Diels-Alder reactions of pinacol alkenylboronates: An experimental and theoretical study

Article abstract of DOI:10.1039/c4ra07415g

We have studied the Diels-Alder reactions of pinacol alkenylboronates with cyclopentadiene under two different sets of conditions: thermal heating at 170 °C in a pressure tube and with catalytic TFA (5 mol%) at 80 °C. Yields varied significantly from system to system and also for the uncatalyzed and catalyzed methodologies. Moderate to excellent exo-stereoselectivities were obtained in all cases. The theoretical study of the thermal reactions sheds some light on the intriguing substituent effects observed experimentally. A variety of substituted 5-norbornen-2-ols were easily generated by subsequent in situ oxidation of the cycloadducts with alkaline hydrogen peroxide. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4ra07415g

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Diels–Alder reactions of pinacol alkenylboronates:
an experimental and theoretical study†
Cite this: RSC Adv., 2014, 4, 36385
Margarita M. Vallejos, Nicolas Grimblat and Silvina C. Pellegrinet*
´
We have studied the Diels–Alder reactions of pinacol alkenylboronates with cyclopentadiene under two
ꢀ
different sets of conditions: thermal heating at 170 C in a pressure tube and with catalytic TFA (5 mol%)
ꢀ
at 80 C. Yields varied significantly from system to system and also for the uncatalyzed and catalyzed
Received 22nd July 2014
Accepted 1st August 2014
methodologies. Moderate to excellent exo-stereoselectivities were obtained in all cases. The theoretical
study of the thermal reactions sheds some light on the intriguing substituent effects observed
experimentally. A variety of substituted 5-norbornen-2-ols were easily generated by subsequent in situ
oxidation of the cycloadducts with alkaline hydrogen peroxide.
DOI: 10.1039/c4ra07415g
www.rsc.org/advances
demonstrating the utility of these intermediates for direct C–O
bond-forming reactions.
Introduction
The Diels–Alder (DA) reactions of boron-activated dienophiles
As part of our continuing work in the eld, we have now
were rst described more than ve decades ago. In the last few studied the Diels–Alder reactions of cyclopentadiene with
years, a renewed interest in such processes has arisen, both pinacol alkenylboronates with different substitution patterns
1
–32
from the experimental and theoretical viewpoints.
We have under different reaction conditions with the aims of developing
recently shown that the Diels–Alder reactions of vinylboronates new methodologies, gaining additional knowledge about the
can be easily performed using microwave irradiation giving reactivity of boron-substituted dienophiles and analyzing their
excellent yields of the cycloadducts. Vinylboronic acid pinacol possible use as synthetic equivalents of substituted enols.
ester showed good stability towards hydrolysis, operational
simplicity and yields of Diels–Alder products. The [4 + 2]
cycloadditions of pinacol vinylboronate with a variety of cyclic Results and discussion
and acyclic dienes under microwave irradiation generated the
To carry out this study we have used cyclopentadiene, which was
chosen for being a reactive cyclic 1,3-diene and also for the
boronate cycloadducts in excellent yields in short reaction
32
times (1–6 h) (Scheme 1). For example, the reaction with
interesting structural and synthetic properties of the bicyclo
ꢀ
cyclopentadiene was complete in 1 h at 150 C, affording the
33
[
2.2.1]heptane products. To investigate the substituent effect
products in quantitative yield with a 38 : 62 endo/exo ratio.
Subsequent in situ oxidation of the cycloadducts with
alkaline hydrogen peroxide yielded the alcohols efficiently,
on the outcome of the thermal Diels–Alder reaction, we tested a
range of commercially available alkenylboronates with alkyl or
aryl groups with different substitution patterns in the 1- and 2-
positions of the carbon–carbon double bond. Initial screening
reactions under microwave heating with the pinacol esters of
trans-1-penten-1-ylboronic acid and trans-2-phenylvinylboronic
acid suggested that the presence of substituents in the double
bond of the substrates retarded the cycloaddition process
considerably. Therefore, the use of microwave irradiation
proved impractical. We then re-investigated the Diels–Alder
reaction of pinacol vinylboronate with cyclopentadiene under a
large number of thermal conditions using conventional heat-
ing. Table 1 summarizes the outcome of some descriptive
experiments. Entry 1 shows the result previously obtained in our
Scheme 1
Instituto de Qu ´ı mica Rosario (CONICET), Facultad de Ciencias Bioqu ´ı micas y
Farmac ´e uticas, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000,
Argentina. E-mail: pellegrinet@iquir-conicet.gov.ar
ꢀ
32
laboratories at 150 C under microwave irradiation for 1 h.
When the reaction was performed in reuxing xylenes under
conventional heating, a 54% yield was obtained (entry 2). We
managed to get a 96% yield in reuxing toluene with a longer
reaction time (entry 3). As an alternative, use of a pressure tube
1
13
†
Electronic supplementary information (ESI) available: H and C NMR spectra
of all novel compounds. Reaction coordinates and geometries of transition
structures not included in the paper. See DOI: 10.1039/c4ra07415g
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Table 1 Diels–Alder reaction of pinacol vinylboronate (1a) with cyclopentadiene
Yield (%)
a
Entry
Conditions
endo/exo
ꢀ
32
1
2
3
4
5
6
7
Toluene, 150 C, MW, 1 h
100
3
8 : 62
Xylenes, reux, 1 h
54
3
5 : 65
Toluene, reux, 5 h
96
3
5 : 65
ꢀ
Toluene, 150 C, 1 h, pressure tube
79
3
2 : 68
ꢀ
Toluene, 150 C, 2 h, pressure tube
86
3
7 : 63
ꢀ
Toluene, 170 C, 5 h, pressure tube, BHT (5 mol%)
92
4
0 : 60
ꢀ
Toluene, 170 C, 1 h, pressure tube, BHT (5 mol%)
96
3
5 : 65
a
1
Determined by H NMR.
ꢀ
at 150 C in 1 h gave the cycloadduct in 79% yield (entry 4), 9), while alkenylboronates with alkyl groups in the 2-position
while increasing the time to 2 h raised the yield to 86% (entry 5). exhibited endo/exo ratios higher than 20 : 80 (entries 2–4). The
ꢀ
If the bath temperature was set to 170 C, a 92% yield was aromatic compounds showed moderate exo-selectivities,
generated in 5 h, and a nearly quantitative yield was obtained in similar to the one obtained with the unsubstituted system
1
h (entries 6 and 7). BHT (5 mol%) was added to prevent (endo/exo ꢁ 40 : 60).
undesired radical side reactions. The endo/exo ratios varied
slightly around 38 : 62 for all reactions.
In the next stage, we aimed to determine whether milder
conditions could be used so we embarked in the development of
Having optimized the conditions for the thermal reaction of the acid-catalyzed version of the reaction under study
34–37
pinacol vinylboronate under conventional heating, we next (Table 3).
Many experiments were run for the Diels–Alder
turned our attention to the [4 + 2] cycloadditions of the reactions of pinacol esters of vinylboronic acid (1a), trans-1-
substituted substrates (Table 2). All the reactions were opti- penten-1-ylboronic acid (1b) and trans-2-phenylvinylboronic
mized to yield the greatest amount of products. Lower acid (1e) to determine the optimal conditions. Brønsted acids
temperatures or shorter reaction times afforded poorer yields gave better results than Lewis acids, due to the greater poly-
while higher temperatures or longer reaction times either did merization of the diene in the presence of the latter. Among the
not increase the yield or led to some decomposition.
Brønsted acids, we tried acetic acid, triuoroacetic acid (TFA)
As found in our initial experiments with microwave heating, and triic acid. We tested up to 2 equivalents of Brønsted acids
longer reactions times than for the parent dienophile (1a) were and 10 equivalents of cyclopentadiene, solvents like toluene,
needed in all cases, excluding 1h (entry 8). However, for the dichloromethane and water, and temperatures ranging from
ꢀ
latter the yield was very low and did not increase by extending room temperature to 150 C. For the reaction of 1a, we deter-
the reaction time (25% in 1 h endo/exo 10 : 90, 21% in 12 h endo/ mined that best yields of the cycloadducts were obtained in 5 h
ꢀ
exo 41 : 59). Alkyl-substituted substrates performed much at 80 C with 5 mol % of TFA (entry 1, 88%, endo/exo 36 : 64).
better than the aromatic analogues, giving yields in the range When we run the reaction in the absence of TFA, a 20% yield
7
2–89% (entries 2–4 and 9). We reasoned that the conjugated was generated, with the same endo/exo ratio. Use of a pressure
ꢀ
aromatic ring donated electron density to the carbon–carbon tube, though not necessary in toluene at 80 C, was preferred to
double bond. However, the introduction of electron-with- avoid evaporation of the small loading of the catalyst (Bp
ꢀ
drawing substituents on the phenyl ring did not improve the 72.4 C). Quite unexpectedly, under catalyzed conditions only
reactivity of such systems (entries 5–8 and 10). Regarding the 1-phenylvinylboronic acid pinacol ester (1h) performed well
stereoselectivities, the exo cycloadduct predominated in all (entry 8, 83%, endo/exo 6 : 94). The other dienophiles gave yields
reactions. The highest exo-stereoselectivity was observed for below 45%. However, it is interesting to note that in this case
isopropenylboronic acid pinacol ester (1i) (endo/exo 9 : 91, entry aromatic alkenylboronates afforded better yields than the
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Table 2 Thermal Diels–Alder reaction of alkenylboronates with cyclopentadiene
a
Yield (%)
b
Entry
1
Dienophile
Time (h)
endo/exo
Products
1
96
35 : 65
7
1
8 (100)
7 : 83
2
3
24
24
8
2
9
0 : 80
4
5
24
24
88 (100)
15 : 85
2
3
9 (90)
5 : 65
2
4
0 (70)
0 : 60
6
24
1
3
9 (48)
7 : 63
7
8
24
1
25 (91)
0 : 90
1
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Table 2 (Contd.)
a
Yield (%)
b
Entry
Dienophile
Time (h)
endo/exo
Products
7
9
2 (80)
: 91
9
24
c
1
0
12
Traces
a
b
1
c
Yields based on recovered starting materials (BRSM) in parenthesis. Relative to the pinacol boronate moiety, determined by H NMR. The
starting material was recovered.
aliphatic compounds. Also, considerably higher exo-selectivities reaction has been surpassed and that some retro Diels–Alder
than for the uncatalyzed reactions were observed. Possibly, the might have taken place. For that reason, we submitted cyclo-
acid catalyst interacts with the p electrons of the aromatic ring adduct 2g (endo/exo 10 : 90) to the conditions of the uncatalyzed
and therefore withdraws electron density from the conjugated thermal reaction (Scheme 3). Indeed, the retro Diels–Alder
unsaturated system leading to the activation of the double reaction occurred, giving 76% of alkenylboronate 1g and 15% of
bond. Within the aliphatic alkenylboronates, 1d, having a recovered cycloadduct 2g (a mixture with a very similar
possible site for protonation (oxygen atom) gave better results composition to the one obtained when submitting the direct
than 1b and 1c.
reaction).
