Transition-metal-free superbase-promoted stereoselective α-vinylation of ketones with arylacetylenes: A general strategy for synthesis of β,γ-unsaturated ketones

Article abstract of DOI:10.1021/jo301005p

A wide variety of β,γ-unsaturated ketones of E configuration have been obtained in good to excellent yields via KO^tBu/DMSO promoted α-vinylation of aliphatic, cycloaliphatic, and alkyl aromatic (heteroaromatic) ketones with diverse arylacetylenes.

Full text of DOI:10.1021/jo301005p

Article
pubs.acs.org/joc
Transition-Metal-Free Superbase-Promoted Stereoselective
α‑Vinylation of Ketones with Arylacetylenes: A General Strategy for
Synthesis of β,γ-Unsaturated Ketones
Boris A. Trofimov,* Elena Yu. Schmidt, Nadezhda V. Zorina, Elena V. Ivanova, and Igor' A. Ushakov
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, 1 Favorsky Str., 664033 Irkutsk, Russia
S
* Supporting Information
ABSTRACT: A wide variety of β,γ-unsaturated ketones of E
configuration have been obtained in good to excellent yields via
KOtBu/DMSO promoted α-vinylation of aliphatic, cycloaliphatic,
and alkyl aromatic (heteroaromatic) ketones with diverse
arylacetylenes.
unsaturated ketones was developed.21 The procedure included
oxidation of the alcohols to aldehydes in the presence of an
allylating reagent (allyl stannane with catalytic Yb(OTf)3 or
INTRODUCTION
■
The importance of the vinylation reactions of ketones stems
not only from frequent appearance of the C−C double bond-
allyl trifluoroborate with boron trifluoride etherate) and in situ
carbonyl entities in natural products and biologically active
compounds1 but also from the rich and well-studied chemistry
of β,γ-unsaturated ketones that enables expedient synthesis of
complex structures.2 Many synthetic approaches to β,γ-
unsaturated ketones have been documented. Among these are
palladium-catalyzed cross-coupling of ketones with alkenyl-
bromides3 or alkenyltriflates4 and α-iodoenones with alkenyl-
zinc5 and Yb-mediated coupling of oxonitriles with allylbromi-
des.2b The InBr3 reactions of acylchlorides with allyl silanes6 or
allylic mercuric iodides7 in the presence of AlCl3 were also
employed to reach this aim. A series of β,γ-unsaturated ketones
were synthesized by addition of allylzinc bromide to nitriles in
the presence of AlCl3.8 Also, there were reported a number of
other syntheses including the alkenylation of enol silyl ethers
with alkenylbismuth,9 Et3B-catalyzed alkenylation of α-halo
ketones with alkenylindium10 or allyltributyltin in the presence
of SnCl2,11 allylation of arylpentamethylcyclopentadienyl
ketones with allyldimethylaluminum,2d and allylation of
borolanes.12 Moreover, β,γ-unsaturated ketones were synthe-
sized by the cross-coupling of allylic halides with acylstan-
nanes,13 -silanes,14 and -zirconocenes.15 Alternatives to the
above syntheses were the oxidation of homoallylic alcohols,16
ruthenium-catalyzed hydration dimerization of arylacetylenes,17
and ruthenium hydride-catalyzed addition of aldehydes to
dienes.18 The list of efforts toward reasonably simple
preparation of β,γ-unsaturated ketones may be even further
extended by cerium-mediated addition of organolithiums to
silylated enaminones19 and acid-catalyzed transformation of 2-
(1-hydroxyalkyl)-1-alkylcyclopropanols.20 However, some of
these methods are based on tedious procedures that narrow
their applicability, and others require hardly accessible starting
materials or transition metal catalysts. In view of the synthetic
importance of β,γ-unsaturated ketones, it would be desirable to
develop convenient methodologies for their synthesis from
readily available starting materials. Along this line, most
recently one-pot conversion of benzylic alcohols into β,γ-
oxidation of the allylic alcohols.21
The base-promoted addition of ketones to acetylenes might
be a convenient straightforward route to the chemistry of β,γ-
unsaturated ketones, but such an addition seemed to be
precluded because in the presence of basic catalysts the
formation of propargyl alcohols usually took place (Favorsky
reaction).22 Recently, contrary to this common knowledge, we
have found alkylarylketones to be capable of vinylation by
arylacetylenes in the superbasic heterogeneous system KOH/
DMSO to give the β,γ-unsaturated ketones in good yields.23
However, for aliphatic and cycloaliphatic ketones this protocol
happened to be inefficient; the yields of the adducts were from
low to modest.
Therefore, a further search for a more efficient promoting
system that would be suitable for both aliphatic, cycloaliphatic,
and alkylaromatic ketones remained an obvious challenge.
RESULTS AND DISCUSSION
■
To develop a general strategy of the superbase-induced
vinylation of ketones with acetylenes, we have evaluated the
catalytic activity of a series of DMSO-tailored superbases and
found that the system of KOtBu/DMSO secured efficient α-
vinylation of various ketones including aliphatic, cycloaliphatic,
and alkylaromatic ones. Herein, we summarize the results of
this study.
As models for the screening promoting systems, we have
chosen two reactions: vinylation of acetone 1 and cyclo-
hexanone 6 with phenylacetylene 15 (Tables 1, 2).
As seen from Table 1, the MOH/DMSO system (except for
LiOH) promotes the formation of the expected β,γ-unsaturated
Received: May 24, 2012
Published: July 27, 2012
© 2012 American Chemical Society
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The E configuration of the minor α,β-ethylenic ketones was
supported by the presence of characteristic cross-peaks in their
NOESY spectra.
Table 1. Promoting Activity of the MOR/DMSO Systems in
the α-Vinylation of Acetone 1 with Phenylacetylene 15
a
Meanwhile, other promoting systems facilitated the for-
mation of α,β-unsaturated isomers, their content increasing to
20%. However, we obtained convincing experimental proof that
these regioisomers are readily separable by the column
chromatography (SiO2, eluent hexane/benzene with gradient
from 1:0 to 0:1).
Notably, other potentially promoting superbase systems of
the type KOtBu/nonhydroxylic polar solvent appeared to be
inefficient in the reaction studied. For example, with KOtBu/
THF and KOtBu/DMF pairs under the conditions of Table 1,
none of the products were detected in the reaction mixtures,
and in the KOtBu/N-methylpyrrolidone system, a complicated
mixture of inseparable components including vinylated acetone
21 was obtained.
