mol%, the
yield of 3a was decreased to 80% (entry 18). On the
other hand, increasing the catalyst loading to
[a]
Reaction conditions: 0.5 mmol of 1a and 0.5 mmol of 2a.
Yield was determined by H NMR of crude reaction mix-
[b]
1
ture using 1,3,5-trimethoxybenzene as an internal stan-
dard.
Reaction was carried out at 708C (incomplete conver-
sion).
Reaction was carried out at 808C.
1 mol% of Pd-BNP was used.
0.5 mol% of Pd-BNP was used.
2.5 mol% of Pd-BNP were used.
Reaction was carried without Pd-BNP.
[c]
[d]
[e]
[f]
[g]
[h]
Scheme 2. Substrate scope of aryl iodides. Reaction condi-
tions: 1a (0.5 mmol), 2a (0.5 mmol), Pd-BNP (0.005 mmol),
Furthermore, the effect of different solvents has
been screened to improve the yield of 3a selectively, DIPEA (2 equiv.) and THF (1 mL) at 808C; isolated yields.
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2.5 mol% gave an 83% of yield of 3a (entry 19) indi-
Initially, the substrate scope for the reductive Heck
cating that 1 mol% catalyst loading is the optimum to reaction was inspected using various substituted aryl
obtain the desired selectivity and reactivity. The 1,4- iodides 2 with chalcone 1a. The results obtained are
conjugate addition reaction did not proceed in the ab- delightful and display that electron-rich, neutral and
sence of Pd-BNP catalyst which reveals that the Pd- electron-deficient aryl iodides gave good to excellent
BNP catalyst had an essential aspect in 1,4-conjugate yields (65–92%) of reductive Heck product (3a–3g).
addition reaction (entry 20). In the addition, no prod- A separate class of bromo- and fluoro-substituted aryl
uct formation was observed in absence of base iodides also gave good yields without affecting the
(DIPEA), displaying that the base also plays a crucial substituents on the aryl ring that can be a scaffold for
role in the 1,4-conjugate addition reaction (entry 21). further transformations (3f and 3g).
Similar reactivity was witnessed even when reaction
In addition, the screening of ortho, meta- and para-
was performed in open air atmosphere conditions, re- substituted aryl iodides also displayed a promising
sulting in acceptable yields of 3a of 81% and 6% of effect. Electron-releasing groups such as OMe or CH3
4a.
groups provided better results than electron-with-
To probe the potential of Pd-BNP catalyst in 1,4- drawing group (3a, 3b vs. 3d, 3e). Sterically hindered
conjugate addition of a,b-unsaturated carbonyl com- ortho-methyliodobenzene also gave an 81% (3i) yield.
pounds (chalcones), we have explored the scope of When the electron-releasing group is at the para-posi-
this methodology using the optimized conditions with tion of the aryl iodide, it provided a higher yield than
an immense batch of substrates and the results are the corresponding meta-substituted aryl iodides (3a,
compiled in Scheme 2 and Scheme 3.
3b vs. 3j, 3k). However, the presence of more than
one electron-releasing group reduced the yield of the
Scheme 3. Substrate scope of chalcones. Reaction conditions: 1a (0.5 mmol), 2a (0.5 mmol except 3bb where 1 mmol was
used), Pd-BNP (0.005 mmol), DIPEA (2 equiv.) and THF (1 mL) at 808C; isolated yields.
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products (3l–3o). Heteroaryl iodides failed to give the poorly affording the products in 13:1 ratio respective-
expected product. Di- and trisubstituted aryl iodides ly (Scheme 4).
also gave satisfactory yields from 77% to 82% (3l–
3o).
To ensure scalability of the optimized reaction con-
ditions, a gram scale reaction was performed using
Finally, the substrate scope in terms of the Michael chalcone 1a (7.21 mmol) and para-iodoanisole
acceptor was examined using aryl iodide 2a as aryl (7.21 mmol) which afforded a promising yield of the
donor and results are compiled in Scheme 3. The re- corresponding reductive Heck product (Scheme 5).
action of 2a with ortho-substituted chalcones 3t and
3u gave 72% and 78% yields, respectively. It has been
found that halogen group-containing chalcones, such
as fluoro-, chloro- and bromo-substituted chalcones
reacted without affecting the halogen substituents and
gave good yields of the reductive Heck products 3q
(84%), 3r (88%) and 3s (82%). These products (3q,
3r and 3s) can be a precursor for further transforma-
tions to useful derivatives. Heteroaromatic and naph-
thyl-containing chalcones also afford the correspond-
ing reductive Heck products (3v and 3w) in 72% and
86% yield, respectively. In addition to benzylidene-
ACHTUNGTRENNUNGacetone, dibenzyledeneacetone also withstands the
transformation to provide the corresponding product
(3z and 3bb) with pleasing yields of 91% and 89%, re-
spectively. Due to our curiosity towards aliphatic chal-
cones, we also tested the linear and alicyclic chain-
containing chalcones: hept-3-en-2-one gave a 75%
yield of 3cc with 4-iodotoluene and a 69% yield of
3dd with 4-iodobenzonitrile. Also another aliphatic
enone, cyclohex-2-en-1-one, gave 72% of 3ee with 4-
iodoanisole.
Scheme 5. Gram-scale synthesis.
From the above screening of different substrates, it
Our further efforts towards the synthesis of the
has been observed that the electron-rich aryl iodides conjugate addition product from the less reactive bro-
afford excellent yields as compared to electron-defi- moarens 5a were carried out under the optimized re-
cient aryl iodides. When a competitive reaction was action conditions (Scheme 6). In this reaction, only a
carried out using a 1:1 ratio of para-methoxyphenyl trace amount of product formation was observed. But
iodide and para-nitrophenyl iodide, the results ob- when the reaction was performed in a sealed tube at
tained shows that in presence of an electron-rich aryl 1008C with a higher catalyst loading (5 mol%) for
iodide, the electron-deficient aryl iodide performed 36 h, it afforded the reductive Heck product 3c in
60% yield. Gratifyingly, other electron-deficient moi-
Scheme 6. Substrate scope of aryl bromides. Reaction condi-
Scheme 4. Intermolecular competitive reaction between
electron-rich vs. electron-deficient aryl iodide (yield deter-
mined by H NMR).
tions: 1 (0.5 mmol), 5a (0.5 mmol), Pd-BNP (0.025 mmol),
DIPEA (2 equiv.) and THF (1 mL) at 1008C in sealed tube;
isolated yields.
