Synthesis of Densely Substituted Conjugated Dienes by Transition-Metal-Free Reductive Coupling of Allenylboronic Acids and Tosylhydrazones

Article abstract of DOI:10.1021/acs.joc.8b01104

Tosylhydrazones and allenylboronic acids underwent a transition-metal-free reductive coupling reaction. This process is suitable for synthesis of tetra- and pentasubstituted conjugated dienes. The corresponding allenyl-Bpin substrate showed a very poor re

Full text of DOI:10.1021/acs.joc.8b01104

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Note
Synthesis of Densely Substituted Conjugated Dienes by Transition-metal-
free Reductive Coupling of Allenylboronic Acids and Tosylhydrazones
Dong Wang, Martin J. M. de Wit, and Kalman J. Szabo
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01104 • Publication Date (Web): 24 May 2018
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Synthesis of Densely Substituted Conjugated Dienes by
Transition-metal-free Reductive Coupling of Allenylboronic
Acids and Tosylhydrazones
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Dong Wang, Martin J. M. de Wit and Kálmán J. Szabó*
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-10691 Stockholm, Sweden
ABSTRACT: Tosylhydrazones and allenylboronic acids underwent a transition metal-free reductive
coupling reaction. This process is suitable for synthesis of tetra- and pentasubstituted conjugated dienes.
The corresponding allenyl-Bpin substrate showed a very poor reactivity. The reaction is suggested to
involve coupling of the in situ formed diazo compound and allenylboronic acid. The intermediate
formed in this coupling undergoes allenyl migration followed by protodeboronation to furnish a
conjugated diene as major product.
Allenylboron compounds1 are useful reagents for selective introduction of propargyl, allenyl and dienyl
functional units.2 The most widespread use of these reagents is carbon-carbon bond formation with
carbonyl compounds and imines.2c However, recently even cross-coupling reactions with allenylboron
species have attracted interest in organic synthesis.1f,3 As a part of our organoboron chemistry
program,1b,4 we reported a new transition metal-catalyzed method for synthesis of allenylboronic acids.1d
We have shown that these species are more reactive and more versatile reagents than the corresponding
allenyl-Bpin compounds and other boronates.1d In a couple of recent papers we have shown that Cu- and
Pd-catalyzed cross-coupling of allylboronic acids with diazoketones can be easily performed.5 Now, our
attention turned to studying transition metal-free cross-coupling of allenylboronic acids with diazo
compounds. The groups of (Jianbo) Wang,6 Barluenga,7 Valdés,8 Ley9 and others10 have demonstrated
that transition metal-free reductive coupling of alkyl-, aryl- and alkenylboronic acids can be performed
by diazo compounds. In many of these reactions, the diazo compounds have been generated in situ, prior
to the coupling by the Bamford-Stevens reaction11 using tosylhydrazones in the presence of base. The
overall reaction can be used for homologization of alkyl, aryl and vinyl boronates (Scheme 1a). As far
as we know, this method has never been used with allenylboron reagents. We have found that the major
product of the coupling reaction of diazo compounds and allenylboronic acids are 1,3-dienes (Scheme
1b). Using trisubstituted allenylboronic acid reagents, this process is suitable for synthesis of densely
substituted dienes with high diastereoselectivity.
Initially, we reacted allenylboronic acid 1a and phenyl-tosylhydrazone 2a (precursor for the diazo
compound11) in the presence of CsF at 110 °C (Table 1, entry 1) in dioxane. The main product (38%) of
this reaction was conjugated diene 3a, in which the phenyl group (arising from 2a) and the n-butyl group
possess the E-geometry. The Z-isomer 3b was formed as a minor product (6%).