With the optimal conditions in hand, we examined the
KOtBu/DMSO system for α-vinylation of various ketones 1−
14 with acetylenes 15−20. Table 3 illustrates the wide
generality and substrate scope of this reaction. As follows
from Table 3, the methodology thus developed demonstrates
excellent efficacy toward aliphatic, cycloaliphatic (including
macrocyclic), alkyl aromatic, and alkyl heteroaromatic ketones
and an appropriate range of arylacetylenes. Gratifyingly,
acylated condensed aromatics and diphenyl derivatives as well
as 1,4-diethynylbenzene tolerate the reaction conditions
(entries 14 and 15).
Noteworthy, for all 18 ketone/acetylene pairs, good (or in
some cases, total) regioselectivity and total stereoselectivity are
preserved. In particular, α-vinylation of alkylaryl(hetaryl)
ketones (entries 10−18) resulted in the formation of β,γ-
unsaturated ketones exclusively. Regarding the predominance
of β,γ- versus α,β-unsaturated isomers, this is a well-known
consequence of kinetic protonation of a dienolate (see below,
Scheme 1). At the same time there is a contest between olefin
conjugation with carbonyl versus with aryl, and the latter is
likely thermodynamically favored, which is supported by
quantum chemical calculations (see below).
b
MOR
LiOH
temp (°C)
time (min)
yield of 21 (%)
c
80−120
80
60−180
120
120
120
60
nd
NaOH
NaOH
KOH
traces
10
100
80
17
KOH
100
100
100
100
20
KOH/tBuOH
KOtBu
KOtBu
120
60
29
63
30
70
a
Reaction conditions: acetone 1 (4 mmol, 230 mg), phenylacetylene
15 (4 mmol, 410 mg), 4 mmol MOR in 10 mL of DMSO. Isolated
b
c
yield after column chromatography. Not detected.
Table 2. Promoting Activity of the MOR/DMSO Systems in
the α-Vinylation of Cyclohexanone 6 with Phenylacetylene
a
15
b
MOR
LiOH
temp (°C)
time (min)
yield of 28 (%)
c
100−120
80
60
nd
NaOH
120
60
7
NaOH
100
27
57
61
39
83
KOH
80
60
KOH
100
60
LiOH/CsF
KOH/tBuOH
KOtBu
100
120
60
100
100
30
90
a
b
The reaction conditions were the same as Table 1. Isolated yield
c
after column chromatography. Not detected.
ketone 21 (10−29% yields), and the system of KOtBu/DMSO
proved to be the most effective (yield of 21 being 70%).
In the case of α-vinylation of cyclohexanone 6, the same
trend is observed (the reaction proceeds almost quantitatively,
and yields of the corresponding ketone 28 reach 90%, Table 2),
albeit KOH/DMSO systems ensure quite appropriate isolated
When the CH3 and CH2 groups of a ketone competed for
the addition to the triple bond, the latter in the case of 2-
butanone 2 won the competition (entry 2) to give the 4:1
mixture of the regioisomers. However, when the CH2 moiety
was sterically screened by two methyl groups, as in the case of
4-methyl-2-pentanone 39, the methyl α-group became equally
competitive with the CH2 group. The two expected
regioisomeric β,γ-unsaturated ketones 40 and 41 (both of E
configuration) were formed in a ∼1:1 ratio (77% total yield):
t
yield (up to 61%) and the BuOH additive provides for even
further improvement (83% yield).
In all of the experiments presented in Tables 1 and 2, the
vinylation proceeded as a regioselective and close to 100%
stereoselective process, i.e., only E isomers of adducts were
formed. The E configuration of β,γ-ethylenic ketones was
3
confirmed by J values (16.1 Hz) between protons at the
double bond.
For the reaction with the KOtBu/DMSO system, the
anticipated regioisomers, i.e., the corresponding α,β-unsatu-
rated ketones (also exclusively of E configuration), originated
from prototropic isomerization of ketones 21 and 28 were just
minor admixtures (5−10%) in major β,γ-isomers:
Surprisingly, 3,3-dimethyl-2-butanone 3 was capable of
double vinylation to give along with the monoadducts 23 and
24 (entries 3, 4) also the divinyl derivative 42 in a yield of 34%
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Table 3. Substrate Scope of α-Vinylation of Ketones 1−14 with Acetylenes 15−20 in the Presence of the KOtBu/DMSO
a
System
a
b
c
The reaction conditions were the same as Table 1. Isolated yield after column chromatography. The sample contained 20% of admixture of the
d
regioisomer formed over the methyl group. Ketone/acetylene molar ratio was 2:1.
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mol, which corresponds to approximately equal population of
the E and Z isomers at the thermodynamic equilibrium. Thus,
the high E stereoselectivity observed in the reaction is
kinetically controlled, i.e., is determined by the rate of chelate
D formation.
Scheme 1. Plausible Mechanism
To gain a better insight into of the mechanistic aspects of the
reaction studied, we have carried out the synthesis of adduct
30a in which the reaction mixture after 30 min has been
1
quenched with D2O, and in the H NMR spectrum of the
crude, only the β,γ-isomer having one deuterium atom in the
CHD group has been discernible.
(when 2 equiv of phenylacetylene was employed and the
reaction was carried out for a longer time):
This selective isotope exchange supports our previous
suggestion23 that the dienolate C is present as the stable
intermediate and that the β,γ-unsaturated ketones of E
configuration are kinetic products.
Also, we have performed the quantum chemical calculations
[MP2/6-311++G(d,p)] of energy difference between α,β- and
β,γ-isomers of adduct 21, both of E configuration, to
theoretically determine their thermodynamical distribution.
The energy difference has been found to be 0.36 kcal/mol. This
corresponds to the 35:65 ratio of the above isomers in the
equilibrium. This confirms that the observed β,γ- versus α,β-
selectivity is kinetically controlled.