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eties like para-nitrobromobenzene and para-cyano-
bromobenzene also reacted smoothly to afford 3d in
44% and 3e in 48% yield, respectively. The electron-
rich para-methoxybromobenzene afforded a 65%
yield of reductive Heck product 3a.
The reductive Heck product 3a can be transformed
to a wide array of substrates. For instance, the keto
group can be transformed to alcohol and oxime with
simple manipulations (6a and 8a) or can be reduced
to afford a dibenzene derivative (7a). These transfor-
mations can be precursors for the synthesis of impor-
tant chemical substrates (Scheme 7).
Figure 2. Pd-BNP recovery cycles and effect on yield of 3a.
Figure 3. HR-TEM images showing same particle size: (a)
freshly prepared Pd-BNP and (b) after the fifth catalytic
cycle.
Scheme 7. Functionalization of reductive Heck product 3a.
The potential for recyclability of the catalyst was
inspected in up to five cycles; the catalyst was success-
fully recovered by centrifugation; the results are
promising and the catalyst was reused for up to five
cycles without any appreciable loss in yield of the
products (Figure 2).
The above results are in agreement with the HR-
TEM analysis, which displays the same particle size
without any obvious agglomeration even after the
fifth catalytic cycle (Figure 3).
To decide whether the active species of the Pd-
BNP catalyst is either a leached homogeneous Pd spe-
cies or not, the hot filtration test (Figure 4) and the
mercury poisoning test were carried out. The reaction
Figure 4. Effect of the hot filtration experiment on the yield
of the reaction.
mixture was filtered in the middle of the reaction at residue Pd-BNP after hot filtration was similar to that
different time intervals. Then the filtrate was allowed of Pd-BNP.
to stir for next 24 h. It was observed that no reaction
Furthermore, the mercury poisoning test was con-
proceeded with the filtrate. The catalytic activity of ducted to support our observation that the reaction
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1,3-Diphenyl-3-(p-tolyl)propan-1-one (3b): yield: 138 mg
(92%); white solid; mp 95–978C (Lit.[23] mp 95.3–97.88C);
Rf =0.8 (hexanes:ethyl acetate, 90:10 v/v); 1H NMR
(400 MHz, CDCl3): d=2.28 (s, 3H), 3.72 (d, J=7.2 Hz, 2H),
4.78 (t, J=7.2 Hz, 1H), 7.07 (d, J=8.0 Hz, 2H), 7.12–7.19
(m, 3H), 7.22–7.28 (m, 4H), 7.40–7.46 (m, 2H), 7.51–7.57
(m, 1H), 7.90–7.95 (m, 2H); 13C NMR (100 MHz, CDCl3):
d=21.1, 44.9, 45.7, 126.4, 127.8, 127.9, 128.2, 128.7, 128.7,
129.4, 133.2, 136.0, 137.0, 137.2, 141.3, 144.5; FT-IR (KBr):
n=2924, 2840, 1680, 1607, 1251, 1033, 820 cmÀ1; HR-MS:
m/z=301.1591 [M+H]+, calcd. for C22H20O: 301.1592.
1,3,3-Triphenylpropan-1-one (3c): yield: 124 mg (87%);
white solid; mp 95–978C (Lit.[23] mp 94.1–96.38C); Rf =0.7
(hexanes:ethyl acetate, 90:10 v/v); 1H NMR (400 MHz,
CDCl3): d=3.76 (d, J=7.2 Hz, 2H), 4.85 (t, J=7.6 Hz, 1H),
7.15–7.33 (m, 10H), 7.41–7.49 (m, 2H), 7.49–7.62 (m, 1H),
7.92–7.98 (m, 2H); 13C NMR (100 MHz, CDCl3): d=44.8,
46.1, 126.5, 127.5, 128.2, 128.7, 128.7, 133.2, 137.2, 144.3,
198.1; FT-IR (KBr): n=2924, 2856, 1683, 1600, 1254, 1024,
747 cmÀ1; HR-MS: m/z=309.1235 [M+Na]+, calcd. for
C21H18ONa: 309.1255.
was catalyzed by heterogeneous Pd and not by leach-
ed homogeneous Pd; this confirmed that there was no
leaching of Pd in reaction mixture. In this experiment,
Pd-BNP catalyst (1 mol%) and Hg (30 equivalents)
were first stirred at room temperature for 2 h, then
the other reagents 1a (0.5 mmol), 2a (0.5 mmol) and
DIPEA (2 equiv.) were added and the mixture stirred
at 808C for next 24 h. Complete inhibition of product
formation was observed.
Conclusions
In conclusion, we have developed an efficient Pd-
BNP catalyst for the 1,4-conjugate addition reaction
of enones with aryl iodides to synthesize reductive
Heck products. Substituted aryl iodides, including
electron-deficient aryl iodides also afforded good to
excellent yields of the reductive Heck product. The
less reactive aryl bromides also gave acceptable
yields. From hot filtration and mercury poisoning
tests, it was confirmed that the reaction was catalyzed
3-(4-Nitrophenyl)-1,3-diphenylpropan-1-one (3d): yield:
107 mg (65%); yellow semi-solid; Rf =0.36 (hexanes:ethyl
acetate, 90:10 v/v); 1H NMR (400 MHz, CDCl3): d=3.71–
by heterogeneous Pd and not by leached homogene- 3.86 (m, 2H), 4.93 (t, J=7.2 Hz, 1H), 7.19–7.28 (m, 2H),
7.28–7.35 (m, 2H), 7.40–7.49 (m, 4H), 7.53–7.61 (m, 1H)
7.75–7.81 (m, 1H), 7.91–7.97 (m, 2H), 8.09–8.15 (m, 2H),
8.32–8.39 (m, 1H); 13C NMR (100 MHz, CDCl3): d=44.4,
45.9, 124.0, 124.5, 127.2, 127.9, 128.2, 128.5, 128.9, 129.1,
133.6, 136.8, 142.7, 145.1, 151.9, 197.3; FT-IR (neat): n=
2922, 2854, 1682, 1514, 1340, 744, 695 cmÀ1; HR-MS: m/z=
354.1107 [M+Na]+, calcd. for C21H17NO3Na: 354.1106.