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Scheme 1. Transition Metal-Free Coupling of Tosylhydrazones and Organoboron Compounds
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We have found that the variation of the base influenced the selectivity and the yield of the reaction
(entries 1-10). When CsF was replaced by Bu4NF, the ratio of the E/Z products was improved but a new
regio-isomer, allene 4 appeared as a minor product (entry 2). We have also considered application of
organic bases, such as Et3N and DBU (entries 3-4). The yield and selectivity was poor with Et3N (entry
3), but application of DBU substantially improved the yield of 3a, albeit the selectivity decreased by
formation of a considerable amount of allenyl product 4 (entry 4). Application of strong inorganic bases,
such as NaOMe and KOH, led to poor yields (entries 5 and 6). Although, using Na2CO3 (entry 7) was
inefficient, application of Cs2CO3 (entry 8) and K2CO3 (entry 9) led to improved yields (up to 49%) and
selectivities. The relatively high temperature (110 °C) was important for the successful generation of the
diazo compound intermediate from 2a.12 When the reaction was carried out at 80 °C, the yield was
sharply decreased (entry 10). The reaction can also be performed in toluene (entry 11). However, we
found that addition of small amounts (10 equiv) of water improved the yields (entries 13, 15 and 16),
and therefore we employed dioxane (miscible with water) in the further applications. Addition of water
increased the solubility of K2CO3 in dioxane, which led to increased yield (entry 13). Increasing of the
amount of K2CO3 (to 3 equiv) and application of water increased the yield to 68% (entries 13-14). Valdés
and co-workers,8b recommended use of a combination of K2CO3 and CsF in related reactions. Although,
the exact reason for the better performance of using K2CO3 and CsF together (instead of using solely
K2CO3) was not clarified, the yield was increased (68%), when we used K2CO3/CsF mixture (entry 14).
The highest yields and selectivities were achieved by using this combination of bases and addition of
small amounts of water (entries 15-16). Using these conditions, the coupling reaction of 1a and 2a could
be performed in half an hour, affording a single diasteoremer of diene 3a with 88% yield together with
traces of allene 4 (Table 1).
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Table 1. Screening of the Conditions for the Reductive Coupling of Allenylboronic Acid 1a and
Tosylhydrazone 2aa
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a In a typical reaction 0.1 mmol tosylhydrazone 2a, 0.15 mmol allenylboronic acid 1a, 1.5 equiv of base,
0.5 mL solvent, 4 h. b The yield was determined by GC-MS using benzyl acetate as an internal standard.
c The reactions were performed with 3.0 equiv K2CO3. d The reaction time was 0.5 h. (nd = not detected).
When the coupling reaction was performed with Bpin derivative 5 instead of allenylboronic acid 1a
(Scheme 2), using the above optimal conditions, the yield of 3a was very poor (10%). This finding is in
line with the observation by J. Wang and co-workers6b that phenylboronic acid (or boroxine) reacted
readily with diazoesters, while the corresponding phenyl-Bpin compound was not efficient in the cross-
coupling reaction.
Scheme 2. Reaction of Allenylboronic Acid Pinacol Ester 5 and Tosylhydrazone 2a
Subsequently, we studied the synthetic scope of the reductive coupling (Scheme 3, Table 2) of
allenylboronic acids (1a-d) with various tosylhydrazones (2a-k) using the above described optimal
conditions. First we studied the reactions using aldimine type hydrazones 2a-e as precursors for the
corresponding diazo compound (entries 1-5). The yields were slightly dependent on the electronic
effects of the aromatic substituents. Methyl-substituted hydrazone 2b (entry 2) reacted with similar yield
(70%) as the parent compound 2a (80%, entry 1). However, in the presence of electron-donating OMe
substituent in 2c (entry 3), the yield dropped (56%). The yields were improved (to 77%), when the
reaction was performed with tosylhydrazones (2d-e) bearing electron-withdrawing substituents (entries
4-5). Not only aromatic but even aliphatic hydrazones could be used as substrates. For example, 2f with
allenylboronic acid 1a gave product 3g with 55% yield. In this reaction, a substantial amount (13%) of
the E-isomer was also formed, but it could be separated from 3g by chromatography.
Scheme 3. Cross-Coupling of Allenylboronic Acids and Tosylhydrazones in the Presence of Base
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Table 2. Scope of the Reductive Coupling of Tosylhydrazones and Allenylboronic Acidsa
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aUnless otherwise stated, 0.1 mmol tosylhydrazone, 0.15 mmol boronic acid, 0.3 mmol K2CO3, 0.15
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mmol CsF, 1 mmol H2O and 0.5 mL 1,4-dioxane, 110 C. Performed at 1 mmol reaction scale.
cPerformed at 100 oC; 13% of the E diastereomer was separated. d Performed without H2O. eThe product
f
was contaminated with 7% of the E diastereomer. Performed using 3 equiv of boronic acid added in
g
two portions. The product is a mixture of Z/E diastereomers (C3-C4) in a 1:1 ratio.