The reaction mechanism obviously represents the nucleo-
philic attack of the enolate A at an acetylene. Such reactions are
commonly known to proceed as a concerted trans-addition24 to
deliver the adduct B of Z configuration (Scheme 1), but a
challenging issue here is the E stereoselectivity of the reaction
under study. Apparently, the intermediate B tends to the Z → E
isomerization in its deprotonated form C in which a free
rotation of the phenyl group around the former double bond
becomes allowable. The driving force of such an isomerization
might be chelating of the potassium cation in the enolate D
with the participation of π-electrons of the arylethenyl moiety
thus forming six-p-electron quasi-aromatic cycle D. Actually,
the whole process is an equilibration, mediated by HOtBu. The
subsequent aqueous workup of this chelate leads to final
adducts 21−38 of E configuration.
This mechanism is supported by the following experimental
evidence: (i) the highest yields were reached only with the
equimolar ratio of starting ketone and KOtBu that fit with the
binding of K+ in the chelate D, i.e., the neutralization of the
promoting base in the reaction process; (ii) at a lower
temperature (60 °C, 60 min) with KOH/DMSO, the E:Z
isomer ratio for adduct 30 was 3:2, indicating the incomplete
conversion of the intermediate B to chelate D; (iii) the
replacement of K+ by the bulkier diffuse Cs+ (when CsOH/
DMSO was used instead of KOH/DMSO, 100 °C, 60 min)
also led to the violation of the E stereoselectivity (the E and Z
isomers of adduct 30 in a ∼1:1 ratio were formed) thus
corresponding to a lower rate of the D-type chelating; (iv)
when ∼1:1 E/Z mixture of adduct 30 obtained in the presence
of Cs+ as described above was treated with the KOtBu/DMSO
system under the same conditions, only E-adduct 30 was
observed in the reaction mixture; (v) with NaOH/DMSO
(other reaction conditions being as in Table 3) the E:Z ratio of
adduct 30 was 9:1, likely due to the stronger Na−O bond that
hindered the chelating of the type D; (vi) the energy difference
between E and Z isomers of adduct 21 has been quantum
chemically calculated [MP2/6-311++G(d,p)] to be 0.07 kcal/
CONCLUSION
■
In conclusion, we have disclosed a novel general methodology
of the transition-metal-free base-promoted stereoselective α-
vinylation of ketones with arylacetylenes. The methodology
provides a straightforward entry to a wide variety of β,γ-
unsaturated ketones of E configuration that are obtained in
good to excellent yields.
EXPERIMENTAL SECTION
■
General Information. 1H and 13C NMR spectra were recorded at
400.13 and 100.61 MHz, respectively, on an instrument equipped with
an inverse gradient 5 mm probe in CDCl3 with hexamethyldisiloxane
(HMDS) as an internal standard. Coupling constants are given in
Hertz. All 2D NMR spectra were recorded by using a standard
gradient Bruker pulse program. Standard COSY spectra with a 90°,
45° pulse sequence were recorded.25 The NOESY spectra were
recorded in the phase-sensitive TPPI mode with amixing time of 1−
1.4 s.26 HSQC spectra via double INEPT transfer in the phase
sensitive TPPI mode with GARP decoupling during acquisition were
recorded.27 HMBC spectra were obtained with the inverse technique
and processed in the magnitude mode.28 IR spectra were taken with
FT-IR. All chemicals and solvents are commercially available and were
used without further purification. The elaborated procedure does not
require degassing of DMSO and use of inert atmosphere, and the
benefit of DMSO as a solvent is that it is stable up to 150 °C for a long
time (24 h, weight lost 0.1−1.0%).29
General Procedure for α-Vinylation of Ketones with
Acetylenes (Example of the Reaction of Acetone 1 with
Phenylacetylene 15; Table 3, Entry 1). A mixture of acetone 1
(232 mg, 4.0 mmol), phenylacetylene 15 (409 mg, 4.0 mmol), and
KOtBu (449 mg, 4.0 mmol) in DMSO (10 mL) was heated (100 °C)
and stirred at 100 °C for 30 min. The reaction mixture, after cooling
(20−25 °C), was diluted with H2O (10 mL), neutralized with NH4Cl,
and extracted with Et2O (10 mL × 4). The organic extract was washed
with H2O (5 mL × 3) and dried (MgSO4). After removal of the Et2O,
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a crude residue (612 mg) was obtained. Column chromatography
(SiO2, eluent hexane/benzene with gradient from 1:0 to 0:1) gave the
pure β,γ-unsaturated ketone 21 (449 mg, 70%) as yellow oil.
Compounds 22−38 and 40−41 were prepared analogously.
(E)-5-Phenylpent-4-en-2-one (21; Table 3, Entry 1). Yellow oil.
Elemental Analysis Calcd (%) for C11H12O (160.21): C 82.46; H 7.55.
Found: C 82.15, H 7.59. IR (film): νmax = 3026, 2958, 1715, 1668,
1599, 1495, 1357, 1157, 1073, 965, 741, 694 cm−1. 1H NMR: δ 7.26−
7.24 (m, 2H; Ho), 7.20−7.18 (m, 2H; Hm), 7.13−7.11 (m, 1H; Hp),
6.49 (d, 3J = 16.1 Hz, 1H; H5), 6.20 (dt, 3J = 16.1 Hz, 3J = 7.1 Hz, 1H;
H4), 3.35 (d, 3J = 7.1 Hz, 2H; H3), 2.22 ppm (s, 3H; H1). 13C NMR:
δ 206.6 (CO), 137.0 (Ci), 133.9 (C5), 128.7 (Cm), 127.7 (Cp),
126.4 (Co), 122.0 (C4), 47.9 (C3), 29.7 ppm (Me).
6.87−6.86 (m, 1H; H2), 6.77−6.75 (m, 1H; H4), 6.43 (d, 3J = 15.8 Hz,
3
3
1H; H1), 6.05 (dd, J = 15.8 Hz, J = 9.2 Hz, 1H; H2), 3.78 (s, 3H;
OMe), 3.15−3.09 (m, 1H; H3), 2.50−2.33 (m, 2H; H5), 1.85−1.78,
1.59−1.54 (m, 4H; CH2Me, H6), 0.89−0.85 ppm (m, 6H; CH2Me,
H7). 13C NMR: δ 210.8 (CO), 159.7 (C3), 138.1 (C1), 132.5 (C1),
129.3 (C5), 128.0 (C2), 118.6 (C6), 112.3 (C4), 111.4 (C2), 58.3 (C3),
54.9 (OMe), 43.5 (C5), 24.4 (CH2Me), 16.8 (C6), 13.5 (C7), 11.6
ppm (CH2Me).
