Regioselectivity observed in manganese(III) acetate mediated addition of acetylacetone to various alkenes: mechanistic and theoretical studies

Article abstract of DOI:10.1016/j.tet.2016.09.015

Various alkenes substituted at the 1,2-positions by 2-thiophenyl, 3-thiophenyl, and phenyl substituted by electron-withdrawing and electron-donating groups were treated with acetylacetone in the presence of Mn(OAc)₃in acetic acid. In cases wher

Full text of DOI:10.1016/j.tet.2016.09.015

Accepted Manuscript
Regioselectivity observed in manganese(III) acetate mediated addition of
acetylacetone to various alkenes: mechanistic and theoretical studies
Selin Ceyhan, Yasin Cetinkaya, Akin Akdag, Metin Balci
PII:
S0040-4020(16)30922-X
10.1016/j.tet.2016.09.015
TET 28086
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 20 May 2016
Revised Date: 26 August 2016
Accepted Date: 9 September 2016
Please cite this article as: Ceyhan S, Cetinkaya Y, Akdag A, Balci M, Regioselectivity observed in
manganese(III) acetate mediated addition of acetylacetone to various alkenes: mechanistic and
theoretical studies, Tetrahedron (2016), doi: 10.1016/j.tet.2016.09.015.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Graphical Abstract

ACCEPTED MANUSCRIPT
Regioselectivity Observed in Manganese(III) Acetate Mediated
Addition of Acetylacetone to Various Alkenes: Mechanistic and
Theoretical Studies
a
a,b
a,*
a,*
Selin Ceyhan, Yasin Cetinkaya, Akin Akdag, Metin Balci
a
Department of Chemistry, Middle East Technical University, 06800 Ankara, Turkey
b
Oltu Vocational School, Department of Food Technology, Atatürk University, 25400 Oltu-Erzurum,
Turkey
aakdag@metu.edu.tr; mbalci@metu.edu.tr
Abstract
Various alkenes substituted at the 1,2-positions by 2-thiophenyl, 3-thiophenyl, and phenyl
substituted by electron-withdrawing and electron-donating groups were treated with
acetylacetone in the presence of Mn(OAc) in acetic acid. In cases where the thiophene ring
3
was connected at the C-2 carbon atom to the double bond, a single regioisomer was formed
whereas in case of substitution at the C-3 positions two regioisomers were formed. Stilbene
derivatives also gave two regioisomers under the same reaction conditions. However, 1-
methoxy-4-(4-nitrostyryl)benzene provided a single cycloaddition product. The observed
regioselectivity was discussed in terms of atomic charge distribution on the olefinic double
bond carbon atoms. Furthermore, activation barriers for transtion states were calculated.
Keywords: Cycloaddition; Substituent effects; Oxidation; Regioselectivity; Mn(OAc)3
2

ACCEPTED MANUSCRIPT
1
. Introductıon
Mn(OAc) , a one-electron oxidant, is one of the most popular reagents in the field of free-
3
radical chemistry. It has found extensive use in the construction of a wide variety of
1
interesting molecules. It is well known that Mn(OAc) in acetic acid converts olefins into γ-
3
2
lactones. Moreover, 1,3-dicarbonyl compounds 1 undergo [3+2] cycloaddition to various
3
alkenes and form dihydrofurans, which are important scaffolds and building blocks in natural
4
products and pharmaceuticals. Generally, an oxidatively or reductively generated radical 2
preferentially attacks an electron rich double bond forming a new radical 3, which can be
reductively or oxidatively terminated. Recently, we showed that the cyclization reaction takes
place after oxidation of radical 3 to the corresponding cation 4 to form dihydrofuran
5
derivative 5 (Scheme 1).
Scheme 1
.
Mechanism for the addition of 1,3-dicarbonyl compounds to C=C double bonds in
the presence of Mn(OAc)3.
In the case of unsymmetrically substituted alkenes two regioisomers as well as two
stereoisomers may be formed. Recently, we treated trans- and cis-styrylthiophene 6a and 6b
6
(
also some furan derivatives) with 3-(4-methoxyphenyl)-3-oxopropanenitrile 7 in the
presence of Mn(OAc) and observed exclusive formation of a single isomer 8 irrespective of
3
3

ACCEPTED MANUSCRIPT
7
the configuration of the starting olefins (Scheme 2). We were not able to find any trace
amount of the other expected regioisomer 9.
Scheme 2. Reactions of alkenes 6a and 6b with 7 in the presence of Mn(OAc) ·2H O.
3
2
The exact constitution of 8 was determined with the help of 1D and 2D NMR
spectroscopic data. The cis-configuration of thiophenyl and phenyl rings was established from
NOE-DIFF and NOESY spectra. The reaction proceeded with complete regiocontrol and
8
excellent stereoselectivity.
We assumed that the sulfur atom in the thiophene ring was responsible for the observed
regioselectivity. We suggested the formation of an intermediate where Mn(OAc) undergoes
3
an interaction with the sulfur atom of thiophene, by forming a complex like 10, which can
transfer the radical generated from the intermediate 10 directly to the carbon atom next to the
benzene ring to form the intermediate 11 due to the geometric reasons (Scheme 3).
Scheme 3. Proposed mechanism for the formation of 8.
To shed more light on the mechanism of this regioselectivity, we decided to switch the
position of the styryl group from C-2 to C-3 on the thiophene ring and run the reaction with
4

ACCEPTED MANUSCRIPT
compounds 12 and 13 (Figure 1). Furthermore, we had the intention to change the electron
density distribution on the olefinic double bond by attaching phenyl groups having electron-
withdrawing (EWG) and electron-donating groups (EDG) to the double bond as in 14 to see
whether the atomic charges affects the regioseletivity or not.
Figure 1. Structures of 12-14
2
. Results and Discussion
For consistency of the addition reactions we used acetylacetone (15) as a 1,3-dicarbonyl
compound in all experiments. The known alkenes 6a and 6b were synthesized as described
7
,9
before. Treatment of pure isomers 6a or 6b with acetylacetone in the presence of Mn(OAc)
3
in acetic acid resulted in the formation of adduct 16 as the sole product in a yield of 77%
Scheme 4).
(
Scheme 4. Reactions of alkenes 6a and 6b with acetylacetone (15) in the presence of
Mn(OAc) ·2H O.
3
2
5