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The reaction could also be performed with ketimine-type tosylhydrazones 2g-k, affording
pentasubstituted conjugated dienes 3h-i (entries 7-11). The ketimine type of hydrazones 2g-k had lower
reactivity than their aldimine type of counterparts 2a-f. Therefore, the reaction time was extended from
half an hour to one or two hours. However, extension of the reaction time at 110 °C led to extensive
protodeboronation of 1a. This side reaction could be avoided by performing the reaction under water-
free conditions. Under these conditions, benzophenone based-hydrazone 2g gave pentasubstituted diene
3h with 64% yield (entry 7). Methyl or bromo substitution of the aromatic ring gave a relatively small
change in the yield of the reaction (entries 8-9). In case of diene product 3j, we could not remove the
minor component (7%) of the Z-isomer by silica gel chromatography. Ketimine-type cyclic
tosylhydrazones 2j-k were also considered as substrates (entries 10-11). In the case of indane-type
substrate 2j, we obtained the corresponding pentasubstituted diene 3k with satisfactory yield (63%, entry
11). However, the reaction with 2k required longer reaction time, and substantial protodeboronation of
1a occurred. The best yield (35%) was obtained by elongation of the reaction time to 2 hours and
application of 3 equiv of 1a (entry 11). We have also varied the allenylboronic acid component of the
coupling reaction (entries 12-14). When cyclohexane-based substrates 1b-c were used, the
corresponding dienes 3m-n were formed in up to 69% yield (entries 12-13). In the above reactions,
achiral allenylboronic acids 1a-c were used as substrates. When the reaction was performed with racemic
allenylboronic acid 1d (entry 14), an (inseparable) mixture of isomeric dienes 3o was formed in 59%
yield. The reaction could be scaled up to 1 mmol scale with a slight decrease of the yield (65%, entry
1). The reductive coupling of 1a and 2a can be performed by in situ generation of the tosylhydrazone
component 2a.8c In this one-pot sequence benzaldehyde and tosylhydrazide was reacted to form 2a in
situ, followed by addition of 1a, K2CO3, CsF and a small amount of water, yielding 3a in 58% yield
(Scheme 4).
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Considering the above, the coupling reaction can be performed for aliphatic, aromatic and ketimine
type of tosylhydrazones. However, the reaction requires relatively harsh conditions, such as 110°C and
presence of strong base for generation of the diazo compound intermediate (see below). This method
imposes limitation to the functional group tolerance of the process. Tosylhydrazones with base and
thermosensitive functional groups cannot be applied. However, development of new (mild)
methodology for in situ generation of diazo compounds and/or appearance of new methodology for
synthesis of functionalized allenylboronic acids,1d will certainly broaden the synthetic scope of the above
reaction.
Scheme 4. One-Pot Reductive Coupling
Based on the above results and on the studies presented on the coupling of diazo compounds with
alkyl, vinyl and arylboronic compounds,6a,6b 7,8b,8c,9d,9e,10a we propose a mechanism of the reaction of
tosylhydrazones and allenylboronic acids in Scheme 5. For the sake of clarity, we exemplified the
process for the coupling of 1a and 2a. The first step of the reaction is base-mediated formation of the
diazo compound from 2a under thermal conditions.11 The next step is the electrophilic attack of the
boron atom of 1a in the diazo compound affording 6. According to DFT modelling studies for related
substrates by Valdés and co-workers,8c this reaction may proceed via a cyclic TS with relatively low
activation energy. The Lewis-acidity of the boron is apparently influenced by the steric effects of the
substituents. A relatively slow reaction by allenyl-Bpin compound 5 (Scheme 2) can be explained by the
steric effects of the pinacol moiety. The allenyl moiety of 6 undergoes a Matteson-type13 migration to
give homoallenylboronic acid 7. Ley,9c Pastre,9e and their co-workers have shown that a similar process
occurred when a diazo compound (TMS-CHN2) and vinylboronic acids were reacted. In these reactions,
allylboronic acids were formed, which could be trapped by aldehydes or indole derivatives.9c,9e
Homoallenylboronic acids (such as 7), similarly to allylboronic acids, are probably very reactive and
oxygen sensitive species,4b,4d which are difficult to observe as reaction intermediates under harsh
reaction conditions (110°C, in the presence of strong bases) by spectroscopical methods (such as NMR).