(E)-4-Styrylnonan-5-one (27; Table 3, Entry 7). With admixture
(∼20%) of the α,β-isomer. Total yield: 606 mg, 62%. Yellow oil.
Elemental Analysis Calcd (%) for C17H24O (244.37): C 83.55, H 9.90.
Found: C 83.68, H 9.98. IR (film): νmax = 3027, 2959, 2935, 2863,
1713, 1669, 1600, 1495, 1465, 1452, 1378, 1259, 1157, 1126, 1072,
1044, 1030, 968, 750, 694 cm−1. 1H NMR: δ 7.25−7.23 (m, 2H; Ho),
(E)-5-(3-Methoxyphenyl)-3-methylpent-4-en-2-one (22;
Table 3, Entry 2). With admixture (∼20%) of the regioisomer
formed over the methyl group. Total yield: 539 mg, 66%. Yellow oil.
Elemental Analysis Calcd (%) for C13H16O2 (204.27): C 76.44, H
7.90. Found: C 76.48, H 7.67. IR (film): νmax= 2972, 2934, 2836, 1716,
1600, 1582, 1489, 1459, 1434, 1356, 1265, 1160, 1046, 971, 779, 691
cm−1. 1H NMR for 22: δ 7.24−7.21 (m, 1H; H5), 6.98−6.96 (m, 1H;
3
7.23−7.21 (m, 2H; Hm), 7.16−7.14 (m, 1H; Hp), 6.38 (d, J = 15.9
Hz, 1H; Hγ), 6.01 (dd, 3J = 15.9 Hz, 3J = 9.3 Hz, 1H; Hβ), 3.18−3.12
(m, 1H; H4), 2.38−2.34 (m, 2H; H6), 1.72−1.68, 1.47−1.44 (m, 2H;
H3), 1.49−1.42 (m, 2H; H7), 1.28−1.21 (m, 2H; H2), 1.22−1.18 (m,
2H; H8), 0.83 (m, 3H; H9), 0.82 ppm (m, 3H; H1). 13C NMR: δ
209.9 (CO), 136.5 (Ci), 132.2 (Cγ), 128.1 (Cm), 128.0 (Cβ), 127.0
(Cp), 125.6 (Co), 56.2 (C4), 40.9 (C6), 33.1 (C3), 25.5 (C7), 21.9
(C8), 20.0 (C2), 13.5 (C1), 13.5 ppm (C9).
3
H4), 6.81−6.82 (m, 1H; H6), 6.80−6.79 (m, 1H; H2), 6.50 (d, J =
3
15.8 Hz, 1H; H5), 6.18 (dd, J = 15.8 Hz, 3J = 8.5 Hz, 1H; H4), 3.82
(s, 3H; OMe), 3.36−3.32 (m, 1H; H3), 2.21 (s, 3H; Me), 1.28 ppm
(d, 3J = 6.9 Hz, 3H; CHMe). 13C NMR for 22: δ 209.3 (CO), 159.9
(C3), 138.3 (C1), 132.1 (C5), 129.6 (C4), 129.1 (C5), 119.0 (C6),
113.4 (C2), 111.6 (C4), 55.2 (OMe), 51.3 (C3), 28.2 (C1), 16.2 ppm
(CHMe).
(E)-2-Styrylcyclohexanone (28; Table 3, Entry 8). Yield: 721
mg, 90%. Yellow oil. Elemental Analysis Calcd (%) for C14H16O
(200.28): C 83.96, H 8.05. Found: C 84.10, H 8.09. IR (film): νmax
=
3027, 2937, 2863, 1951, 1709, 1613, 1495, 1450, 1249, 1143, 1127,
1
1071, 966, 748, 696, 495 cm−1. H NMR: δ 7.40−7.39 (m, 2H; Ho),
3
(E)-2,2-Dimethyl-6-phenylhex-5-en-3-one (23; Table 3, Entry
3). Yield: 744 mg, 92%. Yellow oil. Elemental Analysis Calcd (%) for
C14H18O (202.29): C 83.12, H 8.97. Found: C 83.18, H 9.00. IR
(film): νmax = 3027, 2969, 2934, 2871, 1706, 1599, 1496, 1478, 1449,
1394, 1366, 1294, 1206, 1094, 1072, 1053, 1028, 992, 965, 768, 733,
7.31−7.29 (m, 2H; Hm), 7.23−7.22 (m, 1H; Hp), 6.42 (dd, J = 16.1
3
3
Hz, J = 6.4 Hz, 1H; Hβ), 6.35 (d, J = 16.1 Hz, 1H; Hγ), 3.21−3.15
(m, 1H; H2), 2.45−2.34 (m, 2H; 6-CH2), 2.16−1.72 (m, 2H; 3-CH2),
2.01−1.72 (m, 2H; 4-CH2), 1.91−1.73 ppm (m, 2H; 5-CH2). 13C
NMR: δ 211.2 (CO), 137.1 (Ci), 131.3 (Cγ), 128.6 (Cm), 127.4
(Cβ), 126.4 (Cp), 126.2 (Co), 53.8 (C2), 41.6 (C6), 34.3 (C3), 27.6
(C4), 24.3 ppm (C5).
1
692 cm−1. H NMR: δ 7.31−7.29 (m, 2H; Ho), 7.25−7.21 (m, 2H;
Hm), 7.18−7.14 (m, 1H; Hp), 6.37 (d, 3J = 16.0 Hz, 1H; H6), 6.29 (dt,
3
3
3J = 16.0 Hz, J = 6.4 Hz, 1H; H5), 3.37 (d, J = 6.4 Hz, 2H; H4),
(E)-2-Styrylcyclododecanone (29; Table 3, Entry 9). Yield: 717
mg, 63%. White powder: mp 58−60 °C. Elemental Analysis Calcd (%)
for C20H28O (284.44): C 84.45, H 9.92. Found: C 84.31, H 9.67. IR
(KBr): νmax = 2930, 2862, 1701, 1667, 1495, 1469, 1445, 1347, 1247,
1128, 1072, 1017, 968, 754, 731, 692 cm−1. 1H NMR: δ 7.22−7.21 (m,
2H; Ho), 7.20−7.19 (m, 1H; Hm3), 7.12−7.11 (m, 2H; Hp), 6.37 (d, 3J
1.165 ppm (s, 9H; C(Me)3). 13C NMR: δ=212.6 (CO), 137.2 (Ci),
132.8 (C6), 128.4 (Co), 127.3 (Cp), 126.2 (Cm), 123.3 (C5), 44.4
(C(Me)3), 40.6 (C4), 26.5 ppm (C(Me)3).
