Pd-catalyzed substitution of the oh group of nonderivatized allylic alcohols by phenols

Article abstract of DOI:10.1021/acs.joc.7b03274

Nonactivated phenols have been employed as nucleophiles in the allylation of nonderivatized allylic alcohols to generate allylated phenolic ethers with water as the only byproduct. A Pd[BiPhePhos] catalyst was found to be reactive to give the O-allylated phenols in good to excellent yields in the presence of molecular sieves. The reactions are chemoselective in which the kinetically favored O-allylated products are formed exclusively over the thermodynamically favored C-allylated products.

Full text of DOI:10.1021/acs.joc.7b03274

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Pd-catalyzed substitution of the OH group of
non-derivatized allylic alcohols by phenols
Thanya Rukkijakan, Sunisa Akkarasamiyo, Supaporn Sawadjoon, and Joseph S. M. Samec
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b03274 • Publication Date (Web): 08 Mar 2018
Downloaded from http://pubs.acs.org on March 9, 2018
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The Journal of Organic Chemistry
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Pdꢀcatalyzed substitution of the OH group of nonꢀderivatized
allylic alcohols by phenols
Thanya Rukkijakan, Sunisa Akkarasamiyo, Supaporn Sawadjoon, and Joseph S. M. Samec*
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Address: Department of Organic Chemistry, Stockholm University, 106 91, Stockholm, (Sweden)
E-mail: joseph.samec@su.se
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Abstract: Non-activated phenols have been employed as nucleophiles in the allylation of non-
derivatized allylic alcohols to generate allylated phenolic ethers with water as the only by-product. A
Pd[BiPhePhos] catalyst was found to be reactive to give the O-allylated phenols in good to excellent
yields in the presence of molecular sieves. The reactions are chemoselective in which the kinetically
favored O-allylated products are formed exclusively over the thermodynamically favored C-allylated
products.
Aryl allyl ethers are important precursors in organic synthesis,1 for example as monomers for the
preparation of epoxy resins,2 and as substrates in Claisen rearrangements.3 Traditionally, the aryl allyl
ethers are prepared by Williamson’s ether synthesis in which potassium phenoxide (ArOK) and allylic
halides as substrates are used.4 Aryl allyl ethers can also be synthesized via metal5 or zeolite catalyzed
reactions.6 However, these methodologies require multiꢀstep procedures in which the hydroxyl (OH)
group is derivatized to promote the leaving group ability and the phenols are deprotonated to enhance
the nucleophilicity. These additional steps do not only lead to a lower atom economy but also an
increased environmental factor due to additional purification steps.7
The direct substitution of the OH group in alcohols without prior derivatization with uncharged
nucleophiles has attracted considerable attention with respect to lowering the number of reaction steps
and chemicals used where water is generated as the only byꢀproduct.8 In the allylation of phenols,
there are several challenges that need to be addressed. In addition to the poor leaving group ability of
the OH group of allylic alcohols and the poor nucleophilicity of the phenol, a competition between the
kinetically favored Oꢀallylation and the thermodynamically favored Cꢀallylation needs to be taken
into account. Only a few reports with respect to a direct substitution of the OH group in allylic
alcohols by phenols are found in the literature (Scheme 1). In 1997, Miura reported an Oꢀallylation of
phenols using allylic alcohols by palladium.9 To activate the OH group, Ti(OiPr)4 was required.
Recently, Kim reported a palladium catalyzed Oꢀallylation of phenols activated in situ by amide
acetal.10 A Cꢀallylation was reported by Kuntz in which a palladium TPPTS was used.11 In this case,
the presence of base was needed to activate the nucleophile. A Pdꢀcatalyzed Cꢀallylation reaction was
reported by Tamaru using BEt3 as additive.12 Bouwman and coworkers have reported the direct
substitution of allylic alcohols by phenols using Ruꢀcatalysts under acidic conditions in which
mixtures of Oꢀallylation and Cꢀallylation products were observed.13 Ruꢀcatalyzed formation aryl allyl
ether without any additive was reported by Kitamura. Unfortunately, low yields were obtained with
phenolic substrates.14 Thereby, previous reports show that there are both challenges in activating
substrates as well as obtaining high chemoselectivity especially when Oꢀallylation is desired. This
encouraged us to study this reaction and to develop an efficient methodology for the selective Oꢀ
allylation of phenols. Herein we report an efficient Pd[BiPhePhos] catalyzed Oꢀallylation of phenols
using nonꢀderivatized allylic alcohols without acidic or basic activation.