Finally, we studied the tandem Diels–Alder reaction of
We were surprised to note that the background reaction of
dienophile 1h afforded a very high yield of the corresponding alkenylboronates with cyclopentadiene-oxidation (Table 4).
boronate cycloadduct (91%) with excellent exo-selectivity (endo/ Except for the compounds with aryl groups at the 2-position
exo 5 : 95) (Scheme 2). Under the same conditions, vinylboronic (entries 5–7), we coupled the non-catalyzed thermal conditions
acid pinacol ester (1a) gave a lower yield (45%), which was a bit shown in Table 2 for the cycloaddition step with the nal
unexpected since previous experiments at higher temperatures oxidation with alkaline hydrogen peroxide in one-pot. Overall
suggested that the parent compound was more reactive than 1h yields for the two-step sequence were very similar to the ones
(Table 2).
obtained in the Diels–Alder reactions, which suggests that in
We tested whether we could perform the catalyzed reaction situ transformation of the boronate cycloadducts to the corre-
of alkenylboronate 1h at room temperature using the same sponding alcohols occurs very efficiently. In general, the
amount of diene, catalyst, and BHT, but we only obtained a 17% substituted 5-norbornen-2-ols were obtained with acceptable to
yield with a 3 : 97 endo/exo ratio (96% BRSM) aer 12 h.
very good yields, which demonstrated that alkenylboronic
Since, as commented above, prolonged exposure to the esters can be used as synthetic equivalents of substituted enols.
reaction conditions did not increase the yields of the products Due to their high functionalization, the alcohol products can be
we gured that thermodynamic equilibria had been reached. foreseen as valuable synthetic intermediates towards a variety of
ꢀ
Also, dienophile 1h gave a 25% (91% BRSM) in 1 h at 170 C chemical structures. We anticipate that other transformations
(
8
entry 8, Table 2), while the yield was much better aer 12 h at of the cycloadduct intermediates could be developed for further
0 C (91%, Scheme 2), so we suspected that under the initial elaboration of C–C, C–O and C–N bonds.
ꢀ
thermal conditions the energy barrier of the Diels–Alder
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Table 3 TFA-catalyzed Diels–Alder reaction of alkenylboronates with cyclopentadiene
a
Yield (%)
b
Entry
1
Dienophile
Time (h)
endo/exo
Products
88
5
36 : 64
c
2
3
24
24
Traces
c
Traces
1
1
7 (75)
4 : 86
2
4
2
7
26 (68)
4
5
1
0 : 90
3
1
2 (92)
7 : 83
2
4
2
7
38 (98)
17 : 83
2
3
0 (70)
6 : 64
2
4
2
7
31 (70)
29 : 71
6
2
1
4 (78)
0 : 90
2
4
2
7
45 (73)
7
8
1
0 : 90
8
6
3
: 94
12
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Table 3 (Contd.)
a
Yield (%)
b
Entry
Dienophile
Time (h)
endo/exo
Products
1
5 (24)
9
24
9 : 91
c
1
0
12
Traces
a
b
1
c
Yields based on recovered starting materials (BRSM) in parenthesis. Relative to the pinacol boronate moiety, determined by H NMR. The
starting material was recovered.
in toluene of the reactants, the transition structures and the
products to compute the activation and reaction energies
ꢀ
at 170 C. In addition, we analyzed the geometries and the
properties of the dienophiles and the transition structures with
the aim of rationalizing the reactivity and selectivity trends.
Computational methods
38
All calculations were performed with the Gaussian 09 package.
Scheme 2
We carried out thorough conformational analyses to locate the
lowest energy geometry for all the structures under study. Final
geometry optimizations were carried out using MPWB1K global-
39
hybrid meta-GGA functional together with 6-311G* basis.
Solvent effects of toluene were taken into account through full
optimizations using the polarizable continuum model (PCM) as
40
developed by Tomasi's group in the framework of self-
41–43
consistent reaction eld (SCRF).
The vibrational frequencies
were calculated to determine the nature of the stationary points
and to evaluate zero-point vibrational energy (ZPVE) and
thermal corrections at 443 K (170 C). The frontier molecular
Scheme 3
ꢀ
orbitals (FMOs) were computed with the same method.
Intrinsic Reaction Coordinate (IRC) calculations were run to
verify if the transition structures were directly connected to the
reactants and the products.
Fig. 1 shows the free energy proles for the Diels–Alder
reactions of selected dienophiles with cyclopentadiene as a
means to compare the reaction channels (for all the energy
proles see the ESI†). Also, the optimized geometries for the
corresponding transition structures with selected distances and
Computational study
To gain a deeper insight into the mechanism of the Diels–Alder
reactions of the dienophiles under study we performed a theo-
retical study. In particular, we intended to examine the revers-
ibility of such processes and whether the starting material/
products distribution was determined by thermodynamic or
kinetic control. Therefore, we optimized the geometries
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Table 4 Tandem Diels–Alder reaction of alkenylboronates with cyclopentadiene-oxidation
Overall yield (%)
a
Entry
1
Dienophile
endo/exo
Products DA + [O]
b
9
3
3
9 : 61
b
7
1
9
2
5 : 85
b
8
1
2
3
4
5
4 : 86
b
8
1
2
2 : 88
c
3
1
7
3 : 87
c
28
6
13 : 87
c
44
7
8
9 : 91
d
8
3
8
: 97
b
6
9
6
9
: 91
a
b
c
d
Determined by NMR integration. Non TFA-catalyzed thermal conditions were used. TFA-catalyzed conditions were used. Conditions shown in
Scheme 2 were used.
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Fig. 1 MPWB1K/6-311G* free energy profiles for the Diels–Alder reactions of pinacol alkenylboronates 1a (top left), 1b (top right), 1e (bottom left)
ꢀ
ꢂ1
and 1h (bottom right) with cyclopentadiene (free activation energies in toluene at 170 C for the direct and reverse reaction, in kcal mol ). The
optimized geometries in toluene for the transition structures with selected distances in A˚ and Wiberg bond indexes in parentheses are also
shown.
Wiberg bond indexes are shown. Table 5 gathers the computed alkenylboronates with aromatic susbtituents in C-1 (1h and 1j)
free energies of activation, reaction free energies and endo/exo are extremely asynchronic, with asynchronicities as high as
ꢀ
˚
selectivities at 170 C in toluene for all the Diels–Alder reactions 0.66 A. Nonetheless, IRC calculations connected the transition
under study. All transition structures exhibit classical [4 + 2] structures with the reactants and the products, therefore all
geometries and are asynchronic. However, the ones corre- reactions were computed to be concerted. In this case,
sponding to the dienophiles with aromatic substituents in C-2 comparison of the atomic coefficients corresponding to the
(1e–1g) are less asynchronic and the asynchronicity is reversed, LUMOs of the dienophiles suggests that the higher asyn-
i.e. the carbon atom directly attached to boron (C-1) is closer to chronicity is determined by steric effects rather than electronic
the diene carbon than C-2. Carbon–carbon distances for the effects. The non-classical [4 + 3] carbon–boron interactions are
˚
other systems are in line with previous results: the presence of weak (C–B distances 2.70–3.15 A, WBI 0.04-002) and very similar
the boron atom makes C-2 more electron decient, so it for the endo and exo approaches. Consequently, the observed
becomes closer to the corresponding carbon atom in the diene moderate to high exo-selectivities seems to be a consequence of
44
than C-1. Analysis of FMOs indicates that the reactions under unfavorable van der Waals interactions in the endo transition
study are normal electron-demand Diels–Alder reactions. From structures.
˚
the atomic coefficients for the LUMOs of the dienophiles, it
Also, the short distance (ca. 2.4 A) between one of the
appears that the computed reversal of asynchonicity is methylene hydrogens of the cyclopentadiene moiety and one of
caused by electronic effects since compounds 1e–1g have larger the oxygens of the pinacol boronate in the exo transition
coefficients at C-1 than at C-2, in contrast to the rest of the structures suggests the possibility that hydrogen bond interac-
dienophiles. However, we do not discard the contribution of tions contribute to determine the diastereoselectivity. NBO
steric effects. In addition, the transition structures of calculations indicate that this accounts for a stabilization of
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Table
5
MPWB1K/6-311G* free energies of activation, reaction boronate cycloadducts should predominate while that the
ꢀ
energies and endo/exo selectivities at 170 C in toluene for the Diels–
Alder reactions of pinacol alkenylboronates 1a–1j with
cyclopentadiene
reactions with 1e–1g and 1j should be endergonic and the
starting alkenylboronates should be the major components of
the reaction mixtures. Therefore, free energy trends, gave us a
a
#
Dienophile
TS
DGTol
endo/exo
68 : 32
18 : 82
17 : 83
10 : 90
2 : 98
DGTol
endo/exo hint to better understand the reaction mechanism.
Another point that deserves to be remarked is the high
reactivity of substrate 1h. Inspection of the geometry of the
corresponding transition structures reveals that a non-classical
hydrogen bond (NCHB) between an aromatic proton at the
ortho position and one of the oxygens of the pinacol boronate
might be responsible for the peculiar reactivity. Such interac-
1
1
1
1
1
1
1
1
1
1
a
b
c
d
e
f
endo
exo
endo
exo
endo
exo
endo
exo
endo
exo
endo
exo
endo
exo
endo
exo
36.04
36.71
41.71
40.36
41.25
39.81
39.44
37.53
42.37
39.01
40.75
39.97
40.72
39.59
38.77
36.65
40.25
38.13
41.92
40.91
ꢂ5.62
ꢂ6.11
0.28
ꢂ0.31
ꢂ1.09
ꢂ0.70
ꢂ3.99
ꢂ4.15
2.34
2.03
1.36
2.53
2.16
2.19
0.84
ꢂ2.15
ꢂ1.30
ꢂ1.24
1.47
37 : 63
34 : 66
61 : 39
46 : 54
41 : 59
79 : 21
51 : 49
3 : 97
tion is much stronger in the exo transition structure than in its
ꢂ1
˚
˚
endo counterpart (exo: 2.17 A, 1.25 kcal mol , endo: 2.38 A, 0.28
ꢂ1
˚
kcal mol ), and also than in the starting dienophile (2.55 A,
0.15 kcal mol ). The unexpected lack of reactivity of structur-
ꢂ1
29 : 71
22 : 78
8 : 92
ally related analogue 1j is reected in a higher free energy
barrier obtained from the calculations, which might result from
geometric constraints imposed by the bulky chlorine atom. The
dihedral angle between the aromatic ring and the double bond
in the optimized geometry of the reactant is 54 degrees, making
the approach of the diene more difficult. The aforementioned
dihedral angle is reduced to roughly 26 degrees in the transition
structures, in contrast to the planar geometries corresponding
to 1-phenylvinylboronic acid pinacol ester (1h).
g
h
i
endo
exo
endo
exo
8 : 92
51 : 49
79 : 21
j
24 : 76
2.65
a
ꢂ1
Energies in kcal mol
.
Conclusions
ꢂ1
0
.30–0.75 kcal mol of the exo transition structures relative to
We have investigated the Diels–Alder reactions of pinacol
alkenylboronates with cyclopentadiene. The outcome of the
studied transformation was shown to be very sensitive to the
substitution of the dienophile both under thermal and TFA-
catalyzed conditions. Theoretical calculations disclosed some
interesting substituent effects for these [4 + 2] cycloadditions.
We have found that the thermal Diels–Alder reactions of alke-
nylboronates with aryl groups in the 2-position give low yields
because they are highly reversible. The high reactivity of 1-
phenylvinylboronic acid pinacol ester (1h) was explained in
terms of a stabilizing non-classical hydrogen bond between an
aromatic proton and the boronate moiety. We have also
synthesized a range of substituted 5-norbornen-2-ols in one-pot
by performing the tandem Diels–Alder reactions – alkaline
hydrogen peroxide oxidation, demonstrating the versatility of
alkenylboronic esters as synthetic equivalents of substituted
enols.
their endo counterparts.
The lowest energy barriers correspond to the reactions of
substrates 1a and 1h, while the one for analogue 1j is the
highest one, in accordance with the experimental reactivities.
However, the free energies of activation for the other reactions
do not match the reactivity trend accurately. For that reason, we
optimized the geometries of the products and computed the
reaction energies. By analyzing the barriers for the direct reac-
tions (Diels–Alder reaction) and the reverse reaction (retro
Diels–Alder reaction) we propose that the low product yields for
ꢀ
the reactions of dienophiles 1e–1g at 170 C, might be related to
the higher reversibility of the reactions as a result of the higher
energies of the products and the resulting lower energy barriers
for the retro Diels–Alder reactions. The higher energies of the
products corresponding to the reactions of aromatic alke-
nylboronates 1e–1g appear to be originated from steric clashes
between the aromatic ring and the [2.2.1] backbone.
For 1b–1d and 1i, the endo/exo selectivities calculated from
activation free energies are in agreement with the experimental
Experimental section
values. For the more reactive dienophiles 1a and 1h the calcu- General experimental procedures
lated endo/exo selectivities from the reaction energies are in
All reagents and solvents were used directly as purchased or
excellent accordance with the experimental outcome, indicating
the dominance of the thermodynamical control in these reac-
tions. The endo/exo ratios for 1e–1g are closer to the gures
obtained from reaction energies, which supports that in these
cases the starting material/products distribution is a conse-
quence of thermodynamic equilibration. On the other hand,
free reaction energies of the products predict that the reactions
with the 1a–1d and 1h–1i should be exergonic and therefore, the
puried according to standard procedures. Analytical thin layer
chromatography was carried out using commercial silica gel
plates (Merck, Silica Gel 60 F254) and visualization was effected
with short wavelength UV light (254 nm) and a p-anisaldehyde
solution (2.5 mL of p-anisaldehyde + 2.5 mL of H SO + 0.25 mL
2
4
of AcOH + 95 mL of EtOH). Column chromatography was per-
formed with silica gel 60 H (Merck), slurry packed, run under
low pressure of nitrogen. The Diels–Alder reactions were
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monitored using TLC and B NMR analysis in CDCl
Paper
1
1
3
13
. NMR
(b) Procedure B: reaction time: 5 h. Yield: 88% (54.2 mg),
1
spectra were recorded at 300 MHz for H, 75 MHz for C, 96 endo/exo 36 : 64.