(E)-6-(2,5-Dimethylphenyl)-2,2-dimethylhex-5-en-3-one (24;
Table 3, Entry 4). Yield: 838 mg, 91%. Yellow oil. Elemental Analysis
Calcd (%) for C16H22O (230.35): C 83.43, H 9.63. Found: C 83.20, H
9.60. IR (film): νmax = 3039, 3017, 2969, 2924, 2870, 1708, 1612, 1496,
1478, 1463, 1394, 1380, 1366, 1294, 1160, 1088, 1053, 994, 967, 910,
3
= 15.8 Hz, 1H; Hγ), 6.06 (dd, J = 15.8 Hz, J = 8.8 Hz, 1H; Hβ),
3.44−3.39 (m, 1H; H2), 2.57−2.48 (m, 2H; 12-CH2), 2.37−2.30 (m,
2H; 3-CH2), 1.98−1.92 (m, 2H; 11-CH2), 1.77−1.70 (m, 2H; 4-CH2),
1.53−1.42 (m, 2H; 5-CH2), 1.21−1.20 ppm (m, 10H; 6-CH2, 7-CH2,
8-CH2, 9-CH2, 10-CH2). 13C NMR: δ 212.2 (CO), 136.9 (Cβ),
131.9 (Ci), 128.4 (Cm), 127.6 (Cp), 126.5 (Cγ), 126.3 (Co), 55.1 (C2),
38.7 (C3), 30.7 (C12), 25.5, 24.9, 24.8, 24.7, 24.4, 24.3, 24.1, 23.4
ppm (C4−C11).
1
808, 734 cm−1. H NMR: δ 7.25−7.23 (m, 1H; H6), 6.99−6.96 (m,
3
4
1H; H3), 6.92−6.91 (m, 1H; H4), 6.59 (dt, J = 15.9 Hz, J = 1.1 Hz,
1H; H6), 6.17 (dt, 3J = 15.9 Hz, 3J = 7.0 Hz, 1H; H5), 3.44−3.42 (dd,
4
3J = 7.0 Hz, J = 1.1 Hz, 2H; H4), 2.27, 2.26 (s, 6H; C2-Me, C5-Me),
1.17 ppm (s, 9H; C(Me)3). 13C NMR: δ 213.2 (CO), 135.9 (C1),
135.0 (C5), 131.7 (C2), 130.6 (C6), 129.8 (C6), 127.8 (C4), 126.2
(C3), 124.3 (C5), 44.1 (C(Me)3), 40.7 (C4), 26.2 (C(Me)3), 20.8
(C5-Me), 19.1 ppm (C2-Me).
(E)-1,4-Diphenyl-3-buten-1-one (30; Table 3, Entry 10). Yield:
756 mg, 85%. White crystals: mp 92−94 °C. Elemental Analysis Calcd
(%) for C16H14O (222.28): C 86.45, H 6.35. Found: C 86.67, H 6.57.
IR (KBr): νmax = 3082, 3061, 3023, 1683, 1597, 1496, 1449, 1399,
1356, 1334, 1296, 1277, 1208, 1071, 983, 908, 749, 732, 688, 566, 501
(E)-3-Ethyl-1-phenylhept-1-en-4-one (25; Table 3, Entry 5).
Yield: 787 mg, 91%. Yellow oil. Elemental Analysis Calcd (%) for
C15H20O (216.32): C 83.28, H 9.32. Found: C 83.26, H 9.41; IR
(film): νmax = 3027, 2964, 2933, 2875, 1712, 1667, 1601, 1494, 1453,
1378, 1196, 1073, 1055, 1029, 968, 748, 697 cm−1. 1H NMR: δ 7.37−
7.35 (m, 2H; Ho), 7.32−7.30 (m, 2H; Hm), 7.28−7.26 (m, 1H; Hp),
1
cm−1. H NMR: δ 8.00−7.98 (m, 2H; Ho), 7.58−7.55 (m, 1H; Hp),
7.47−7.44 (m, 2H; Hm), 7.37−7.34 (m, 2H; Ho′), 7.30−7.27 (m, 2H;
3
Hm′), 7.18−7.20 (m, 1H; Hp′), 6.53 (d, J = 16.1 Hz, 1H; Hγ), 6.45
(dt, 3J = 16.1 Hz, 3J = 6.1 Hz, 1H; Hβ), 3.90 ppm (d, 3J = 6.1 Hz, 2H;
CH2). 13C NMR: δ 198.1 (CO), 137.0 (Ci′), 136.5 (Ci), 133.5 (Cγ),
133.1 (Cp), 128.6 (Cm), 128.4 (Cm′), 128.3 (Co), 127.3 (Cp′), 126.2
(Co′), 122.6 (Cβ), 42.8 ppm (CH2).
3
3
3
6.45 (d, J = 15.9 Hz, 1H; H1), 6.04 (dd, J = 15.9 Hz, J = 9.3 Hz,
1H; H2), 3.16−3.10 (m, 1H; H3), 2.46−2.44 (m, 2H; H5), 1.82−
1.79, 1.57−1.55 (m, 2H; CH2Me), 1.63−1.61 (m, 2H; H6), 0.90 (m,
3H; H7), 0.89−0.87 ppm (m, 3H; CH2Me). 13C NMR: δ 211.0 (C
O), 136.9 (Ci), 132.8 (C1), 128.5 (Cm), 127.9 (C2), 127.0 (Cp), 126.1
(Co), 58.5 (C3), 43.5 (C5), 24.4 (CH2Me), 16.9 (C6), 13.7 (C7), 11.7
ppm (CH2Me).