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Scheme 1. Previous reported methodologies struggle with chemoꢀ/regioselectivity (above), current
report gives the kinetically favored Oꢀallylated product (below).
Cinnamyl alcohol 1a and pꢀcresol 2a were used as substrates for the optimization of the reaction
conditions. We have previously reported a successful allylic amination using Pd[P(OPh)3]3 as catalyst
precursor.15 In the present reaction, low conversion to 3a was observed using the monodentate
phosphiteꢀbased ligand (Table 1, entry 1). The ligand and catalyst precursor were changed to
[Pd(allyl)Cl]2 and bidentate BINAP without any success (Table 1, entry 2). Next, the bidentate
phosphiteꢀbased BiPhePhos ligand was tested in combination with Pd(dba)2 and a 34% conversion to
3a was observed (Table 1, entry 3). Changing the palladium precursor had a significant effect on the
reaction outcome where [Pd(allyl)Cl]2 gave best results together with the BiPhePhos ligand (Table 1,
entries 3ꢀ6). As expected, the reaction is sensitive to water and the addition of molecular sieves had a
dramatic influence on the reaction, however, full conversion was not reached (Table 1, entry 7).
Therefore, a gentle heating was employed and full conversion to product 3a was obtained (Table 1,
entry 8). Noteworthy, no traces of Cꢀallylation was observed using the employed reaction conditions.
Taking into account that the molecular sieves easily can be regenerated, this is a remarkable mild and
atom efficient reaction giving high chemoselectivity towards the kinetically favored product. An
excess of the phenol is necessary to inhibit selfꢀcondensation of the allylic alcohols (Table 1, entry 9).
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Table 1. Optimization of the reaction conditions.[a]
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9
Temp
(°C)
rt
rt
rt
rt
rt
rt
rt
Conversion (%)[b]
Entry
[Pd] (mol %)
Ligand (mol %)
Additive
3
15
0
34
0
0
40
64
>95
13[e]
1
2
3
4
5
Pd(dba)2 (5)
[Pd(allyl)Cl]2 (2.5)
Pd(dba)2 (5)
Pd(OAc)2 (5)
PdCl2 (5)
[Pd(allyl)Cl]2 (2.5)
[Pd(allyl)Cl]2 (2.5)
[Pd(allyl)Cl]2 (2.5)
[Pd(allyl)Cl]2 (2.5)
P(OPh)3 (40)
BINAP (5.5)
ꢀ
ꢀ
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BiPhePhos (5.5)
BiPhePhos (5.5)
BiPhePhos (5.5)
BiPhePhos (5.5)
BiPhePhos (5.5)
BiPhePhos (5.5)
BiPhePhos (5.5)
ꢀ
ꢀ
ꢀ
6
7[c]
8[c]
3Å MS
3Å MS
3Å MS
40
40
9[d]
[a]
Reaction condition: allylic alcohol (0.25 mmol), nucleophile (0.5 mmol), toluene (0.5
[b]
1
[c]
[d]
ml) 24 hours.
Determined by HꢀNMR.
3Å MS (60 mg).
allylic alcohol (0.25
mmol), nucleophile (0.25 mmol), 3Å MS (60 mg), toluene (0.5 ml) 24 hours.
[e]Homocoupling of allylic alcohol was obtained as a major product.