ACCEPTED MANUSCRIPT
Because of the asymmetric environment of the olefinic double bonds in 6a and 6b, the
initially formed complex between Mn(OAc) and acetylacetone (15) can add to the double
3
bond in two different paths, forming the compounds 16 and 17. However, a careful
examination of the reaction mixture did not show the formation of 17 not even in traces. The
exact constitution of the adduct 16 was determined with the help of the HMBC spectrum,
which showed a strong correlation between the alkoxy carbon atom of the dihydrofuran ring
resonating at 87.7 ppm and the α-proton of the thiophene ring resonating at 7.03 ppm. On the
basis of the determined coupling constants between the ring protons of dihydrofuran, we
1
0
assigned the cis-configuration to the substituents. Since thiophene electronically behaves
like a benzene, one would expect the formation of the regioisomers 16 and 17. Because of the
sole formation of 16 we assume that the sulfur atom forms a complex with manganese(III) as
depicted in Scheme 3 and the complex formation controls the transfer of acetylacetonyl
radical to the double bond.
To determine the effect of the position of sulfur atom in the thiophene on the mode of this
reaction, we altered the connectivity of the thiophene ring to the double bond by synthesizing
the compounds 12a and 12b. The reaction of benzyltriphenylphosphonium bromide (18) with
thiophene-3-carbaldehyde (19) gave an isomeric mixture of (E)- and (Z)-3-styrylthiophene
1
1
1
2a and 12b in 54% and 43% yields, respectively (Scheme 5).
6

ACCEPTED MANUSCRIPT
Scheme 5. Synthesis of starting alkenes 12a and 12b and reaction with acetylacetone (15) in
the presence of Mn(OAc) ·2H O.
3
2
Treatment of separated isomers 12a or 12b with acetylacetone in the presence of
Mn(OAc) in acetic acid gave two regioisomeric cyclization products 20 and 21 in a ratio of
3
2
:1 irrespective of the configuration of starting alkenes 12a and 12b (Scheme 5). The major
product 20 was again characterized by 1D and 2D NMR spectra. The most important part of
the HMBC spectrum was the correlation between the thiophene carbon atom C-4 and the
alkoxy proton of the dihydrofuran ring. When the connection of the thiophene ring to the
olefinic double bond from the C-2 carbon atom was changed to the C-3 carbon atom, the
regioselectivity, which is observed in the case of 6a/6b, was lost. These results show that the
position of the sulfur atom of the thiophene ring plays an important role in the formation of
the products. Of course, complexation between the sulfur atom and Mn(OAc) is also possible
3
in the case of 12. However, the geometrical reasons can prevent the regiospecific transfer of
an acetylacetonyl radical to the double bond. We assume that the atomic charge distribution
on the olefinic double bond carbon atoms plays an important role in this outcome.
To extend the scope of the cyclization reaction and compare the behavior of two
thiophene rings connected to the double bond at the C-2 and C-3 positions, we first
7

ACCEPTED MANUSCRIPT
synthesized the corresponding isomeric alkenes 13a and 13b by the reaction of thiophene-3-
carbaldehyde (19) with triphenyl(thiophen-2-ylmethyl)phosphonium chloride (22) in the
presence of NaOEt/EtOH. The expected coupling products 13a and 13b were formed in 55%
and 30% yields, respectively (Scheme 6). Compound 13a was reacted by the same synthetic
route with acetylacetone in the presence of Mn(OAc) in acetic acid which was mentioned
3
before. The NMR spectral analysis indicated the exclusive formation of the cyclization
product 23 in 83% yield (Scheme 6). Again the exact constitution was determined with the
help of the HMBC spectrum. This experiment clearly demonstrates that the connection of the
thiophene rings (from the C-2 carbon or from the C-3 carbon atom of the thiophene ring) to
the olefinic double bond plays an important role in determining the mode of the addition
reaction. According to the experimental results, in cases where the sulfur atom is closer to the
olefinic carbon atoms as in 6 and 13, the formation of a complex such as 10 dominates and
single cyclization products 16 and 23 are exclusively formed.
Scheme 6. Synthesis of alkenes 13a/13b and their reactions with acetylacetone (15) in the
presence of Mn(OAc) ·2H O.
3
2
8

ACCEPTED MANUSCRIPT
To strengthen the proposed theory and see the effect of atomic charge distribution on the
alkene double bonds, we synthesized a series of stilbene derivatives having electron-donating
and electron-withdrawing groups at different positions of the benzene rings. For this purpose,
1
3-15
stilbene derivatives 28-31
were synthesized by the reaction of substituted benzaldehydes
2
5-27 with appropriate phosphonium salts 18/18a. The corresponding cis- and trans-stilbene
derivatives 28-31 were formed in high yields (Table 1). All synthesized stilbene derivatives
were characterized properly. The isomeric cis- and trans-isomers were distinguished by
measuring the coupling constant between the double bond protons.
Table 1. Synthesized stilbene derivatives 28-31.
Aldehyde
Phosphonium salt
trans-stilbene (%)
cis-stilbene (%)
+
Ph
3
P
CH
2
Br
1
8
H
3
CO
CHO
+
Ph
3
P
CH
2
Br
2
6
1
8
+
Ph
3
P
CH
2
O N
2
Br
1
8
trans-30 (64%)
trans-Stilbene derivatives 28-31 were reacted with acetylacetone (15) in the presence of
Mn(OAc) in acetic acid at 80 °C and cyclization products 32-38 were isolated and
3
characterized (Scheme 7). The exact constitution of the products were determined in all cases
by HMBC spectra.
9

ACCEPTED MANUSCRIPT
Scheme 7. Reaction of stilbene derivatives 28-31 with acetylacetone (15) in the presence of
Mn(OAc) ·2H O.
3
2
Reaction of trans-28 formed two products 32 and 33 in yields of 64% and 36%,
respectively. We expected the involvement of the oxygen atom to control the mode of the
reaction and form a single product 32 as discussed above. However, the isomer 33 was also
formed as a minor product. By changing the position of the methoxy group from ortho- to
para-position as in trans-29, again two regio isomers 34 and 35 were formed. However, the
ratio of these isomers changed from 2:1 to 4:1 compared to the previous reaction. The remote
1
0

ACCEPTED MANUSCRIPT
methoxy group cannot control the direction of the addition reaction upon complexation with
Mn(OAc) . It is likely that the atomic charge distribution on the olefinic carbon atoms
3
controls the regioselectivity. Treatment of trans-30, having an electron-withdrawing group at
the para-position of one of the benzene rings with Mn(OAc) under the same reaction
3
conditions resulted in the formation of two cyclization products 36 and 37 in a ratio of 1:9,
where the constitution of the major product was the same as that of the minor products
obtained from the reaction of 28 and 29. We assume that the change in atomic charge at the
olefinic carbon atoms might cause this dramatic change in product distribution. Finally,
reaction of 31 with acetylacetone in the presence of Mn(OAc) provided a single isomer 38 in
3
high yield (89%). Careful inspection of the reaction mixture did not reveal the formation of
any other isomer. All these results indicate that the atomic charge distribution on the olefinic
double bond affects the final product distribution at least for substituted stilbene derivatives.
Theoretical Calculations. To support experimental results we performed theoretical
16
calculations. Natural bond orbital (NBO) analysis was carried out at the level of M06/TZVP.
The atomic charges on the olefinic double bonds calculated for trans- as well as cis-isomers
of 6, 12-13, and 28-31 are given in Table 2.
1
1