(E)-4-(2,5-Dimethylphenyl)-1-phenylbut-3-en-1-one (31;
Table 3, Entry 11). Yield: 801 mg, 80%. Pale yellow crystals: mp
58−60 °C. Elemental Analysis Calcd (%) for C18H18O (250.34): C
86.36, H 7.25. Found: C 86.51, H 7.21. IR (KBr): νmax = 3040, 3023,
2920, 1684, 1595, 1579, 1495, 1447, 1400, 1327, 1206, 1180, 1070,
(E)-3-Ethyl-1-(3-methoxyphenyl)hept-1-en-4-one (26; Table
3, Entry 6). Yield: 798 mg, 81%. Yellow oil. Elemental Analysis Calcd
(%) for C16H22O2 (246.35): C 78.01, H 9.00. Found: C 78.12, H 8.99.
IR (film): νmax = 3026, 2963, 2932, 2875, 2834, 1711, 1666, 1599,
1489, 1464, 1455, 1434, 1289, 1262, 1156, 1048, 971, 871, 780, 690
1
983, 958, 797, 753, 692, 558 cm−1. H NMR: δ 8.01−7.99 (m, 2H;
Ho), 7.58−7.54 (m, 1H; Hp), 7.49−7.45 (m, 2H; Hm), 7.27−7.26 (m,
1H; H6), 7.01−6.99 (m, 1H; H3), 6.95−6.92 (m, 1H; H4), 6.72 (d, 3J
= 16.1 Hz, 1H; Hγ), 6.45 (dt, 3J = 16.1 Hz, 3J = 6.8 Hz, 1H; Hβ), 3.91
1
3
3
cm−1. H NMR: δ 7.23−7.17 (m, 1H; H5), 6.93−6.91 (m, 1H; H6),
(dd, J = 6.8 Hz, J = 1.5 Hz, 2H; CH2), 2.28 (s, 3H; C5-Me), 2.27
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Article
ppm (s, 3H; C2-Me). 13C NMR: δ 198.1 (CO), 136.7 (Ci), 135.9
(C1), 135.4 (C5), 133.2 (Cγ), 132.1 (C2), 131.6 (Cp), 130.1 (C6),
128.6 (Cm), 128.4 (Co), 128.2 (C4), 126.4 (C3), 123.6 (Cβ), 43.1
(CH2), 21.1 (C5-Me), 19.4 ppm (C2-Me).
(E)-4-Phenyl-1-thiophen-2-yl-3-buten-1-one (37; Table 3,
Entry 17). Yield: 749 mg, 82%. Pale yellow crystals: mp 42 °C.
Elemental Analysis Calcd (%) for C14H12OS (228.31): C 73.65, H
5.30, S 14.04. Found: C 73.74, H 5.45, S 14.00. IR (KBr): νmax = 3436,
3026, 1660, 1516, 1495, 1353, 1299, 1208, 1053, 963, 945, 859, 839,
765, 726, 692, 583, 498, 463 cm−1. 1H NMR: δ 7.77 (dd, 3J = 3.8 Hz,
4J = 1.2 Hz, 1H; H3), 7.63 (dd, 3J = 4.9 Hz, 4J = 1.2 Hz, 1H; H5), 7.36
(E)-4-(4-Methoxyphenyl)-1-phenylbut-3-en-1-one (32; Table
3, Entry 12). Yield: 686 mg, 68%. Yellow crystals: mp 96−98 °C.
Elemental Analysis Calcd (%) for C17H16O2 (252.31): C 80.93, H
6.39. Found: C 80.89, H 6.43. IR (KBr): νmax = 3062, 2957, 2836,
1679, 1606, 1578, 1510, 1449, 1398, 1357, 1327, 1283, 1206, 1174,
1108, 1032, 978, 837, 812, 758, 743, 688 cm−1. 1H NMR: δ 8.03−8.01
(m, 2H; Ho), 7.60−7.58 (m, 1H; Hp), 7.50−7.48 (m, 2H; Hm), 7.34−
7.32 (m, 2H; Ho′), 6.86−6.84 (m, 2H; Hm′), 6.51 (d, 3J = 15.9 Hz, 1H;
3
(m, 2H; Ho), 7.29 (m, 2H; Hm), 7.21 (m, 1H; Hp), 7.13 (dd, J = 3.8
Hz, 3J = 4.9 Hz, 1H; H4), 6.56 (d, 3J = 16.1 Hz, 1H; Hγ), 6.42 (dt, 3J =
3
3
16.1 Hz, J = 6.8 Hz, 1H; Hβ), 3.82 ppm (d, J = 6.8 Hz, 2H; CH2).
13C NMR: δ 190.8 (CO), 143.8 (C2), 136.9 (Ci), 133.9 (Cβ), 133.4
(C5), 132.4 (C3), 128.6 (Cm), 128.2 (C4), 127.6 (Cp), 126.4 (Co),
122.3 (Cγ), 43.7 ppm (CH2).
3
3
3
Hγ), 6.34 (dt, J = 15.9 Hz, J = 6.9 Hz, 1H; Hβ), 3.90 (dd, J = 6.9
Hz, J = 1.5 Hz, 2H; CH2), 3.81 ppm (s, 3H; OMe). 13C NMR: δ
3
(E)-4-(3-Methoxyphenyl)-2-methyl-1-(thiophen-2-yl)but-3-
en-1-one (38; Table 3, Entry 18). Yield: 872 mg, 80%. Yellow oil.
Elemental Analysis Calcd (%) for C16H16O2S (272.36): C 70.56, H
5.92, S 11.77. Found: C 70.61, H 5.96, S 11.75. IR (film): νmax = 3102,
3026, 2972, 2933, 2835, 1661, 1599, 1579, 1518, 1490, 1464, 1454,
1433, 1415, 1355, 1318, 1289, 1266, 1242, 1203, 1157, 1042, 969, 936,
853, 780, 726, 689, 656, 565, 452 cm−1. 1H NMR: δ 7.82 (dd, 3J = 3.9
Hz, 4J = 1.0 Hz, 1H; H3), 7.60 (dd, 3J = 4.9 Hz, 4J = 1.0 Hz, 1H; H5),
198.3 (CO), 159.3 (Cp′), 136.8 (Ci), 133.3 (Cp), 133.1 (Cγ), 130.0
(Ci′), 128.8 (Cm), 128.4 (Co), 127.5 (Co′), 120.4 (Cβ), 114.0 (Cm′),
55.4 (OMe), 42.8 ppm (CH2).
