Ascorbic Acid Promoted Oxidative Arylation of Vinyl Arenes to 2-Aryl Acetophenones without Irradiation at Room Temperature under Aerobic Conditions

Article abstract of DOI:10.1021/acs.joc.5b00825

A convenient and general protocol for oxidative arylation of vinyl arenes by aryl radicals generated in situ from arene diazonium fluoroborates promoted by ascorbic acid in air at room temperature has been developed in the absence of any additive and visible light irradiation. A series of diversely substituted 2-aryl acetophenones have been obtained in good yields by this procedure.

Full text of DOI:10.1021/acs.joc.5b00825

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Note
Ascorbic Acid Promoted Oxidative Arylation of Vinyl
Arenes to 2-Aryl Acetophenones without Irradiation
at Room Temperature under Aerobic Conditions
Biju Majhi, Debasish Kundu, and Brindaban Chandra Ranu
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 08 Jul 2015
Downloaded from http://pubs.acs.org on July 9, 2015
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Ascorbic Acid Promoted Oxidative Arylation of Vinyl Arenes to 2ꢀAryl
Acetophenones without Irradiation at Room Temperature under Aerobic
Conditions
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Biju Majhi, Debasish Kundu and Brindaban C. Ranu*
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur,
Kolkata – 700032, India
ABSTRACT: A convenient and general protocol for oxidative arylation of vinyl arenes by aryl
radicals generated in situ from arene diazonium fluoroborates promoted by ascorbic acid in air at
room temperature has been developed in absence of any additive and visible light irradiation. A
series of diversely substituted 2ꢀaryl acetophenones have been obtained in good yields by this
procedure.
ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ
The ease of generation of aryl radicals from arene diazonium salts under visible light
1
photo catalysis in presence of eosin Y or [Ru(bpy)3]Cl2 has offered a powerful tool for arylation
of various substrates leading to the synthesis of a wide variety of useful organic molecules.2 As
an arene diazonium ion functions as one electron oxidizing agent, interaction of a suitable
reductant can also form an instant radical from the ion.3,4 Lꢀthreo ascorbic acid (vitamin C) is
reported to act as an appropriate reducing agent to generate an aryl radical from arene diazonium
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salt in absence of a metal and visible light photocatalysis.5 Recently Carrillo and coꢀworkers
reported the use of this protocol for the synthesis of 2ꢀaryl heterocycles involving aryl radicals
from arene diazonium salts.6 We report here a metal free oxidative arylation of vinyl arenes by
aryl radical generated in situ from aryl diazonium fluoroborate promoted by ascorbic acid at
room temperature without any irradiation leading to the synthesis of 2ꢀaryl acetophenones
(Scheme 1). In recent past Cai and his group reported similar oxidative arylation of vinyl arenes
under visible light photocatalyzed conditions.7 However, this procedure lacks generality being
not applicable to electronꢀdonating substituted and unsubstituted arene diazonium salts. Thus it
has limited scope being effective only to electronꢀwithdrawing substrates.
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2ꢀAryl acetophenones are versatile synthons, used as a common precursor for the
synthesis of a large variety of organic molecules such as heterocycles (quinoxaline,8 furan,9
imidazole10), terminal alkenes,11 αꢀhydroxy ketones,12 1,2ꢀdiketones,13 ketones,14 and arylꢀ
substituted 2ꢀaryl acetophenones15 (Figure 1). They are also found as structural motifs in
different biologically active molecules and pharmaceuticals such as oxcarbazepine
(anticonvulsant activity) and ketotifen (H1ꢀantihistamine activity).7 Thus convenient synthesis of
2ꢀaryl acetophenones is of much importance in organic synthesis.
Ar
Ar
N
N
Ar
Ar
O
O
Ar
Ar
Ar
O
ref 8
ref 15
Ar1
ref 9
Ar
O
N
ref 10
ref 11
ref 14
Ar
Ar
Ar
N
Ar
Ar
ref 13
Ar
O
ref 12
O
Ar
Ar
Ar
O
Ar
Ar
O
Ar
OH
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Figure 1. Use of 2ꢀaryl acetophenones as important precursor
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Scheme 1. Ascorbic Acid Promoted Oxidative Arylation of Vinyl Arenes
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O
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ascorbic acid
rt (30 oC), DMF
Ar1
N2BF4
+
Ar
Ar
Ar1
air, 20 h
Table 1. Optimization of Reaction Conditionsa
entry
diazonium
fluoroborate
(equiv.)
1
reducing agents
(equiv.)
solvent
time (h)
yield (%)b
1
2
3
4
5
6
ascorbic acid
(1)
THF
CH3CN
DMSO
20
20
20
20
20
20
29
trace
23
ꢀ
1
1
1
1
1
ascorbic acid
(1)
ascorbic acid
(1)
ascorbic acid
(1)
1,4ꢀdioxane
toluene
NMP
ascorbic acid
(1)
5
ascorbic acid
11
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(1)
5
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1
1.5
2
ascorbic acid
(1)
DMF
DMF
DMF
DMF
DMF
DMF
20
20
20
20
24
19
53
69
85
85
85
79
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ascorbic acid
(1.5)
9
ascorbic acid
(2)
10
11
12
3
ascorbic acid
(3)
2
ascorbic acid
(2)
2
ascorbic acid
(2)
13
14
15
16
2
2
2
2
KI (2)
DMF
DMF
DMF
DMF
20
20
20
20
33
21
12
85
PhꢀNHNH2 (2)
vitamin E (2)
ascorbic acid
(3)
17c
2
ascorbic acid
(1)
DMF
20
ꢀ
18
2
2
ꢀ
DMF
DMF
20
20
trace
73
19d
ascorbic acid
(2)
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aReaction conditions. bIsolated yields. cIn presence of TEMPO. dUnder pure O2.
.
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To optimize the reaction conditions a series of experiments were performed with
variation of reaction parameters, such as solvent, reducing agent, time for a representative
reaction of 2ꢀvinylnaphthalene (1i) and 4ꢀnitro phenyl diazonium fluoroborate (2c). The results
are summarized in Table 1. The use of THF, CH3CN, DMSO, 1,4ꢀdioxane, toluene, NMP as
solvent furnished relatively low yield (Table 1, entries 1ꢀ6) where as DMF was found to be more
effective compared to others (Table 1, entry 7). The use of 1.5 equivalent of 4ꢀnitro phenyl
diazonium fluoroborate with respect to 1 equivalent of 2ꢀvinylnaphthalene improved the yield
(Table 1, entry 8). However, the best yield of product was obtained using 2 equivalents of
diazonium fluoroborate and 2 equivalents of ascorbic acid for 1 equivalent of styrene in DMF for
20 h at room temperature (Table 1, entry 9). The increase of the amount of 4ꢀnitro phenyl
diazonium fluoroborate and ascorbic acid beyond 2 equivalents did not alter the outcome of the
reaction (Table 1, entries 10 and 16). Other reducing agents, such as PhꢀNHNH2, vitamin E were
not so effective (Table 1, entries 14ꢀ15) although KI provided relatively improved yield (Table 1,
entry 13). The reaction did not proceed at all in the presence of TEMPO (Table 1, entry 17). In
absence of any reducing agent, only trace amount of product was isolated (Table 1, entry 18).