1
1
19
MHz for B and 282 MHz for F NMR on a Bruker Avance-300
4,4,5,5-Tetramethyl-2-(3-propyl-bicyclo[2.2.1]hept-5-en-2-yl)-
1
DPX spectrometer with CDCl as solvent and (CH ) Si ( H) and [1,3,2]dioxaborolane (2b). Boronate 2b was obtained as a
3
3 4
1
3
11
19
CDCl
3
( C, 76.9 ppm) as internal standards. B and F NMR mixture of diastereomers according to the general procedure A,
–Et O and CFCl using alkenylboronate 1b (0.22 mmol) and cyclopentadiene
spectra were externally referenced to BF
3
2
3
,
respectively. Chemical shis are reported in delta (d) units in (0.66 mmol). A small fraction of the exo diastereomer could be
parts per million (ppm) and splitting patterns are designated as separated and characterized. Reaction time: 24 h. Yield: 78%
s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet and br, (45.0 mg), endo/exo 17 : 83.
broad. Coupling constants are recorded in Hertz (Hz). Isomeric
ratios were determined by H NMR integration. Infrared spectra 2956, 2926, 2870, 2359, 2344, 1371, 1312, 1146, 978, 853, 698
Boronate 2b-X (major compound, yellowish oil). IR (lm) nmax
1
ꢂ1
1
were recorded on a Shimadzu IR Prestige-21 spectrometer cm . H NMR (300 MHz, CDCl ) d 6.17 (dd, J ¼ 5.6, J ¼ 2.9
3
5,6
1,6
using sodium chloride plates or potassium bromide pellets. Hz, 1H, H-6), 5.87 (dd, J5,6 ¼ 5.6, J4,5 ¼ 2.9 Hz, 1H, H-5), 2.77 (br
Absorbance frequencies are recorded in reciprocal centimeters s, 1H, H-4), 2.74 (br s, 1H, H-1), 2.15–2.04 (m, 1H, H-3), 1.36–
ꢂ1
(
cm ). The high resolution mass spectra (HRMS) were 1.26 (m, 4H, H-7 and H-11), 1.24 (br s, 12H, H-9), 1.10–0.92 (m,
obtained with a Bruker MicroTOF-Q II instrument (Bruker 2H, H-10), 0.85 (t, J11,12 ¼ 7.3 Hz, 3H, H-12), 0.16 (dd, J2,3 ¼ 5.3,
1
3
Daltonics, Billerica, MA). Detection of the ions was performed
J
1,2 ¼ 1.6 Hz, 1H, H-2). C NMR (75 MHz, CDCl
3
) d 138.3 (CH, C-
with electrospray ionization (ESI), positive ion mode and 6), 131.5 (CH, C-5), 82.8 (2C, C-8), 48.5 (CH , C-7), 46.1 (CH, C-4),
2
Atmospheric Pressure Chemical Ionization (APCI). The struc- 45.0 (CH, C-1), 42.2 (CH, C-3), 37.6 (CH , C-10), 24.7 (2CH , C-9),
2
3
ture of the products were determined by a combination of 24.6 (2CH , C-9), 21.8 (CH , C-11), 14.4 (CH , C-12), C-2 signal
3
2
3
1
1
spectroscopic methods such as IR, 1D and 2D NMR (including missing. B NMR (96 MHz, CDCl
NOE, DEPT, COSY, HSQC and HMBC experiments) and HRMS. Boronates 2b-X and 2b-N (yellowish oil). IR (lm) nmax 2957,
In some cases, NMR calculations were also performed to 2926, 2870, 2359, 2342, 1371, 1312, 1244, 1146, 968, 853, 692
3
) d 34.2.
ꢂ1
1
corroborate the stereochemistry and the assignment. In addi- cm . H NMR (300 MHz, CDCl
3
) d 6.17 (dd, J5,6 ¼ 5.6, J1,6 ¼ 2.9
tion, we conrmed the structure of the Diels–Alder products by Hz, 1H, H-6X), 6.10 (dd, J5,6 ¼ 5.5, J4,5 ¼ 3.1 Hz, 1H, H-5N), 5.98
oxidation of the boronates to the alcohols, some of which were (dd, J5,6 ¼ 5.5, J ¼ 2.8 Hz, 1H, H-6N), 5.87 (dd, J ¼ 5.6, J
¼
4,5
5,6
4,5
described in the literature.
2.9 Hz, 1H, H-5X), 2.92 (br s, 1H, H-1N), 2.77 (br s, 1H, H-4X),
2
3
1
.74 (br s, 1H, H-1X), 2.50 (br s, 1H, H-4N), 2.15–2.04 (m, 1H, H-
X), 1.40–1.26 (m, 11H, H-7X, H-11X, H-3N, H-7N, H-10N and H-
1N), 1.24 (s, 12H, H-9X), 1.18 (s, 12H, H-9N), 1.10–0.92 (m, 2H,
Diels–Alder reactions of alkenylboronates: synthesis of
boronates 2a–2i
H-10X), 0.92–0.78 (m, 4H, H-2N and H-12N), 0.85 (t, J11,12 ¼ 7.3
13
Hz, 3H, H-12X), 0.16 (dd, J2,3 ¼ 5.3, J1,2 ¼ 1.6 Hz, 1H, H-2X).
C
General procedure A. To a pressure tube equipped with a NMR (75 MHz, CDCl
stirring bar were added dry toluene (1.5 mL), vinylboronate 1 135.1 (CH, C-6N), 131.5 (CH, C-5X), 82.7 (2C, C-8N), 82.2 (2C, C-
typically 0.25 mmol), 2,6-di-tert-butyl-4-methylphenol (BHT, 5 8X), 48.5 (CH , C-7X), 47.2 (CH , C-7N), 47.1 (CH, C-4N), 46.1
3
) d 138.3 (CH, C-6X), 137.2 (CH, C-5N),
(
2
2
mol %) and cyclopentadiene (0.75 mmol) under nitrogen atmo- (CH, C-4X), 45.0 (CH, C-1X), 44.7 (CH, C-1N), 42.2 (CH, C-3X),
ꢀ
sphere. The resulting reaction mixture was stirred at 170 C for the 42.0 (CH, C-3N), 39.6 (CH
2
, C-10N), 37.6 (CH
, C-9X), 24.6 (2CH , C-9X), 24.5 (2CH
, C-11N), 21.8 (CH , C-11X), 14.4 (2CH , C-12X
and C-12N), C-2 signals missing. B NMR (96 MHz, CDCl ) d
(M + H) 263.2177,
2
, C-10X), 24.8
reported time (1–24 h). The solvent was removed under reduced (2CH
pressure, and the crude was puried by column chromatography C-9N), 21.9 (CH
hexane/AcOEt) to afford the corresponding boronate.
General procedure B. To a pressure tube equipped with a 34.1. HRMS (APCI) calcd for C16
stirring bar were added dry toluene (1.5 mL), vinylboronate 1 found 263.2178.
3
, C-9N), 24.7 (2CH
3
3
3
,
2
2
3
1
1
(
3
+
H28BO
2
(typically 0.28 mmol), 2,6-di-tert-butyl-4-methylphenol (BHT, 5
2-[3-(3-Chloro-propyl)-bicyclo[2.2.1]hept-5-en-2-yl]-4,4,5,5-
mol %), cyclopentadiene (0.84 mmol) and triuoroacetic acid tetramethyl-[1,3,2]dioxaborolane (2c). Boronate 2c was
(
TFA, 5 mol %) under nitrogen atmosphere. The resulting obtained as a mixture of diastereomers according to the general
ꢀ
reaction mixture was stirred at 80 C for the reported time (5–72 procedure A, using alkenylboronate 1c (0.21 mmol) and cyclo-
h). The solvent was removed under reduced pressure, and the pentadiene (0.63 mmol). A small fraction of exo diastereomer
crude was puried by column chromatography (hexane/AcOEt) could be separated and characterized. Reaction time: 24 h.
to afford the corresponding boronate.
-Bicyclo[2.2.1]hept-5-en-2-yl-4,4,5,5-tetramethyl-[1,3,2]diox-
aborolane (2a). Boronate 2a was obtained as a mixture of 2965, 2926, 2358, 2341, 1373, 1314, 1144, 852, 669, 430, 411
Yield: 89% (55.5 mg), endo/exo 20 : 80.
Boronate 2c-X (major compound, yellowish oil). IR (lm) nmax
2
32
ꢂ1
1
diastereomers according to the general procedures A and B cm . H NMR (300 MHz, CDCl
using vinylboronate 1a (0.28 mmol) and cyclopentadiene Hz, 1H, H-6), 5.88 (dd, J5,6 ¼ 5.3, J4,5 ¼ 2.9 Hz, 1H, H-5), 3.51 (t,
0.84 mmol). A small fraction of each diastereomer could be
11,12 ¼ 6.9 Hz, 2H, H-12), 2.78 (br s, 2H, H-1 and H-4), 2.14–2.04
separated and characterized.
(m, 1H, H-3), 1.75 (quintet, J10,11 ¼ J11,12 ¼ 7.2 Hz, 2H, H-11),
a) Procedure A: reaction time: 1 h. Yield: 96% (59.1 mg), 1.34–1.27 (m, 2H, H-7), 1.24 (s, 12H, H-9), 1.16–1.02 (m, 2H, H-
) d 6.20 (dd, J5,6 ¼ 5.3, J1,6 ¼ 3.2
3
(
J
(
1
3
endo/exo 36 : 65.
10), 0.18 (br d, J2,3 ¼ 5.2 Hz, 1H, H-2). C NMR (75 MHz, CDCl
3
)
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d 138.6 (CH, C-6), 131.2 (CH, C-5), 83.0 (2C, C-8), 48.6 (CH
2
, C-7),
J
10a,10b ¼ 9.4 Hz, 1H, H-10bN), 3.14 (dd, J10a,10b ¼ 9.5, J3,10a ¼ 5.7
4
6.2 (CH, C-1), 45.3 (CH , C-12), 45.0 (CH, C-4), 41.6 (CH, C-3), Hz, 1H, H-10aX), 2.93 (br s, 2H, H-4X and H-1N), 2.84 (t, J
¼
2
3,10b
3
2.5 (CH , C-10), 31.8 (CH, C-11), 24.7 (4CH , C-9), C-2 signal J10a,10b ¼ 9.5 Hz, 1H, H-10bX), 2.79 (br s, 1H, H-1X), 2.75 (br s,
2
1
3
1
missing. B NMR (96 MHz, CDCl ) d 33.8.
1H, H-4N), 2.42 (m, 1H, H-3X), 1.81 (dt, J
¼ 9.4, J
¼ J
¼
3
3,10b
3,10a
2,3
Boronates 2c-X and 2c-N (yellowish oil). IR (lm) nmax 2965, 5.3 Hz, 1H, H-3N), 1.33 (br s, 4H, H-7X and H-7N), 1.23 (s, 12H,
ꢂ1
1
2
930, 2358, 2342, 1373, 1144, 852, 717, 546, 411, 401 cm . H H-9X), 1.17 (s, 12H, H-9N), 0.78 (dd, J2,3 ¼ 5.2, J1,2 ¼ 3.3 Hz, 1H,
13
NMR (300 MHz, CDCl
3
) d 6.20 (dd, J5,6 ¼ 5.3, J1,6 ¼ 3.2 Hz, 1H, H- H-2N), 0.08 (br d, J2,3 ¼ 5.9 Hz, 1H, H-2X). C NMR (75 MHz,
CDCl ) d 138.4 (CH, C-6X), 136.9 (CH, C-5N), 135.9 (CH, C-6N),
.6, J1,6 ¼ 2.8 Hz, 1H, H-6N), 5.88 (dd, J5,6 ¼ 5.3, J4,5 ¼ 2.9 Hz, 131.5 (CH, C-5X), 83.0 (2C, C-8X), 82.9 (2C, C-8N), 77.5 (CH , C-
H, H-5X), 3.58 (t, J1 ¼ 6.9, 10N), 76.5 (CH , C-10X), 58.6 (2CH , C-11X and C-11N), 48.4
¼ 6.8, 1H, H-12N), 3.57 (t, J
6
5
1
1
1
2
1
X), 6.17 (dd, J5,6 ¼ 5.6, J4,5 ¼ 3.2 Hz, 1H, H-5N), 6.00 (dd, J5,6
¼
3
2
1,12
11,12
2
3
H, H-12N), 3.51 (t, J11,12 ¼ 6.9 Hz, 2H, H-12X), 2.95 (br s, 1H, H- (CH , C-7X), 46.7 (CH , C-7N), 44.4 (CH, C-1X), 44.2 (CH, C-4X),
2
2
N), 2.78 (br s, 2H, H-1X and H-4X), 2.51 (br s, 1H, H-4N), 2.14– 44.1 (CH, C-4N), 44.0 (CH, C-1N), 42.3 (CH, C-3N), 41.9 (CH, C-
.04 (m, 1H, H-3X), 1.84 (quintet, J10,11 ¼ J11,12 ¼ 7.0 Hz, 2H, H- 3X), 24.7 (4CH , C-9X), 24.6 (4CH , C-9N), C-2 signals missing.