With the optimized reaction conditions in hand, the substrate scope of the phenolic allylation was
studied (Table 2). Cresols 2a-2c (oꢀ ,mꢀ, and pꢀ) gave Oꢀallylated products 3a-3c in 93ꢀ99% yield
(Table 2, entries 1ꢀ3). This shows that the reaction has tolerance to phenols substituted in the
sterically demanding orthoꢀposition. To further test this, sterically hindered 2,6ꢀdimethylphenol 2d
was employed as substrate. Even this substrate gave the desired product, albeit in a lower yield (Table
2, entry 4). Also, the challenging 2,4ꢀdiꢀtertbutylphenol 2e worked as nucleophile in the present
reaction and gave product 3e in a 70% yield (Table 2, entry 5). Next, the electronic effect of the
phenol was studied. As expected, the electronꢀrich paraꢀmethoxyꢀphenol was very reactive in the
allylation reaction and gave substituted product 3f in excellent yield (Table 2, entry 6). When the
phenol was substituted in the para-position with an electronꢀwithdrawing fluoride, product 3h could
be isolated in 74% isolated yield, showing that the catalyst is very reactive also with challenging
phenols (Table 2, entry 8). The substrate scope with respect to the allyl alcohol was then studied.
Allyl alcohol 1b reacted smoothly with 2a to give product 3i in a good yield (Table 2, entry 9).
Secondary allylic alcohols were even more reactive in the reaction with phenols than the primary
allylic alcohols where the reactions were finished within two hours and the products 3a, 3j, 3k, 3l, 3m
and 3n were isolated in moderate to good yields (Table 2, entries 10ꢀ15). Noteworthy, the substrates
1c and 1a in which the OH and the double bond have been juxtapositioned, gave the same product
(Table 2, entries 1 and 10). This shows that the reaction proceeds through a Pdꢀπꢀallyl intermediate.
The same trend with respect to the electronic effect of the phenol was observed (Table 2, entries 12ꢀ
14). Cyclic nonꢀaromatic cyclohexenol 1e reacted with 2a to yield product 3n in a good yield (Table 2,
entry 15). Thereby, the employed catalyst shows a remarkable reactivity with respect to both the
electrophile as well as the nucleophile.
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Table 2 Palladium catalyzed allylation of phenols.[a]
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Entry
Allylic alcohol
Phenol
Product
Time (h)
Yield (%)[b]
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1
24
93
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2
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24
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24
99
96
55
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24
70
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74
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70
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[a] Reaction condition: allylic alcohol (0.25 mmol), nucleophile (0.5 mmol), [Pd(πꢀallyl)Cl]2 (2.5
mol%), BiPhePhos (5.5 mol%), 3Å MS (60 mg), toluene (0.5 mL). [b] Isolated yield.
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Allylation of Bisphenol A 2i with allyl alcohol 1b gave the diallylated product 3o in 77% yield
(Scheme 2). This intermediate can then be epoxidized using a Moꢀcatalyst to yield the diepoxy
precursor 4 using known literature procedures.16 As epoxy resins are commonly synthesized by the
reaction of a biphenolic precursor with epichlorohydrin that is produced from allyl chloride, this result
opens up green synthetic pathways to Bisphenol derivatives where the allylic alcohol easily can be
varied.
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Scheme 2 Synthesis of bisallyl ether of bisphenol A (3o), a precursor to epoxy resin.
The mechanism of the C–O bond cleavage of allylic alcohol has been proposed in which the OH
group of allylic alcohol was activated by palladium hydride intermediate (Scheme 3). The
intermediacy of a palladium hydride in C–O bond cleavage of allylic alcohol has previously been
proposed by Ozawa and Yoshifuji.17,15a The phenol attacks the Pdꢀπꢀallyl in an outersphere
mechanism (Table 2, entries 1 and 10).8j Regarding the chemoselectivity of the Oꢀallylation of
phenols, the reactions that give the thermodynamically favored Cꢀallylation with phenols have been
proposed to proceed through an innersphere reaction mechanism (Scheme 4, route A). In the case of
palladium, decoordination of one of the ligands must precede the coordination of the phenol. From
this intermediate, an ortho allylation or a FiedelꢀCraft reaction takes place to generate the ortho
allylated phenol.13 With the present Pd[BiPhePhos] catalyst, this pathway is inhibited. The πꢀacidic
bidentate phosphite ligand is less prone to decoordinate as compared to monodentate phosphite
ligands or even bidentate phosphine ligands. Thereby the present catalytic system is tuned to promote
Oꢀallylation where the phenol attacks the Pdꢀπꢀallyl in an outersphere reaction mechanism (Scheme 4,
route B). Also, the mild reaction conditions without requirement of acids, inhibit thermal or acidꢀ
catalyzed Claisen rearrangement to form the Cꢀallylated product.