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Table 2. Oxidative Arylation of Vinyl Arenesa
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O
OMe
OMe
O
O
O
Me
MeO
Me
F
3aa
, (69%)
3db
, (52%)
3ba
, (70%)
3ca
, (67%)
O
O
O
O
Me
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F
Me
, (57%)
O
3gb
, (70%)
3da, (71%)
PhO
3ea
3fa, (71%)
O
Me
O
O
Cl
Me
Me
Me
3ia
, (69%)
3ja, (71%)
3ha
, (21%)
Br
NO2
Me
O
O
O
Cl
Me
3be
, (72%)
3bf
, (80%)
3bc
, (83%)
NO2
O
NO2
OMe
S
F
O
O
O
S
3kd
, (81%)
3lc
, (61%)
3lb, (49%)
Br
3ic, (85%)
O
F
O
O
O
F
F3CO
3pa, (68%)
OH
, (62%)
OCH3
CHO
3ma
3ig, (74%)
NO2
3nh, (60%)
OCF3
O
O
O
O2N
O
3oi, (38%)
3ra
, (63%)
3sc, (66%)
3qa
, (71%)
O
F
O
OMe
OMe
O
F
O
Me
Cl
F
Me
3ek
Me
O
3fj
OH
, (48%)
, (55%)
3tg
, (77%)
3ua, (71%)
O
O
Me
O
O
F
O
Me
Me
Me
F
F
3vl
, (61%)
3dm, (63%)
Me
OMe
3wm, (62%)
3xn
, (64%)
Cl
aReaction conditions: vinyl arenes (1 equiv.), aryl diazonium fluoroborate (2 equiv.), ascorbic
acid (2 equiv.), air, room temperature, DMF, 20 h.
Thus in a typical reaction procedure a mixture of vinyl arene (1 equiv), aryl diazonium
fluoroborate (2 equiv) and ascorbic acid (2 equiv) was stirred for 20 hours under air at room
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temperature (TLC). Standard workup followed by column chromatography provided the product.
A series of vinyl arenes and heteroarenes were subjected to reaction by this procedure to produce
a library of 2ꢀaryl/heteroaryl acetophenones involving a variety of diazonium salts. The results
were summarized in Table 2. The diazonium fluoroborates with electron withdrawing groups ( ꢀ
NO2, ꢀF, ꢀCl, ꢀOCF3 ) in the aromatic ring underwent efficient reaction with vinyl arenes to form
the corresponding 2ꢀaryl acetophenones (Table 2, 3bc, 3be, 3ic, 3kd, 3ld, 3lc, 3ig, 3oi, 3tg and
3ek). Interestingly the aryl diazonium fluoroborates with electron donating groups ( ꢀOMe, ꢀMe,
ꢀOCHMe2) in the aromatic ring at ꢀo, ꢀm or ꢀp positions reacted readily with vinyl arenes under
this condition to produce the corresponding products (Table 2, 3db, 3gb, 3lb, 3nh, 3fj, 3vl,
3wm, 3dm and 3xn). Reactions with unsubstituted aryl diazonium fluoroborate were also
successful (Table 2, 3aa, 3ba, 3ca, 3da, 3ea, 3fa, 3ia, 3ja, 3ma, 3pa, 3ra and 3ua). It is
worthwhile to mention that recently Cai and coꢀworkers reported virtually no reaction (trace of
product) with challenging diazonium fluoroborates having electron donating moieties (ꢀOMe, ꢀ
Me) in the aromatic ring and with unsubstituted aryl diazonium fluoroborate under visible light
photoredox catalysis.7 Obviously this demonstrates the superior efficacy of the present procedure
over the other.16 The vinyl heteroarene bearing thiophene unit (1l) and vinyl polynuclear
hydrocarbons (1q, 1r) were also found to be reactive under the reaction conditions. The halogen
moieties (F, Cl, Br) in the aromatic ring are compatible. The halogen substituted acetophenones
are of potential for further functionalization. The sterically hindered vinyl arenes bearing –Me
group at two ortho positions provided relatively low yield of products (3ea, 3ha). In general,
when moderate or low yield of products were obtained substantial amount of vinyl arenes
remained unreacted other than a small percentage of unidentifiable side products. Easily
oxidizable –CHO functionality in the aromatic ring also remained unaffected under the reaction
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conditions (3pa). Reactions in absence (dark) or in presence of light did not show any marked
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difference in the formation of product. The yields remained comparable in both the conditions.
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Table 3. Outcome of Reactions in Absence and in Presence of Light
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vinyl
styrene
(1)
aryl
diazonium
fluoroborate
(2)
products
(3)
yield in
presence
of light
yield in
absence
of light
1a
1c
1b
2a
2a
2f
3aa
3ca
3bf
69%
67%
80%
67%
66%
78%
Although reaction with βꢀmethyl styrene (4a) with phenyl diazonium fluoroborate (2a)
was successful, stilbene failed to undergo any reaction (Scheme 2).
Scheme 2. Reaction with βꢀSubstituted Styrene
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The reaction shows excellent regioꢀselectivity with vinyl arenes bearing an allyl substituent at β
position. The aryl radical interacts selectively at styrenyl double bond leaving allyl double bond
intact (Scheme 3).
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Scheme 3. Regioselective Oxidative Arylation of βꢀAllyl Substituted Vinyl Arenes
O
ascorbic acid
(2 equiv.)
4c
+
DMF, rt, 20 h
N2BF4
air
5ca, 55%
2a
OH
OH
O
ascorbic acid
(2 equiv.)
4d
+
DMF, rt, 20 h
air
N2BF4
5da, 47%
2a
Similar regioꢀselectivity was also observed in the vinyl arenes bearing propargyl moiety at the β
position (Scheme 4).
Scheme 4. Regioselective Oxidative Arylation of βꢀPropargyl Substituted Vinyl
Arenes
O
ascorbic acid
(2 equiv.)
4e
DMF, rt, 20 h,
+
air
N2BF4
5ea, 56%
2a
OH
OH
O
ascorbic acid
(2 equiv.)
4f
+
N2BF4
DMF, rt, 20 h,
air
5fa, 49%
2a
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To extend it further, when the compounds, 4g and 4h containing multiple double and
triple bonds were subjected to reaction with phenyl diazonium fluoroborate, the products, 5ga
and 5ha were obtained via radical attack selectively at β styryl carbon keeping the double and
triple bonds inert (Scheme 5).
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Scheme 5. Regioselective Oxidative Arylation of Substrates Containing Multiple
Double and Triple Bonds
O
O
O
ascorbic acid
(2 equiv.)
4g
+
DMF, rt, 20 h,
air
N2BF4
5ga, 56%
2a
O
O
O
4h
ascorbic acid
(2 equiv.)
+
N2BF4
DMF, rt, 20 h,
air
5ha, 58%
2a
The complete arrest of the reaction in presence of TEMPO (2,2,6,6ꢀtetramethyl
piperidineꢀ1ꢀoxy radical) (Table 1, entry 17) suggests a radical mechanistic pathway. Thus a
probable radical mechanism is proposed in Scheme 6 in accordance with the reported reaction
pathway for similar reactions.3,4,5 In the first step the aryl diazonium salt A interacts with
ascorbic acid B to generate an intermediate diazoether D via nucleophilic attack of ascorbate
anion to diazonium ion.17 Subsequently this diazoether D undergoes a homolytic cleavage to
produce an aryl radical E. In the next step the aryl radical attacks at βꢀposition of vinyl arene F to
form a relatively stable benzyl radical G which captures O2 from air to produce the peroxy
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radical H. This peroxy radical then reacts with another molecule of G to provide an oxyl radical
I which leads to 2ꢀphenyl acetophenone by abstraction of a hydrogen radical.18
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8
9
To ascertain the source of O2 either from air or from trace of moisture (H2O) we
performed two experiments by carrying out a representative reaction of styrene and phenyl
diazonium fluoroborate with addition of labeled H2O (H2O18) in argon atmosphere and in
atmospheric condition separately. No product was formed in the reaction in argon atmosphere
whereas the corresponding product, 2ꢀphenyl acetophenone was obtained without any O18ꢀ
incorporation (HRMS) in the second experiment. This observation confirms the participation of
atmospheric O2 in the reaction.