(E)-1-(4-Fluorophenyl)-4-phenylbut-3-en-1-one (33; Table 3,
Entry 13). Yield: 836 mg, 87%. White crystals: mp 117−119 °C.
Elemental Analysis Calcd (%) for C16H13FO (240.27): C 79.98, H
5.45, F 7.91. Found: C 80.00, H 5.48, F, 7.93. IR (KBr): νmax = 3064,
2872, 1686, 1597, 1505, 1449, 1408, 1393, 1357, 1298, 1272, 1232,
1207, 1158, 1092, 1069, 1030, 993, 975, 839, 805, 767, 731, 688, 599,
3
4
7.21 (m, 1H; H5), 7.10 (dd, J = 3.9 Hz, J = 4.9 Hz, 1H; H4), 6.96
3
(m, 1H; H6), 6.92 (m, 1H; H2), 6.79 (m, 1H; H4), 6.56 (d, J = 15.9
Hz, 1H; Hγ), 6.38 (dd, J = 15.9 Hz, J = 8.3 Hz, 1H; Hβ), 4.15 (m,
1
558, 499 cm−1. H NMR: δ 8.03−8.00 (m, 2H; Ho), 7.37−7.35 (m,
3
3
3
2H; Ho′), 7.30−7.27 (m, 2H; Hm′), 7.25−7.22 (m, 1H; Hp′), 7.15−
1H; CHMe), 3.77 (s, 3H; OMe), 1.46 ppm (d, J = 6.9 Hz, 3H;
7.11 (m, 2H; Hm), 6.53 (d, 3J = 16.1 Hz, 1H; Hγ), 6.43 (dt, 3J = 16.1
CHMe). 13C NMR: δ 193.6 (CO), 159.6 (C3), 143.4 (C2), 138.1
(C1), 133.6 (C5), 132.2 (C3), 131.59 (Cγ), 129.4 (C5), 129.7 (Cβ),
128.1 (C4), 118.8 (C6), 113.2 (C4), 111.3 (C2), 54.9 (OMe), 46.5
(CHMe), 17.6 ppm (CHMe).
3
3
Hz, J = 6.1 Hz, 1H; Hβ), 3.90 ppm (d, J = 6.1 Hz, 2H; CH2). 13C
1
NMR: δ 196.4 (CO), 165.8 (d, J = 254.9 Hz, Cp), 136.9 (Ci′),
133.7 (Cγ), 133.0 (d, 4J = 3.1 Hz, Ci), 130.9 (d, 3J = 9.6 Hz, Co), 128.5
2
(Cm′), 127.5 (Cp′), 126.3 (Co′), 122.3 (Cβ), 115.8 (d, J = 21.8 Hz,
(E)-6-Methyl-1-phenylhept-1-en-4-one (40). Yield: 307 mg,
38%. Yellow oil. Elemental Analysis Calcd (%) for C14H18O (202.29):
C 83.12, H 8.97. Found: C 83.17, H 8.92. IR (film): νmax = 3027, 2957,
2931, 2872, 1714, 1673, 1599, 1495, 1467, 1450, 1366, 1294, 1170,
1072, 1031, 966, 746, 695 cm−1. 1H NMR: δ 7.40−7.39 (m, 2H; Ho),
Cm), 42.7 ppm (CH2).
(E)-1-[1,1′-Biphenyl]-4-yl-4-(4-pentylphenyl)-3-buten-1-one
(34; Table 3, Entry 14). Yield: 1.31 g, 89%. White powder: mp 132
°C. Elemental Analysis Calcd (%) for C27H28O (368.51): C 88.00, H
7.66. Found: C 87.96, H 7.71. IR (KBr): νmax = 3033, 2927, 2857,
1681, 1603, 1512, 1486, 1399, 1202, 1119, 1022, 991, 974, 845, 823,
3
7.33−7.32 (m, 2H; Hm), 7.26−7.24 (m, 1H; Hp), 6.49 (d, J = 16.1
Hz, 1H; H1), 6.34 (dt, 3J = 16.1 Hz, 3J = 7.1 Hz, 1H; H2), 3.32 (d, 3J
= 7.1 Hz, 2H; H3), 2.39 (d, 3J = 7.1 Hz, 2H; H5), 2.20−2.19 (m, 1H;
1
759, 688 cm−1. H NMR: δ 8.10−8.08 (m, 2H; Ho), 7.72−7.70 (m,
2H; Hm), 7.65−7.64 (m, 2H; Ho′), 7.51−7.47 (m, 2H; Hm′), 7.43−
7.40 (m, 1H; Hp′), 7.33−7.31 (m, 2H; Ho”), 7.14−7.12 (m, 2H,
3
H6), 0.95 ppm (d, J = 6.6 Hz, 6H; H7, C6-Me). 13C NMR: δ 208.5
(CO), 137.0 (Ci), 133.6 (C1), 128.6 (Cm), 127.5 (Cp), 126.3 (Co),
122.2 (C2), 51.5 (C5), 47.4 (C3), 24.5 (C6), 22.6 ppm (C6-Me, C7).
(E)-3-Isopropyl-5-phenylpent-4-en-2-one (41). Yield: 316 mg,
39%. Yellow oil. Elemental Analysis Calcd (%) for C14H18O (202.29):
C 83.12, H 8.97. Found: C 83.08, H 8.64. IR (film): νmax = 3027, 2959,
2930, 2871, 1711, 1673, 1599, 1495, 1466, 1450, 1367, 1354, 1158,
3
Hm”), 6.57 (d, J = 16.0 Hz, 1H, Hγ), 6.45 (dt, 3J = 16.0 Hz, 3J = 6.6
Hz, 1H, Hβ), 3.94 (d, 3J = 6.6 Hz, 2H, CH2), 2.59, 1.59, 1.33 (m, 8H,
CH2), 0.90 ppm (m, 3H, Me). 13C NMR: δ 197.6 (CO), 145.9
(Cp), 142.4 (Cp”), 139.9 (Ci), 135.3 (Ci′), 134.4 (Ci”), 133.5 (Cγ),
128.9, (Co, Cm′), 128.6 (Cm”), 128.2 (Cp′), 127.3 (Co′, Cm), 126.2
(Co”), 121.6 (Cβ), 42.9 (COCH2), 35.6, 31.5, 31.1, 22.5 (4CH2), 14.0
ppm (Me).