4-(3-Oxo-1,3-diphenylpropyl)benzonitirile (3e): yield:
110 mg (71%); white solid; mp 90–918C (Lit.[23] mp 89.1–
91.68C); Rf =0.36 (hexanes:ethyl acetate, 90:10 v/v);
1H NMR (400 MHz, CDCl3): d=3.69–3.81 (m, 2H), 4.87 (t,
J=7.2 Hz, 1H), 7.18–7.26 (m, 3H), 7.26–7.33 (m, 2H), 7.37
(d, J=8.4 Hz, 2H), 7.44 (t, J=8.0 Hz, 2H), 7.51–7.59 (m,
3H), 7.90–7.96 (m, 2H); 13C NMR (100 MHz, CDCl3): d=
44.2, 46.0, 110.3, 118.9, 127.0, 127.9, 128.1, 128.8, 129.0,
129.1, 132.5, 133.5, 136.8, 142.8, 149.7, 197.3; FT-IR (KBr):
n=2920, 2854, 2227, 1688, 1597, 691 cmÀ1; HR-MS: m/z=
334.1209 [M+Na]+, calcd. for C22H17NONa: 334.1208.
ous Pd. In light of the industrial and environmental
benefits, Pd-BNP was successfully recovered in up to
five catalytic cycles, without any significant loss of cat-
alytic activity and particle size.
Experimental Section
Typical Experimental Procedure for the Pd-BNP-
Catalyzed Reductive Heck Reaction
To an oven-dried Schlenk tube, equipped with stopper and
stirrer bar, was charged aryl iodide 2 (0.5 mmol), and chal-
cone 1a (0.5 mmol), then alternated through three cycles of
vacuum and nitrogen. To this mixture, THF (1.0 mL) and
DIPEA (2 equiv.) were added sequentially while stirring,
followed by Pd-BNP (1.0 mol%). The Schlenk tube was
placed into a preheated oil bath at 808C. Upon completion,
the reaction mixture was cooled to room temperature,
poured into HCl (v/v) solution (10%, 10 mL) and extracted
with ethyl acetate. The extract was concentrated under re-
duced pressure and the concentrate was purified using silica
gel column chromatography to afford the desired product.
3-(4-Bromophenyl)-1,3-diphenylpropan-1-one (3f): yield:
132 mg (73%); white solid; mp 101–1028C; (Lit.[24] mp
101.1–102.18C); Rf =0.66 (hexanes:ethyl acetate, 90:10 v/v);
1H NMR (400 MHz, CDCl3): d=3.64–3.78 (m, 2H), 4.79 (t,
J=7.6 Hz, 1H), 7.11–7.32 (m, 7H), 7.35–7.41 (m, 2H), 7.41–
7.49 (m, 2H), 7.53–7.61 (m, 1H), 7.90–7.96 (m, 2H);
13C NMR (100 MHz, CDCl3): d=44.7, 45.5, 120.4, 126.8,
127.9, 128.2, 128.8, 128.8, 129.8, 131.8, 133.4, 137.1, 143.3,
143.8, 197.8; FTIR (KBr): n=3058, 2924, 1678, 1587, 742,
3-(4-Methoxyphenyl)-1,3-diphenylpropan-1-one
(3a):
yield: (142 mg (90%); white solid; mp 91–938C (Lit.[23] mp
92–94.38C); Rf =0.48 (hexanes:ethyl acetate, 90:10 v/v);
1H NMR (400 MHz, CDCl3): d=3.68 (d, J=7.6 Hz, 2H),
3.70 (s, 3H), 4.77 (t, J=7.2 Hz, 1H), 6.75–6.83 (m, 2H),
7.09–7.19 (m, 3H), 7.21–7.29 (m, 4H), 7.39 (t, J=8 Hz, 2H),
7.50 (t, J=8 Hz, 1H), 7.90 (d, 2H); 13C NMR (100 MHz,
CDCl3): d=45.0, 45.3, 55.3, 114.0, 126.5, 127.9, 128.2, 128.7,
128.7, 128.9, 133.2, 136.4, 137.2, 144.7, 158.2, 198.3; IR
(KBr): n=2927, 2849, 1684, 1606, 1453, 1264, 744 cmÀ1; HR-
MS: m/z=339.1340 [M+Na]+, calcd. for C22H20O2Na:
339.1361.
694 cmÀ1
;
HR-MS: m/z=403.0090 [M+K]+, calcd. for
C21H17OBrK: 403.0100.
3-(4-Fluorophenyl)-1,3-diphenylpropan-1-one (3g): yield:
119 mg (78%); white solid; mp 97–988C; (Lit.[24] mp 95.3–
97.28C); Rf =0.42 (hexanes:ethyl acetate, 90:10 v/v);
1H NMR (400 MHz, CDCl3): d=3.63–3.78 (m, 2H), 4.81 (t,
J=7.6 Hz, 1H), 6.90–6.99 (m, 2H), 7.14–7.32 (m, 7H), 7.38–
7.48 (m, 2H), 7.48–7.60 (m, 1H), 7.89–7.96 (m, 2H);
13C NMR (100 MHz, CDCl3): d=44.9, 45.3, 115.4 (d, J=
21 Hz), 126.7, 127.9, 128.2, 128.9, 129.4 (d, J=8 Hz), 133.3,
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137.0, 139.9 (d, J=4 Hz), 144.1, 161.5 (d, J=242 Hz), 198.0;
FT-IR (KBr): n=2924, 2840, 1085, 1600, 1506, 1246,
3-(3,4-Methoxyphenyl)-1,3-diphenylpropan-1-one
(3m):
yield: 140 mg (81%); pale yellow solid; mp 57–588C; Rf =
1
834 cmÀ1
;
HR-MS: m/z=305.1357 [M+H]+, calcd. for
0.59 (hexanes:ethyl acetate, 80:20 v/v); H NMR (400 MHz,
CDCl3): d=3.65–3.74 (m, 2H), 3.79 (s, 3H), 3.81 (s, 3H),
4.77 (t, J=7.2 Hz, 1H), 6.74–6.82 (m, 3H), 7.14–7.20 (m,
1H), 7.23–7.31 (m, 4H), 7.40–7.47 (m, 2H), 7.51–7.57 (m,
1H), 7.90–7.95 (m, 2H); 13C NMR (100 MHz, CDCl3): d=
45.0, 45.7, 56.0, 111.3, 111.8, 119.5, 126.4, 127.8, 128.1, 128.6,
128.7, 133.1, 136.8, 137.2, 144.5, 147.7, 149.0, 198.3; FT-IR
(KBr): n=2940, 2838, 1683, 1589, 1244, 1124, 698 cmÀ1; HR-
MS: m/z=369.1486 [M+Na]+, calcd, for C23H22O3Na:
369.1467.