Scheme 3. The proposed mechanism.
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Scheme 4. Cꢀallylation by the phenoxyꢀPd intermediate requires a vacant cooridination site on
palladium (route A). The bidentate πꢀacidic BiPhePhos ligand inhibits the decoordination and hence
favor route B.
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To our knowledge, this is the first report of a selective Oꢀallylation of phenols using nonꢀderivatized
allylic alcohols as substrates without addition of either acids or bases. Due to the nature of the catalyst,
where a πꢀacidic bidentate phosphite ligand is used, no free coordination sites are available and thus
the Cꢀallylation route is inhibited and only Oꢀallylation is observed. The substrate scope is broad with
respect to both the phenol and the allylic alcohol. Application towards epoxy resins using a halide free
route has been demonstrated.
EXPERIMENTAL SECTION
General information
Toluene and dichloromethane were distilled from calcium hydride under argon. The reactions were
carried out under an atmosphere of argon using standard Schlenk techniques. Thinꢀlayer
chromatography (TLC) was conducted using Merck analytical TLC plates (silica gel 60 Fꢀ254).
Compounds were visualized by ultraviolet light and/or by heating the plate after dipping in a 1%
solution of vanillin in 0.1 M sulfuric acid in ethanol. Flash column chromatography was performed on
silica gel (35ꢀ70 micron). Infrared (IR) spectra were recorded on a Perkin–Elmer FTꢀIR spectrometer.
Proton and carbon nuclear magnetic resonance (NMR) spectra were obtained using a Varian 400 MHz
spectrometer and Bruker 400 MHz spectrometer. Chemical shifts were recorded as δ values in ppm.
Coupling constants (J) are given in Hz, and multiplicity is defined as follows: br = broad, s = singlet,
d = doublet, dd = doublet of doublet, ddd = doublet of doublet of doublet, dt = doublet of triplet, dq =
doublet of quintet, t = triplet, td = triplet of doublet, tt = triplet of triplet, q = quartet, quint = quintet,
hep = heptet, m = multiplet. High resolution mass spectrometry was recorded on Bruker Daltonics
MicrOTOF.
General procedure of allylation of phenol derivatives: A dried schelenk tube was charged with
[Pd(allyl)Cl]2 (2.3 mg, 2.5 mol%) and BiPhePhos (11 mg, 5.5 mol%) and CH2Cl2 (0.5 mL). The
mixture was degassed by three freezeꢀpumpꢀthaw cycles and stirred at room temperature for 30 min,
after which the solvent was removed under vacuum. A solution of allylic alcohol (0.25 mmol) in
toluene (0.5mL, 0.5 M), phenol (0.50 mmol) and 3Å molecular sieve (60 mg) were added to the
schelenk tube. The mixture was degassed by three freezeꢀpumpꢀthaw cycles and stirred at 40°C for 2ꢀ
24 h. The reaction mixture was purified by column chromatography on silica gel.
1-(cinnamyloxy)-4-methylbenzene (3a) Purification by flash column chromatography (1ꢀ2%
EtOAc/pentane) gave a white solid (52.1 mg 93%). mp: 76ꢀ77 °C. IR (neat.) v 3037, 2935, 2863, 1611,
1
1512, 1448, 1242, 1015, 966, 757 cmꢀ1; H NMR (400 MHz, CDCl3) δ 7.49 – 7.44 (m, 2H), 7.42 –
7.34 (m, 2H), 7.35 – 7.26 (m, 1H), 7.15 (d, J = 8.0 Hz, 1H), 6.92 (d, J = 8.6 Hz, 2H), 6.78 (d, J = 16.1
Hz, 1H), 6.47 (dt, J = 16.0, 5.8 Hz, 1H), 4.73 (dd, J = 5.8, 1.5 Hz, 2H), 2.35 (s, 3H); 13C NMR (100
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MHz, CDCl3) δ 156.7, 136.7, 133.0, 130.3, 130.1, 128.7, 128.0, 126.7, 124.9, 114.8, 68.9, 20.6;
HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C16H16ONa 247.1093; Found 247.1096.