ACCEPTED MANUSCRIPT
Table 2. NBO charges (in coulombs) at the olefinic double bonds of 6, 12, 13, and 28-31.
-0.186
-0.191
S
-0.179
-0.172
-0.172
-0.168
S
S
S
-
0.188
-0.167
12a
6
a
6b
12b
-0.196
-0.188
-0.184
S
S
S
S
-0.168
1
3a
13b
-0.164
-
0.178
-0.143
-0.183
-0.196
-0.170
CH O
3
OCH3
H CO
3
H CO
3
-0.162
-0.171
trans-28
cis-28
0.200
trans-29
cis-29
-0.214
-0.139
-
-0.148
-0.133
-0.125
OCH3
O2N
O N
O N
2
2
O N
OCH3
2
-0.194
-0.207
trans-30
cis-30
trans-31
cis-31
In the case of styrylthiophene derivatives 6, 12, and 13 there was no remarkable
difference in the atomic charge distribution on the olefinic double bond carbon atoms. In 6
and 13, the greater negative charges are located on the carbons of the alkenes that are bonded
to the 2-thiophenyl groups. Radicals (e.g. acetylacetone radical) are electrophilic species.
Therefore, one expects that a radical attacks the more negatively charged carbon atom on the
starting alkene. Specifically, the reactions of acetylacetone radical with 6a and 13 were likely
to furnish 17 and 24. However, formation of the compounds 17 and 24 were not observed,
instead cyclization products 16 and 23 were formed for the corresponding reactions.
Seemingly, the radical attacks on the less negatively charge carbon occurred. Here, the atomic
charge distribution at the alkene double bond cannot be responsible for the sole formation of
1
2

ACCEPTED MANUSCRIPT
the single isomers 16 and 23. We assume that a complex formation, as shown in 10, controls
the mode of the reaction. However, in the case of 12, there is no significant polarization at the
olefinic double bond, where the double bond carbon atom next to the benzene ring in 12 is
slightly more electronegative. The major cyclization product 20 is formed by the attack of
acetylacetonyl radical at the carbon atom next to the benzene ring. The effect of the sulfur
atom is suppressed due to geometric reasons.
The behavior of stilbene derivatives was different and the formation of the products can be
explained by atomic charge distribution. The compound trans-28 shows almost equal atomic
charge distribution on the olefinic carbon atoms. For this reason the formation of two
cyclization products 32 and 33 were expected. The formation of 32 as the major product can
be attributed to the steric effect caused by the methoxy group as well as the partial directing
effect of the oxygen atom of the methoxy group by forming a complex. When the methoxy
group is placed at the para-position, there is a remarkable atomic charge difference between
the olefinic double bond carbon atoms. The intermediate radical will preferentially attack the
carbon atom next to the unsubstituted benzene ring with higher atomic charge. The product
distribution of 34 and 35 (4:1) was in agreement with the atomic charge distribution. When
the methoxy group in 29 was replaced by an electron-withdrawing group, such as a nitro
group as in 30, the atomic charge distribution at the olefinic double bond was also changed.
Now, the carbon atom next to the p-nitrobenzene ring is much more electronegative. It is
plausible that the radical will attack mainly this carbon atom and form 37 as the major product
and 36 as the minor product in a ratio of 9:1. To increase the atomic charge difference
between the double bond carbon atoms, we introduced an electron-withdrawing group to one
of the benzene rings and an electron-donating group to the other benzene ring. NBO
calculations showed that the difference in charge distribution at the olefinic double bond was
further increased. The fact that only a single cyclization product 38 was formed from the
1
3

ACCEPTED MANUSCRIPT
reaction of trans-31 and this result was completely in agreement with our proposal that the
atomic charge distribution on the olefinic carbon atoms is responsible for the product
distribution by the reaction with substituted stilbene derivatives.
In order to further shed light on the mechanism of these reactions, we performed
calculations to locate transition states and intermediates on the potential energy diagram. A
plausible mechanism of the reaction was proposed as given in Scheme 1. After the formation
of the acetylacetone radical, the first step is the addition of acetylacetone radical to the alkene
to form a new radical. The radical eventually forms a cyclic compound. As can be inferred
from the mechanism, the first step involves determining the fate of regioselectivity. Therefore,
we located the transition states for the addition of the acetylacetone radical to the alkene at the
1
6
level of M06/TZVP as implemented in the Gaussian09 electronic structure software package
1
7
program.
The new radical relative stabilities were also calculated at the same level of
theory. As a representative potential energy diagram, the reaction of 6a with the acetylacetone
radical is depicted in Figure 2. The first step is C-C bond formation, for this step, two possible
transition states and intermediates are proposed. In the Figure 2, transition states for the both
cases were calculated and they are 2.16 kcal/mol apart from each other. This leads to an
kinetic intermediate formation. The results are summarized in the Table 3.
1
4

ACCEPTED MANUSCRIPT
Figure 2. The calculated potential energy diagram for 6a and acetylacetone radical.
Table 3. Calculated activation barriers and the resulting radical intermediates Gibbs free
energies at the level of M06/TZVP
a
a,b
Transition States
∆G(TS) (kcal/mol) ∆G(Int) (kcal/mol)
9
1
.100
1.26
-8.78
-9.39
1
0.21
-3.49
1
5

ACCEPTED MANUSCRIPT
9
9
6
.83
.34
.58
-3.51
-9.65
-9.97
7
8
.14
.55
-5.41
-5.52
-6.51
9
.80
.31
9
-3.76
-5.92
-2.35
1
0.87
0.98
1
1
6