C21H17OF: 305.1342.
3-(2-Methoxyphenyl)-1,3-diphenylpropan-1-one
(3h):
yield: 125 mg (79%); white solid; mp 123–1248C; Rf =0.52
(hexanes:ethyl acetate, 90:10 v/v); 1H NMR (400 MHz,
CDCl3): d=3.70 (d, J=7.6 Hz, 2H), 3.74 (s, 3H), 5.17 (t, J=
7.6 Hz, 1H), 6.81–6.90 (m, 2H), 7.09–7.20 (m, 3H), 7.21–
7.31 (m, 4H), 7.39–7.46 (m, 2H), 7.50–7.56 (m, 1H), 7.91–
7.97 (m, 2H); 13C NMR (100 MHz, CDCl3): d=39.9, 43.9,
55.5, 111.0, 120.7, 126.2, 127.6, 128.2, 128.2, 128.4, 128.6,
132.8, 133.0, 137.3, 143.7, 157.0, 198.5; FT-IR (KBr): n=
2927, 2846, 1685, 1457, 1259, 743 cmÀ1; HR-MS: m/z=
339.1374 [M+Na]+, calcd. for C22H20O2Na: 339.1361.
3-(3,5-Methoxyphenyl)-1,3-diphenylpropan-1-one
(3n):
yield: 138 mg (80%); light yellow solid; mp 98–998C (Lit.[23]
mp 99–101.98C); Rf =0.7 (hexanes:ethyl acetate, 80:20 v/v);
1H NMR (400 MHz, CDCl3): d=3.68 (d, J=2.4 Hz, 2H),
3.70 (s, 6H), 4.77 (t, J=7.6 Hz, 1H), 6.27 (t, J=2.4 Hz, 1H),
6.41 (d, J=2.4 Hz, 2H), 7.11–7.19 (m, 1H), 7.21–7.29 (m,
4H) 7.38–7.45 (m, 2H), 7.48–7.56 (m, 1H), 7.91 (dd, J=8.4,
1.2 Hz, 2H); 13C NMR (100 MHz, CDCl3): d=44.7, 46.3,
55.3, 98.0, 106.4, 126.5, 127.9, 128.2, 128.7, 128.7, 133.2,
137.2, 143.9, 146.7, 160.9, 198.1; FT-IR (KBr): n=2918, 1685,
1600, 754, 699 cmÀ1; HR-MS: m/z=369.1486 [M+Na]+,
calcd. for C23H22O3Na: 369.1467.
1,3-Diphenyl-3-(o-tolyl)propan-1-one (3i): yield: 121 mg
(81%); white solid; mp 80–828C (Lit.[24] mp 89.2–90.2); Rf =
1
0.5 (hexanes:ethyl acetate, 90:10 v/v); H NMR (400 MHz,
CDCl3): d=2.34 (s, 3H), 3.66–3.78 (m, 2H), 5.03 (t, J=
7.2 Hz, 1H), 7.09–7.29 (m, 9H), 7.41–7.47 (m, 2H), 7.52–
7.58 (m, 1H), 7.91–7.96 (m, 2H); 13C NMR (100 MHz,
CDCl3): d=39.9, 43.9, 55.5, 111.0, 120.7, 126.2, 127.6, 128.2,
128.3, 128.4, 128.6, 132.8, 133.0, 137.0, 137.3, 147.7, 157.0,
198.6; FT-IR (KBr): n=2919, 2842, 1684, 1595, 697 cmÀ1
;
3-(3,5-Dimethylphenyl)-1,3-diphenylpropan-1-one
(3o):
HR-MS: m/z=323.1416 [M+Na]+, calcd. for C22H20ONa:
yield: 128 mg (82%); yellow solid; mp 83–848C (Lit.[25] mp
82–848C); Rf =0.48 (hexanes:ethyl acetate, 90:10 v/v);
1H NMR (400 MHz, CDCl3): d=2.25 (s, 6H), 3.65–3.78 (m,
2H), 4.74 (t, J=7.6 Hz, 1H), 6.80 (s, 1H), 6.88 (s, 2H),
7.12–7.19 (m, 1H), 7.22–7.29 (m, 4H), 7.39–7.46 (m, 2H),
7.50–7.57 (m, 1H), 7.90–7.96 (m, 2H); 13C NMR (100 MHz,
CDCl3): d=21.5, 44.9, 46.0, 125.8, 126.4, 128.0, 128.1, 128.3,
128.6, 128.6, 128.7, 133.1, 137.3, 138.1, 144.2, 144.4, 198.3;
323.1412.
3-(3-Methoxyphenyl)-1,3-diphenylpropan-1-one
(3j):
yield: 136 mg (86%); white solid; mp 86–888C (Lit.[24] mp
85.1–86.38C); Rf =0.48 (hexanes:ethyl acetate, 90:10 v/v);
1H NMR (400 MHz, CDCl3): d=3.77 (d, J=7.2 Hz, 2H),
3.80 (s, 3H), 4.84 (t, J=7.6 Hz, 1H), 6.74–6.80 (m, 1H)
6.84–6.96 (m, 2H),7.19–7.27 (m, 2H), 7.27–7.36 (m, 4H),
7.45–7.53 (m, 2H), 7.56–7.63 (m, 1H) 7.95–8.01 (m, 2H);
13C NMR (100 MHz, CDCl3): d=44.8, 46.1, 55.3, 111.5,
114.2, 120.3, 126.5, 127.9, 128.2, 128.7, 128.7, 129.6, 133.2,
137.2, 144.1, 145.9, 159.8, 198.1; FT-IR (KBr): n=2930, 2839,
1684, 1591, 1487, 1258, 1045, 697 cmÀ1; HR-MS: m/z=
339.1374 [M+Na]+, calcd. for C22H20O2Na: 339.1361.
FT-IR (KBr): n=2918, 2858, 1685, 1600, 1451, 698 cmÀ1
;
HR-MS: m/z=337.1573 [M+Na]+, calcd. for C23H22O Na:
337.1568.