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Therefore, we attempted to intercept 7 with various electrophiles (i.e., benzaldehyde and indole), but
these reactions were not fruitful. The possible reasons are the high reactivity of 1a with electrophiles,
and/or the high temperature required for the in situ formation of the diazo compound. As far as we know,
the above reaction is the first one, in which migration of the allenyl moiety was suggested in a boronic
acid ate-complex, such as 6. The thermal protodeboronation of 7 gives the final products. Apparently,
the protonation at the -position is easier than at the -position of 7, as the major product of the reaction
is diene 3a. To verify this hypothesis, we performed the coupling reaction of 1a and 2a in the presence
of D2O instead of H2O (Scheme 6). In this reaction we observed 67% deuterium uptake at the -position
in diene 3a. This finding indicates a -protodeboronation mechanism of 7 for formation of the conjugated
diene product 3a (Scheme 5). The stereoselectivity of the protodeboronation is probably dependent on
the substituent pattern of 7, which leads to variation of the E/Z selectivity of the products.
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Scheme 5. Proposed Mechanism of the Reductive Coupling Reaction Exemplified by Allenylboronic
Acid 1a and Tosylhydrazone 2a
Scheme 6. Deuterium Isotope Experiment
In summary, we have reported a new reaction of tosylhydrazones with allenylboronic acids in the
presence of base. This coupling reaction can be carried out under thermal conditions without using
transition metal catalysis. The reaction is suitable for synthesis of densely substituted conjugated dienes.
The reaction is suggested to take place via diazo compound intermediate. The key step of the reaction
is probably migration of the allenyl group from the boron to the diazocarbon atom.
EXPERIMENTAL SECTION
General Information. All reactions were performed under argon atmosphere unless otherwise stated.
Allenylboronic acids 1a-d,1d allenylboronic acid pinacol ester 51b and tosylhydrazones 2a-k14 were
prepared according to published literature procedures. All other chemicals unless otherwise stated were
obtained from commercial sources and used as received. 1H NMR and 13C NMR spectra were recorded
on a Bruker Ascend 400 MHz spectrometer. Chemical shifts are reported relative to the residual solvent
signals (CDCl3 7.26 ppm for 1H, 77.16 ppm for 13C). The following abbreviations are used to designate
signal multiplicity: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, dd = doublet of doublet,
ddd = doublet of doublet of doublet, dt = doublet of triplet, td = triplet of doublet. Gas Chromatography-
Mass Spectrometry (GC-MS) analysis was performed on a Shimadzu GCMS-QP2020 instrument. High
resolution mass (HRMS) data were recorded on a micrOTOF instrument using ESI or APCI ionization
method. For column chromatography, silica gel (35-70 microns) was used.
General Procedure A for the Transition Metal-Free Reductive Coupling of Allenylboronic
Acids and Tosylhydrazones. A flask filled with allenylboronic acid (0.15 mmol) was charged with
potassium carbonate (42.0 mg, 0.3 mmol), cesium fluoride (23.0 mg, 0.15 mmol) and tosylhydrazone
(0.1 mmol). Water (18.0 µL, 1.0 mmol) and 1,4-dioxane (0.5 ml) was added to the mixture. Then the
reaction vial was placed in an oil bath at 110 °C and the reaction mixture was stirred vigorously. After
30 min the reaction mixture was allowed to cool down to room temperature, filtered and concentrated
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to yield the crude product. The crude mixture was purified by column chromatography. The products
are isolated as a colorless oils.
Procedure for One-Pot Reductive Coupling of Allenylboronic Acids and Carbonyl Compounds.
A solution of benzaldehyde (10.6 mg, 0.1 mmol) and tosylhydrazide (18.6 mg, 0.1 mmol) in 0.4 mL of
1,4-dioxane was stirred at 80 ºC for 90 min. Then the reaction mixture was allowed to reach room
temperature. Subsequently, potassium carbonate (42.0 mg, 0.3 mmol), cesium fluoride (23.0 mg, 0.15
mmol), water (16.2 µL, 0.9 mmol) and a solution of allenylboronic acid in 1,4-dioxane (1.5 M, 0.1 mL)
were added to the reaction under Ar. The reaction mixture was placed in an oil bath under 110 °C and
stirred vigorously. After 30 min the reaction mixture was allowed to cool down to room temperature,
filtered and concentrated to yield the crude product. Purification of the crude mixture by column
chromatography afforded the product as a colorless oil.