ACCEPTED MANUSCRIPT
1
0.26
-2.32
-7.19
O N
2
OCH3
10.67
trans-31-TS2
a) These energies are relative to the corresponding alkene and acetylacetone radical.
b) The free energy of the radical intermediate after addition of the acetylacetone
radical at the indicated position
The results tabulated in Table 3 show the free energies of the transition states and the
intermediates, relative to acetylacetone radical and the corresponding alkene. The raw data for
the reactions are provided in the Supporting Information. The transition state enthalpies were
all negative energies compared to the corresponding starting materials. This could be justified
by the fact that any new radical formation route on the given reactions will generate a more
stable radical. Nevertheless, Table 3 shows a free energy barrier for the reaction which is due
to the entropy term in the Gibbs Free Energy. Although the energy values for the transition
states of the compounds 6, 12, and 13 (compounds with thiophene units) are consistent with
the experimental observations (the transition states leading to the expected product have lower
activation barrier), the calculated energy barriers for the substituted stilbene derivatives shows
discrepancy. Regardless, reactions of trans-28, trans-29, and trans-30 are expected to furnish
mixtures of regioisomers as judged from calculations. As the activation barriers of the
corresponding regioisomers are getting closer to each other energetically, the relative energies
(
stabilities) of the intermediates become critical. With this in mind, the reaction of trans-31
and acetylacetone radical is expected to provide a mixture of regioisomers as shown in Table
. This is due to the difference in energy barrier (0.4 kcal/mol) for the formation of the both
regioisomers. However, the radical intermediate leading to the observed regioisomer 38 is
.87 kcal/mol more stable. Consequently, the intermediate stability contributes to the
3
4
1
7

ACCEPTED MANUSCRIPT
observed regioselectivity as well. At 80 °C (the reaction temperature), the low activation
barriers (6.58 kcal/mol-10.98 kcal/mol) seem to be influencing the reaction outcome less.
3
. Conclusion
We first synthesized various alkenes substituted at the 1,2-positions by 2-thiophenyl, 3-
thiophenyl, and phenyl substituted by electron-withdrawing and electron-donating groups.
When the thiophene ring was connected at the C-2 carbon atom to the double bond, a single
regioisomer was formed whereas in case of substitution at the C-3 positions two regioisomers
were formed. On the other hand, stilbene derivatives gave two regioisomers under the same
reaction conditions, whereas 1-methoxy-4-(4-nitrostyryl)benzene provided a single
cycloaddition product. The observed regioselectivity was examined. A complexation between
the sulfur atom and Mn(OAc) was proposed for the formation of a single addition product
3
when the thiophene ring was connected at the C-2 carbon atom to the double bond. The
calculations revealed that both the activation barriers and the intermediate stabilities play an
important role along with the charge distribution in regioselectivity of the reaction. Moreover,
the charge distribution can provide an initial guess for the expected regioisomers. A plausible
reaction mechanism was proposed and supported by the DFT calculations to explain the
observed regioselectivity of the reactions.
4
4
. Experimental Section
.1. General Methods. NMR spectra were recorded on a 400 MHz spectrometer. Infrared
-1
(
IR) spectra were recorded in the range 4000-600 cm via ATR diamond. Melting points were
determined using a melting point apparatus and were uncorrected. Mass spectra were recorded
by LC-MS TOF electrospray ionization technique. Column chromatography was performed
on silica gel (60-mesh), TLC was carried out on 0.2 mm silica gel 60 F254 analytical
aluminum plates. Evaporation of solvents was performed at reduced pressure, using a rotary
vacuum evaporator.
1
8

ACCEPTED MANUSCRIPT
4
.2. General Procedure for Addition of Mn(OAc) ·2H O to Double Bonds in the Presence of
3
2
Acetylacetone (15): rel-1-((4R,5S)-2-methyl-4-phenyl-5-(thiophen-2-yl)-4,5-dihydro-furan-3-
yl)ethanone (16). Mn(OAc) ·2H O (2.89 g, 10.08 mmol) was dissolved in glacial acetic acid
3
2
(
(
(
30 mL) and the flask was heated to 80 °C under nitrogen. A mixture of (E)-2-styrylthiophene
6a or 6b) (0.67 g, 3.6 mmol) and acetylacetone (15) (7.22 g, 72.1 mmol) in glacial acetic acid
50 mL) was added dropwise to the solution of Mn(OAc) . The resulting mixture was stirred
3
at 80 °C under nitrogen for 24 h. The reaction mixture was cooled to the room temperature
and saturated NaHCO solution was added to the reaction mixture. Then the solution was
3
extracted with ethyl acetate (3 × 50 mL). The combined organic layers were dried over
MgSO . Evaporation of solvent under the reduced pressure afforded the residue, which was
4
then separated by column chromatography on silica gel eluting with hexane/EtOAc (20:1) to
1
yield 16 as a pale yellow liquid (0.79 g, 77% isolated yield). R (5% EtOAc/hexane) 0.26; H-
f
NMR (400 MHz, CDCl ) δ 7.37-7.24 (m, 6H), 7.03 (bd, J = 3.5 Hz, 1H, thiophene), 6.99 (dd,
3
J = 5.0, 3.5 Hz, 1H, thiophene), 5.54 (d, J = 5.6 Hz, 1H), 4.46 (dd, J = 5.6, 1.1 Hz, 1H, H-4’),
1
3
2
.42 (d, J = 1,1 Hz, 3H), 1.93 (s, 3H). C-NMR (100 MHz, CDCl ) δ 195.0, 168.1, 143.3,
3
1
42.5, 129.1 (2C), 127.5, 127.4 (2C), 126.9, 125.8, 125.3, 115.2, 87.7, 58.1, 29.7, 15.1. IR
-1
(
ATR, cm ) 1669, 1593, 1372, 1309, 1217, 1127, 1075, 981, 929, 832, 770. HRMS Calcd for
+
C H O S [M+H] : 285.0944; Found: 285.0950.
17
16
2
4
.2.1.
rel-1-((4R,5S)-2-methyl-4-phenyl-5-(thiophen-3-yl)-4,5-dihydrofuran-3-yl)ethanone
(
20) and rel-1-((4R,5R)-2-methyl-5-phenyl-4-(thiophen-3-yl)-4,5-dihydrofuran-3-yl)ethanone
20). Mn(OAc) ·2H O (0.890 g, 3.3 mmol) in 30 mL of glacial acetic acid and the flask was
(
3
2
heated to 80 °C under nitrogen. Then a mixture of 3-[(E)-2-phenylethenyl]thiophen (12a/12b)
0.206 g, 1.1 mmol) and acetylacetone (15) (2.21 g, 22 mmol) in 50 mL of glacial acetic acid
(
were added and reacted as described above. Evaporation of the solvent under the reduced
pressure afforded the residue. NMR analysis of the mixture indicated the formation of two
1
9