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Scheme 6. Plausible Mechanism
Step I
N
N
HO
OH
HO
N
N
H
HBF4
O
BF4
O
O
HO
H
+
O
HO
OH
HO
B
O
A
C
HO
HO
H
O
O
HO
.
N2
H
O
N
OH
O
O
+
HO
N
.
D
O
O
OH
E
.
Step II
O
.
.
O2
+
H
G
G
F
E
.
H
.
O
O
I
To conclude, we have developed a convenient protocol for oxidative arylation of vinyl
arenes by aryl radicals, generated in situ from aryl diazonium fluoroborates promoted by
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ascorbic acid under air at room temperature in absence of any additive and ligand leading to the
synthesis of 2ꢀaryl acetophenones. The significant improvement in this procedure over the
reported one under photocatalysis7 is its applicability to reactions with more challenging electron
donating substituted and unsubstituted aryl diazonium fluoroborates. These substrates are
reported to remain inert in earlier procedure.7 The other advantages offered by this procedure are
reaction at room temperature, use of inexpensive ascorbic acid in place of expensive
photosensitizer in photocatalytic procedure, tolerance to a wide range of functionalities,
applicability to vinyl heteroarene and considerably good yield of products. Certainly, this
procedure is of much potential and it provides an easy access to a library of diversely substituted
aryl acetophenones.
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EXPERIMENTAL SECTION
General. NMR spectra were recorded on 500, 400, 300 MHz instruments for 1H spectra and 125,
100, 75 MHz instrument for 13C spectra. HRMS analysis was performed in a Qtof mass analyzer
using ESI ionization method. Elemental analyses are done at our Institute using an autoanalyser.
General Experimental Procedure for Oxidative Arylation of Vinyl Arenes.
Representative Procedure for the Synthesis of 1ꢀ(Naphthalenꢀ2ꢀyl)ꢀ2ꢀ(4ꢀ
nitrophenyl)ethanone (3ic, Table 2). To an ice cooled solution of 2ꢀ vinylnaphthalene (1i,
0.5 mmol, 77 mg), in dry DMF (3 mL), 4ꢀnitro phenyl diazonium fluoroborate (2c, 1 mmol, 237
mg) and (L)ꢀthreo ascorbic acid (1 mmol, 176 mg) were added under air. The resulting mixture
was stirred for 5 minutes at cooled condition, and was then allowed to reach to room temperature
and was further stirred for 20 h. After the reaction was complete (TLC), it was extracted with
ethyl acetate (60 mL). The extract was washed with water (10 mL) and brine solution (10 mL).
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The organic layer was dried over anhydrous Na2SO4. After removal of the solvent, the residue
(crude product) was purified by column chromatography over silica gel to afford the pure
product 1ꢀ(naphthalenꢀ6ꢀyl)ꢀ2ꢀ(4ꢀnitrophenyl) ethanone (3ic) as a light yellow solid (124 mg,
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85%); H NMR (500 MHz, CDCl3) δ 4.50 (s, 2H), 7.47 (d, J = 8.5 Hz, 2H), 7.57ꢀ7.65 (m, 2H),
7.88ꢀ7.94 (m, 2H), 7.98 (d, J = 8 Hz, 1H), 8.05 (d, J = 8.5 Hz, 1H), 8.20 (d, J = 8.5 Hz, 2H), 8.54
13
(s, 1H); C NMR (75 MHz, CDCl3): δ 45.1, 123.9 (2C), 124.0, 127.2, 128.0, 128.9, 129.0,
129.7, 130.4, 130.8 (2C), 132.6, 133.6, 135.9, 142.3, 147.2, 196.1; IR (neat): 3016, 1672, 1603,
1524, 1485, 1454, 183, 1217 cmꢀ1. Anal. Calcd for C18H13NO3: C, 74.22, H, 4.50. Found: C,
74.26, H, 4.47. These data are in perfect match with the reported one.16r
This procedure was followed for all the reactions listed in Table 2, Scheme 2, Scheme 3, Scheme
4 and Scheme 5. Although this data was obtained based on 1 mmol scale the reaction was shown
to produce similar result in higher scale too. The known compounds were identified by
comparison of their spectroscopic data with those reported (3aa,16h 3ba,16h 3ca,16g 3db,16s 3da,16h
3ea,16t 3fa,16u 3gb,16v 3ha,16w 3ia,16h 3ja,16h 3bc,16g 3be,16g 3bf,16h 3ic,16r 3kd,16s 3ma,16x and
5aa,16h). The unknown products were characterized by H NMR, C NMR, IR and HRMS or
elemental analysis. These data are given below in the order of their entries in Table 2, Scheme 2,
Scheme 3, Scheme 4 and Scheme 5.
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2ꢀ(4ꢀMethoxyphenyl)ꢀ1ꢀ(thiophenꢀ3ꢀyl)ethanone (3lb, Table 2): Colorless gummy liquid (57
1
mg, 49%), H NMR (300 MHz, CDCl3) δ 3.76 (s, 3H), 4.09 (s, 2H), 6.85ꢀ6.88 (m, 2H), 7.17ꢀ
7.20 (m, 2H), 7.25ꢀ7.28 (q, J = 3 Hz, 1H), 7.55 (dd, J1 = 5.1 Hz, J2 = 1.2 Hz, 1H), 8.07 (dd, J1 =
13
3 Hz, J2 = 1.2 Hz, 1H); C NMR (75 MHz, CDCl3) δ 45.9, 55.1, 114.1 (2C), 126.3, 126.4,
127.2, 130.4 (2C), 132.6, 141.8, 158.5, 192.1; IR (KBr): 3080, 1672, 1612, 1512, 1248, 1171 cmꢀ
1; HRMS calcd for C13H12O2S [M+H]+ 233.0631, found 233.0629.
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2ꢀ(4ꢀNitrophenyl)ꢀ1ꢀ(thiophenꢀ3ꢀyl)ethanone (3lc, Table 2): Light yellow solid (76 mg, 61%),
mp 132ꢀ134 oC; 1H NMR (300 MHz, CDCl3) δ 4.31 (s, 2H), 7.34ꢀ7.37 (q, J = 2.7 Hz, 1H), 7.41ꢀ
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7.45 (m, 2H), 7.57 (dd, J1 = 5.1 Hz, J2 = 1.2 Hz, 1H), 8.14ꢀ8.19 (m, 3H); C NMR (75 MHz,
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CDCl3) δ 46.2, 123.8 (2C), 127.0, 127.1, 130.7 (2C), 133.0, 141.5, 141.9, 147.2, 190.2; IR
(KBr): 3086, 1678, 1601, 1510, 1348, 1315, 1176 cmꢀ1; HRMS calcd for C12H9NO3S [M+H]+
248.0376, found 248.0374.