1-(4-Flurophenyl)-3-(4-methoxyphenyl)-3-phenylpropan-
1-one (3q): yield: 140 mg (84%); white solid; mp 76–788C
(Lit.[24] mp 75.5–76.58C); Rf =0.36 (hexanes:ethyl acetate,
90:10 v/v); 1H NMR (400 MHz, CDCl3): d=3.66 (d, J=
7.2 Hz, 2H), 3.75 (s, 3H), 4.75 (t, J=7.2 Hz, 1H), 6.80 (d,
J=8.4 Hz, 2H), 7.09 (t, J=8.4 Hz, 2H), 7.16 (d, J=8 Hz,
3H), 7.21–7.31 (m, 4H), 7.90–7.98 (m, 2H); 13C NMR
(100 MHz, CDCl3): d=44.9, 45.4, 55.3, 114.1, 115.8 (d, J=
22 Hz), 126.5, 127.8, 128.7, 128.7, 130.8 (d, J=9.3 Hz), 133.6
(d, J=2.8 Hz), 136.2, 144.5, 158.2, 165.8 (d, J=253 Hz),
196.7; FTIR (KBr): n=3058, 1683, 1592, 843 cmÀ1; HR-MS:
m/z=357.1282 [M+Na]+, calcd. for C22H19FO2Na: 357.1267.
1-(4-Chlorophenyl)-3-(4-methoxyphenyl)-3-phenylpropan-
1-one (3r): yield: 154 mg (88%); pale yellow solid; mp
1,3-Diphenyl-3-(m-tolyl)propan-1-one (3k): yield: 128 mg
(85%); white solid; mp 73–748C (Lit.[24] mp 72.5–73.28C);
Rf =0.74 (hexanes:ethyl acetate, 90:10 v/v); 1H NMR
(400 MHz, CDCl3): d=2.28 (s, 3H), 3.72 (dd, J=7.6, 1.2 Hz,
2H), 4.78 (t, J=7.6 Hz, 1H), 6.97 (d, J=7.2 Hz, 1H), 7.04–
7.09 (m, 2H), 7.13–7.19 (m, 2H), 7.22–7.28 (m, 4H), 7.39–
7.45 (m, 2H), 7.50–7.56 (m, 1H), 7.90–7.95 (m, 2H);
13C NMR (100 MHz, CDCl3): d=21.6, 44.9, 46.0, 124.8,
126.4, 127.3, 127.9, 128.1, 128.6, 128.7, 128.7, 128.9, 133.2,
137.2, 138.2, 144.2, 144.4, 198.2; FT-IR (KBr): n=2919,
2842, 1684, 1595, 697 cmÀ1; HR-MS: m/z=323.1403 [M+
Na]+, calcd. for C22H20ONa: 323.1412.
1
578C; Rf =0.54 (hexanes:ethyl acetate, 90:10 v/v); H NMR
3-(3,4,5-Trimethoxyphenyl)-1,3-diphenylpropan-1-one (3l):
yield: 145 mg (77%); yellow solid; mp 102–1048C (Lit.[23]
mp 101.3–103.68C); Rf =0.6 (hexanes:ethyl acetate, 80:20 v/
(400 MHz, CDCl3): d=3.64 (d, J=7.6 Hz, 2H), 3.74 (s, 3H),
4.74 (t, J=7.6 Hz, 1H), 6.76–6.83 (m, 2H), 7.11–7.19 (m,
3H), 7.20–7.29 (m, 4H), 7.36–7.42 (m, 2H) 7.80–7.87 (m,
2H); 13C NMR (100 MHz, CDCl3): d=45.0, 45.3, 55.3, 114.1,
126.5, 127.8, 128.7, 128.9, 129.0, 129.6, 135.5, 136.2, 139.7,
144.4, 158.2, 197.2; FT-IR (KBr): n=2927, 2843, 1686, 1590,
1251, 829 cmÀ1; HR-MS: m/z=373.0951 [M+Na]+, calcd.
for C22H19ClO2Na: 373.0971.
1
v); H NMR (400 MHz, CDCl3): d=3.65–3.75 (m, 2H), 3.77
(s, 6H), 3.79 (s, 3H), 4.77 (t, J=7.2 Hz, 1H), 6.45 (s, 2H),
7.26–7.32 (m, 5H), 7.45 (t, J=8 Hz, 2H), 7.53–7.59 (m, 1H)
7.91–7.97 (m, 2H); 13C NMR (100 MHz, CDCl3): d=45.0,
46.5, 56.2, 60.9, 105.2, 126.6, 127.8, 128.2, 128.7, 128.8, 129.1,
133.3, 137.3, 139.9, 144.0, 153.3, 198.3; FT-IR (KBr): n=
2931, 2838, 1683, 1589, 1244, 1124, 698 cmÀ1; HR-MS: m/z=
377.1727 [M+H]+, calcd. for C24H24O4Na: 377.1753.
1-(3-Bromophenyl)-3-(4-methoxyphenyl)-3-phenylpropan-
1-one (3s): yield: 162 mg (82%); yellow solid; mp 588C;
Rf =0.43 (hexanes:ethyl acetate, 90:10 v/v); 1H NMR
Adv. Synth. Catal. 0000, 000, 0 – 0
8
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(400 MHz, CDCl3): d=3.64 (dd, J=7.2, 0.8 Hz, 2H), 3.73 (s,
3H) 4.73 (t, J=7.2 Hz, 1H), 6.70 (d, J=8.8 Hz, 2H), 7.11–
7.18 (m, 3H), 7.20–7.32 (m, 5H), 7.61–7.65 (m, 1H) 7.80–
7.84 (m, 1H), 8.01 (t, J=2 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d=45.1, 45.2, 55.3, 114.1, 123.1, 126.5, 126.7, 127.8,
128.7, 128.8, 130.3, 131.3, 136.0, 138.9, 144.3, 158.2, 198.0;
FT-IR (KBr): n=2924, 2856, 1688, 1616, 1257, 1033,
128.6, 128.9, 129.4, 134.7, 136.5, 143.9, 144.7, 158.1, 197.9;
FT-IR (KBr): n=2924, 2841, 1680, 1251, 1034, 819 cmÀ1
;
HR-MS: m/z=353.1541 [M+Na]+, calcd. for C23H22O2Na:
353.1517.