B NMR (96 MHz, CDCl ) d 33 8.
4,4,5,5-Tetramethyl-2-(3-phenylbicyclo[2.2.1]hept-5-en-2-yl)-
3
3
1
1
1N), 1.75 (quintet, J10,11 ¼ J11,12 ¼ 7.2 Hz, 2H, H-11X), 1.44–1.41
3
(
m, 1H, H-3N), 1.38–1.32 (m, 2H, H-7N), 1.34–1.27 (m, 2H, H-
7
4
¼
X), 1.24 (s, 12H, H-9X), 1.18 (br s, 12H, H-9N), 1.16–1.02 (m, [1,3,2]-dioxaborolane (2e). Boronate 2e was obtained as a
H, H-10X and H-10N), 0.84–0.79 (m, 1H, H-2N), 0.18 (br d, J2,3 mixture of diastereomers according to the general procedures A
1
3
5.2 Hz, 1H, H-2X). C NMR (75 MHz, CDCl ) d 138.7 (CH, C- and B, using alkenylboronate 1e (0.20 mmol) and cyclo-
3
6
X), 137.1 (CH, C-5N), 135.4 (CH, C-6N), 131.2 (CH, C-5X), 83.0 pentadiene (0.60 mmol).
(a) Procedure A: reaction time: 24 h. Yield: 29% (17.3 mg),
, C-12X and C-12N), endo/exo 35 : 65.
5.0 (CH, C-1X), 44.6 (CH, C-1N) 41.6 (CH, C-3X), 41.0 (CH, C- (b) Procedure B: reaction time: 24 h. Yield: 32% (19 mg),
N), 32.5 (2CH , C-10X and C-10N), 31.8 (2CH , C-11X and C- endo/exo 17 : 83. Reaction time: 72 h. Yield: 38% (22.5 mg),
1N), 24.8 (2CH , C-9N), 24.7 (4CH , C-9X), 24.5 (2CH
signals missing. B NMR (96 MHz, CDCl
(
2C, C-8X), 82.8 (2C, C-8N), 48.6 (CH , C-7X), 47.2 (CH , C-7N
2 2
and CH, C-4N), 46.2 (CH, C-4X), 45.3 (2CH
2
4
3
1
2
2
2
3
3
3
, C-9N), C- endo/exo 17 : 83.
1
1
3
) d 34.0. HRMS
Boronates 2e-X and 2e-N (yellowish oil). IR (lm) nmax 2957,
+
ꢂ1
1
(APCI) calcd for C H BClO (M + H) 297.1787, found 2928, 2870, 1468, 1454, 1404, 1371, 1146, 853, 679 cm . H
16 27 2
297.1822.
NMR (300 MHz, CDCl ) d 7.35–7.08 (m, 10H, ArH-X and ArH-N),
3
2
-(3-Methoxymethylbicyclo[2.2.1]hept-5-en-2-yl)-4,4,5,5-tetra- 6.30 (dd, J5,6 ¼ 5.6, J ¼ 3.2 Hz, 1H, H-6X), 6.26 (dd, J ¼ 5.6,
1,6
5,6
methyl-[1,3,2]dioxaborolane (2d). Boronate 2d was obtained as a
J
4,5 ¼ 3.3 Hz, 1H, H-5N), 6.15 (dd, J5,6 ¼ 5.6, J1,2 ¼ 2.9 Hz, 1H, H-
mixture of diastereomers according to the general procedures A 6N), 5.79 (dd, J5,6 ¼ 5.6, J4,5 ¼ 2.7 Hz, 1H, H-5X), 3.51 (dd, J2,3
¼
and B, using alkenylboronate 1d (0.22 mmol) and cyclo- 5.8, J ¼ 3.2 Hz, 1H, H-3X), 3.16 (br s, 1H, H-4X), 3.11 (br s, 1H, H-
pentadiene (0.66 mmol). A small fraction of exo diastereomer 1N), 2.95 (br s, 2H, H-1X and H-4N), 2.86 (br d, J2,3 ¼ 5.9 Hz, 1H,
could be separated and characterized.
H-3N), 1.63 (br d, J7a,7b ¼ 8.6, 1H, H-7aN), 1.56 (br d, J7a,7b ¼ 8.3
(a) Procedure A: reaction time: 24 h. Yield: 88% (51.1 mg), Hz, 1H, H-7aX), 1.49–1.41 (m, 1H, H-7bN), 1.42–1.36 (m, 2H, H-
endo/exo 15 : 85.
7bX and H-2N), 1.25 (s, 12H, H-9X), 1.22 (s, 12H, H-9N), 1.02
1
3
(b) Procedure B: reaction time: 72 h. Yield: 26% (15.1 mg), (dd, J2,3 ¼ 5.9, J ¼ 1.8, 1H, H-2X). C NMR (75 MHz, CDCl ) d
3
endo/exo 10 : 90.
146.7 (C, Ar-N), 145.1 (C, Ar-X), 138.6 (CH, C-6X), 137.6 (CH, C-
Boronate 2d-X (major compound, yellowish oil). IR (lm) nmax 5N), 136.5 (CH, C-6N), 132.1 (CH, C-5X), 128.2 (2CH, Ar-N), 128.1
3
055, 2976, 2926, 2868, 1406, 1369, 1313, 1145, 1109, 852, 723 (2CH, Ar-X), 127.7 (2CH, Ar-X), 127.5 (2CH, Ar-N), 125.5 (CH, Ar-
ꢂ1
1
cm . H NMR (300 MHz, CDCl
3
) d 6.18 (dd, J5,6 ¼ 5.6, J1,6 ¼ 3.0 X), 125.3 (CH, Ar-N), 83.2 (2C, C-8X), 83.1 (2C, C-8N), 49.0 (CH
2
,
Hz, 1H, H-6), 5.90 (dd, J5,6 ¼ 5.6, J4,5 ¼ 3.0 Hz, 1H, H-5), 3.29 (s, C-7X), 48.9 (CH, C-4X), 48.0 (CH
2
, C-7N), 47.9 (CH, C-4N), 46.5
3
2
2
H, H-11), 3.14 (dd, J10a,10b ¼ 9.5, J
¼ 5.7 Hz, 1H, H-10a), (2CH, C-3X and C-3N), 45.9 (CH, C-1X), 45.2 (CH, C-1N), 24.9
¼ 9.5 Hz, 1H, H-10b), (2CH , C-9N), 24.8 (2CH , C-9X), 24.7 (2CH , C-9X), 24.6 (2CH ,
3,10a
.93 (br s, 1H, H-4), 2.84 (t, J10a,10b ¼ J
3,10b
3
3
3
3
1
1
.79 (br s, 1H, H-1), 2.42 (m, 1H, H-3), 1.33 (br s, 2H, H-7), 1.23 C-9N), C-2 signals missing. B NMR (96 MHz, CDCl ) d 33.3.
3
1
3
+
(
s, 12H, H-9), 0.08 (br d, J2,3 ¼ 5.9 Hz, 1H, H-2). C NMR (75 HRMS (APCI) calcd for C19
MHz, CDCl ) d 138.4 (CH, C-6), 131.5 (CH, C-5), 83.0 (2C, C-8), 297.2033.
, C-10), 58.6 (CH , C-11), 48.4 (CH , C-7), 44.4 (CH, C- 4,4,5,5-Tetramethyl-2-[3-(4-chlorophenyl)bicyclo[2.2.1]hept-
), 44.2 (CH, C-4), 41.9 (CH, C-3), 24.7 (4CH , C-9), C-2 signal 5-en-2-yl]-[1,3,2]-dioxaborolane (2f). Boronate 2f was obtained
) d 34.0. HRMS (APCI) calcd as a mixture of diastereomers according to the general proce-
for C H BO (M + H) 265.1970, found 265.1967. dures A and B, using alkenylboronate 1f (0.17 mmol) and
Boronates 2d-X and 2d-N (yellowish oil). IR (lm) nmax 3055, cyclopentadiene (0.51 mmol).
976, 2927, 2889, 2868, 1371, 1313, 1145, 1107, 974, 852, 723 (a) Procedure A: reaction time: 24 h. Yield: 20% (11.2 mg),
2
H26BO (M + H) 297.2020, found
3
7
1
6.5 (CH
2
3
2
3
1
1
missing. B NMR (96 MHz, CDCl
3
+
1
5
26
3
2
ꢂ1
1
cm . H NMR (300 MHz, CDCl
3
) d 6.18 (dd, J5,6 ¼ 5.6, J1,6 ¼ 3.0 endo/exo 40 : 60.
Hz, 1H, H-6X), 6.10 (dd, J5,6 ¼ 5.6, J4,5 ¼ 3.1 Hz, 1H, H-5N), 6.04
(b) Procedure B: reaction time: 24 h. Yield: 20% (11.2 mg),
(
3
1
dd, J5,6 ¼ 5.5, J1,6 ¼ 2.8 Hz, 1H, H-6N), 5.90 (dd, J5,6 ¼ 5.6, J4,5
¼
endo/exo 36 : 64. Reaction time: 72 h. Yield: 31% (17.4 mg),
.0 Hz, 1H, H-5X), 3.49 (dd, J10a,10b ¼ 9.4, J3,10a ¼ 5.4 Hz, 1H, H- endo/exo 29 : 71.
0 aN), 3.34 (s, 3H, H-11N), 3.29 (s, 3H, H-11X), 3.22 (t, J3,10b
¼
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Boronates 2f-X and 2f-N (yellowish oil). IR (lm) nmax 3059,
4,4,5,5-Tetramethyl-2-(2-phenylbicyclo[2.2.1]hept-5-en-2-yl)-
2
7
974, 2931, 2870, 1492, 1371, 1315, 1143, 1091, 1014, 972, 848, [1,3,2]-dioxaborolane (2h). Boronate 2h was obtained as a
98, 729 cm . H NMR (300 MHz, CDCl ) d 7.24 (s, 4H, H-11N mixture of diastereomers according to the general procedures A
3
ꢂ1
1
and H-12N), 7.17 (br d, J11,12 ¼ 8.5 Hz, 2H, H-11X), 7.07 (br d, and B, using alkenylboronate 1h (0.17 mmol) and cyclo-
12,11 ¼ 8.5 Hz, 2H, H-12X), 6.31 (dd, J5,6 ¼ 5.6, J1,6 ¼ 3.1 Hz, 1H, pentadiene (0.51 mmol).
H-6X), 6.25 (dd, J5 ¼ 5.7, J ¼ 3.1 Hz, 1H, H-5N), 6.15 (dd, J (a) Procedure A: reaction conditions: 12 h at 170 C. Yield:
5.7, J1,6 ¼ 2.9 Hz, 1H, H-6N), 5.76 (dd, J ¼ 5.6, J ¼ 2.8 Hz, 21% (10.6 mg), endo/exo 41 : 59. Reaction conditions: 12 h at
J
ꢀ
,6
4,5
5,6
¼
5,6
4,5
ꢀ
1
2
H, H-5X), 3.45 (dd, J2 ¼ 6.0, J ¼ 3.8 Hz, 1H, H-3X), 3.11 (br s, 80 C. Yield: 91% (45.8 mg), endo/exo 5 : 95.