(Z)-(2-(2-methylprop-1-en-1-yl)hex-1-en-1-yl)benzene (3a). The title compound was prepared
according to the general procedure A. Product 3a was isolated in 80% yield (17.0 mg) as a colorless
oil using cyclohexane as eluent for column chromatography. 1H NMR (400 MHz, CDCl3): δ 7.38 –
7.32 (m, 2H), 7.26 – 7.19 (m, 2H), 7.15 – 7.08 (m, 1H), 6.23 (s, 1H), 5.75 (s, 1H), 2.20 (t, J = 7.5 Hz,
2H), 1.75 (d, J = 1.5 Hz, 3H), 1.50 – 1.26 (m, 7H), 0.92 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ 140.7, 138.9, 134.7, 128.5, 128.1, 126.2, 125.9, 124.1, 39.6, 30.7, 25.8, 22.7, 19.7, 14.2.
HRMS (pos. APCI) m/z: Calcd for C16H23 [M+H]+ 215.1794. Found 215.1792. The connectivity of
compound 3a was determined by 1H NMR, 13C NMR, and COSY analysis. The stereochemistry of the
double bond was determined by dNOE experiments. Considering the spectral similarities in the diene
products, we assigned the same stereochemistry for dienes 3c-k and 3m-o. The deuterium isotope
labelling experiment (Scheme 6) was carried out using general procedure A, except that D2O was used
instead of H2O.
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Scheme 7. The Stereochemistry of 3a Determined by dNOE Experiments
(Z)-1-methyl-4-(2-(2-methylprop-1-en-1-yl)hex-1-en-1-yl)benzene (3c). The title compound was
prepared according to the general procedure A. Product 3c was isolated in 70% yield (16.0 mg) as a
1
colorless oil using cyclohexane as eluent for column chromatography. H NMR (400 MHz, CDCl3): δ
7.25 (d, J = 8.1 Hz, 2H), 7.05 (d, J = 8.1 Hz, 2H), 6.20 (s, 1H), 5.75 (s, 1H), 2.30 (s, 3H), 2.19 (t, J =
7.4 Hz, 2H), 1.76 (d, J = 1.5 Hz, 3H), 1.48 – 1.28 (m, 7H), 0.92 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (101
MHz, CDCl3) δ 139.7, 136.0, 135.5, 134.5, 128.8, 128.4, 126.1, 124.3, 39.6, 30.8, 25.8, 22.7, 21.3, 19.7,
14.2. HRMS (pos. APCI) m/z: Calcd for C17H25 [M+H]+ 229.1951. Found 229.1955.
(Z)-1-methoxy-4-(2-(2-methylprop-1-en-1-yl)hex-1-en-1-yl)benzene (3d). The title compound was
prepared according to the general procedure A. Product 3d was isolated in 56% yield (13.7 mg) as a
1
colorless oil using pentane/EtOAc (30:1) as eluent for column chromatography. H NMR (400 MHz,
CDCl3): δ 7.30 (d, J = 8.7 Hz, 2H), 6.78 (d, J = 8.8 Hz, 2H), 6.17 (s, 1H), 5.73 (s, 1H), 3.79 (s, 3H),
2.18 (t, J = 7.6 Hz, 2H), 1.76 (d, J = 1.5 Hz, 3H), 1.53 – 1.09 (m, 7H), 0.91 (t, J = 7.2 Hz, 3H). 13C{1H}
NMR (101 MHz, CDCl3) δ 157.8, 138.7, 134.5, 131.7, 129.7, 125.6, 124.3, 113.5, 55.3, 39.6, 30.8, 25.8,
22.7, 19.7, 14.2. HRMS (pos. APCI) m/z: Calcd for C17H25O [M+H]+ 245.1900. Found 245.1903.
(Z)-1-bromo-4-(2-(2-methylprop-1-en-1-yl)hex-1-en-1-yl)benzene (3e). The title compound was
prepared according to the general procedure A. Product 3e was isolated in 77% yield (22.6 mg) as a
1
colorless oil using cyclohexane as eluent for column chromatography. H NMR (400 MHz, CDCl3): δ
7.34 (d, J = 8.5 Hz, 2H), 7.22 (d, J = 8.5 Hz, 2H), 6.16 (s, 1H), 5.70 (s, 1H), 2.18 (t, J = 7.2 Hz, 2H),
1.74 (d, J = 1.5 Hz, 3H), 1.48 – 1.28 (m, 7H), 0.92 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3)
δ 141.7, 137.9, 135.1, 131.1, 130.1, 125.0, 123.8, 119.5, 39.6, 30.6, 25.8, 22.6, 19.7, 14.2. HRMS (pos.