2ꢀ(2,4ꢀDifluorophenyl)ꢀ1ꢀ(naphthalenꢀ3ꢀyl)ethanone (3ig, Table 2): White solid (105 mg,
74%), mp 126 ꢀ128 oC; 1H NMR (300 MHz, CDCl3) δ 4.41 (s, 2H), 6.83ꢀ6.0 (m, 1H), 7.24 (q, J
= 8.1 Hz, 1H), 7.54ꢀ7.65 (m, 2H), 7.86ꢀ7.91 (m, 2H), 7.97 (d, J = 8.1 Hz, 1H), 8.07 (dd, J1 = 8.7
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Hz, J2 = 1.8 Hz, 1H), 8.56 (s, 1H); C NMR (75 MHz, CDCl3) δ 38.1 (d, JCꢀF = 1.5 Hz, 1C),
103.92 (d, JCꢀF = 51.7 Hz, 1C), 103.93, 111.4 (dd, J1 = 21 Hz, J2 = 3.8 Hz, 1C), 117.9 (dd, J1 =
16.5 Hz, J2 = 3.7 Hz, 1C), 123.9, 127.0, 127.9, 128.7 (d, JCꢀF = 6 Hz, 1C), 129.7, 130.2, 132.4 (q,
JCꢀF = 3.7 Hz, 1C), 132.6, 133.7, 135.8, 161.1 (dd, J1 = 246.7 Hz, J2 = 12 Hz, 1C), 162.3 (dd, J1 =
246.7 Hz, J2 = 1 Hz, 1C), 196.0; IR (neat): 2926, 1666, 1591, 1485, 1283, 1246 cmꢀ1. Anal.
Calcd for C18H12F2O: C, 76.59, H, 4.28. Found: C, 76.63, H, 4.29.
2ꢀ(2ꢀMethoxyphenyl)ꢀ1ꢀ(4ꢀ(trifluoromethoxy)phenyl)ethanone (3nh, Table 2): White solid
(93 mg, 60%), mp 52ꢀ54 oC, 1H NMR (300 MHz, CDCl3): δ 3.79 (s, 3H), 4.27 (s, 2H), 6.89ꢀ6.97
(m, 2H), 7.18ꢀ7.21 (m, 1H), 7.25ꢀ7.31 (m, 3H), 8.08ꢀ8.11 (m, 2H); 13C NMR (75 MHz, CDCl3):
δ 40.1, 55.5, 110.7, 120.40 (2C), 120.42 (q, JCꢀF = 257.3 Hz, 1C), 123.4, 125.4, 128.7, 130.6
(2C), 131.1, 135.3, 152.6, 157.2, 196.6; IR (KBr): 2945, 1688, 1603, 1497, 1261, 1161 cmꢀ1;
HRMS calcd for C16H13F3O3 [M+H]+ 311.0890, found 311.0891.
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1ꢀ(4ꢀNitrophenyl)ꢀ2ꢀ(4ꢀ(trifluoromethoxy)phenyl)ethanone (3oi, Table 2): Light yellow solid
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(62 mg, 38%), mp 74ꢀ76 C; H NMR (300 MHz, CDCl3): δ 4.41 (s, 2H), 7.31 (d, J = 8.1 Hz,
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2H), 7.41 (d, J = 8.7 Hz, 2H), 8.04ꢀ8.09 (m, 2H), 8.13 (d, J = 8.4 Hz, 2H); C NMR (75 MHz,
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CDCl3): δ 44.9, 120.3 (q, JCꢀF = 257.3 Hz, 1C), 120.6, 123.8, 130.6 (2C), 130.7 (2C), 134.4,
141.7, 147.2, 153.1 (d, JCꢀF = 2.3 Hz, 1C), 194.6; IR (neat): 3061, 1666, 1579, 1519, 1433, 1304,
1026 cmꢀ1. Anal. Calcd for C15H10F3NO4: C, 55.39, H, 3.10, N 4.31. Found C, 55.41, H, 3.15, N,
4.29.
3ꢀ(2ꢀPhenylacetyl)benzaldehyde (3pa, Table 2): Light yellow gummy liquid (76 mg, 68%), 1H
NMR (300 MHz, CDCl3) δ 4.34 (s, 2H), 7.26ꢀ7.34 (m, 5H), 7.63 (t, J = 7.5 Hz, 1H), 8.04ꢀ8.08
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(m, 1H), 8.24ꢀ8.28 (m, 1H), 8.50 (t, J = 1.5 Hz, 1H), 10.07 (s, 1H); C NMR (75 MHz, CDCl3)
δ 45.7, 127.2, 128.7, 128.9 (2C), 129.5 (2C), 129.7, 129.9, 133.7, 134.2, 136.7, 137.4, 191.6,
196.7; IR (neat): 3018, 1734, 1701, 1684, 1506, 1456, 1215 cmꢀ1. Anal. Calcd for C15H12O2: C,
80.34, H, 5.39. Found C, 80.31, H, 5.36.
1ꢀ(1,2ꢀDihydroacenaphthylenꢀ5ꢀyl)ꢀ2ꢀphenylethanone (3qa, Table 2): White solid (77 mg,
71%), mp 112ꢀ114 oC; 1H NMR (300 MHz, CDCl3) δ 3.26ꢀ3.33 (m, 4H), 4.40 (s, 2H), 7.22 (d, J
= 7.5 Hz, 1H), 7.30ꢀ7.36 (m, 2H), 7.40 (d, J = 4.5 Hz, 4H), 7.60ꢀ7.65 (m, 1H), 8.12 (d, J = 7.2
13
Hz, 1H), 8.85 (d, J = 8.4 Hz, 1H); C NMR (75 MHz, CDCl3) δ 30.1, 30.3, 47.3, 117.9, 120.2,
122.3, 126.6, 128.5 (2C), 129.2, 129.3 (2C), 129.5, 130.3, 132.5, 135.4, 139.5, 145.9, 153.0,
199.5; IR (KBr): 3026, 2901, 1687, 1595, 1497, 1309, 1155 cmꢀ1; HRMS calcd for C20H17O
[M+H]+ 273.1274, found 273.1277.
1ꢀ(Phenanthrenꢀ9ꢀyl)ꢀ2ꢀphenylethanone (3ra, Table 2): Light yellow solid (94 mg, 63%), mp
o
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127ꢀ129 C; H NMR (300 MHz, CDCl3) δ 4.46 (s, 2H), 7.31ꢀ7.42 (m, 5H), 7.60ꢀ7.74 (m, 4H),
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7.91 (d, J = 7.8 Hz, 1H), 8.19 (s, 1H), 8.60ꢀ8.68 (m, 3H); C NMR (75 MHz, CDCl3) δ 48.9,
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122.6, 122.8, 126.6, 126.9, 127.0, 127.1, 127.5, 128.5, 128.7 (2C), 128.8, 129.3, 129.6 (2C),
129.7, 129.8, 130.7, 131.7, 134.5, 134.8, 201.5; IR (KBr): 2891, 1686, 1495, 1450, 1309, 1117
cmꢀ1; HRMS calcd for C22H16O [M+H]+ 297.1274, found 297.1272.
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1ꢀ(Naphthalenꢀ1ꢀyl)ꢀ2ꢀ(4ꢀnitrophenyl)ethanone (3sc, Table 2): Light yellow solid (96 mg,
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66%), mp 123ꢀ125 C; H NMR (300 MHz, CDCl3) δ 4.45 (s, 2H), 7.41 (d, J = 8.4 Hz, 2H),
7.48ꢀ7.60 (m, 3H), 7.85ꢀ7.88 (m, 1H), 7.96ꢀ8.02 (m, 2H), 8.13 (d, J = 8.1 Hz, 2H), 8.62 (d, J =
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8.4 Hz, 1H); C NMR (75 MHz, CDCl3) δ 48.1, 123.7 (2C), 124.3, 125.6, 126.7, 128.3 (2C),
128.6, 130.3, 130.6 (2C), 133.5, 134.0, 134.6, 142.2, 146.9, 199.6; IR (KBr): 3078, 1670, 1510,
1346, 1301, 1090 cmꢀ1; HRMS calcd. for C18H13NO3 [M+H]+ 292.0968, found 292.0969.