,3
3,4
H, H-4X and H-1N), 2.94 (br s, 2H, H-1X and H-4N), 2.80 (br d,
(b) Procedure B: reaction time: 12 h. Yield: 83% (41.8 mg),
J
(
2
J
2,3 ¼ 5.6 Hz, 1H, H-3N), 1.58–1.51 (m, 2H, H-7X and H-7N), 1.47 endo/exo 6 : 94.
br d, J7a,7b ¼ 8.3, 1H, H-7N), 1.40 (m, 1H, H-7X), 1.33 (m, 1H, H- Boronates 2h-X and 2h-N (white solid, mp 81.5–83.3 C). IR
N), 1.25 (s, 12H, H-9X), 1.22 (s, 12H, H-9N), 0.95 (dd, J2,3 ¼ 6.0, (KBr) nmax 3065, 2976, 2864, 1371, 1327, 1314, 1215, 1138,
ꢀ
1
3
ꢂ1
1
1,2 ¼ 2.0 Hz, 1H, H-2X). C NMR (75 MHz, CDCl
0N), 143.6 (C, C-10X), 138.9 (CH, C-6X), 137.4 (CH, C-5N), 136.7 (m, 10H, ArH-X and ArH-N), 6.25 (dd, J5,6 ¼ 5.4, J ¼ 2.9 Hz, 1H,
3 3
) d 145.2 (C, C- 1051 856, 698, 611 cm . H NMR (300 MHz, CDCl ) d 7.39–7.00
1
1,6
(
1
1
CH, C-6N), 131.8 (CH, C-5X), 131.2 (C, C-13X), 129.4 (2CH, C- H-6N), 6.21 (dd, J5,6 ¼ 5.4, J ¼ 3.0 Hz, 1H, H-5N), 6.03 (dd, J
4,5
5,6
1X), 128.8 (2CH, C-11N), 128.2 (2CH, C-12N), 127.8 (2CH, C- ¼ 5.6, J ¼ 2.9 Hz, 1H, H-5X), 5.90 (dd, J ¼ 5.6, J ¼ 2.6 Hz,
4
,5
5,6
1,6
2
2X), 83.3 (2C, C-8X), 83.2 (2C, C-8N), 49.1 (CH , C-7X), 48.9 (CH, 1H, H-6X), 3.58 (br s, 1H, H-1X), 3.48 (br s, 1H, H-1N), 2.88 (br s,
C-4X), 47.9 (CH, C-4N and CH
X), 45.8 (CH, C-1X), 45.1 (CH, C-1N), 24.9 (2CH
2CH , C-9X), 24.7 (2CH , C-9X), 24.6 (2CH
, C-9N), C-2 and C- 11.2, J3x,4 ¼ 3.4 Hz, 1H, H-3
3N signals missing. B NMR (96 MHz, CDCl
2
, C-7N), 46.1 (2CH, C-3N and C- 2H, H-4X and H-4N), 2.48 (dd, J3n,3x ¼ 11.5, J3x,4 ¼ 3.9 Hz, 1H, H-
3
(
1
3
, C-9N), 24.8
3
x
X), 2.05 (br d, J3n,3x ¼ 11.2 Hz, 1H, H-3
n
N), 1.93 (dd, J3n,3x
¼
3
3
3
x
N), 1.51–1.39 (m, 4H, H-3
n
X, H-7aX,
1
1
3
) d 33.3. HRMS and H-7N), 1.31 (br d, J7a,7b ¼ 8.3 Hz, 1H, H-7bX), 1.11 (s, 6H, H-
+
13
(APCI) calcd for C H BClO (M + H) 331.1631, found 9X), 1.10 (s, 12H, H-9X and H-9N), 1.08 (s, 6H, H-9N). C NMR
19 25 2
3
31.1628.
,4,5,5-Tetramethyl-2-[3-(3-triuoromethylphenyl)bicyclo- C-6X), 136.0 (CH, C-6N), 134.9 (CH, C-5X), 128.1 (2CH, Ar-X),
2.2.1]hept-5-en-2-yl]-[1,3,2]dioxaborolane (2g). Boronate 2g was 127.8 (2CH, Ar-X), 127.6 (2CH, Ar-N), 125.2 (2CH, Ar-N), 124.5
obtained as a mixture of diastereomers according to the general (CH, Ar-X), 83.3 (2C, C-8X), 83.2 (2C, C-8N), 49.0 (CH , C-7X),
procedures A and B, using alkenylboronate 1g (0.27 mmol) and 47.8 (CH, C-1X), 47.3 (CH, C-1N), 47.2 (CH , C-7N), 43.4 (CH, C-
cyclopentadiene (0.81 mmol). 4N), 42.4 (CH, C-4X), 39.0 (CH , C-3N) 35.6 (CH , C-3X), 24.5
a) Procedure A: reaction time: 24 h. Yield: 19% (18.7 mg), (2CH , C-9N) 24.3 (2CH , C-9X), 24.2 (4CH , C-9X and C-9X), C-2,
(75 MHz, CDCl ) d 146.4 (C, Ar-X), 138.8 (CH, C-5N), 136.4 (CH,
3
4
[
2
2
2
2
(
3
3
3
1
1
endo/exo 37 : 63.
C-10N and C-13N signals missing. B NMR (96 MHz, CDCl ) d
3
+
(
b) Procedure B: reaction time: 24 h. Yield: 24% (23.6 mg), 33.3. HRMS (APCI) calcd for C H BO (M + H) 297.1010,
1
9
26
2
endo/exo 10 : 90. Reaction time: 72 h. Yield: 45% (44.3 mg), found 297.2016.
endo/exo 10 : 90. 4,4,5,5-Tetramethyl-2-(2-methylbicyclo[2.2.1]hept-5-en-2-yl)-
Boronates 2g-X and 2g-N (yellowish oil). IR (lm) nmax 3045, [1,3,2]-dioxaborolane (2i). Boronate 2i was obtained as a
ꢂ1
1
2
926, 1715, 1445, 1354, 1265, 1080, 737, 664, 600 cm . H NMR mixture of diastereomers according to the general procedures A
(
(
3
300 MHz, CDCl ) d 7.78–7.26 (m, 8H, ArH-X and ArH-N) 6.34 and B, using alkenylboronate 1i (0.5 mmol) and cyclo-
3
dd, J5,6 ¼ 5.6, J1,6 ¼ 2.9 Hz, 1H, H-6X), 6.27 (dd, J5,6 ¼ 5.5, J4,5
¼
pentadiene (1.5 mmol). A small fraction of exo diastereomer
.0 Hz, 1H, H-5N), 6.17 (dd, J ¼ 5.5, J ¼ 2.8 Hz, 1H, H-6N), could be separated and characterized.
5
,6
1.6
5
.76 (dd, J5,6 ¼ 5.6, J ¼ 2.9 Hz, 1H, H-5X), 3.53 (dd, J ¼ 5.8,
(a) Procedure A: reaction time: 24 h. Yield: 72% (84.3 mg),
4,5
2,3
J3,4 ¼ 3.3 Hz, 1H, H-3X), 3.15 (br s, 2H, H-4X and H-1N), 2.98 (br endo/exo 9 : 91.
(b) Procedure B: reaction time: 24 h. Yield: 15% (17.6 mg),
.45 (m, 3H, H-7aX, and H-7N), 1.44–1.34 (m, 2H, H-7bX and H- endo/exo 9 : 91.
N), 1.26 (s, 12H, H-9X), 1.23 (s, 12H, H-9N), 1.02 (dd, J2,3 ¼ 5.8, Boronate 2i-X (major compound, yellowish liquid). IR (lm) nmax
s, 2H, H-1X and H-4N), 2.89 (br d, J2,3 ¼ 5.7 Hz, 1H, H-3N), 1.60–
1
2
J
1
3
ꢂ1
1,2 ¼ 2.1 Hz, 1H, H-2X). C NMR (75 MHz, CDCl
3
) d 147.7 (C, 3055, 2958, 2927, 2866, 1456, 1371, 1354, 1303, 1145, 719 cm .
1
Ar-N), 146.1 (C, Ar-X), 139.1 (CH, C-6X), 137.4 (CH, C-5N), 136.7
H NMR (300 MHz, CDCl
3
) d 6.12 (dd, J5,6 ¼ 5.6, J1,6 ¼ 3.1 Hz,
(
1
CH, C-6N), 131.7 (CH, C-5X), 131.4 (CH, Ar-X), 130.6 (CH, Ar-N), 1H, H-6), 6.00 (dd, J5,6 ¼ 5.6, J ¼ 2.9 Hz, 1H, H-5), 2.75 (br s,
4,5
30.4 (C, JC,F ¼ 29.5 Hz, Ar-X), 128.6 (CH, Ar-N), 128.1 (CH, Ar-X), 2H, H-1 and H-4), 2.03 (dd, J
¼ 11.3, J ¼ 3.8 Hz, 1H, H-3 ),
3n,3x
x
1
25.0 (CH, Ar-N), 124.8 (CH, J ¼ 3.7 Hz, Ar-X), 122.6 (CH, Ar- 1.28–1.12 (m, 2H, H-7), 1.24 (s, 12H, H-9), 0.81 (s, 3H, H-10),
C,F
13
N), 122.5 (CH, Ar-N), 122.4 (CH, JC,F ¼ 3.7 Hz, Ar-X), 83.3 (2C, C- 0.53 (dd, J3n,3x ¼ 11.3, J ¼ 2.5 Hz, 1H, H-3
n
). C NMR (75 MHz,
8
2 3
X), 83.2 (2C, C-8N), 49.2 (CH , C-7X), 48.9 (CH, C-4X), 48.0 CDCl ) d 136.3 (CH, C-6), 133.8 (CH, C-5), 83.0 (2C, C-8), 49.7
(
CH
CH, C-1X), 45.2 (CH, C-1N), 24.9 (2CH
X), 24.7 (2CH , C-9X), 24.6 (2CH
2
, C-7N), 47.5 (CH, C-4N), 46.5 (2CH, C-3X and C-3N), 45.9 (CH
2
, C-7), 48.9 (CH, C-4), 43.4 (CH, C-1), 36.6 (CH
2
, C-3), 24.6
1
1
(
3
, C-9N), 24.8 (2CH
3
, C- (4CH
3
, C-9), 22.1 (CH
) d 35.0.
Boronates 2i-X and 2i-N (yellow liquid). IR (lm) nmax 2954,
MHz, CDCl ) d ꢂ62.5. HRMS (APCI) calcd for C H BF O (M + 2924, 2852, 1604, 1463, 1446, 1435, 1359, 1303, 1145, 1022, 746
3
, C-10), C-2 signal missing. B NMR (96
9
3
3
, C-9N), C-12N, C-2 and CF
3
MHz, CDCl
3
1
1
19
signals missing. B NMR (96 MHz, CDCl ) d 33.6. F NMR (282
3
3
20 25
3 2
+
ꢂ1
1
H) 365.1894, found 365.1879.
cm . H NMR (300 MHz, CDCl ) d 6.14 (dd, J ¼ 5.6, J1,6 ¼ 3.1
3
5,6
36396 | RSC Adv., 2014, 4, 36385–36400
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1
3
Hz, 1H, H-6N), 6.12 (dd, J5,6 ¼ 5.6, J1,6 ¼ 3.1 Hz, 1H, H-6X), 6.00
C NMR (75 MHz, CDCl
3
) d 141.2 (CH, C-5N), 137.3 (CH, C-5X),
(
dd, J5,6 ¼ 5.6, J ¼ 2.9 Hz, 2H, H-5X and H-5N), 2.76 (br s, 3H, 133.8 (CH, C-6X), 131.6 (CH, C-6N), 79.9 (CH, C-2N), 79.0 (CH, C-
4,5
H-1X, H-4X and H-4N), 2.53 (br s, 1H, H-1N), 2.03 (dd, J
¼
2X), 50.9 (CH, C-4X), 50.8 (CH, C-3N), 50.5 (CH, C-3X), 48.3 (CH,
3
n,3x
1
1.3, J ¼ 3.8 Hz, 1H, H-3 X), 1.52–1.12 (m, 6H, H-7X, H-3N and C-1N), 47.3 (CH, C-4N), 46.6 (CH , C-7X), 45.2 (CH , C-7N), 44.5
x
2
2
H-7N), 1.24 (s, 12H, H-9X), 1.19 (s, 12H, H-9N), 1.13 (s, 3H, H- (CH, C-1X), 36.9 (CH
2
, C-8N), 35.8 (CH
2
2
, C-8X), 21.7 (CH , C-9N),
1
0N), 0.81 (s, 3H, H-10X), 0.53 (dd, J3n,3x ¼ 11.3, J ¼ 2.5 Hz, 1H, 21.6 (CH
2 3
, C-9X), 14.2 (2CH , C-10X and C-10N). HRMS (APCI)
1
3
+
n 3
H-3 X). C NMR (75 MHz, CDCl ) d 137.0 (CH, C-6N), 136.6 calcd for C10H17O (M + H) 153.1274, found 153.1277.