APCI) m/z: Calcd for C16H22Br [M+H]+ 293.0899. Found 293.0899.
(Z)-1-(2-(2-methylprop-1-en-1-yl)hex-1-en-1-yl)-4-(trifluoromethyl)benzene (3f). The title compound
was prepared according to the general procedure A. Product 3f was isolated in 68% yield (19.2 mg) as
a colorless oil using cyclohexane as eluent for column chromatography. 1H NMR (400 MHz, CDCl3): δ
7.48 – 7.42 (m, 4H), 6.25 (s, 1H), 5.74 (s, 1H), 2.21 (t, J = 7.4 Hz, 2H), 1.75 (d, J = 1.2 Hz, 3H), 1.49 –
1.40 (m, 2H), 1.40 – 1.29 (m, 5H), 0.92 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 143.4,
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142.5, 135.6, 128.5, 127.5 (q, J = 32.2 Hz), 125.0 (q, J = 4.0 Hz), 124.9, 124.5 (q, J = 272.2 Hz), 123.5,
39.6, 30.5, 25.8, 22.6, 19.7, 14.2. HRMS (pos. ESI) m/z: Calcd for C17H21F3Na [M+Na]+ 305.1488.
Found 305.1486.
(Z)-(4-(2-methylprop-1-en-1-yl)oct-3-en-1-yl)benzene (3g). The title compound was prepared
according to the general procedure A except that the reaction was performed at 100 oC. Product 3g was
isolated in 55% yield (13.3 mg) as a colorless oil using cyclohexane as eluent for column
chromatography. 1H NMR (400 MHz, CDCl3): δ 7.32 – 7.23 (m, 2H), 7.21 – 7.14 (m, 3H), 5.48 (s, 1H),
5.23 (td, J = 7.0, 1.1 Hz, 1H), 2.63 (t, J = 7.8 Hz, 2H), 2.20 (q, J = 7.8 Hz, 2H), 1.99 (t, J = 7.1 Hz, 2H),
1.76 (d, J = 1.4 Hz, 3H), 1.54 (d, J = 1.4 Hz, 3H), 1.41 – 1.17 (m, 4H), 0.88 (t, J = 7.0 Hz, 3H). 13C{1H}
NMR (101 MHz, CDCl3) δ 142.7, 138.5, 134.2, 128.6, 128.3, 125.7, 125.6, 123.9, 38.1, 36.1, 31.2, 30.7,
25.6, 22.6, 19.8, 14.2. HRMS (pos. APCI) m/z: Calcd for C18H27 [M+H]+ 243.2107. Found 243.2101.
(Z)-(3-(2-methylprop-1-en-1-yl)hept-2-en-2-yl)benzene (3h). The title compound was prepared
according to the general procedure A except that the reaction was performed without water and the
reaction time was 2 hours. Product 3h was isolated in 64% yield (14.6 mg) as a colorless oil using
pentane as eluent for column chromatography. 1H NMR (400 MHz, CDCl3): δ 7.24 – 7.05 (m, 5H), 5.52
(d, J = 1.5 Hz, 1H), 2.20 (t, J = 7.4, 2H), 2.05 (d, J = 1.5 Hz, 3H), 1.50 (d, J = 1.2 Hz, 3H), 1.45 – 1.31
(m, 4H), 1.15 (d, J = 0.9 Hz, 3H), 0.93 (t, J = 7.0 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 145.8,
135.2, 132.5, 132.2, 128.8, 127.4, 126.4, 125.5, 33.6, 30.4, 25.4, 23.1, 20.1, 19.7, 14.3. HRMS (pos.
APCI) m/z: Calcd for C17H25 [M+H]+ 229.1951. Found 229.1942.