2ꢀ(2,4ꢀDifluorophenyl)ꢀ1ꢀ(2ꢀfluorophenyl)ethanone (3tg, Table 2): Colorless solid (97 mg,
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77%), mp 95ꢀ97 C; H NMR (300 MHz, CDCl3) δ 4.29 (d, JCꢀF = 2.4 Hz, 2H), 6.79ꢀ6.89 (m,
13
2H), 7.13ꢀ7.27 (m, 3H), 7.51ꢀ7.59 (m, 1H), 7.87ꢀ7.92 (m, 1H); C NMR (75 MHz, CDCl3): d
43.2 (dd, J1 = 9 Hz, J2 = 1.5 Hz, 1C), 103.93, 103.94 (d, JCꢀF = 51 Hz, 1C), 111.3 (dd, J1 = 21 Hz,
J2 = 3.8 Hz, 1C), 116.8 (d, JCꢀF = 24 Hz, 1C), 124.8 (d, JCꢀF = 3 Hz, 1C), 125.2 (d, JCꢀF = 12.7 Hz,
1C), 131.0 (d, JCꢀF = 2.3 Hz, 1C), 132.5 (q, JCꢀF = 6 Hz, 1C), 135.1 (d, JCꢀF = 9 Hz, 1C), 161.3
(dd, J1 = 246.7 Hz, J2 = 12 Hz, 1C), 162.1 (d, JCꢀF = 252.7 Hz, 1C), 162.4 (dd, J1 = 234.7 Hz, J2 =
12 Hz, 1C), 194.4 (d, JCꢀF = 4.5 Hz, 1C). IR (KBr): 1688, 1608, 1508, 1452, 1275, 1213, 1089
cmꢀ1. Anal. Calcd for C14H9F3O: C, 67.20, H, 3.63. Found: C, 67.23, H, 3.67.
1ꢀ(1ꢀHydroxynaphthalenꢀ6ꢀyl)ꢀ2ꢀphenylethanone (3ua, Table 2): Colorless gummy liquid (93
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mg, 71%), H NMR (500 MHz, DMSOꢀD6) δ 4.39 (s, 2H), 6.81 (d, J = 8 Hz, 2H), 7.18 (d, J =
7.5 Hz, 2H), 7.58ꢀ7.65 (m, 2H), 7.94ꢀ7.98 (m, 2H), 8.04 (d, J = 9 Hz, 1H), 8.12 (d, J = 8 Hz,
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1H), 8.78 (s, 1H), 9.39 (s, 1H); C NMR (125 MHz, DMSOꢀD6) δ 43.9, 115.3 (2C), 124.0,
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125.2, 126.9, 127.6, 128.3, 128.6, 129.6, 130.3, 130.6 (2C), 132.2, 133.7, 135.0, 156.1, 198.0; IR
(Kbr): 1659, 1589, 1485, 1283, 1248, 1013 cmꢀ1. Anal. Calcd for C18H14O2: C, 82.42, H, 5.38.
Found: C, 82.45, H, 5.39.
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1ꢀ(4ꢀIsopropoxyphenyl)ꢀ2ꢀ(3,4ꢀdimethoxyphenyl)ethanone (3fj, Table 2): White solid (76
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mg, 48%), mp 126ꢀ128 C; H NMR (300 MHz, CDCl3) δ 1.29 (d, J = 6 Hz, 6H), 3.77 (s, 3H),
3.78 (s, 3H), 4.10 (s, 2H), 4.49ꢀ4.62 (m, 1H), 6.75 (s, 3H), 6.83 (d, J = 9 Hz, 2H), 7.92 (dd, J1 =
6.9 Hz, J2 = 1.8 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 21.7 (2C), 44.6, 55.6, 55.7, 69.9, 111.2,
112.4, 114.9 (2C), 121.4, 127.4, 129.0, 130.8 (2C), 147.7, 148.8, 161.9, 196.2; IR (KBr): 2899,
1678, 1599, 1518, 1268, 1163 cmꢀ1; HRMS calcd for C19H22O4 [M+H]+ 315.1591, found
315.1593.
2ꢀ(2ꢀChlorophenyl)ꢀ1ꢀoꢀtolylethanone (3ek, Table 2): Colorless viscous liquid (68 mg, 55%),
1H NMR (300 MHz, CDCl3) δ 2.55 (s, 3H), 4.38 (s, 2H), 7.24ꢀ7.33 (m, 5H), 7.38ꢀ7.44 (m, 2H),
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7.81ꢀ7.83 (m, 1H); C NMR (75 MHz, CDCl3) δ 21.3, 46.2, 125.7, 126.9, 128.6 (2C), 129.5,
131.5, 131.9, 132.1, 133.4, 134.5, 137.5, 138.6, 199.9; IR (neat): 3020, 2928, 1693, 1681, 1574,
1445, 1323, 1217 cmꢀ1. Anal. Calcd for C15H13ClO: C, 73.62, H, 5.35. Found C, 73.60, H, 5.38.
1ꢀ(3ꢀChlorophenyl)ꢀ2ꢀ(4ꢀisopropoxyphenyl)ethanone (3vl, Table 2): White solid (88 mg,
o
61%), mp 83ꢀ85 C; 1H NMR (300 MHz, CDCl3) δ 1.33 (d, J = 6.3 Hz, 6H), 4.16 (s, 2H), 4.56ꢀ
4.64 (m, 1H), 6.88 (dd, J1 = 7.2 Hz, J2 = 1.8 Hz, 2H), 7.12ꢀ7.14 (m, 1H), 7.18ꢀ7.20 (m, 2H), 7.25
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(s, 1H), 7.95 (dd, J1 = 6.9 Hz, J2 = 1.8 Hz, 2H); C NMR (75 MHz, CDCl3) δ 21.7 (2C), 44.3,
70.1, 115.1 (2C), 126.8, 127.7, 128.8, 129.5, 129.7, 130.8 (2C), 134.1, 136.9, 162.2, 195.3; IR
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(neat): 3018, 2979, 1676, 1599, 1261 cmꢀ1; HRMS calcd for C17H18ClO2 [M+H]+ 289.0990,
found 289.0992.
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62%), 1H NMR (300 MHz, CDCl3) δ 2.56 (s, 3H), 3.79 (s, 3H), 4.24 (s, 2H), 6.91 (d, J = 8.4 Hz,
1H), 6.99 (t, J = 7.5 Hz, 1H), 7.23ꢀ7.34 (m, 4H), 7.37ꢀ7.42 (m, 1H), 7.80 (d, J = 7.8 Hz, 1H); 13C
NMR (75 MHz, CDCl3) δ 20.9, 43.4, 55.2, 110.4, 120.6, 123.8, 125.5, 128.4, 128.5, 131.0,
131.2, 131.7, 137.9, 138.2, 157.2, 202.5; IR (neat): 2964, 1691, 1601, 1495, 1248 cmꢀ1; HRMS
calcd for C16H16O2 [M+H]+ 241.1223, found 241.1225.