1,3-Bis(4-methoxyphenyl)-3-phenylpropan-1-one
(3y):
yield: 156 mg (90%); white solid; mp 898C (Lit.[24] mp 88.4–
89.28C); Rf =0.36 (hexanes:ethyl acetate, 90:10 v/v);
1H NMR (400 MHz, CDCl3): d=3.64 (dd, J=7.2, 0.8 Hz,
2H), 3.74 (s, 3H), 3.84 (s, 3H), 4.76 (t, J=7.6 Hz, 1H),
6.66–6.82 (m, 2H), 6.87–6.93 (m, 2H), 7.12–7.19 (m, 3H).
7.22–7.29 (m, 4H), 7.88–7.94 (m, 2H); 13C NMR (100 MHz,
CDCl3): d=44.7, 45.4, 55.3, 55.6, 113.8, 114.0, 126.4, 127.9,
128.6, 128.9, 130.3, 130.5, 136.6, 144.8, 158.1, 163.6, 196.8;
FT-IR (KBr): n=2930, 2839, 1674, 1602, 1507, 1253, 1174,
833, cmÀ1; HR-MS: m/z=369.1446 [M+Na]+, calcd. for
C23H22O3Na: 369.1467.
741 cmÀ1
;
HR-MS: m/z=395.0670 [M+H]+, calcd. for
C22H19BrO2: 395.0647.
3-(2,6-Dichlorophenyl)-3-(4-methoxyphenyl)-1-phenylpro-
pan-1-one (3t): yield: 138 mg (72%); yellow semi-solid; Rf =
1
0.54 (hexanes:ethyl acetate, 90:10 v/v); H NMR (400 MHz,
CDCl3): d=3.76 (s, 3H), 3.88–4.23 (m, 2H), 5.81 (t, J=
7.2 Hz, 1H), 6.76–6.84 (m, 2H), 7.05–7.15 (m, 3H), 7.22–
7.36 (m, 2H), 7.43–7.51 (m, 2H), 7.54–7.61 (m, 1H) 7.99–
8.05 (m, 2H); 13C NMR (100 MHz, CDCl3): d=40.5, 40.8,
55.3, 113.6, 128.3, 128.3, 128.4, 128.4, 128.5, 128.8, 133.9,
133.3, 136.9, 139.7, 158.0, 198.1; HR-MS: m/z=407.0612
[M+Na]+, calcd. for C22H18Cl2O2Na: 407.0582.
4-(4-Methoxyphenyl)-4-phenylbutan-2-one (3z): yield:
116 mg (91%); yellow solid; mp 638C (Lit.[24] mp 58.0–
59.08C); Rf =0.3 (hexanes:ethyl acetate, 90:10 v/v);
1H NMR (400 MHz, CDCl3): d=1.96 (s, 3H), 3.04 (d, J=
7.6 Hz, 2H), 3.64 (s, 3H), 4.44 (t, J=7.6 Hz, 1H), 6.69–6.74
(m, 2H), 7.02–7.20 (m, 7H); 13C NMR (100 MHz, CDCl3):
d=30.7, 45.3, 50.0, 55.2, 114.0, 126.4, 127.6, 128.6, 128.7,
136.0, 144.3, 158.1, 207.1; FT-IR (KBr): n=2942, 2838, 1713,
1503, 1249, 1030, 832 cmÀ1; HR-MS: m/z=255.1381 [M+
H]+, calcd. for C17H18O2: 255.1379.
1-Methoxy-4-(2-nitro-1-phenylethyl) benzene (3aa): yield:
93 mg (72%); brown oil; Rf =0.43 (hexanes:ethyl acetate,
90:10 v/v); 1H NMR (400 MHz, CDCl3): d=3.77 (s, 3H),
4.86 (t, J=6.8 Hz, 1H), 4.95 (dd, J=6.8, 2 Hz, 2H), 6.83–
6.89 (m, 2H), 7.13–7.17 (m, 2H), 7.20–7.27 (m, 3H) 7.29–
7.36 (m, 2H); 13C NMR (100 MHz, CDCl3): d=29.7, 48.2,
55.3, 114.4, 127.5, 127.6, 128.7, 129.0, 131.2, 139.5, 158.9;
HR-MS: m/z=257.1055 [M+H]+, calcd. for C15H15NO3:
257.1052.
1-(2-Methoxyphenyl)-3-(4-methoxyphenyl)-3-phenylpro-
pan-1-one (3u): yield: 135 mg (78%); pale yellow solid; mp
1
898C; Rf =0.4 (hexanes:ethyl acetate, 90:10 v/v); H NMR
(400 MHz, CDCl3): d=3.64 (dd, J=7.6, 1.2 Hz, 2H), 3.75 (s,
3H), 3.86 (s, 3H), 4.77 (t, J=7.6 Hz, 1H), 6.77–6.83 (m,
2H), 6.87–6.93 (m, 2H), 7.13–7.19 (m, 3H), 7.22–7.29 (m,
4H), 7.89–7.94 (m, 2H); 13C NMR (100 MHz, CDCl3): d=
44.2, 44.5, 55.3, 114.0, 125.0, 127.7, 128.0, 128.2, 128.7, 128.7,
129.2, 133.3, 133.5, 134.6, 137.0, 143.5, 158.2, 197.7; FT-IR
(KBr): n=2923, 1684, 1509, 1249, 1028, 750 cmÀ1; HR-MS:
m/z=369.1446 [M+Na]+, calcd. for C23H22O3 Na: 369.1467.
3-(4-Methoxyphenyl)-3-phenyl-1-(thiophen-2-yl)propan-1-
one (3v): yield: 116 mg (72%); pale yellow solid; mp 1488C;
Rf =0.38 (hexanes:ethyl acetate, 90:10 v/v); 1H NMR
(400 MHz, CDCl3): d=3.61 (dd, J=7.6, 1.2 Hz, 2H), 3.74 (s,
3H), 4.76 (t, J=7.2 Hz, 1H), 6.77–6.83 (m, 2H), 7.06–7.09
(m, 1H), 7.13–7.20 (m, 3H), 7.22–7.29 (m, 4H), 7.58 (dd, J=
5.2, 1.2 Hz, 1H), 7.68 (dd, J=3.6, 0.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d=44.5, 45.8, 55.3, 114.1, 126.5, 127.9,
128.2, 128.7, 128.9, 131.9, 133.8, 136.1, 144.4, 144.6, 158.2,
191.1; FT-IR (KBr): n=2924, 2840, 1660, 1608, 1250,
726 cmÀ1; HR-MS: m/z=345.0934 [M+Na]+, calcd. for
C20H18O2SNa: 345.0925.