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(Z)-1-methyl-4-(3-(2-methylprop-1-en-1-yl)hept-2-en-2-yl)benzene (3i). The title compound was
prepared according to the general procedure A except that the reaction was performed without water
and the reaction time was 1 hour. Product 3i was isolated in 65% yield (15.8 mg) as a colorless oil using
cyclohexane as eluent for column chromatography. 1H NMR (400 MHz, CDCl3): δ 7.12 – 6.92 (m, 4H),
5.52 (d, J = 1.3 Hz, 1H), 2.30 (s, 3H), 2.20 (t, J = 7.5 Hz, 2H), 2.03 (d, J = 1.5 Hz, 3H), 1.51 (d, J = 1.5
13
Hz, 3H), 1.43 – 1.30 (m, 4H), 1.18 (d, J = 1.2 Hz, 3H), 0.92 (t, J = 7.0 Hz, 3H). C{1H} NMR (101
MHz, CDCl3) δ 142.8, 134.83, 134.80, 132.2, 132.0, 128.7, 128.2, 126.6, 33.6, 30.5, 25.4, 23.1, 21.2,
20.2, 19.7, 14.3. HRMS (pos. APCI) m/z: Calcd for C18H27 [M+H]+ 243.2107. Found 243.2108.
(Z)-1-bromo-4-(3-(2-methylprop-1-en-1-yl)hept-2-en-2-yl)benzene (3j). The title compound was
prepared according to the general procedure A except that the reaction was performed without water
and the reaction time was 1 hour. Product 3j was isolated in 70% yield (21.5 mg) as a colorless oil using
cyclohexane as eluent for column chromatography. 1H NMR (400 MHz, CDCl3): δ 7.33 – 7.29 (m, 2H),
7.06 – 7.00 (m, 2H), 5.50-5.46 (m, 1H), 2.20 – 2.12 (m, 2H), 2.01 (d, J = 1.6 Hz, 3H), 1.50 (d, J = 1.5
Hz, 3H), 1.38 – 1.29 (m, 4H), 1.12 (d, J = 1.3 Hz, 3H), 0.94 – 0.88 (m, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ 144.6, 136.0, 133.0, 130.9, 130.6, 130.5, 126.0, 119.1, 33.6, 30.2, 25.4, 23.1, 19.9, 19.7, 14.3.
HRMS (pos. APCI) m/z: Calcd for C17H24Br [M+H]+ 307.1056. Found 307.1057.
(Z)-1-(2-methyloct-2-en-4-ylidene)-2,3-dihydro-1H-indene (3k). The title compound was prepared
according to the general procedure A except that the reaction was performed without water and the
reaction time was 1 hour. Product 3k was isolated in 63% yield (15.1 mg) as a colorless oil using
cyclohexane as eluent for column chromatography. 1H NMR (400 MHz, CDCl3) δ 7.64 – 7.57 (m, 1H),
7.24 – 7.19 (m, 1H), 7.13 – 7.04 (m, 2H), 5.84 (s, 1H), 2.95 (dd, J = 9.0, 5.4 Hz, 2H), 2.78 (td, J = 6.8,
2.1 Hz, 2H), 2.19 (t, J = 7.5 Hz, 2H), 1.85 (d, J = 1.4 Hz, 3H), 1.50 (d, J = 1.2 Hz, 3H), 1.47 – 1.29 (m,
13
4H), 0.91 (t, J = 7.1 Hz, 3H). C{1H} NMR (101 MHz, CDCl3) δ 147.4, 142.0, 137.0, 134.4, 131.9,
126.5, 126.2, 125.8, 125.0, 124.4, 35.9, 30.1, 29.9, 29.9, 25.5, 23.1, 19.6, 14.3. HRMS (pos. APCI) m/z:
Calcd for C18H25 [M+H]+ 241.1951. Found 241.1951.
(2-methyloct-2-en-4-ylidene)cyclohexane (3l). The title compound was prepared according to the
general procedure A except that the reaction was performed using 3 equiv of allenylboronic acid 1a in
two portions and the reaction time was 2 hours. Product 3l was isolated in 35% yield (7.2 mg) as a
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colorless oil using cyclohexane as eluent for column chromatography. H NMR (400 MHz, CDCl3) δ
5.51 (s, 1H), 2.18 (t, J = 5.4 Hz, 2H), 2.06 – 1.97 (m, 4H), 1.74 (d, J = 1.4 Hz, 3H), 1.58 – 1.42 (m, 9H),
1.33 – 1.20 (m, 4H), 0.91 – 0.85 (m, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 134.3, 132.6, 128.7,
126.4, 32.1, 32.0, 31.1, 30.2, 28.4, 27.9, 27.2, 25.3, 22.9, 19.6, 14.3. HRMS (pos. APCI) m/z: Calcd for
C15H27 [M+H]+ 207.2107. Found 207.2108.