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8
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(E)-1-(cinnamyloxy)-3-methylbenzene (3b) Purification by flash column chromatography (1ꢀ2%
EtOAc/pentane) gave a colorless oil (55.5 mg 99%). IR (neat.) v 3027, 2921, 2854, 1599, 1489, 1449,
1260 cmꢀ1; 1H NMR (400 MHz, CDCl3) δ 7.49 – 7.41 (m, 2H), 7.36 (t, J = 7.4 Hz, 2H), 7.31 – 7.27
(m, 1H), 7.26 – 7.17 (m, 1H), 6.87 – 6.72 (m, 4H), 6.45 (dt, J = 16.0, 5.7 Hz, 1H), 4.71 (dd, J = 5.8,
1.6 Hz, 2H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.7, 139.6, 136.6, 132.9, 129.3, 128.6,
127.9, 126.6, 124.7, 121.8, 115.7, 111.7, 68.5, 21.6; HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C16H16ONa 247.1093; Found 247.1088.
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1-(cinnamyloxy)-2-methylbenzene (3c) Purification by flash column chromatography (1ꢀ2%
EtOAc/pentane) gave a white solid (53.8 mg 96%). mp: 40ꢀ41 °C. IR (neat.) v 3026, 2925, 1601, 1495,
1450, 1241, 1122, 965 cmꢀ1; 1H NMR (400 MHz, CDCl3,) δ 7.43 – 7.37 (m, 2H), 7.34 – 7.28 (m, 2H),
7.26 – 7.21 (m, 1H), 7.17 – 7.10 (m, 2H), 6.92 – 6.83 (m, 2H), 6.72 (d, J = 15.8, 1.6 Hz, 1H), 6.42 (dt,
J = 16.0, 5.6 Hz, 1H), 4.68 (dd, J = 5.6, 1.6 Hz, 2H), 2.28 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
156.9, 136.7, 132.4, 130.9, 128.7, 127.9, 127.1, 126.9, 126.7, 125.1, 120.7, 111.6, 68.7, 16.5. HRMS
(ESIꢀTOF) m/z: [M + Na]+ Calcd for C16H16ONa 247.1093; Found 247.1091.
2-(cinnamyloxy)-1,3-dimethylbenzene (3d) Purification by flash column chromatography (1 %
EtOAc/pentane) gave a brown oil (32.7 mg, 55%). IR (neat.) v 3025, 2921, 2855, 1591, 1495, 1475,
1262, 1196 cmꢀ1; 1H NMR (400 MHz, CDCl3) δ 7.34 (d, J = 8.3 Hz, 2H), 7.28 – 7.21 (m, 2H), 7.20 –
7.12 (m, 1H), 6.93 (d, J = 7.4 Hz, 2H), 6.89 – 6.78 (m, 1H), 6.65 (d, J = 15.9 Hz, 1H), 6.39 (dt, J =
15.8, 5.9 Hz, 1H), 4.38 (d, J = 5.9 Hz, 1H), 2.23 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 156.0, 136.8,
132.6, 131.2, 128.9, 128.7, 127.9, 126.7, 125.5, 124.0, 73.0, 16.6; HRMS (ESIꢀTOF) m/z: [M + Na]+
Calcd for C17H18ONa 261.1250; Found 261.1243.
2,4-di-tert-butyl-1-(cinnamyloxy)benzene (3e) Purification by flash column chromatography (1 %
EtOAc/pentane) gave a white solid (56.4 mg 70%). mp: 111ꢀ112 °C IR (neat.) v 3005, 2963, 1601,
1496, 1455, 1217, 1093 cmꢀ1; 1H NMR (400 MHz, CDCl3) δ 7.42 (d, J = 6.9 Hz, 2H), 7.37 – 7.30 (m,
3H), 7.29 – 7.22 (m, 1H), 7.17 (dd, J = 8.4, 2.3 Hz, 1H), 6.85 (d, J = 8.5 Hz, 1H), 6.76 (d, J = 16.0 Hz,
1H), 6.46 (dt, J = 16.0, 5.5 Hz, 1H), 4.72 (dd, J = 5.5, 1.6 Hz, 2H), 1.43 (s, 9H), 1.31 (s, 9H); 13C
NMR (100 MHz, CDCl3) δ 155.4, 142.9, 137.7, 136.9, 132.2, 128.7, 127.9, 126.7, 125.5, 124.1, 123.5,
112.1, 68.9, 35.3, 34.4, 31.8, 30.1; HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C23H30ONa 345.2189;
Found 345.2197.