ACCEPTED MANUSCRIPT
isomers 20 and 21 in a ratio of 2:1), which was then separated by column chromatography on
silica gel eluting with hexane/EtOAc (20:1) to yield 20 as the first fraction: pale yellow liquid,
1
0
7
5
1
2
.205 g (65% crude yield). R 0.41(5% EtOAc/hexane); H NMR (400 MHz, CDCl ) δ 7.39-
f
3
.20 (m, 7H), 7.07 (dd, J = 5.0, 1.2 Hz, 1H, thiophene), 5.41 (d, J = 5.8 Hz, 1H), 4.34 (dd, J =
1
3
.8, 1.1 Hz, 1H), 2.44 (d, J = 1.1 Hz, 3H), 1.90 (s, 3H). C NMR (100 MHz, CDCl ) δ 195.1,
3
68.6, 143.1, 141.7, 129.1 (2C), 127.4 (2C), 127.2, 125.1, 124.9, 121.7, 115.2, 88.3, 57.2,
9.7, 15.1. IR (ATR) 1715, 1669, 1595, 1517, 1346, 1217, 932, 851, 758, 699. HRMS Calcd
+
for C H O S [M+H] : 285.0944; Found: 285.0943.
1
7
17
2
1
The second isomer 21 could not be isolated in pure state. However, the data for H-NMR was
1
extracted from a spectrum of a mixture. R (5% EtOAc/hexane) 0.40; H-NMR (400 MHz,
f
CDCl ) δ 7.41-7.22 (m, 7H), 7.07 (dd, J = 5.0, 1.2 Hz, 1H, thiophene), 5.35 (d, J = 5.8 Hz,
3
1
H), 4.42 (dd, J = 5.8, 0.8 Hz, 1H), 2.46 (d, J = 1.2 Hz, 3H), 1.92 (s, 3H).
4
.3. (E)-2-(2-(Thiophen-3-yl)vinyl)thiophene (13a) and (Z)-2-(2-(Thiophen-3-yl)vinyl)-
thiophene (13b). Triphenyl(thiophen-2-ylmethyl)phosphonium chloride (22) (1.73 g, 4.38
mmol) was added to a solution of NaOEt, which was prepeared by addition of metallic
sodium (0.121 g, 5.26 mmol) in 50 mL of EtOH. Thiophene-3-carbaldehyde (19) (0.45 g, 4.01
mmol) was added to the reaction mixture. The resulting mixture was reacted as described (see
Supporting Information). The residue was separated by column chromatography on silica gel
eluting with hexane to yield (Z)-isomer (13b) as a first fraction colorless liquid, 0.230 g (30%,
isolated yield).
1
4
.3.1.(Z)-2-(2-(Thiophen-3-yl)vinyl thiophene (13b). R (100% hexane) 0.37; H NMR (400
f
MHz, CDCl ) δ 7.19-7.17 (m, 2H), 7.06 (d, J = 5.0 Hz, 1H), 6.95 (dd, J = 4.0, 2.1 Hz, 1H),
3
6
1
1
.92 (d, J = 3.6 Hz, 1H,), 6.83 (dd, J = 4.9, 3.5 Hz, 1H), 6.55 (d, A-part of AB system J =
1
3
1.9 Hz, 1H), 6.37 (d, B-part of AB system J = 11.9 Hz, 1H). C-NMR (100 MHz, CDCl ) δ
3
39.9, 137.8, 128.1, 128.0, 126.7, 125.7, 125.5, 124.2, 123.8, 123.3. IR (ATR) 3102, 3011,
2
0

ACCEPTED MANUSCRIPT
2
923, 2853, 1732, 1435, 1411, 1350, 1261, 1214, 1108, 1079, 1044, 949, 855, 835, 807, 757.
-
HRMS Calcd for C H S [M-H] : 190.9989; Found: 191.0014.
1
0
7 2
4
.3.2. (E)-2-(2-(Thiophen-3-yl)vinyl thiophene (13a) was isolated as the second fraction.
White needles from hexane (0,427 g, 55 %, isolated yield). Mp 136-137 °C. R (hexane) 0.34;
f
1
H-NMR (400 MHz, CDCl ) δ 7.24 (dd, A-part of AB system, J = 5.1, 2.6 Hz, 1H), 7.23 (dd,
3
B-part of AB system, J = 5.1, 1.5 Hz, 1H), 7.16 (dd, J = 2.6, 1.5 Hz, 1H), 7.10 (bd, J = 5.0
Hz, 1H), 7.00 (d, A-part of AB system J = 16.1 Hz, 1H), 6.96 (bd, J = 3.3 Hz, 1H), 6.92 (dd,
1
3
J = 5.0, 3.3 Hz, 1H, H-4), 6.90 (d, B-part of AB system J = 16.1 Hz, 1H). C-NMR (100
MHz, CDCl ) δ 142.8, 139.7, 127.6, 126.3, 125.7, 124.8, 124.1, 122.7, 122.2, 121.8. IR
3
(ATR) 3091, 1744, 1429, 1374, 1273, 1213, 1076, 1040, 951, 866, 856, 816, 769. HRMS
-
Calcd for C H S [M-H] : 190.9989; Found: 191.0014.
1
0
7 2
4
.4.
rel-1-((4R,5R)-1-(2-Methyl-5-(thiophen-2-yl)-4-(thiophen-3-yl)-4,5-dihydrofuran-3-
yl)ethanone (23). Mn(OAc) ·2H O (0.1.59 g, 5.94 mmol) in 30 mL of glacial acetic acid and
3
2
the flask was heated to 80 °C under nitrogen. Then a solution of (E)-2-(2-(thiophen-3-yl)vinyl
thiophene (13a) (0.381 g, 1.98 mmol) and acetylacetone (15) (3.97 g, 39.6 mmol) in glacial
acetic acid (50 mL) was added and the resulting mixture reacted as described above.
Evaporation of the solvent under the reduced pressure afforded the residue, which was then
purified by column chromatography on silica gel eluting with hexane/EtOAc (20:1) to yield
1
adduct (23) as pale yellow liquid (0.477 g, 83%). R (5% EtOAc/hexane) 0.13; H-NMR (400
f
MHz, C D ) δ 6.63 (dd, J = 5.0, 2.9 Hz, 1H), 6.61 (dd, J = 5.0, 1.2 Hz, 1H), 6.5 (dd, J = 5.0,
6
6
1
2
3
1
.2 Hz, 1H), 6.46 (ddd, J = 3.5, 1.2, 0.6 Hz, 1H), 6.43 (dd, J = 5.0, 3.5 Hz. 1H), 6.41 (dd, J =
.9, 1.2 Hz. 1H), 5.15 (d, J = 5.4 Hz, 1H), 4.23 (bdd, J = 5.4, 1.0 Hz, 1H), 2.06 (d, J = 1.0 Hz,
13
H), 1.52 (s, 3H). C-NMR (100 MHz, C D ) δ 193.0, 166.8, 143.8, 143.7, 126.8, 126.8,
6
6
26.5, 125.6, 125.1, 121.5, 115.2, 86.7, 53.3, 29.1, 14.7. IR (ATR) 3096, 2962, 2921, 1744,
2
1