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1ꢀ(4ꢀFluorophenyl)ꢀ2ꢀoꢀtolylethanone (3dm, Table 2): White solid (72 mg, 63%), mp 56ꢀ58
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oC; H NMR (300 MHz, CDCl3) δ 2.48 (s, 3H), 4.19 (s, 2H), 6.99ꢀ7.05 (m, 2H), 7.19ꢀ7.30 (m,
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4H), 7.36ꢀ7.41 (m, 1H), 7.71ꢀ7.74 (m, 1H); C NMR (75 MHz, CDCl3) δ 21.3, 47.4, 115.4 (d,
JCꢀF = 21 Hz, 2C), 125.7, 128.6, 130.2 (d, JCꢀF = 3 Hz, 1C), 131.1 (d, JCꢀF = 8.3 Hz, 2C), 131.5,
132.1, 137.4, 138.5, 161.9 (d, JCꢀF = 243.75 Hz, 1C), 201.1; IR (neat): 3018, 1713, 1693, 1666,
1601, 1504, 1454, 1292, 1219, 1157 cmꢀ1; HRMS calcd for C15H13FO [M+H]+ 229.1023, found
229.1020.
1ꢀ(2,4ꢀDifluorophenyl)ꢀ2ꢀmꢀtolylethanone (3xn, Table 2): White solid (79 mg, 64%), mp 82ꢀ
84 oC, 1H NMR (300 MHz, CDCl3) δ 2.42 (s, 3H), 4.28 (s, 2H), 6.80ꢀ6.89 (m, 2H), 7.16ꢀ7.24 (m,
13
1H), 7.35ꢀ7.42 (m, 2H), 7.82ꢀ7.85 (m, 2H); C NMR (75 MHz, CDCl3) δ 21.4, 38.1 (d, JCꢀF
=
1.5 Hz, 1C), 103.8, 103.9 (d, JCꢀF = 51.8 Hz, 1C), 111.3 (dd, J1 = 17.3 Hz, J2 = 3.8 Hz, 1C),
118.0 (dd, J1 = 16.5 Hz, J2 = 3.8 Hz, 1C), 125.6, 128.8 (d, JCꢀF = 18 Hz, 1C), 132.4 (q, JCꢀF = 6
Hz, 1C), 134.3, 136.4, 138.6, 161.1 (dd, J1 = 246.7 Hz, J2 = 12 Hz, 1C), 162.3 (dd, J1 = 234 Hz,
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J2 = 12 Hz, 1C), 196.2; IR (neat): 3020, 1686, 1605, 1508, 1217 cmꢀ1. Anal. Calcd for
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C15H12F2O: C, 73.16, H, 4.91. Found C 73.13, H 4.87%.
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1,2ꢀDiphenylpentꢀ4ꢀenꢀ1ꢀone (5ca, Scheme 3): Colorless viscous liquid (65 mg, 55%), H
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NMR (300 MHz, CDCl3) δ 2.41ꢀ2.50 (m, 1H), 2.80ꢀ2.90 (m, 1H), 4.51 (t, J = 7.2 Hz, 1H), 4.82ꢀ
4.95 (m, 2H), 5.56ꢀ5.70 (m, 1H), 7.01ꢀ7.06 (m, 1H), 7.11ꢀ7.31 (m, 7H), 7.84 (d, J = 7.2 Hz, 2H);
13C NMR (75 MHz, CDCl3): δ 38.3, 53.7, 116.8, 127.2, 128.3 (2C), 128.6 (2C), 128.8 (2C),
129.0 (2C), 133.0, 136.1, 136.8, 139.2, 199.2; IR (neat): 1717, 1682, 1597, 1448, 1269 cmꢀ1.
Anal. Calcd for C17H16O: C, 86.40, H, 6.82. Found: C, 86.43, H, 6.80.
1ꢀ(2ꢀHydroxyphenyl)ꢀ2ꢀphenylpentꢀ4ꢀenꢀ1ꢀone (5da, Scheme 3): Colorless viscous liquid (60
mg, 47%), 1H NMR (300 MHz, CDCl3) δ 2.56ꢀ2.66 (m, 1H), 2.93ꢀ3.02 (m, 1H), 4.69 (t, J = 7.2
Hz, 1H), 4.99ꢀ5.11 (m, 2H), 5.70ꢀ5.84 (m, 1H), 6.80ꢀ6.85 (m, 1H), 6.97 (dd, J1 = 8.4 Hz, J2 = 0.6
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Hz, 1H), 7.22ꢀ7.35 (m, 6H), 7.83ꢀ7.86 (m, 1H), 12.43 (s, 1H); C NMR (75 MHz, CDCl3) δ
37.9, 53.0, 117.2, 118.8, 118.9, 119.1, 127.5, 128.2 (2C), 129.2 (2C), 130.4, 135.7, 136.4, 138.9,
163.3, 205.4; IR (neat): 3020, 2979, 1643, 1633, 1579, 1485, 1446, 1217, 1155 cmꢀ1. Anal. Calcd
for C17H16O2: C, 80.93, H, 6.39. Found: C, 80.95, H, 6.43.
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1,2ꢀDiphenylpentꢀ4ꢀynꢀ1ꢀone (5ea, Scheme 4): White solid (66 mg, 56%), mp 76ꢀ78 C; H
NMR (300 MHz, CDCl3) δ 1.97 (t, J = 2.4 Hz, 1H), 2.70ꢀ2.78 (m, 1H), 3.03ꢀ3.12 (m, 1H), 4.82
(t, J = 7.5 Hz, 1H), 7.24ꢀ7.29 (m, 1H), 7.31ꢀ7.40 (m, 6H), 7.45ꢀ7.50 (m, 1H), 7.97ꢀ8.00 (m, 2H);
13C NMR (75 MHz, CDCl3) δ 23.4, 52.9, 69.9, 82.3, 127.6, 128.2 (2C), 128.6 (2C), 128.9 (2C),
129.1 (2C), 133.1, 136.2, 138.1, 197.9; IR (neat): 1681, 1578, 1491, 1270 cmꢀ1. Anal. Calcd for
C17H14O: C, 87.15, H, 6.02. Found: C, 87.11, H, 6.00.
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1ꢀ(2ꢀHydroxyphenyl)ꢀ2ꢀphenylpentꢀ4ꢀynꢀ1ꢀone (5fa, Scheme 4): Colorless viscous liqud (62
mg, 49%), 1H NMR (300 MHz, CDCl3) δ 1.95 (t, J = 2.7 Hz, 1H), 2.65ꢀ2.73 (m, 1H), 2.99ꢀ3.07
(m, 1H), 4.82 (t, J = 7.5 Hz, 1H), 6.75ꢀ6.80 (m, 1H), 6.94 (dd, J1 = 8.4 Hz, J2 = 0.9 Hz, 1H),
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7.22ꢀ7.39 (m, 6H), 7.76 (dd, J1 = 8.1 Hz, J2 = 1.5 Hz, 1H), 12.26 (s, 1H); C NMR (75 MHz,
CDCl3) δ 23.2, 52.4, 70.2, 81.9, 118.7, 119.0, 127.9, 128.0 (3C), 129.3 (2C), 130.5, 136.6, 138.0,
163.3, 203.9; IR (neat): 3018, 1640, 1629, 1480, 1441, 1150 cmꢀ1. Anal. Calcd for C17H14O2: C,
81.58, H, 5.64. Found: C, 81.55, H, 5.61.