1-(cinnamyloxy)-4-methoxybenzene (3f) Purification by flash column chromatography (1ꢀ4%
EtOAc/pentane) gave a colorless solid (59.4 mg 99%). mp: 107ꢀ108 °C. IR (neat.) v 3072, 2955, 1638,
1512, 1449, 1240, 1039, 830 cmꢀ1; 1H NMR (400 MHz, CDCl3) δ 7.45 – 7.41 (m, 2H), 7.36 – 7.31 (m,
2H), 7.31 – 7.22 (m, 1H), 6.97 – 6.88 (m, 2H), 6.90 – 6.81 (m, 2H), 6.73 (dt, J = 16.0, 1.6 Hz, 1H),
6.43 (dt, J = 16.0, 5.8 Hz, 1H), 4.66 (dd, J = 5.8, 1.6 Hz, 2H), 3.78 (s, 3H). 13C NMR (100 MHz,
CDCl3,) δ 154.1, 152.9, 136.6, 132.9, 128.7, 128.0, 126.7, 124.9, 116.0, 114.8, 69.5, 55.8; HRMS
(ESIꢀTOF) m/z: [M + Na]+ Calcd for C16H16O2Na 263.1043; Found 263.1048.
(cinnamyloxy)benzene (3g) Purification by flash column chromatography (1ꢀ2% EtOAc/pentane)
gave a white solid (51.0 mg 97%). mp: 67ꢀ68 °C. IR (neat.) v 3027, 2098, 1599, 1448, 1241, 1041,
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963 cmꢀ1; H NMR (400 MHz, CDCl3): δ 7.45 – 7.37 (m, 2H), 7.35 – 7.21 (m, 5H), 6.99 – 6.88 (m,
3H), 6.72 (d, J = 16.0 Hz, 1H), 6.40 (dt, J = 16.0, 5.8 Hz, 1H), 4.68 (dd, J = 5.8, 1.6 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ 158.7, 136.6, 133.1, 129.6, 128.7, 128.0, 126.7, 124.6, 121.0, 114.9, 68.7;
HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C15H14ONa 233.0937; Found 233.0934.
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1-(cinnamyloxy)-4-fluorobenzene (3h) Purification by flash column chromatography (1ꢀ2%
EtOAc/pentane) a yellow light solid. mp: 84ꢀ85 °C. IR (neat.) v 3064, 3028, 2926, 2836, 1598, 1506,
1449, 1217, 831 cmꢀ1; 1H NMR (400 MHz, CDCl3) δ 7.40 – 7.36 (m, 2H), 7.34 – 7.28 (m, 2H), 7.26 –
7.19 (m, 1H), 6.99 – 6.92 (m, 2H), 6.89 – 6.84 (m, 2H), 6.69 (d, J = 16.0 Hz, 1H), 6.37 (dt, J = 15.9,
5.8 Hz, 1H), 4.63 (dd, J = 5.8, 1.5 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 157.5 (d, 1JCF = 238.4 Hz),
154.9 (d, 4JCF = 2.1 Hz), , 136.5, 133.2, 128.7, 128.1, 126.7, 124.4, 115.96 (dd, 2JCF = 23.1, 3JCF = 7.9
Hz), 69.4; HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C15H13FONa 251.0843; Found 251.0831.