ACCEPTED MANUSCRIPT
1
668, 1592, 1417, 1370, 1326, 1260, 1227, 1119, 1078, 1017, 930, 857, 833, 793, 704.
+
HRMS Calcd for C H O S [M+H] : 291.0514; Found: 291.0545.
1
5
15
2 2
4
.5. rel-1-((4S,5R)-5-(2-Methoxyphenyl)-2-methyl-4-phenyl-4,5-dihydrofuran-3-yl)ethanone
32) and rel-1-((4R,5S)-4-(2-Methoxyphenyl)-2-methyl-5-phenyl-4,5-dihydrofuran-3-yl)-
ethanone (33). Mn(OAc) ·2H O (2.91 g, 10.8 mmol) in 30 mL of glacial acetic acid and the
(
3
2
flask was heated to 80 °C under nitrogen. Then a solution of (E)-1-methoxy-2-styrylbenzene
28) (0.76 g, 3.6 mmol) and acetylacetone (15) (7.24 g, 72.3 mmol) in glacial acetic acid (50
(
mL) was added and the resulting mixture was reacted as described above. Evaporation of the
solvent gave the crude product, which was separated by column chromatography on silica gel
eluting with (CH Cl /hexane, 5:1). The isomer 32 was isolated as the second fraction. Pale
2
2
yellow liquid (0.704 g, 64% isolated yield). From the integration of the signals it was
determined that the regiosimer 32 and 33 were formed in a ratio of 64:36.
1
4
7
1
4
.5.1. 32: R (5% EtOAc/hexane) 0.46; H-NMR (400 MHz, CDCl ) δ 7.31-7.26 (m, 2H),
f
3
.25 (bd, J = 1.3 Hz, 1H), 7.23 (dd, J = 3.9, 1.8 Hz, 1H), 7.21-7.18 (m, 2H), 7.14 (dd, J = 7.5,
.3 Hz, 1H), 6.91 (dt, J = 7.5, 0.7 Hz, 1H), 6.86 (bd, J = 8.2 Hz, 1H), 5.57 (d, J = 4.2 Hz, 1H),
13
.09 (dd, J = 4.2, 1.0 Hz, 1H), 3.72 (s, 3H), 2.45 (s, 3H), 1,79 (s, 3H). C-NMR (100 MHz,
CDCl ) δ 195.5, 169.1, 156.1, 143.8, 129.2, 129.1, 128.7 (2C), 127.6 (2C), 127.0, 125.2,
3
1
1
20.5, 115.4, 110.5, 87.6, 57.0, 55.0, 29.5, 15.1. IR (ATR) 2988, 2900,1669, 1438, 1491,
455, 1378, 1286, 1188, 1075, 1066, 1050, 1027, 930, 753, 700, 653, 628. HRMS Calcd for
+
C H O [M+H] : 309.1485; Found: 309.1504.
20
21
3
4
.5.2.
rel-1-((4R,5S)-4-(2-Methoxyphenyl)-2-methyl-5-phenyl-4,5-dihydrofuran-3-yl)-
ethanone (33). The NMR data were extracted from the spectrum of a mixture. R (5%
f
1
EtOAc/hexane) 0.45; H-NMR (400 MHz, CDCl ) δ 7.32-7.17 (m, 7H), 7.06 (dd, J = 7.6, 1.6
3
Hz, 1H), 6.90 (bt, J = 7.5 Hz, 1H), 6.85 (bd, J = 8.2 Hz, 1H), 5.23 (d, J = 4.3 Hz, 1H), 4.66
(bd, J = 4.3 Hz, 1H), 3.74 (s, 3H), 2.43 (d, J = 1.0 Hz, 3H), 1,81 (s, 3H).
2
2

ACCEPTED MANUSCRIPT
4
.6. rel-1-((4S,5R)-5-(4-Methoxyphenyl)-2-methyl-4-phenyl-4,5-dihydrofuran-3-yl)ethanone
(34) and rel-1-((4R,5S)-4-(4-methoxyphenyl)-2-methyl-5-phenyl-4,5-dihydrofuran-3-yl)etha-
none (35). Mn(OAc) ·2H O (2.91 g, 10.8 mmol) in 30 mL of glacial acetic acid and the flask
3
2
was heated to 80 °C under nitrogen. Then a solution of (E)-1-methoxy-4-styrylbenzene (29)
0.76 g, 3.6 mmol) and acetylacetone (15) (7.24 g, 72.3 mmol) in glacial acetic acid (50 mL)
(
was added and the resulting mixture was reacted as described above. Evaporation of the
solvent gave the crude product, which was separated by column chromatography on silica gel
eluting with (CH Cl /hexane, 5:1). The major isomer 34 was isolated as the second fraction.
2
2
Pale yellow liquid (0.869 g, 79% isolated yield). From the integration of the signals it was
determined that the regiosimer 34 and 35 were formed in a ratio of 79:21.
4
.6.1. rel-1-((4S,5R)-5-(4-Methoxyphenyl)-2-methyl-4-phenyl-4,5-dihydrofuran-3-yl)ethanone
1
(
34). R (20% CH Cl /hexane) 0.18; H-NMR (400 MHz, CDCl ) δ 7.37-7.34 (m, 2H), 7.30-
f
2
2
3
7
5
1
1
1
7
3
.27 (m, 1H), 7.22-7.18 (m, 4H), 6.92 (quasi d, B-part of AA'BB' system, J = 8.6 Hz, 2H),
3,4
.28 (d, J = 6.0 Hz, 1H), 4.30 (dd, J = 6.0, 1.2 Hz, 1H), 3.83 (s, 3H), 2.46 (d, J = 1.1 Hz, 3H),
1
3
.88 (s, 3H). C-NMR (100 MHz, CDCl ) δ 195.3, 168.9, 159.8, 143.4, 133.0, 129.1 (2C),
3
27.4 (2C), 127.3, 126.8 (2C), 115.1, 114.2 (2C), 91.9, 58.2, 55.3, 29.7, 15.2. IR (ATR) 2932,
741, 1667, 1593, 1512, 1422, 1377, 1304, 1243, 1174, 1128, 1111, 1076, 1029, 931, 826,
+
74, 750, 700, 645, 628, 606, 558. HRMS Calcd for C H O [M+H] : 309.1485; Found:
20
21
3
09.1502.
.6.2. rel-1-((4R,5S)-4-(4-methoxyphenyl)-2-methyl-5-phenyl-4,5-dihydrofuran-3-yl)ethanone
4
(
35). The NMR data were extracted from the spectrum of a mixture. R (20% CH Cl /hexane)
f 2 2
0
.17; (400 MHz, CDCl ) δ 7.38-7.33 (m, 2H), 7.29-7.25 (m, 1H), 7.21-7.19 (m, 2H), 7.15-
3
7
.12 (m, 2H), 6.91-6.88 (m, 2H), 5.30 (d, J = 6.0 Hz, 1H), 4.24 (dd, J = 6.0, 1.1 Hz, 1H), 3.80
(s, 3H), 2.47 (d, J = 1.1 Hz, 3H), 1.87 (s, 3H).
2
3