(CH, C-5N), 136.3 (CH, C-6X), 133.8 (CH, C-5X), 83.0 (2C, C-8X),
3-(3-Chloro-propyl)-bicyclo[2.2.1]hept-5-en-2-ol (3c). Alcohol
82.8 (2C, C-8N), 50.0 (CH, C-1N), 49.7 (CH
2
, C-7X), 48.9 (CH, C- 3c was obtained as a mixture of diastereomers according to the
4
X), 45.6 (CH , C-3N), 43.4 (CH, C-1X), 42.9 (CH, C-4N), 37.9 general procedure C, using alkenylboronate 1c (0.21 mmol) and
2
(
(
(
CH , C-7N), 36.6 (CH , C-3X), 24.6 (8CH , C-9X and C-9N), 24.2 cyclopentadiene (0.63 mmol). A small fraction of exo diaste-
2 2 3
1
1
CH , C-10N), 22.1 (CH , C-10X), C-2 signals missing. B NMR reomer could be separated and characterized. Diels–Alder
3
3
ꢀ
96 MHz, CDCl
3
) d 34.3. HRMS (APCI) calcd for C14
H24BO
2
(M + reaction step conditions: 24 h at 170 C. Overall yield: 82% (32.1
+
H) 235.1864, found 235.1770.
mg), endo/exo 14 : 86.
Alcohol 3c-X (major compound, yellowish oil). IR (lm) nmax
3
1
362, 2963, 2868, 2359, 2344, 2322, 1558, 1541, 1489, 1456,
373, 1339, 1214, 995, 849, 718 cm . H NMR (300 MHz, CDCl )
3
Tandem Diels–Alder reaction of alkenylboronates – oxidation:
synthesis of alcohols
ꢂ1
1
d 6.13 (dd, J5,6 ¼ 5.7, J ¼ 2.7 Hz, 1H, H-5), 6.05 (dd, J ¼ 5.7,
1,6
5,6
General procedure C. To a pressure tube equipped with a
J
4,5 ¼ 3.1 Hz, 1H, H-6), 3.54 (t, J9,10 ¼ 6.3 Hz, 2H, H-10), 3.36 (br
stirring bar were added dry toluene (1.5 mL), vinylboronate 1 s, 1H, H-2), 2.68 (br s, 1H, H-1), 2.66 (br s, 1H, H-4), 1.89–1.77
typically 0.27 mmol), cyclopentadiene (0.81 mmol) and BHT (5 (m, 3H, H-7a and H-9), 1.68–1.59 (m, 2H, H-3 and H-7b), 1.52 (br
(
1
3
mol%) under nitrogen atmosphere. Triuoroacetic acid (5 s, 1H, OH), 1.47–1.28 (m, 2H, H-8). C NMR (75 MHz, CDCl
3
) d
mol%) was also added to the reactions of alkenylboronates 1e, 137.0 (CH, C-5), 134.2 (CH, C-6), 78.8 (CH, C-2), 51.0 (CH, C-4),
1
f and 1g. The resulting reaction mixture was stirred at the 49.8 (CH, C-3), 46.6 (CH
2
, C-7), 45.1 (CH
, C-8).
Alcohols 3c-X and 3c-N (yellowish oil). IR (lm) nmax 3345,
N (1 mL) the solution was 3327, 3059, 2964, 2935, 2870, 1456, 1339, 1028, 849, 717, 648
3
2
, C-10), 44.5 (CH, C-1),
ꢀ
reported temperature (170/80 C) for the reported time (5–72 h), 31.5 (CH
then diluted with THF (3 mL) and transferred to a 25 mL round-
bottom ask. Aer the addition of Et
cooled to 0 C, treated alternately with 3 N NaOH (3 mL) and cm . H NMR (300 MHz, CDCl
2
, C-9), 30.7 (CH
2
ꢀ
ꢂ1
1
) d 6.49 (dd, J5,6 ¼ 5.8, J4,5 ¼ 3.0
3
3
0% H
to warm to room temperature and stirred overnight. The reac- (m, 1H, H-6N), 6.05 (dd, J5,6 ¼ 5.7, J1,6 ¼ 3.1 Hz, 1H, H-6X), 3.93
tion mixture was diluted with water (10 mL) and extracted with (br s, 1H, H-2N), 3.58 (t, J9,10 ¼ 6.5 Hz, 2H, H-10N), 3.54 (t, J9,10
Et
O (3 ꢃ 15 mL). The combined organic layers were washed 6.3 Hz, 2H, H-10X), 3.36 (br s, 1H, H-2X), 2.91 (br s, 1H, H-1N),
with NH Cl (15 mL) and brine (15 mL) and dried over anhydrous 2.68 (br s, 1H, H-1X), 2.66 (br s, 1H, H-4X), 2.51 (br s, 1H, H-4N),
Na SO
. The solvent was removed under reduced pressure at 1.98–1.77 (m, 7H, H-7aX, H-9X, H-8N and H-9N), 1.68–1.49 (m,
C, and the crude was puried by column chromatography 5H, H-3X, H-7bX, OH-X and H-7N), 1.47–1.28 (m, 2H, H-8X),
2
O
2
(3 mL) under nitrogen atmosphere, and then allowed Hz, 1H, H-5N), 6.13 (dd, J5,6 ¼ 5.7, J4,5 ¼ 2.7 Hz, 1H, H-5X), 6.11
¼
2
4
2
4
ꢀ
0
1
3
(
pentane/Et
alcohols 3b–3h) to afford the corresponding alcohol (3a–3i).
Bicyclo[2.2.1]hept-5-en-2-ol (3a). Alcohol 3a was obtained as (CH, C-2N), 78.8 (CH, C-2X), 51.0 (CH, C-4X), 50.2 (CH, C-3N),
a mixture of diastereomers according to the general procedure 49.8 (CH, C-3X), 48.3 (CH, C-1N), 47.4 (CH, C-4N), 46.6 (CH , C-
, C-10X and C-10N), 44.5 (CH,
, C-8N), 31.5 (2CH , C-9X and C-9N), 30.7 (CH
C-8X). HRMS (APCI) calcd for C10
2
O for alcohols 3a and 3i and hexane/AcOEt for 1.04–0.96 (m, 1H, H-3N). C NMR (75 MHz, CDCl
3
) d 141.1 (CH,
C-5N), 137.0 (CH, C-5X), 134.2 (CH, C-6X), 131.8 (CH, C-6N); 79.6
2
C, using vinylboronate 1a (0.28 mmol) and cyclopentadiene 7X), 45.2 (CH
2
, C-7N), 45.1 (2CH
2
ꢀ
(0.84 mmol). Diels–Alder reaction step conditions: 1 h at 170 C. C-1X), 31.8 (CH
2
2
2
,
+
Overall l yield: 93% (28.6 mg), endo/exo 39 : 61.
H15ClO (M + H–H O)
2
3
-Propyl-bicyclo[2.2.1]hept-5-en-2-ol (3b). Alcohol 3b was 169.0779, found 169.0810.
obtained as a mixture of diastereomers according to the general
Methoxymethyl-bicyclo[2.2.1]hept-5-en-2-ol (3d). Alcohol 3d
procedure C, using alkenylboronate 1b (0.22 mmol) and cyclo- was obtained as a mixture of diastereomers according to the
pentadiene (0.66 mmol). Diels–Alder reaction step conditions: general procedure C, using alkenylboronate 1d (0.22 mmol) and
ꢀ
2
4 h at 170 C. Overall yield: 79% (26.1 mg), endo/exo 15 : 85.
cyclopentadiene (0.66 mmol). A small fraction of exo diaste-
Alcohols 3b-X and 3b-N (yellowish oil). IR (lm) nmax 3404, reomer could be separated and characterized. Diels–Alder
ꢂ1
1
ꢀ
2
957, 2922, 2851, 2358, 1717, 1024, 849, 667 cm . H NMR (300 reaction step conditions: 24 h at 170 C. Overall yield: 82% (27.8
) d 6.48 (dd, J5,6 ¼ 5.6, J4,5 ¼ 3.1 Hz, 1H, H-5N), 6.11 mg), endo/exo 12 : 88.
dd, J5,6 ¼ 5.7, J4,5 ¼ 2.6 Hz, 1H, H-5X), 6.09 (m, 1H, H-6N), 6.02
Alcohol 3d-X (major compound, yellowish oil). IR (lm) nmax
dd, J5,6 ¼ 5.7, J1,6 ¼ 3.1 Hz, 1H, H-6X), 3.91 (br s, 1H, H-2N), 3.33 3400, 2970, 2920, 2891, 2872, 2850, 1109, 1033, 717 cm . H
br s, 1H, H-2X), 2.89 (br s, 1H, H-1N), 2.67 (br s, 1H, H-1X), 2.65 NMR (300 MHz, CDCl
) d 6.11 (dd, J5,6 ¼ 5.7, J1,6 ¼ 2.7 Hz, 1H, H-
MHz, CDCl
3
(
(
(
(
7
8
ꢂ1
1
3
br s, 1H, H-4X), 2.50 (br s, 1H, H-4N), 1.79 (d, J7a,7b ¼ 8.5, 1H, H- 5), 6.06 (dd, J5,6 ¼ 5.5, J4,5 ¼ 3.3 Hz, 1H, H-6), 3.43 (br s, 1H, H-2),
aX), 1.66–1.56 (m, 2H, H-3X and H-7bX), 1.54–1.07 (m, 10H, H- 3.33 (s, 3H, H-9), 3.22 (dd, Jgem ¼ 14.4, J3,8 ¼ 8.0 Hz, 1H, H-8),
X, H-9X, H-7N, H-8N and H-9N), 1.02–0.98 (m, 1H, H-3N), 0.93 3.19 (dd, Jgem ¼ 14.4, J3,8 ¼ 7.9 Hz, 1H, H-8), 2.78 (br s, 1H, H-4),
(
t, J9,10 ¼ 7.2 Hz, 3H, H-10N), 0.90 (t, J9,10 ¼ 6.9 Hz, 3H, H-10X). 2.71 (br s, 1H, H-1), 1.90 (m, 1H, H-3), 1.85 (br d, J7a,7b ¼ 8.5 Hz,
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1
H, H-7b), 1.75 (br s, 1H, OH), 1.66 (dd, J7a,7b ¼ 8.5, J2,7a ¼ 1.6 7.09 (m, 2H, ArH-X), 6.63 (dd, 1H, J5,6 ¼ 5.9, J4,5 ¼ 3.3 Hz, H-5N),
13
Hz, 1H, H-7a). C NMR (75 MHz, CDCl ) d 137.1 (CH, C-5), 6.25 (dd, 1H, J5,6 ¼ 5.8, J ¼ 3.0 Hz, H-6N), 6.16 (dd, 1H, J
¼
3
1,6
5,6
1
5
34.4 (CH, C-6), 76.2 (CH, C-2), 75.8 (CH , C-8), 58.8 (CH , C-9), 5.7, J4,5 ¼ 3.3 Hz, H-5X), 6.04 (br d, 1H, J ¼ 5.70 Hz, H-6X), 4.35
2
3
5,6
0.7 (CH, C-3), 50.5 (CH, C-1), 46.7 (CH , C-7), 43.1 (CH, C-4).