(Z)-(3-cyclohexylidene-2-methylprop-1-en-1-yl)benzene (3m). The title compound was prepared
according to the general procedure A except that the reaction time was 1 hour. Product 3m was isolated
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in 52% yield (11.0 mg) as a colorless oil using cyclohexane as eluent for column chromatography. H
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NMR (400 MHz, CDCl3) δ 7.42 – 7.34 (m, 2H), 7.29 – 7.22 (m, 2H), 7.17 – 7.09 (m, 1H), 6.26 (s, 1H),
5.76 (s, 1H), 2.18 – 2.11 (m, 2H), 2.03 – 1.94 (m, 5H), 1.60-1.51 (m, 2H), 1.51 – 1.44 (m, 2H), 1.32 –
1.24 (m, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ 141.9, 138.8, 136.0, 128.8, 128.0, 126.9, 126.0, 121.9,
37.2, 30.3, 28.4, 27.1, 26.7, 26.2. HRMS (pos. ESI) m/z: Calcd for C16H20K [M+K]+ 251.1197. Found
251.1201.
(Z)-(2-cyclohexyl-4-methylpenta-1,3-dien-1-yl)benzene (3n). The title compound was prepared
according to the general procedure A except that the reaction time was 1 hour. Product 3n was isolated
in 69% yield (16.6 mg) as a colorless oil using cyclohexane as eluent for column chromatography. 1H
NMR (400 MHz, CDCl3) δ 7.40 – 7.32 (m, 2H), 7.29 – 7.18 (m, 2H), 7.15 – 7.06 (m, 1H), 6.22 (s, 1H),
5.78 – 5.72 (s, 1H), 2.09-1.98 (m, 1H), 1.84 – 1.63 (m, 8H), 1.38 – 1.07 (m, 8H). 13C{1H} NMR (101
MHz, CDCl3) δ 145.6, 139.1, 134.9, 128.5, 128.0, 125.8, 124.2, 123.1, 47.8, 32.1, 26.9, 26.4, 25.7, 19.6.
HRMS (pos. ESI) m/z: Calcd for C18H24Na [M+Na]+ 263.1770. Found 263.1772.
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((1Z)-2,4,5-trimethylhexa-1,3-dien-1-yl)benzene (3o). The title compound was prepared according to
the general procedure A except that the reaction time was 1 hour. Product 3o was isolated in 59% yield
(11.8 mg) as a colorless oil using cyclohexane as eluent for column chromatography. The product is a
1
mixture of Z/E diastereomers in 1:1 ratio. Spectral data for both diastereomers: H NMR (400 MHz,
CDCl3) δ 7.38 – 7.32 (m, 4H), 7.26 – 7.20 (m, 4H), 7.15 – 7.10 (m, 2H), 6.26 (s, 1H), 6.24 (s, 1H), 5.85
(s, 1H), 5.73 (s, 1H), 2.77 – 2.66 (m, 1H), 2.37 – 2.24 (m, 1H), 1.99 – 1.92 (m, 6H), 1.66 (d, J = 1.5 Hz,
3H), 1.44 (d, J = 1.3 Hz, 3H), 1.03 (s, 3H), 1.01 (s, 3H), 0.80 (s, 3H), 0.78 (s, 3H). 13C{1H} NMR (101
MHz, CDCl3) δ 143.1, 142.7, 138.8, 138.6, 136.5, 136.2, 128.8, 128.6, 128.0, 126.9, 126.7, 126.1, 126.0,
124.3, 122.7, 37.0, 30.1, 26.3, 25.8, 21.3, 20.5, 17.4, 15.1. HRMS (pos. APCI) m/z: Calcd for C15H21
[M+H]+ 201.1638. Found 201.1640.
AUTHOR INFORMATION
Corresponding Author
*E-mail: kalman.j.szabo@su.se. Web: http://www.organ.su.se/ks/. Fax: +46-8-15 49 08
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
The authors thank the financial support of the Swedish Research Council (VR).
ASSOCIATED CONTENT
Supporting Information
Spectral data for all compounds. The material is available free of charge via the Internet at
http://pubs.acs.org.
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