ACCEPTED MANUSCRIPT
4
.7. rel-1-((4S,5R)-2-Methyl-4-(4-nitrophenyl)-5-phenyl-4,5-dihydrofuran-3-yl)ethanone (37)
and rel-1-((4R,5S)-2-Methyl-5-(4-nitrophenyl)-4-phenyl-4,5-dihydrofuran-3-yl)ethanone (36).
Mn(OAc) ·2H O (1.163 g, 4.33 mmol) in 30 mL of glacial acetic acid and the flask was
3
2
heated to 80 °C under nitrogen. Then a solution of (E)-1-nitro-4- styrylbenzene (30) (0.315 g,
.4 mmol) and acetylacetone (15) (2.89 g, 28.9 mmol) in glacial acetic acid (50 mL) was
1
added and the resulting mixture was reacted as described above. Evaporation of the solvent
gave the crude product, which was separated by column chromatography on silica gel eluting
with (hexane/EtOAc, 10:1). The major isomer 37 was isolated as the first fraction. Pale
yellow liquid (0.41 g, 89%). From the integration of the signals it was determined that the
regiosimer 37 and 36 were formed in a ratio of 90:10.
4
.7.1.
rel-1-((4S,5R)-2-Methyl-4-(4-nitrophenyl)-5-phenyl-4,5-dihydrofuran-3-yl)ethanone
1
(
37). R (10% EtOAc/hexane) 0.05; H-NMR (400 MHz, C D ) δ 7.80 (quasi d, A-part of
f
6
6
AA'BB' system, J = 8.7 Hz, 2H), 7.11 (dd, J = 7.4, 1.5 Hz, 2H), 7.08-7.04 (m, 1H), 6.97-6.94
(m, 2H), 6.69 (quasi d, B-part of AA'BB' system, J = 8.7 Hz, 2H), 4.97 (d, J = 6.2 Hz, 1H),
13
3
.90 (dd, J = 6.2, 1.2 Hz, 1H), 2,30 (d, J = 1.2 Hz, 3H), 1.6 (s, 3H). C-NMR (100 MHz,
C D ) δ 193.8, 169.3, 150.7, 147.3, 140.0, 129.1 (2C), 128.9, 128.3 (2C), 125.2 (2C), 124.4
6
6
(2C), 115.6, 91.1, 58.0, 29.6, 15.4. IR (ATR) 1671, 1595, 1518, 1378, 1345, 1314, 1248,
+
1
3
216, 1189, 1108, 1001, 930, 840, 751, 699, 650, 628. HRMS Calcd for C H NO [M+H] :
1
9
18
4
24.1230; Found: 324.1246.
.7.2. rel-1-((4R,5S)-2-Methyl-5-(4-nitrophenyl)-4-phenyl-4,5-dihydrofuran-3-yl)ethanone
4
(
36) was isolated as the second fraction. Pale yellow liquid (0.045 g, 10%. R (10%
f
1
EtOAc/hexane) 0.09; H-NMR (400 MHz, C D ) δ 7.78 (quasi d, A-part of AA'BB' system, J
6
6
=
8.6 Hz, 2H), 7.12-7.10 (m, 3H), 7.02 (bd, J = 6.6 Hz, 2H), 6.66 (quasi d, B-part of AA'BB'
system, J = 8.6 Hz, 2H), 4.95 (d, J = 6.2 Hz, 1H), 4.09 (d, J = 6.2 Hz, 1H), 2.21 (s, 3H), 1.57
'
1
3
(
s, 3H). C-NMR (100 MHz, C D ) δ 192.8, 167,2, 147.8, 147.4, 143.0, 129.2 (2C), 128.4,
6 6
2
4

ACCEPTED MANUSCRIPT
1
1
3
27.4 (2C), 125.4 (2C), 123.8 (2C), 114.9, 90.0, 58.6, 29.2, 14.4. IR (ATR) 1715, 1669, 1595,
+
517, 1346, 1217, 932, 851, 699. HRMS Calcd for C H NO [M+H] : 324.1230; Found:
1
9
18
4
24.1252.
4
.8.
rel-1-((4S,5R)-5-(4-methoxyphenyl)-2-methyl-4-(4-nitrophenyl)-4,5-dihydrofuran-3-
yl)ethanone (38). Mn(OAc) ·2H O (0.80 g, 2.98 mmol) in 30 mL of glacial acetic acid and the
3
2
flask was heated to 80 °C under nitrogen. Then a solution of (E)-1-methoxy-4-(4-
nitrostyryl)benzene-1-nitro-4- styrylbenzene (32) (0.254 g, 0.995 mmol) and acetylacetone
(15) (1.99 g, 19.9 mmol) in glacial acetic acid (50 mL) was added and the resulting mixture
was reacted as described above. Evaporation of the solvent gave the crude product, which was
separated by column chromatography on silica gel eluting with (hexane/EtOAc, 10:1). To
give 38 as a single product. Pale yellow liquid (0.312 g, 89%). R (10% EtOAc/hexane) 0.11;
f
1
H-NMR (400 MHz, CDCl ) δ 8.12 (quasi d, A-part of AA'BB' system, J = 8.7 Hz, 2H), 7.30
3
(quasi d, B-part of AA'BB' system, J = 8.7 Hz, 2H), 7.11 (quasi d, A-part of AA'BB' system, J
=
8.7 Hz, 2H), 6.84 (quasi d, B-part of AA'BB' system, J = 8.7 Hz, 2H) 5.17 (d, J = 6.2 Hz,
1
3
1
H), 4.38 (d, J = 6.2 Hz, 1H), 3.74 (s, 3H), 2.39 (s, 3H), 1.94 (s, 3H). C-NMR (100 MHz,
4
CDCl ) δ 194.0, 169.5, 160.1, 150.8, 147.2, 131.9, 128.3 (2C), 126.9 (2C), 124.3 (2C), 115.6,
3
1
1
14.4 (2C), 91.2, 57.8, 55.4, 29.5, 15.4. IR (ATR) 2935, 2837, 1711, 1670, 1596, 1513, 1462,
418, 1305, 1244, 1175, 1109, 1077, 1030, 982, 931, 851, 824, 767,745, 693, 631, 617.
+
HRMS Calcd for C H NO [M+H] : 354.1336; Found: 354.1352.
2
0
20
5
Acknowledgements
Financial support from the Scientific and Technological Research Council of Turkey
TUBITAK, grant no. TBAG-112 T360), the Turkish Academy of Sciences (TUBA), and the
(
Middle East Technical University (METU) is gratefully acknowledged.
Supplementary data
2
5