1,5-Bis(4-methoxyphenyl)-1,5-diphenylpentan-3-one
(3bb): yield: 202 mg (89%); yellow semi-solid; Rf =0.52
(hexanes:ethyl acetate, 90:10 v/v); 1H NMR (400 MHz,
CDCl3): d=3.05 (d, J=6.4 Hz, 4H), 3.74 (s, 6H), 4.48 (t, J=
6 Hz, 2H) 6.74–6.78 (m, 2H), 6.99–7.04 (m, 4H), 7.07–7.12
(m, 4H), 7.12–7.17 (m, 2H) 7.19–7.25 (m, 4H); 13C NMR
(100 MHz, CDCl3): d=44.9, 49.8, 55.3, 114.0, 126.4, 127.7,
128.6, 128.7, 136.0, 144.3, 158.1, 207.0; FT-IR (neat): n=
2924, 1714, 1613, 1510, 1253, 699, cmÀ1; HR-MS: m/z=
473.2054 [M+Na]+, calcd. for C31H30O3Na: 473.2027.
4-(p-Tolyl)heptan-2-one (3cc): yield: 76 mg (75%); yellow
3-(4-Methoxyphenyl)-3-(naphthalene-2-yl)-1-phenylpro-
pan-1-one (3w): yield: 158 mg (86%); yellow solid; mp
1
1258C; Rf =0.4 (hexanes:ethyl acetate, 90:10 v/v); H NMR
(400 MHz, CDCl3): d=3.73 (s, 3H), 3.76–3.90 (m, 2H), 5.63
(t, J=7.2 Hz, 1H), 6.80 (d, J=8.2 Hz, 2H), 7.14–7.29 (m,
2H), 7.34–7.50 (m, 6H), 7.55 (t, J=7.6 Hz, 1H), 7.73 (d, J=
8.0 Hz, 1H), 7.84 (d, J=7.2 Hz, 1H), 7.95 (d, J=7.6 Hz,
2H), 8.18 (d, J=7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d=40.7, 45.3, 55.3, 114.1, 124.0, 124.3, 125.4, 125.7, 126.3,
127.4, 128.0, 128.2, 128.7, 129.1, 131.6, 133.2, 134.3, 136.1,
137.2, 140.2, 158.1, 198.3; FT-IR (KBr): n=2924, 2842, 1684,
1604, 1454, 1253, 1032, 736 cmÀ1; HR-MS: m/z=389.1537
[M+Na]+, calcd. for C26H22O2Na: 389.1517.
1
liquid; Rf =0.5 (hexanes:ethyl acetate, 80:10 v/v); H NMR
(400 MHz, CDCl3): d=0.84 (t, J=7.2 Hz, 3H), 1.10–1.22
(m, 2H), 1.48–1.62 (m, 2H), 2.01 (s, 3H), 2.31 (s, 3H), 2.69
(dd, J=2.4, 7.2 Hz 2H), 3.03–3.14 (m, 1H), 7.01–7.13 (m,
4H); 13C NMR (100 MHz, CDCl3): d=14.1, 20.6, 21.1, 30.7,
38.9, 40.8, 51.2, 127.4, 129.2, 135.9, 141.6, 208.3; FT-IR
(neat): n=2951, 1698, 1620, 1024, 820 cmÀ1; HR-MS: m/z=
227.1422 [M+Na]+, calcd. for C14H20ONa: 227.1412.
4-(2-Oxoheptan-4-yl)benzonitrile (3dd): yield: 74 mg
(69%); yellow liquid; Rf =0.5 (hexanes:ethyl acetate, 80:20
v/v); 1H NMR (400 MHz, CDCl3): d=0.85 (t, J=7.2 Hz,
3H), 1.06–1.19 (m, 2H), 1.49–1.65 (m, 2H), 2.05 (s, 3H),
2.74 (d, J=6.0 Hz, 2H), 3.13–3.30 (m, 1H), 7.29 (d, J=
7.6 Hz, 2H), 7.57 (d, J=8.0 Hz, 2H); 13C NMR (100 MHz,
CDCl3): d=14.0, 20.5, 30.7, 38.3, 40.8, 50.2, 110.3, 119.1,
128.5, 132.4, 150.6, 206.9; FT-IR (neat): n=2922, 2226, 1705,
3-(4-Methoxyphenyl)-3-phenyl-1-(p-tolyl)propan-1-one
(3x): yield: 147 mg (89%); yellow liquid; Rf =0.51 (hexane-
1
s:ethyl acetate, 90:10 v/v); H NMR (400 MHz, CDCl3): d=
2.39 (s, 3H), 3.67 (dd, J=7.2, 0.8 Hz, 2H), 3.74 (s, 3H), 4.77
(t, J=7.4 Hz, 1H), 6.77–6.82 (m, 2H), 7.12–7.19 (m, 3H),
7.20–7.29 (m, 6H), 7.81–7.86 (m, 2H); 13C NMR (100 MHz,
CDCl3): d=21.8, 44.9, 45.3, 55.3, 114.0, 126.4, 127.9, 128.3,
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1598, 826 cmÀ1; HR-MS: m/z=238.1185 [M+Na]+, calcd.
for C14H17NONa: 238.1208.
p-tolyl-1,3-diphenylpropan-1-one (90 mg, 0.30 mmol), meth-
anol (2 mL) and 5% Pd/C (32 mg, 0.015 mmol). The result-
ing reaction mixture was stirred at room temperature under
an H2 atmosphere for 36 h, the reaction progress being
monitored by TLC. The mixture was passed through a pad
of Celite with ethyl acetate washing (5ꢂ2 mL). After con-
centration of the filtrate, the residue was purified by flash
chromatography to afford the title compound as a colorless
3-(4-Methoxyphenyl)cyclohexan-1-one (3ee): yield: 73 mg
(72%); yellow liquid; Rf =0.32 (hexanes:ethyl acetate, 80:20
v/v); 1H NMR (400 MHz, CDCl3): d=1.65–1.90 (m, 2H),
1.90–2.23 (m, 2H), 2.25–2.65 (m, 4H), 2.85–3.05 (m, 1H),
3.78 (s, 3H), 6.87 (dd, J=8.8, 2.8 Hz, 2H), 7.14 (dd, J=8.8,
2.8 2H); 13C NMR (100 MHz, CDCl3): d=25.5, 33.1, 41.2,
44.0, 49.3, 55.3, 114.1, 127.5, 136.6, 158.3, 211.2; FTIR
(neat): n=2941, 1698, 1610, 1031, 826 cmÀ1; HR-MS: m/z=
227.1063 [M+Na]+, calcd. for C13H16O2Na: 227.1048.