(br s, 1H, H-2N), 3.98 (br s, 1H, H-2X), 3.03 (br s, 1H, H-4N), 2.99
2
Alcohols 3d-X and 3d-N (yellowish oil). IR (lm) nmax 3415, (br s, 3H, H-3X, H-4X and H-1N), 2.83 (br s, 1H, H-1X), 2.32 (t,
059, 2970, 2922, 2872, 2827, 1134, 1111, 1083, 1035, 985, 918, 1H, J2,3 ¼ J3,4 ¼ 3.0 Hz, H-3N), 2.04 (br d, 1H, J7a,7b ¼ 8.6 Hz, H-
3
7
3
6
ꢂ1
1
17 cm . H NMR (300 MHz, CDCl
3
) d 6.47 (dd, J5,6 ¼ 5.7, J1,6
¼
7aX), 1.76 (br d, J7a,7b ¼ 8.6 Hz, 1H, H-7bX), 1.76–1.60 (m, 2H, H-
13
.3 Hz, 1H, H-5N), 6.13 (dd, J5,6 ¼ 5.7, J4,5 ¼ 2.9 Hz, 1H, H-6N), 7N). C NMR (75 MHz, CDCl
3
) d 141.8 (2C, Ar-X and Ar-N), 141.2
.11 (dd, J5,6 ¼ 5.7, J1,6 ¼ 2.7 Hz, 1H, H-5X), 6.06 (dd, J5,6 ¼ 5.5, (CH, C-5N), 137.3 (CH, C-6X), 134.2 (CH, C-5X), 132.9 (CH, C-
J4,5 ¼ 3.3 Hz, 1H, H-6X), 4.00 (br s, 1H, H-2N), 3.56–3.49 (m, 1H, 6N), 131.8 (C, Ar-X), 129.1 (2CH, Ar-X), 128.5 (4CH, Ar-N), 128.1
H-8N), 3.43 (br s, 1H, H-2X), 3.36 (s, 3H, H-9N), 3.40–3.33 (m, (2CH, Ar-X), 80.9 (C, C-2N), 79.5 (C, C-2X), 54.8 (CH, C-3N), 54.6
1
1
H, H-8N), 3.33 (s, 3H, H-9X), 3.21 (dd, Jgem ¼ 17.0, J ¼ 8.0 Hz, (CH, C-3X), 51.3 (CH, C-1X), 48.6 (CH, C-4N), 47.9 (CH, C-1N),
3,8
H, H-8X), 3.18 (dd, Jgem ¼ 17.1, J3,8 ¼ 7.9 Hz, 1H, H-8X), 2.93 (br 47.3 (CH
2
, C-7X), 47.0 (CH, C-4X), 45.7 (CH
2
, C-7N), C-8N not
12Cl (M H–
s, 1H, H-1N), 2.78 (br s, 1H, H-4X), 2.71 (br s, 1H, H-1X), 2.65 (br detected. HRMS (APCI) calcd for
O)+203.0628, found 203.0586.
3-(3-(Triuoromethyl)phenyl)bicyclo[2.2.1]hept-5-en-2-ol (3g).
Alcohol 3g was obtained as a mixture of diastereomers according
C
13
H
+
s, 1H, H-4N), 1.9 (m, 1H, H-3X), 1.85 (br d, J7a,7b ¼ 8.5 Hz, 1H, H-
H
2
7
1
X), 1.76 (br s, 1H, OH-X), 1.66 (dd, J7a,7b ¼ 8.5, J3,7a ¼ 1.6 Hz,
13
H, H-7X), 1.48 (m, 2H, H-7N), 1.43–1.29 (m, 1H, H-3N).
C
NMR (75 MHz, CDCl ) d 140.5 (CH, C-5N), 137.1 (CH, C-5X), to the general procedure C, using alkenylboronate 1g (0.27 mmol)
3
1
2
34.4 (CH, C-6X), 132.4 (CH, C-6N), 76.7 (CH, C-2N), 76.2 (CH, C- and cyclopentadiene (0.81 mmol). Diels–Alder reaction step
ꢀ
X), 75.8 (CH , C-8X), 75.7 (CH , C-8N), 58.9 (CH , C-9N), 58.8 conditions: TFA (5 mol %), 72 h at 80 C. Overall yield: 97% (30.0
2
2
3
(
4
4
CH
3
, C-9X), 50.8 (CH, C-3N), 50.7 (CH, C-3X), 50.5 (CH, C-1X), mg), endo/exo 9 : 91.
8.0 (CH, C-1N), 46.7 (CH , C-7X), 45.2 (CH , C-7N), 44.9 (CH, C- Alcohols 3g-X and 3g-N (yellowish oil). IR (lm) nmax 3343,
N), 43.1 (CH, C-4X). HRMS (APCI) calcd for C 13O (M + H– 3308, 2970, 2916, 2359, 2344, 1331, 1165, 1124, 1074, 1034, 795,
2
2
9
H
+
ꢂ1
1
H
2
O) 137.0961, found 137.0938.
-Phenylbicyclo[2.2.1]hept-5-en-2-ol (3e). Alcohol 3e was ArH-X and ArH-N), 6.65 (dd, J5,6 ¼ 5.4, J4,5 ¼ 3.1 Hz, 1H, H-5N),
obtained as a mixture of diastereomers according to the general 6.27 (dd, J5,6 ¼ 5.4, J ¼ 2.8 Hz, 1H, H-6N), 6.20 (dd, J ¼ 5.7,
3
721, 669 cm . H NMR (300 MHz, CDCl ) d 7.71–7.31 (m, 8H,
3
1,6
5,6
procedure C, using alkenylboronate 1e (0.20 mmol) and cyclo- J1,6 ¼ 3.3 Hz, 1H, H-6X), 6.05 (dd, J ¼ 5.7, J ¼ 2.7 Hz, 1H, H-
5,6
4,5
pentadiene (0.60 mmol). Diels–Alder reaction step conditions: 5X), 4.39 (m, 1H, H-2N), 4.03 (br s, 1H, H-2X), 3.07 (m, 2H, H-3X
ꢀ
TFA (5 mol %), 72 h at 80 C. Overall yield: 37% (13.8 mg), endo/ and H1–N), 3.04 (br s, 2H, H-4X and H-4N), 2.85 (br s, 1H, H-1X),
exo 13 : 87.
2.10 (m, 1H, H-3N), 2.06 (br d, J7a,7b ¼ 8.8 Hz, 1H, H-7aX), 1.90
Alcohols 3e-X and 3e-N (yellowish oil). IR (lm) nmax 3061, (br s 1H, OH-X), 1.82–1.76 (m, 1H, H-7bX), 1.76–1.63 (m, 2H, H-
ꢂ1
1
13
3
3323, 2968, 2939, 2922, 1033, 746, 717, 698 cm . H NMR (300 7N). C NMR (75 MHz, CDCl ) d 144.5 (C, Ar-N), 144.3 (C, Ar-X),
MHz) d 7.39–7.14 (m, 10H, ArH-X and ArH-N), 6.64 (dd, J5,6
¼
141.0 (CH, C-5N), 137.2 (CH, C-5X), 134.4 (CH, C-6X), 133.1 (CH,
5
6
5
3
1
.7, J4,5 ¼ 3.2 Hz, 1H, H-5N), 6.25 (dd, J ¼ 5.7, J ¼ 2.9 Hz, H- C-6N), 131.2 (CH, Ar-X), 130.3 (C, JC,F ¼ 32.0 Hz, Ar-X), 129.7
5,6
1,6
N), 6.20 (dd, J5 ¼ 5.7, J ¼ 3.3 Hz, 1H, H-5X), 6.07 (br d, J
¼
(CH, Ar-N), 128.9 (CH, Ar-N), 128.4 (CH, Ar-X), 126.1 (CH, Ar-N),
,6
5,4
5,6
.7 Hz, 1H, H-6X), 4.42 (br s, 1H, H-2N), 4.04 (br s, 1H, H-2X), 124.6 (CH, Ar-N), 124.5 (CH, JC,F ¼ 3.5 Hz, Ar-X), 122.9 (CH, J
C,F
.02 (br s, 4H, H-3X, H-4X, H-1N and H-4N), 2.83 (br s, 1H, H- ¼ 3.9 Hz, ArX), 122.4 (CH, Ar-N), 80.8 (CH, C-2N), 79.4 (CH, C-
X), 2.36 (t, J2,3 ¼ J3,4 ¼ 3.0 Hz, 1H, H-3N), 2.05 (br d, J7a,7b ¼ 8.3 2X), 55.1 (CH, C-3N), 55.0 (CH, C-3X), 51.4 (CH, C-1X), 48.6 (CH,
Hz, 1H, H-7aX), 1.79 (br d, J7a,7b ¼ 8.5 Hz, 1H, H-7aN), 1.76 (br d, C-4N), 47.3 (CH
2
, C-7X), 47.8 (CH, C-1N), 47.0 (CH, C-4X), 45.7
) d ꢂ62.6. HRMS (APCI)
O) 237.0886, found 237.0902.
2-Phenylbicyclo[2.2.1]hept-5-en-2-ol (3h). Alcohol 3h was
2CH, Ar-N), 128.0 (2CH, Ar-X), 127.8 (2CH, Ar-X), 127.2 (2CH, obtained as a mixture of diastereomers according to the general
Ar-N), 126.0 (2CH, Ar-X and Ar-N), 80.7 (CH, C-2N), 79.4 (CH, C- procedure C using alkenylboronate 1h (0.17 mmol) and cyclo-
X), 55.4 (CH, C-3X), 55.3 (CH, C-3N), 51.3 (CH, C-1X), 48.6 (CH, pentadiene (0.51 mmol). A small fraction of exo diastereomer
1
3
19
J
7a,7b ¼ 8.3 Hz, 1H, H-7bX), 1.67–1.61 (m, 1H, H-7bN). C NMR (CH, C-7N). F NMR (282 MHz, CDCl
3
+
(75 MHz) d 143.8 (C, Ar-N), 143.3 (C, Ar-X), 141.3 (CH, C-5N), calcd for C14
12 3 2
H F (M + H – H
137.6 (CH, C-6X), 134.0 (CH, C-5X), 132.9 (CH, C-6N), 128.5
(
2
C-1N), 48.1 (CH, C-4N), 47.3 (CH
CH , C-7N). HRMS (APCI) calcd for C13
69.1012, found 169.1041.
-(4-Chlorophenyl)bicyclo[2.2.1]hept-5-en-2-ol (3f). Alcohol
2
, C-7X), 47.1 (CH, C-4X), 45.7 could be separated and characterized. Diels–Alder reaction step
+
ꢀ
(
1
2
H
13 (M + H–H
2
O)
conditions: 12 h at 80 C. Overall yield: 100% (28.8 mg), endo/
exo 6 : 94.
ꢀ
3
Alcohol 3h-X (major compound, white solid, mp 62.5–63.0 C).
3
f was obtained as a mixture of diastereomers according to the IR (KBr) nmax 3364, 2986, 2970, 2945, 1493, 1447, 1274, 1061,
ꢂ1
1
general procedure C, using alkenylboronate 1f (0.17 mmol) and 1028, 989, 894, 758, 721, 698 cm . H NMR (300 MHz, CDCl ) d
3
cyclopentadiene (0.51 mmol). Diels–Alder reaction conditions: 7.43–7.19 (m, 5H, ArH), 6.17 (dd, J5,6 ¼ 5.6, J ¼ 3.0 Hz, 1H, H-
4,5
ꢀ
TFA (5 mol %), 72 h at 80 C. Overall yield: 28% (10.5 mg), endo/ 5), 5.78 (dd, J5,6 ¼ 5.6, J1,6 ¼ 3.1 Hz, 1H, H-6), 3.08–3.03 (m, 1H,
exo 13 : 87.
H-1), 2.98 (br s, 1H, H-4), 2.16 (br d, J7a,7b ¼ 8.6 Hz, 1H, H-7b),
Alcohols 3f-X and 3f-N (yellowish oil). IR (lm) nmax 3361, 3340, 2.13 (dd, J3n,3x ¼ 12.2, J3n,4 ¼ 2.3 Hz, 1H, H-3
n
), 2.03 (dd, J3n,3x
), 1.95 (br s, 1H, OH), 1.75–1.68 (m,
NMR (300 MHz) d 7.31–7.19 (m, 6H, ArH-X and ArH-N), 7.14– 1H, H-7a). C NMR (75 MHz, CDCl ) d 146.6 (C, Ar), 138.9
¼
ꢂ1
1
2
964, 2916, 2848, 1490, 1091, 1033, 1012, 798, 727 cm . H 12.2, J3x,4 ¼ 3.5 Hz, 1H, H-3
x
1
3
3
36398 | RSC Adv., 2014, 4, 36385–36400
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(
(
(
CH, C-5), 134.5 (CH, C-6), 128.1 (2CH, Ar), 127.0 (3CH, Ar), 82.7
C, C-2), 54.3 (CH, C-1), 48.2 (CH , C-7), 43.1 (CH , C-3), 41.9
CH, C-4).
3 J. E. Moore, M. York and J. P. A. Harrity, Synlett, 2005, 0860–
0862.