ACCEPTED MANUSCRIPT
Supplementary data related to this article (1D and 2D NMR spectra of the products and
Cartesian Coordinates for the Optimized Structures and NBO charges (91 pages)) can be
found in the online version, at http://dx.doi.org/......
References and notes
(
1) For reviews on Mn(OAc) oxidation see: (a) Mondal, M.; Bora, U. RSC Adv. 2013, 3,
3
1
8716–18754. (b) Pan, X.-Q.; Zou, J.-P.; Zhang, W. Mol Divers. 2009, 13, 421-438. (c)
Demir, A. S.; Emrullahoglu, M. Curr. Org. Synth. 2007, 4, 321-350. (d) Snider, B. B. Chem.
Rev. 1996, 96, 339-363. (e) Iqbal, J.; Bhatia, B.; Nayyar, N. K. Chem. Rev. 1994, 94, 519-564.
(
f) Melikyan, G. G. Synthesis 1993, 833-850.
2) (a) Bush, J. B.; Finkbeiner, H. J. Am. Chem. Soc. 1968, 90, 5903-5905. (b) Heiba, E.
I.; Dessau, R. M.; Koehl, W. J. J. Am. Chem. Soc. 1968, 90, 5905-5906.
3) For recent examples for Mn(OAc) mediated addition of 1,3-dicarbonyl compounds to
(
(
3
olefins see: (a) Liu, X.; Chen, X.; Mohr, J. T. Chem-Eur. J. 2016, 22, 2274–2277. (b)
Matsumotoa, R.; Nishinoa, H Synth. Commun. 2015, 45, 1807–1816. (c) Li, P.; Zhao, J.; Xia,
C.; Li, F. Org. Lett. 2014, 16, 5992-5295. (d) Yue, Y.; Zhang, Y.; Song, W.; Zhang, X.; Liu,
J.; Zhuo, K. Adv. Synth. Catal. 2014, 356, 2459–2464. (e) Fernandes, S.; Bhat, S. V. Synthesis
2
014, 44, 2892–2898. (f) Yuan, W.; Wei, Y.; Shi, M. Tetrahedron 2013, 67, 7139–7142. (g)
Dengiz, C.; Caliskan, R.; Balci, M. Tetrahedron Lett. 2012, 53, 550-552. (h) Sudemen, M. B.;
Zengin, M.; Genc, H.; Balci, M. Turk. J. Chem. 2011, 35, 1–11.
(4) (a) Gribble, G. W.; Joule, J. A. Progress in Heterocyclic Chemistry; Elsevier:
Amsterdam; New York, 2013. (b) Katritzky, A. R. Comprehensive Heterocyclic Chemistry
III, 1st ed; Elsevier: Amsterdam, 2008.
2
6

ACCEPTED MANUSCRIPT
(5) (a) Ali, M. F.; Caliskan, R.; Sahin, E.; Balci, M. Tetrahedron 2009, 65, 1430–1437.
(b) Caliskan, R.; Ali, M. F.; Sahin, E.; Watson, W. H.; Balci, M. J. Org. Chem. 2007, 72,
3
353–3359; (c) Caliskan, R.; Pekel, T.; Watson, W. H.; Balci, M. Tetrahedron Lett. 2005, 46,
6
227–6230.
(
6) For addition of acylacetonitriles to the double bonds in the presence of Mn(OAc) see:
3
(
a) Nguyen, V. H.; Nishino, H.; Kurosawa, K. Tetrahedron Lett. 1996, 37, 4949–4952. (b)
Nguyen, V. H.; Nishino, H.; Kurosawa, K. Synthesis 1997, 899–908.
7) Deliomeroglu, K.; Dengiz, C.; Caliskan, R.; Balci, M. Tetrahedron 2012, 68, 5838–
844.
8) For similar configurational assignments see: (a) Antonioletti, R.; Malancona, S.;
(
5
(
Cattaruzza, F.; Bovicelli, P. Tetrahedron 2003, 59, 1673–1678. (b) Antonioletti, R.;
Malancona, S.; Bovicelli, P. Tetrahedron 2002, 58, 8825-8831.
(
9) (a) Li, J.; Hua, R.-M. Chem-Eur. J. 2011, 17, 8462–8465. (b) Ren, G.; Cui, X.;
Yang, E.; Yang, F.; Wu, Y. Tetrahedron, 2010, 66, 4022–4028.
(10) For detailed discussion for configurational assignment see the reference 7.
(11) Oberholzer, M.; Gerber, R.; Frech, C. M. Adv. Synth. Catal. 2012, 354, 627–641.
(12) Kellogg, R. M.; Groen, M. B.; Wynberg, H. J. Org. Chem. 1967, 32, 3093–100.
(13) (a) Mudududdla, R.; Sharma, R.; Abbat, S.; Bharatam, P. V; Vishwakarma, R. A.;
Bharate, S. B. Chem. Commun. 2014, 50, 12076–12079. (b) Yamataka, H.; Nagareda, K.;
Ando, K.; Hanafusa, T. J. Org. Chem. 1992, 57, 2865–2869.
(
14) Okuma, K.; Sakai, O.; Shioji, K. Bull. Chem. Soc. Jpn. 2003, 76, 1675–1676.
15) (a) Kossmehl, G.; Nuck, R. Chem. Ber. 1981, 114, 2914-2920. (b) Ketcham, R.;
(
Jambotkar, D.; Martinelli, L. J. Org. Chem. 1962, 27, 4666-4667.
2
7

ACCEPTED MANUSCRIPT
(16) (a) Cheng, G.-J.; Song, L.-J.; Yang, Y.-F.; Zhang, X.; Wiest, O; , Wu, Y.-D.
ChemPlusChem 2013, 78, 943-951. (b) Yu, T.; Zheng, J; Truhlar, D.G. Chem. Sci. 2011, 2,
199-2213. (c) Fuller, J. T.; Harrison, D. J.; Leclerc, M. C.; Baker, T. R. ; Ess, D. H.; Hughes,
2
R.P. Organometallics 2015, 34, 5210−5213. (d) Gansäuer, A.; Seddiqzai, M.;Dahmen,
T.;Sure, R.; Grimme, S. Beilstein J. Org. Chem. 2013, 9, 1620–1629.
(17) Gaussian 09, Revision E.01, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria,
G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G.
A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng,
G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.;
Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J.
E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.;
Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.;
Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken,
V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.;
Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.;
Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö.;
Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian, Inc., Wallingford CT, 2009.
2
8