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1-(allyloxy)-4-methylbenzene (3i) Purification by flash column chromatography (0.5 % EtOAc/
pentane) gave a clear oil (32.0 mg 86%). IR (neat.) v 3082, 3028, 2923, 2861, 1874, 1614, 1455, 1241,
817 cmꢀ1; 1H NMR (400 MHz, CDCl3) δ 7.08 (d, J = 8.0 Hz, 2H), 6.82 (d, J = 8.6 Hz, 2H), 6.06 (ddt,
J = 17.3, 10.5, 5.3 Hz, 1H), 5.41 (dq, J = 17.2, 1.7 Hz, 1H), 5.27 (dq, J = 10.5, 1.4 Hz, 1H), 4.51 (dt, J
= 5.3, 1.5 Hz, 2H), 2.29 (s, 3H); 13C NMR (100 MHz, CDCl3,) δ 156.6, 133.7, 130.2, 130.0, 117.6,
114.7, 69.1, 20.6; HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C10H12ONa 171.0772; Found
171.0780.
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(E)-1-methyl-4-((4-phenylbut-3-en-2-yl)oxy)benzene (3j) Purification by flash column
chromatography (1ꢀ4 % EtOAc/pentane) gave a colorless oil (51.8 mg 87%). IR (neat.) v 3028, 2956,
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2924, 1613, 1584, 1509, 1449, 1236, 966 cmꢀ1; H NMR (400 MHz, CDCl3,) δ 7.40 – 7.33 (m, 2H),
7.33 – 7.27 (m, 2H), 7.26 – 7.18 (m, 1H), 7.07 – 6.97 (m, 2H), 6.92 – 6.80 (m, 2H), 6.59 (d, J = 16.0
Hz, 1H), 6.28 (dd, J = 16.1, 6.2 Hz, 0H), 4.97 – 4.84 (m, 1H), 2.27 (s, 3H), 1.51 (d, J = 6.4 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 156.0, 136.7, 131.1, 130.7, 130.2, 130.0, 128.7, 127.8, 126.6, 116.2,
74.9, 21.8, 20.6; HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C17H18ONa 261.1250; Found 261.1258.
(E)-1-methoxy-4-((4-phenylbut-3-en-2-yl)oxy)benzene (3k) Purification by flash column
chromatography (1ꢀ4 % EtOAc/pentane) gave a colorless oil (50.6 mg 81%). IR (neat.) v 3026, 2979,
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2833, 1592, 1505, 1448, 1227, 968 cmꢀ1; H NMR (400 MHz, CDCl3,) δ 7.40 – 7.35 (m, 2H), 7.34 –
7.28 (m, 2H), 7.26 – 7.20 (m, 1H), 6.96 – 6.86 (m, 2H), 6.85 – 6.76 (m, 2H), 6.58 (d, J = 16.1 Hz, 1H),
6.28 (dd, J = 16.1, 6.3 Hz, 1H), 4.90 – 4.79 (m, 2H), 3.76 (s, 3H), 1.51 (d, J = 6.4 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 154.1, 152.2, 136.7, 131.1, 130.8, 128.7, 127.8, 126.6, 117.7, 114.7, 75.9, 55.8,
21.9; HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C17H18O2Na 277.1199; Found 277.1210.
(E)-(3-phenoxybut-1-en-1-yl)benzene (3l) Purification by flash column chromatography (0.5 %
EtOAC/pentane) gave a colorless oil (36.8 mg 70%). IR (neat.) v 3029, 2979, 2929, 1597, 1494, 1448,
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1239 cmꢀ1; H NMR (400 MHz, CDCl3): δ 7.37 – 7.31 (m, 2H), 7.31 – 7.16 (m, 5H), 7.01 – 6.83 (m,
3H), 6.59 (dd, J = 16.1, 1.1 Hz, 1H), 6.27 (dd, J = 16.1, 6.2 Hz, 1H), 4.95 (td, J = 6.3, 1.2 Hz, 1H),
1.51 (d, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 158.2, 136.7, 130.9, 130.8, 129.5, 128.7,
127.8, 126.6, 120.9, 116.2, 74.6, 21.9; HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C16H16ONa
247.1093; Found 247.1100.