1
970, 747, 695 cm−1. H NMR: δ 7.40−7.39 (m, 2H; Ho), 7.33−7.32
(m, 2H; Hm), 7.26−7.24 (m, 1H; Hp), 6.50 (d, 3J = 15.6 Hz, 1H; H5),
6.34 (dd, 3J = 15.6 Hz, 3J = 9.8 Hz, 1H; H4), 2.98 (dd, 3J = 9.8 Hz, 3J =
9.3 Hz, 1H; H3), 2.21 (s, 3H; C1), 2.19−2.17 (m, 1H; CH(Me)2),
(3E,3′E)-4,4′-(1,4-phenylene)bis(1-(naphthalen-2-yl)but-3-
en-1-one) (35; Table 3, Entry 15). Yield: 1.42 g, 76%. Yellow
crystals: mp 163 °C. Elemental Analysis Calcd (%) for C34H26O2
3
0.96, 0.94 ppm (d, J = 6.6 Hz, 6H; CH(Me)2). 13C NMR: δ 209.6
(466.57): C 87.52, H 5.62. Found: C 87.55, H 5.67. IR (KBr): νmax
=
(CO), 136.9 (Ci), 133.7 (C5), 128.7 (Cm), 128.2 (Cp), 127.9 (C4),
126.4 (Co), 65.4 (C3), 30.2 (CH(Me)2), 29.7 (C1), 21.2, 20.0 ppm
(CH-(Me)2).
3053, 1677, 1626, 1596, 1509, 1468, 1408, 1355, 1277, 1183, 1123,
989, 966, 944, 863, 819, 747, 476 cm−1. 1H NMR: δ 8.51 (s, 2H; H1),
8.10−7.80 (m, 8H; HNaphth), 7.70−7.50 (m, 4H; HNaphth), 7.32 (s, 4H;
Ho), 6.55−6.52 (m, 4H; Hγ, Hβ), 4.03 ppm (d, 3J = 5.4 Hz, 4H; CH2).
13C NMR: δ 198.0 (CO), 136.4, 135.8, 134.1, 132.7, 130.1, 129.7,
(E)-2,2-Dimethyl-6-phenyl-4-styrylhex-5-en-3-one (42).
Yield: 414 mg, 34%. Yellow powder: mp 70−72 °C. Elemental
Analysis Calcd (%) for C22H24O (304.43): C 86.80, H 7.95. Found: C
86.91, H 7.99. IR (film): νmax = 3059, 3027, 2969, 2932, 2870, 1704,
1599, 1495, 1477, 1448, 1394, 1366, 1293, 1068, 1052, 1029, 985, 968,
127.9, 126.9, 126.6, 124.1 (20 CNaphth), 133.3 (Cβ), 122.6 (Cγ), 42.9
ppm (COCH2);
(E)-1-(Furan-2-yl)-4-phenylbut-3-en-1-one (36; Table 3,
Entry 16). Yield: 518 mg, 61%. White crystals: mp 78−80 °C.
Elemental Analysis Calcd (%) for C14H12O2 (212.24): C 79.22, H
5.70. Found: C 79.31, H 5.76. IR (KBr): νmax = 3142, 3127, 3057,
3024, 2893, 1689, 1564, 1495, 1468, 1450, 1395, 1306, 1249, 1236,
1161, 1089, 1079, 1070, 1032, 1021, 997, 973, 917, 882, 790, 769, 728,
1
897, 775, 743, 693 cm−1. H NMR: δ 7.40−7.38 (m, 4H; Ho), 7.33−
7.31 (m, 4H; Hm), 7.25−7.23 (m, 2H; Hp), 6.60 (d, 3J = 15.9 Hz, 2H;
Hγ), 6.44 (dd, 3J = 15.9 Hz, 3J = 8.3 Hz, 2H; Hβ), 4.72 (t, 3J = 8.3 Hz,
1H; H4), 1.31 ppm (s, 9H; C(Me)3). 13C NMR: δ 213.8 (CO),
136.9 (Ci), 131.6 (Cγ), 128.6 (Cm), 128.3 (Cβ), 127.7 (Cp), 126.4
(Co), 54.3 (C4), 45.5 (C(Me)3), 26.2 ppm (C(Me)3).
1
690, 619, 596, 527, 498 cm−1. H NMR: δ 7.54−7.53 (m, 1H; H5),
7.32−7.30 (m, 2H; Ho), 7.26−7.22 (m, 2H; Hm), 7.19−7.18 (m, 1H;
Hp), 6.50 (d, 3J = 16.5 Hz, 1H; Hγ), 6.47−6.45 (m, 2H; H3, H4), 6.37
(dt, 3J = 16.5 Hz, 3J = 6.9 Hz, 1H; Hβ), 3.69 ppm (d, 3J = 6.9 Hz, 2H;
CH2). 13C NMR: δ 186.8 (CO), 152.3 (C2), 146.6 (C5), 136.9 (Ci),
133.8 (Cγ), 128.6 (Cm), 126.8 (Co), 127.5 (Cp), 121.8 (Cβ), 117.6
(C3), 112.3 (C4), 42.6 ppm (CH2).
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra of products. This material is available
free of charge via the Internet at http://pubs.acs.org.
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dx.doi.org/10.1021/jo301005p | J. Org. Chem. 2012, 77, 6880−6886

The Journal of Organic Chemistry
Article
(25) Nagayama, K.; Kumar, A.; Wutrich, K.; Ernst, R. R. J. Magn.
Reson. 1980, 40, 321.
AUTHOR INFORMATION
Corresponding Author
*E-mail: boris_trofimov@irioch.irk.ru.
Notes
■
(26) Wagner, G.; Wutrich, K. J. Mol. Biol. 1982, 155, 347.
(27) Bodenhausen, G.; Ruben, D. J. Chem. Phys. Lett. 1980, 69, 185.
(28) Bax, A; Summers, M. F. J. Am. Chem. Soc. 1986, 108, 2093.
(29) Dimethyl Sulfoxide (DMSO); Crown Zellerbach Chemical
Products Division: Vancouver, WA, 1985; Technical Bulletin.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was financially supported by the Russian Foundation
of Basic Research (Grant 11-03-00270). We thank Dr. A. V.
Vashchenko for quantum chemical calculations.
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