1
oil; yield: 84%. H NMR (400 MHz, CDCl3): d=2.34 (q, J=
15.7 Hz, 2H), 2.56 (t, J=8.4 Hz, 2H), 3.74 (s, 3H) 3.86 (t,
J=8 Hz, 1H), 6.81 (d, J=8.4 Hz, 2H), 7.10–7.29 (m, 12H);
13C NMR (100 MHz, CDCl3): d=34.2, 37.6, 49.9, 55.3, 114.0,
125.9, 126.2, 127.9, 128.4, 128.5, 128.5, 128.9, 137.1, 142.3,
145.4, 158.3.
Typical Procedure for Synthesis of Chalcone (1a)
Chalcone 1a was synthesized using the reported literature
procedure:[26] to a mixture of water (6 mL) and ethanol
(100 mL), NaOH (1.2 g, 30 mmol) was added and the mix-
ture cooled to 08C. Acetophenone (4.92 g, 40 mmol) and
benzaldehyde (4.2 mL, 40 mmol) were added slowly and the
mixture was allowed to warm to room temperature. After
4 h, reaction mixture was extracted with EtOH. The solvent
was removed under reduced pressure and crude residue was
purified by column chromatography to give a yellow solid;
yield: 8.0163 g (94%). 1H NMR (400 MHz, CDCl3): d=
7.35–7.62 (m, 9H), 7.76 (d, J=15.7 Hz, 1H). 7.97 (d, J=
7.3 Hz, 2H); 13C NMR (100 MHz, CDCl3): d=122.3, 128.5,
128.6, 128.7, 129.1, 130.6, 132.9, 135.0, 138.4, 144.9, 190.7.
The same procedure was followed for the preparation of
the other chalcones.
Typical Procedure for Synthesis of 3-(4-Methoxy-
phenyl)-1,3-diphenylpropan-1-one O-Methyloxime
(8a)
This compound was synthesized using the reported literature
procedure with modifications:[29] the parent ketone
(10 mmol) was dissolved in MeOH (20 mL) and methoxyla-
mine hydrochloride (3.0 equiv.) was added. The reaction
mixture was stirred at room temperature for 10 min and
then NaHCO3 (3.0 equiv.) was gradually added. Stirring was
continued for further 6 h. The solution was then diluted with
ethyl acetate (30 mL), washed with brine (10 mL),extracted
with ethyl acetate (3ꢂ20 mL), dried over anhydrous
Na2SO4, filtered, and evaporated under vacuum. The crude
residue was purified by column chromatography on silica
gel to afforded the corresponding oxime. as a yellow liquid;
Typical Procedure for Synthesis of 3-(4-Methoxy-
phenyl)-1,3-diphenylpropane-1-ol (6a)
1
yield: 78%. H NMR (400 MHz, CDCl3): d=3.45–3.59 (m,
2H), 3.78 (s, 3H), 3.88 (s, 3H), 4.29 (t, J=8.4 Hz, 1H),
6.77–6.83 (m, 2H), 7.10–7.39 (m, 12H); 13C NMR (100 MHz,
CDCl3): d=33.2, 47.1, 55.4, 61.8, 113.7, 126.4, 126.9, 128.0,
128.3, 128.4, 128.9, 129.1, 136.0, 144.3, 157.8, 158.2; FT-IR
(neat): n=2932, 1606, 1505, 1259, 699, 837 cmÀ1.
This compound was synthesized using a reported literature
procedure with modifications:[27] to a solution of 3-(4-me-
thoxyphenyl)-1,3-diphenylpropan-1-one (1.0 mmol) in anhy-
drous ethanol (2 mL), sodium borohydride (0.55 mmol) was
added portion-wise and the mixture was stirred at room
temperature for 1 h. After completion of the reaction, the
solvent was evaporated under vacuum and the residue treat-
ed with ice water. The aqueous layer was acidified (pHꢀ2)
and extracted using ethyl acetate (3ꢂ10 mL). The combined
organic layer was washed with water (20 mL), brine (20 mL)
and dried over Na2SO4 and then concentrated. The crude re-
action mixture was purified by column chromatography
using hexanes/ethyl acetate as eluent gave 3-(4-methoxy-
phenyl)-1,3-diphenylpropane-1-ol as a colorless liquid; yield:
78%. 1H NMR (400 MHz, CDCl3): d=1.89–2.26 (m, 1H),
2.22–2.36 (m, 1H), 2.36–2.47 (m, 1H), 3.64–3.70 (m, 3H),
3.96–4.08 (m, 1H) 4.34–4.45 (m, 1H), 6.69–6.79 (m, 2H),
7.04–7.12 (m, 3H), 7.14–7.28 (m, 9H); 13C NMR (100 MHz,
CDCl3): d=44.1, 44.1, 45.8, 45.8, 54.3, 71.5, 71.6 113.0, 113.1,
125.1, 125.1, 125.3, 125.3, 126.8, 127.0, 127.6, 127.7, 127.7,
127.8, 128.0, 135.4, 135.9, 143.7, 143.7, 143.8 144.2, 157.1,
157.1; FT-IR (neat): n=3412, 2930, 1607, 1503, 1033,
827 cmÀ1.
Acknowledgements
GS thanks IC and SR, IIT Madras for Exploratory Research
Project (CHY/16-17/846/RFER/GSEK). NP thanks UGC,
New Delhi for a junior research fellowship, and RS thanks
IIT Madras for a senior research fellowship.
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12 Stable and Reusable Palladium Nanoparticles-Catalyzed
Conjugate Addition of Aryl Iodides to Enones: Route to
Reductive Heck Products
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Naziya Parveen, Rajib Saha, Govindasamy Sekar*
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