1ꢀ(2ꢀ(Allyloxy)phenyl)ꢀ2ꢀphenylpentꢀ4ꢀenꢀ1ꢀone (5ga, Scheme 5): Colorless viscous liquid (82
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mg, 56%), H NMR (300 MHz, CDCl3) δ 2.54ꢀ2.64 (m, 1H), 2.94ꢀ3.04 (m, 1H), 4.58ꢀ4.61 (m,
2H), 4.80 (t, J = 7.5 Hz, 1H), 4.95ꢀ5.10 (m, 2H), 5.31ꢀ5.45 (m, 2H), 5.73ꢀ5.82 (m, 1H), 6.00ꢀ6.10
(m, 1H), 6.85ꢀ6.92 (m, 2H), 7.16ꢀ7.22 (m, 1H), 7.25 (d, J = 4.5 Hz, 4H), 7.30ꢀ7.36 (m, 1H), 7.42
(dd, J1 = 7.5 Hz, J2 = 1.8 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 37.7, 57.5, 69.4, 112.7, 116.4,
118.3, 120.8, 126.9, 128.5 (2C), 128.8 (2C), 129.5, 130.5, 132.7, 132.8, 136.4, 138.9, 156.6,
203.1; IR (neat): 3301, 2918, 2124, 1671, 1479 cmꢀ1. Anal. Calcd for C20H20O2: C, 82.16, H,
6.89. Found C, 82.11, H, 6.91.
2ꢀPhenylꢀ1ꢀ(2ꢀ(propꢀ2ꢀynyloxy)phenyl)pentꢀ4ꢀynꢀ1ꢀone (5ha, Scheme 5): Colorless viscous
1
liquid (84 mg, 58%), H NMR (300 MHz, CDCl3) δ 1.89 (t, J = 3 Hz, 1H), 2.54 (t, J = 2.4 Hz,
1H), 2.62ꢀ2.72 (m, 1H), 2.97ꢀ3.06 (m, 1H), 4.66 (d, J = 2.4 Hz, 2H), 4.86ꢀ4.91 (m, 1H), 6.88ꢀ
6.94 (m, 2H), 7.14ꢀ7.24 (m, 5H), 7.32ꢀ7.35 (m, 1H), 7.52 (dd, J1 = 7.8 Hz, J2 = 1.8 Hz, 1H); 13C
NMR (75 MHz, CDCl3) δ 22.9, 56.1, 56.6, 69.7, 76.4, 77.9, 82.6, 112.9, 121.6, 127.3, 128.5
(2C), 128.7 (2C), 128.8, 130.9, 133.2, 137.9, 155.6, 200.9; IR ( neat): 3302, 3028, 2920, 2122,
1674, 1597, 1483, 1452, 1292, 1219 cmꢀ1. Anal. Calcd for C20H16O2: C, 83.31, H, 5.59. Found C,
83.29, H, 5.61.
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ASSOCIATED CONTENT
Supporting Information
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Spectroscopic data of all known products and copies of H NMR and C NMR spectra for all
synthesized compounds. This material is available free of charge via the Internet at
http://pubs.acs.org.
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AUTHOR INFORMATION
Fax: (+91)ꢀ33ꢀ24732805; Phone: (+91)ꢀ33ꢀ2473ꢀ4971; eꢀmail:ocbcr@iacs.res.in
ACKNOWLEDGMENTS
We gratefully acknowledge the financial support from DST, New Delhi, for the J.C. Bose Fellowship to
B.C.R. (Grant No. SR/S2/JCBꢀ11/2008) and Indian National Science Academy, New Delhi for offering
an INSA Senior Scientist position to B.C.R. B.M. and D.K. thank CSIR, New Delhi, for their fellowships.
We thank Dr. T.K. Paine and his group for helping us in the labeling experiment.
REFERENCES
(1) (a) McNally, A.; Prier, C. K.; MacMillan, D. W. C. Science 2011, 334, 1114. (b) Nagib, D.
A.; MacMillan, D. W. C. Nature 2011, 480, 224. (c) Pham, P. V.; Nagib, D. A.; MacMillan, D.
W. C. Angew. Chem. Int. Ed. 2011, 123, 6243. (d) Nicewicz, D. A.; MacMillan, D. W. C.
Science 2008, 322, 77. (e) Shih, H.ꢀW.; Wal, M. N. V.; Grange, R. L.; MacMillan, D. W. C. J.
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1
2
3
4
5
6
7
8
9
Am. Chem. Soc. 2010, 132, 13600. (f) Nagib. D. A.; Scott, M. E.; MacMillan, D. W. C. J. Am.
Chem. Soc. 2009, 131, 10875. (g) Wallentin, C.ꢀJ.; Nguyen, J. D.; Finkbeiner, P.; Stephenson, C.
R. J. J. Am. Chem. Soc. 2012, 134. 8875. (h) Narayanam, J. M. R.; Tucker, J. W.; Stephenson, C.
R. J. J. Am. Chem. Soc. 2009, 131, 8756. (i) Lu. Z.; Shen, M.; Yoon, T. P. J. Am. Chem. Soc.
2011, 133, 1162. (j) Ischay, M. A.; Lu, Z.; Yoon, T. P. J. Am. Chem. Soc. 2010, 132, 8572. (k)
Hari, D. P.; Schroll, P.; Konig, B. J. Am. Chem. Soc. 2012, 134, 2958. (l) Hari, D. P.; Hering, T.;
Konig, B. Org. Lett. 2012, 14, 5334. (m) Xue, D.; Jia, Z.ꢀH.; Zhao, C.ꢀJ.; Zhang, Y.ꢀY.; Wang,
C.; Xiao, J. Chem.-Eur. J. 2014, 20, 2960. (n) Hari, D. P.; Hering, T.; Konig, B. Angew. Chem.
Int. Ed. 2014, 53, 725. (o) Maity, S.; Zhu, M.; Shinabery, R. S.; Zheng, N. Angew. Chem. Int.
Ed. 2012, 51, 222. (p) Zou, Y.ꢀQ.; Liu, X.ꢀP.; Lu, L.ꢀQ.; Davis, R. L.; Jogensen, K. A.; Xiao,
W.ꢀJ. Angew. Chem. Int. Ed. 2012, 51, 784.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
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40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(2) (a) Tucker, J. W.; Stephenson, C. R. J.; J. Org. Chem. 2012, 77, 1617. (b) Tebly, F.; Czech,
C. Chem. Commun. 2011, 76, 859. (c) Hari, D. P.; Konig, B. Angew. Chem. Int. Ed. 2013, 52,
4734. (d) Xuan, J.; Xiao, W.ꢀJ. Angew. Chem. Int. Ed. 2012, 51, 6828. (e) Zeitler, K. Angew.
Chem. Int. Ed. 2009, 48, 9785. (f) Courant, T.; Masson, G. Chem.-Eur. J. 2012, 18, 423. (g) Zou,
Y.ꢀQ.; Lu, L.ꢀQ.; Fu, L.; Chang, N.ꢀJ.; Rong, J.; Chen, J.ꢀR.; Xiao, W.ꢀJ.; Angew. Chem. Int. Ed.
2011, 50, 7171. (h) Neumann, M,; Fuldner, S.; Konig, B.; Zeitler, K. Angew. Chem. Int. Ed.
2011, 50, 951. (i) Su, Y.; Zhang, L.; Jiao, N. Org. Lett. 2011, 13, 2168. (j) Larraufie, M.ꢀH.;
Pellet, R.; Fensterbank, L.; Goddard, J.ꢀP.; Lacote, E.; Malacria, M.; Ollivier, C. Angew. Chem.
Int. Ed. 2011, 50, 4463. (k) Rueping, M.; Zhu, S.; Koenigs, R. M. Chem. Commun. 2011, 47,
8679. (l) Koike, T.; Akita, M. Chem. Lett. 2009, 38, 166.
(3) Galli, C.; Chem. Rev. 1988, 88, 765.