(E)-1-fluoro-4-((4-phenylbut-3-en-2-yl)oxy)benzene (3m) Purification by flash column chromaꢀ
tography (0.5ꢀ2 % EtOAC/pentane) gave a yellow oil (38.2 mg 63%). IR (neat.) v 3057, 3028, 2980,
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2929, 1600, 1504, 1449, 1206, 827 cmꢀ1; H NMR (400 MHz, CDCl3): δ 7.41 – 7.37 (m, 2H), 7.37 –
7.30 (m, 2H), 7.29 – 7.23 (m, 1H), 7.01 – 6.88 (m, 4H), 6.60 (d, J = 16.1 Hz, 1H), 6.28 (dd, J = 16.1,
6.4 Hz, 1H), 4.95 – 4.82 (m, 1H), 1.54 (d, J = 6.3 Hz, 3H); 13C NMR (100 MHz, CDCl3,) δ 157.4 (d,
1JCF = 238.5 Hz),154.2 (d, 4JCF = 2.1 Hz), 154.2, 136.5, 131.0, 130.6, 128.7, 127.9, 126.6, ), 117.6 (d,
4
3JCF = 7.9 Hz) , 115.8 (d, JCF = 22.9 Hz)., 75.7, 21.9; HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C16H15FONa 265.0999; Found 265.1000.
1-(cyclohex-2-en-1-yloxy)-4-methylbenzene (3n) Purification by flash column chromatography (0.5ꢀ
2 % EtOAC/pentane) gave a yellow oil (33.4 mg 71%) IR (neat.) v 3029, 2932, 1614, 1451, 1233,
1175, 1036 cmꢀ1; 1H NMR (400 MHz, CDCl3,) δ 7.13 – 7.00 (m, 2H), 6.92 – 6.77 (m, 2H), 5.96 (dtd,
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J = 10.2, 3.6, 1.3 Hz, 1H), 5.87 (dq, J = 10.1, 2.3 Hz, 1H), 4.75 (ddd, J = 4.2, 3.0, 1.6 Hz, 1H), 2.29 (s,
3H), 2.20 – 1.75 (m, 5H), 1.72 – 1.59 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 155.8, 132.1, 130.1,
126.7, 116.1, 71.2, 28.5, 25.3, 20.6, 19.2; HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C13H16ONa
211.1093; Found 211.1101.
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4,4'-(propane-2,2-diyl)bis((allyloxy)benzene) (3o) A flameꢀdried schelnk tube was charged with
[Pd(allyl)Cl]2 (4.6 mg, 10 mol%), BiPhePhos (22 mg, 11 mol%), AgOTf (32 mg, 50 mol%) and
CH2Cl2 (0.5 mL). The mixture was degassed by three freezeꢀpumpꢀthaw cycles and stirred at room
temperature for 30 min then AgCl was filtered off through syringe filter and the solvent was removed
under vacuum. A solution of allylic alcohol (0.2 mL, 3 mmol) in toluene (1 mL, 0.25 M), bisphenol A
(58 mg, 0.25 mmol) and 3 Å molecular sieve (1 g) were added to the Pd[κ2ꢀBiPhePhos][η3ꢀC3H5]+ +
[OTf]ꢀ complex. The slurry was degassed by three freezeꢀpumpꢀthaw cycles and stirred at 40°C for 38
h. The reaction mixture was purified by column chromatography on silica gel eluting with 10%
EtOAC/pentane to give diallylated product as a brown oil (59 mg, 0.19 mmol, 77% yield) IR (neat.) v
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2966, 2928, 2870, 1608, 1509, 1458, 1298, 1247, 1182, 1024bcmꢀ1; H NMR (400 MHz, CDCl3,) δ
7.20 (d, J= 8.9 Hz, 4H), 6.87 (d, J= 8.9 Hz, 4H), 6.17ꢀ6.05 (m, 2H), 5.47 (dq, J= 1.6, 17.2 Hz), 5.34
(ddd, J= 1.3, 1.4, 10.5 Hz), 4.56 (dt, J= 1.4, 5.4 Hz), 1.69 (s, 6H); 13C NMR (100 MHz, CDCl3) δ
156.4, 143.3, 133.4, 127.8, 117.9, 113.9, 68.8, 41.7, 31.1; HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C21H24O2Na 331.1674; Found 331.1664.
Supporting Information
Copies of 1H and 13C NMR spectra of the products (PDF)
Acknowledgements
Financial support from Swedish Research Council (Formas) and Stiftelsen Olle Engkvist
Byggmästare is gratefully acknowledged. S.A. and T.R. thanks the Erasmus Mundus program.
References
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