4 M. D. Helm, J. E. Moore, A. Plant and J. P. A. Harrity, Angew.
Chem., Int. Ed., 2005, 44, 3889–3892.
5 P. M. Delaney, J. E. Moore and J. P. A. Harrity, Chem.
Commun., 2006, 3323–3325.
2
2
Alcohols 3h-X and 3h-N (white solid). IR (KBr) nmax 3366, 2970,
ꢂ1
2
945, 1491, 1447, 1274, 1061, 1028, 989, 895, 758, 721, 698 cm
.
1
3
H NMR (300 MHz, CDCl ) d 7.63–7.19 (m, 10H, ArH-X and ArH-
N), 6.58 (dd, J5,6 ¼ 5.7, J1,6 ¼ 3.0 Hz, 1H, H-6N), 6.33 (dd, J5,6
¼
6 M. D. Helm, A. Plant and J. P. A. Harrity, Org. Biomol. Chem.,
2006, 4, 4278–4280.
7 E. Gomez-Bengoa, M. D. Helm, A. Plant and J. P. A. Harrity, J.
Am. Chem. Soc., 2007, 129, 2691–2699.
5
.7, J4,5 ¼ 3.0 Hz, 1H, H-5N), 6.17 (dd, J5,6 ¼ 5.6, J4,5 ¼ 3.0 Hz,
H, H-5X), 5.78 (dd, J5,6 ¼ 5.6, J1,6 ¼ 3.1 Hz, 1H, H-6X), 3.24–3.20
1
(m, 1H, H-4N), 3.08–3.03 (m, 1H, H-1X), 2.98 (br s, 2H, H-4X and
H-1N), 2.49 (dd, J3x,3n ¼ 12.6, J
¼ 3.7 Hz, 1H, H-3 N), 2.16 (br
8 M. D. Helm, A. Plant and J. P. A. Harrity, Synlett, 2007, 2885–
2887.
9 D. L. Browne, M. D. Helm, A. Plant and J. P. A. Harrity, Angew.
Chem., Int. Ed., 2007, 46, 8656–8658.
10 P. M. Delaney, J. Huang, S. J. F. Macdonald and
J. P. A. Harrity, Org. Lett., 2008, 10, 781–783.
3x,4
x
d, J7a,7b ¼ 8.6 Hz, 1H, H-7bX), 2.13 (dd, J
¼ 12.2, J
¼ 2.3
3n,3x
3n,4
Hz, 1H, H-3
n
X), 2.03 (dd, J3n,3x ¼ 12.2, J3x,4 ¼ 3.5 Hz, 1H, H-3
x
X),
1.95 (br s, 1H, OH-X), 1.83 (br s, 1H, OH–N), 1.75–1.68 (m, 1H,
1
3
H-7aX), 1.63–1.60 (m, 2H, H-7N), 1.52–1.44 (m, 1H, H-3
n
N).
C
NMR (75 MHz, CDCl ) d 146.6 (2C, Ar-X and Ar-8N), 141.3 (C, C-
3
6N), 138.9 (CH, C-5X), 134.5 (CH, C-6X), 133.6 (C, C-5N), 129.2 11 P. M. Delaney, D. L. Browne, H. Adams, A. Plant and
(
(
CH, Ar-N), 128.1 (4CH, Ar-X and Ar-N), 127.0 (3CH, Ar-X), 82.7
J. P. A. Harrity, Tetrahedron, 2008, 64, 866–873.
C, C-2X), 54.3 (CH, C-1X), 53.2 (CH, C-4N), 49.3 (CH , C-7N), 12 D. L. Browne, J. F. Vivat, A. Plant, E. Gomez-Bengoa and
2
4
8.2 (CH , C-7X), 44.8 (CH , C-3N), 43.3 (CH , C-1N), 43.1 (CH ,
J. P. A. Harrity, J. Am. Chem. Soc., 2009, 131, 7762–7769.
2
2
2
2
C-3X), 41.9 (CH, C-4X). C-2N signal missing. HRMS (ESI) calcd 13 R. S. Foster, J. Huang, J. F. Vivat, D. L. Browne and
+
for C13
H
14ONa (M + Na) 209.1250, found 209.0937.
J. P. A. Harrity, Org. Biomol. Chem., 2009, 7, 4052–4056.
45–48
2
-Methyl-bicyclo[2.2.1]hept-5-en-2-ol (3i).
Alcohol 3i was 14 D. L. Browne and J. P. A. Harrity, Tetrahedron, 2010, 66, 553–
obtained as a mixture of diastereomers according to the general
568.
procedure C using alkenylboronate 1i (0.5 mmol) and cyclo- 15 J. D. Kirkham, P. M. Delaney, G. J. Ellames, E. C. Row and
pentadiene (1.5 mmol). Diels–Alder reaction step conditions: 24
h at 170 C. Overall yield: 66% (40.9 mg), endo/exo 9 : 91.
Alcohols 3i-X and 3i-N (yellowish liquid). IR (lm) nmax 3381,
J. P. A. Harrity, Chem. Commun., 2010, 46, 5154–5156.
16 R. S. Foster, H. Jakobi and J. P. A. Harrity, Tetrahedron Lett.,
2011, 52, 1506–1508.
ꢀ
3
7
061, 2956, 2924, 2868, 2852, 1446, 1330, 1251, 1109, 939, 887, 17 J. Kirkham, A. Leach, E. Row and J. P. A. Harrity, Synthesis,
ꢂ1
1
29, 705 cm . H NMR (300 MHz, CDCl
3
) d 6.42 (dd, J5,6 ¼ 5.63,
2012, 44, 1964–1973.
J
5
5
1,6 ¼ 3.1 Hz, 1H, H-6N), 6.19 (dd, J5,6 ¼ 5.6, J4,5 ¼ 3.0 Hz, 1H, H- 18 J. D. Kirkham, S. J. Edeson, S. Stokes and J. P. A. Harrity, Org.
N), 6.12 (dd, J5,6 ¼ 5.5, J4,5 ¼ 2.9 Hz, 1H, H-5X), 6.06 (dd, J5,6
.5, J1,6 ¼ 3.2 Hz, 1H, H-6X), 2.82 (br s, 2H, H-4X and H-4N), 2.65 19 J. D. Kirkham, R. J. Butlin and J. P. A. Harrity, Angew. Chem.,
¼ 8.5 Hz, Int. Ed., 2012, 51, 6402–6405.
H, H-7X), 1.80 (dd, J3n,3x ¼ 12.2, J ¼ 3.6 Hz, 1H, H-3 N), 1.68 20 R. S. Foster, H. Jakobi and J. P. A. Harrity, Org. Lett., 2012, 14,
¼
Lett., 2012, 14, 5354–5357.
(br s, 1H, H-1N), 2.48 (br s, 1H, H-1X), 1.92 (br d, J
7a,7b
1
x
(
dd, J3n,3x ¼ 12.1, J ¼ 3.8 Hz, 1H, H-3 X), 1.59–1.48 (m, 2H, H-
4858–4861.
N), 1.56 (br d, J7a,7b ¼ 8.5 Hz, 1H, H-7X), 1.49 (s, 3H, H-8N), 21 D. S. Matteson and J. O. Waldbillig, J. Org. Chem., 1963, 28,
.28–1.21 (m, 1H, H-3 X), 1.22 (s, 3H, H-8X), 1.16 (dd, J3n,3x 366–369.
2.3, J ¼ 3.3 Hz, 1H, H-3 ) d 140.0 22 I. S. Bengelsdorf, K. Kiyoshi, G. W. Willcockson and
W. G. Woods, US Pat., 3135781, 1964.
N), 79.1 (C, C-2X), 78.5 (C, C-2N), 54.9 (CH, C-1X), 53.8 (CH, C- 23 W. G. Woods and I. S. Bengelsdorf, J. Org. Chem., 1966, 31,
N), 49.5 (CH , C-7N), 48.4 (CH , C-7X), 44.9 (CH , C-3N), 43.5 2769–2772.
x
7
1
1
n
¼
1
3
n
N). C NMR (75 MHz, CDCl
3
(CH, C-6N), 138.4 (CH, C-5X), 134.5 (CH, C-6X), 133.5 (CH, C-
5
1
2
2
2
(
2
CH , C-3X), 43.0 (CH, C-4N), 42.3 (CH, C-4X), 28.2 (CH , C-8N), 24 D. S. Matteson and M. L. Talbot, J. Am. Chem. Soc., 1967, 89,
2 3
+
7.7 (CH , C-8X). HRMS (APCI) calcd for C H O (M + H)
1123–1126.
3
8
13
125.0966, found 125.0961.
25 D. A. Evans, W. L. Scott and L. K. Truesdale, Tetrahedron
Lett., 1972, 13, 121–124.
2
6 P. Martinez-Fresneda and M. Vaultier, Tetrahedron Lett.,
989, 30, 2929–2932.
We thank CONICET, Universidad Nacional de Rosario, Uni- 27 K. Narasaka and I. Yamamoto, Tetrahedron, 1992, 48, 5743–
Acknowledgements
1
versidad Nacional del Nordeste, ANPCyT and Fundaci ´o n Jose-
na Prats for nancial support.
5754.

28 C. Rasset and M. Vaultier, Tetrahedron, 1994, 50, 3397–3406.
2
9 J. D. Bonk and M. A. Avery, Tetrahedron: Asymmetry, 1997, 8,
149–1152.
1
Notes and references
30 G. Lorvelec and M. Vaultier, Tetrahedron Lett., 1998, 39,
5185–5188.
1
D. G. Hall, Boronic acids: preparation and applications in
organic synthesis and medicine, Wiley-VCH, Weinheim, 2005. 31 R. A. Batey, A. N. Thadani and A. J. Lough, J. Am. Chem. Soc.,
G. Hilt and P. Bolze, Synthesis, 2005, 2091–2115. 1999, 121, 450–451.
2
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3
3
2 A. M. Sarotti, P. L. Pisano and S. C. Pellegrinet, Org. Biomol.
Chem., 2010, 8, 5069–5073.
3 E. Plettner, A. Mohle, M. T. Mwangi, J. Griscti, B. O. Patrick,
R. Nair, R. J. Batchelor and F. Einstein, Tetrahedron:
Asymmetry, 2005, 16, 2754–2763.
J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev,
A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski,
R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth,
P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels,
¨
O. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski,
34 H. Yamamoto and K. Ishihara, Acid catalysis in modern
organic synthesis, Wiley-VCH, Weinheim, 2008.
D. J. Fox, Gaussian 09, Revision D.01 Gaussian, Inc.,
Wallingford, CT, 2009.
35 D. G. Hall, Boronic acids: preparation and applications in 39 Y. Zhao and D. G. Truhlar, J. Phys. Chem. A, 2004, 108, 6908–
organic synthesis, medicine and materials, Wiley-VCH,
6918.
Weinheim, 2nd completely rev. edn, 2011.
40 J. Tomasi and M. Persico, Chem. Rev., 1994, 94, 2027–2094.
´
´
´
`
3
6 S. Roscales, A. Rincon, E. Buxaderas and A. G. Csak ¨y , 41 E. Cances, B. Mennucci and J. Tomasi, J. Chem. Phys., 1997,
Tetrahedron Lett., 2012, 53, 4721–4724. 107, 3032–3041.
7 S. Roscales and A. G. Cs ´a k ¨y , Org. Lett., 2012, 14, 1187–1189. 42 M. Cossi, V. Barone, R. Cammi and J. Tomasi, Chem. Phys.
8 M. J. T. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, Lett., 1996, 255, 327–335.
M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, 43 V. Barone, M. Cossi and J. Tomasi, J. Comput. Chem., 1998,
B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, 19, 404–417.
X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, 44 N. Grimblat and S. C. Pellegrinet, Org. Biomol. Chem., 2013,
J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, 11, 3733–3741.
R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, 45 C. J. Collins and B. M. Benjamin, J. Am. Chem. Soc., 1967, 89,
O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery Jr, 1652–1661.
J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, 46 A. Padwa and W. Eisenberg, J. Am. Chem. Soc., 1972, 94,
E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, 5852–5858.
3
3
J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, 47 R. L. Snowden, Helv. Chim. Acta, 1983, 66, 1031–1038.
S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, N. J. Millam, 48 T. G. Waddell, A. D. Carter, T. J. Miller and R. M. Pagni, J.
M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo,
Org. Chem., 1992, 57, 381–383.
36400 | RSC Adv., 2014, 4, 36385–36400
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