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1
2
3
4
5
6
7
8
9
(4) (a) Kosynkin, D.; Bockman, T. M.; Kochi, J. K. J. Am. Chem. Soc. 1997, 119, 4846. (b)
Wetzel, A.; Ehrhardt, V.; Heinrich, M. R. Angew. Chem. Int. Ed. 2008, 47, 9130. (c) Wetzel, A.;
Pratsch, G.; Kolb, R.; Heinrich, M. R. Chem.- Eur. J. 2010, 16, 2547.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
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43
44
45
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47
48
49
50
51
52
53
54
55
56
57
58
59
60
(5) (a) Reszka, K. J.; Chignell, C. F. Chem.- Biol. Interact. 1995, 96, 223. (b) CostasꢀCostas, U.;
GonzalezꢀRomero, E.; BravoꢀDiaz, C. Helv. Chim. Acta. 2001, 84, 632. (c) SilveiraꢀDorta, G.;
Monzon, D. M.; Crisostoma, F. P.; Martin, V. S.; Carrillo, R. Chem. Commun. 2015, 51, 7027.
(6) Crisostomo, F. P.; Martin, T.; Carrillo, R. Angew. Chem. Int. Ed. 2014, 53, 2181.
(7) Bu, M.; Niu, T. F.; Cai, C. Catal. Sci. Technol. 2015, 5, 830.
(8) (a) Lian, M.; Li, Q.; Zhu, Y.; Yin, G.; Wu, A. Tetrahedron 2012, 68, 9598. (b) Cho, C.S.;
Ren, W. X.; Shim, S. C. Tetrahedron Lett. 2007, 48, 4665. (c) Qi, C.; Jiang, H.; Huang, L.;
Chen, Z.; Chen, H. Synthesis 2011, 3, 387.
(9) (a) Yang, Y.; Yao, J.; Zhang, Y. Org. Lett. 2013, 15, 3206. (b) Naveen, T.; Kancherla, R.;
Maity, D. Org. Lett. 2014, 16, 5446.
(10) Huang, H.; Ji, X.; Wu, W.; Jiang, H. Adv. Synth. Catal. 2013, 355, 170.
(11) (a) Hon, Y.ꢀS.; Hsu, T.ꢀR.; Chen, C.ꢀY.; Lin, Y.ꢀH.; Chang, F.ꢀJ.; Hsieh, C.ꢀH.; Szu, P.ꢀH.
Tetrahedron 2003, 59, 1509. (b) Liu, J.; Yi, H.; Zhang, X.; Liu, C.; Liu, R.; Zhang, G.; Lei, A.
Chem. Commun. 2014, 50, 7636.
(12) (a) Hamed, O. A.; Qisairi, A. E.; Qaseer, H.; Hamed, E. M.; Henry, P. M.; Becker, D. P.
Tet. Lett. 2012, 53, 2699. (b) Stavber, G.; Iskara, J.; Zupan, M.; Stavber, S. Green. Chem. 2009,
11, 1262. (c) Liang, Y.ꢀF.; Wu, K.; Song, S.; Li, X.; Huang, X.; Jiao, N. Org. Lett. 2015, 17, 876.
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7
8
9
(13) (a) Lee, J. C.; Park, H.ꢀJ.; Park, J. Y. Tetrahedron Lett. 2002, 43, 5661. (b) Urgoitia, G.;
SanMartin, R.; Herrero, M. T.; Dominguer, E. Green. Chem. 2011, 13, 2161. (c) Cacchi, S.;
Fabrizi, G.; Goggiamani, A.; IAZZetti, A.; Verdiglione, R. Synthesis 2013, 45, 1701.
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50
51
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53
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55
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57
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59
60
(14) Maji, A.; Rana, S.; Maity, D. Angew. Chem. Int. Ed. 2014, 53, 2428.
(15) (a) Churruca, F.; Sanmartin, R.; Tellitu, I.; Dominguez, E. Tetrahedron Lett. 2006, 47, 3233.
(b) Churruca, F.; Sanmartin, R.; Tellitu, I.; Dominguez, E. Org. Lett. 2002, 4, 1591.
(16) (a) Soriaꢀ Castro, S. M.; Caminos, D. A.; Penenory, A. B. RSC. Adv. 2014, 4, 17490. (b)
Park, J.; Yeon, J.; Lee, P. H.; Lee, K. Tetrahedron Lett. 2013, 54, 4414. (c) Shimada, T.;
Bajracharya, G. B.; Yamamoto, Y. Eur. J. Org. Chem. 2005, 59. (d) CarbreroꢀAntonino, J. R.;
LeyvaꢀPerez, A.; Corma, A. Chem.- Eur. J. 2012, 18, 11107. (e) Huang, K.; Li, G.; Huang, W.ꢀ
P.; Yu, D.ꢀG.; Shi, Z.ꢀJ. Chem. Commun. 2011, 47, 7224. (f) Xu, M.ꢀL.; Huang, W. Tetrahedron
Lett. 2014, 55, 4230. (g) Fu, Y.; Yang, Y.; Hugel, H. M.; Du, Z.; Wang, K.; Huang, D.; Hu, Y.
Org. Biomol. Chem. 2013, 11, 4429. (h) Zhang, J.; Yang, X.; Cui, X.; Wu, Y. Tetrahedron 2011,
67, 8800. (i) Zhao, B.; Lu, X. Tetrahedron Lett. 2006, 47, 6765. (j) Gao, Q.; Li, S.; Pan, Y.; Xu,
Y.; Wang, H. Tetrahedron 2013, 69, 3775. (k) Hamann, H. C.; Hartwig, J. F. J. Am. Chem. Soc.
1997, 119, 12382. (l) Ackermann, L.; Kaspar, L. T. J. Org. Chem. 2007, 72, 6149. (m) Kim, S.ꢀ
H.; Rieke, R. D. J. Org. Chem. 2000, 65, 2322. (n) Zhao, B.; Lu, X. Org. Lett. 2006, 8, 5987. (o)
Wang, X.; Wang, X.; Liu, M.; Ding, J.; Chen, J.; Wu, H. Synthesis 2013, 45, 2241. (p)
Tsuchimoto, T.; Joya. T.; Shirakawa, E.; Kawakami, Y. Synlett. 2000, 12, 1777. (q) Su, Y.; Sun,
X.; Wu, G.; Jiao, N. Angew. Chem. Int. Ed. 2013, 52, 9808. (r) Xu, Q.ꢀL.; Gao, H.; Yousufuddin,
M.; Ess, D. H.; Kurti, L. J. Am. Chem. Soc. 2013, 135, 14048. (s) Khalaf, A. I.; Huggan, J. K.;
Suckling, C. J.; Gibson, C. L.; Stewart, K.; Giordani, F.; Barrett, M. P.; Wong, P. E. Barrack, K.
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L.; Hunter, W. N. J. Med. Chem. 2014, 57, 6479. (t) Motwani, H. V.; Larhed, M. Eur. J. Org.
Chem. 2013, 4729. (u) Rao, M. L. N.; Giri, S.; Jadhav, D. N. Tetrahedron Lett. 2009, 50, 6133.
(v) Mathew, P.; Mathew, D.; Asoken, C. V. Synth. Commun. 2005, 37, 661. (w) Battace, A.;
Feuerstein, M,; Lemhadri, M.; Zair, T.; Doucet, H.; Santelli, M. Eur. J. Org. Chem. 2007, 3122.
(x) Dubrovskiy, A. D.; Larock, R. C. Tetrahedron 2013, 69, 2789.
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(17) Doyle, M. P.; Nesloney, C. L.; Shanklin, M. S.; Marsh, C. A.; Brown, K. C. J. Org. Chem.
1989, 54, 3785.
(18) da Silva, G.; Hamdan, M. R.; Bozzelli, J. W. J. Chem. Theory Comput. 2009, 5, 3185.
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