Room-Temperature Negishi Reaction of Trisubstituted Vinyl Phosphates for the Synthesis of Tetrasubstituted Alkenes

Article abstract of DOI:10.1021/acs.joc.0c01254

The present study investigated the ability of bromovinyl phosphates to react with organozinc reagents at room temperature during palladium-catalyzed reactions. It was determined that both the bromine atom and the phosphate group were successfully substituted by means of the reaction with the organozinc reagents, thereby allowing for the synthesis of cyclic and acyclic tetrasubstituted double bonds. The low stability of the organozinc compounds in an acidic environment was exploited to accomplish the synthesis of alkenes using a one-pot, two-step experimental setup.

Full text of DOI:10.1021/acs.joc.0c01254

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Article
Room-Temperature Negishi Reaction of Trisubstituted Vinyl
Phosphates for the Synthesis of Tetrasubstituted Alkenes
Marek #ubi#ák, and Tomáš Tobrman
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01254 • Publication Date (Web): 16 Jul 2020
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Room-Temperature Negishi Reaction of Trisubstituted Vinyl Phosphates for the Synthesis of
Tetrasubstituted Alkenes
Marek Čubiňáka and Tomáš Tobrman*a
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aDepartment of Organic Chemistry, University of Chemistry and Technology, Prague, Technická 5, 166
28 Prague 6, Czech Republic. Email: tomas.tobrman@vscht.cz
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Abstract
The present study investigated the ability of bromovinyl phosphates to react with organozinc reagents
at room temperature during palladium-catalyzed reactions. It was determined that both the bromine
atom and the phosphate group were successfully substituted by means of the reaction with the
organozinc reagents, thereby allowing for the synthesis of cyclic and acyclic tetrasubstituted double
bonds. The low stability of the organozinc compounds in an acidic environment was exploited to
accomplish the synthesis of alkenes using a one-pot, two-step experimental setup.
Introduction
while Fuwa reported the total synthesis of
gambieric acid A,7 (+)-neopeltolide,8 and the
C15−C38 fragment of okadaic acid.9 The
widespread use of vinyl phosphates in organic
synthesis can be attributed to their high
availability, good stability under various
conditions, and good reactivity in cross-
The intentional construction of a single C−C
bond remains the principal focus of organic
synthesis. More specifically, cross-coupling-
based reactions are frequently used to
synthesize C−C bonds. This synthesis is usually
achieved via the reaction between electrophilic
and nucleophilic templates. It has previously
been determined that a diverse range of
electrophilic templates can be used in cross-
coupling
reactions.
Among
them,
organohalides represent the most commonly
used electrophilic template.1 In recent years, it
has been found that activated C−H,2 C−N,2b,3
and C−S2b,4 bonds can also be used as efficient
reaction partners in cross-coupling chemistry.
In addition to the above-mentioned
templates, the cross-coupling reactions of
activated C−O bonds3b,5 remain popular in
relation to the synthesis of a C−C bond. In
terms of the other possibilities for C−O bond
activation, phosphates, especially vinyl
phosphates, have been found to have a
number of practical applications. For instance,
in 1999, Aggarwal synthesized (+)-Anatoxin-a,6
Scheme 1 Recent examples of the transition-metal-
catalyzed cross-coupling reactions of vinyl phosphates.
coupling reactions.10 For these reasons,
phosphates have previously been coupled with
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organoaluminium,11 boronic acids,12 Grignard
phosphates 7 (Scheme 2). Based on our
previous report,19a,e we chose the cyclic
bromovinyl phosphates 6 as the starting
substrates. However, this type of bromovinyl
phosphate was only coupled with boronic acid
in the temperature range 50–60 °C.19a,b,e
Therefore, we decided to improve its
performance through the use of organozinc
reagents,13 organozinc reagents,12c,12d,13g,14 and
alkenes.15 It is important to note that the
applications of phosphates are not limited to
cross-coupling reactions with alkenes, as the
phosphate group can also be used as a
directing group16 as an electrophilic partner for
C−H activation17 and for the purposes of
carbonylation.18
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The ability of the phosphate group to
react with organometallic reagents during
cross-coupling reactions is influenced by a
number of factors. Aside from the effects of the
utilized catalyst and ligand, the steric effects of
vinyl phosphates as well as the degree of
nucleophilicity of the utilized organometallic
reagents represent the two major factors that
affect the course of cross-coupling reactions.
For instance, Grignard reagents react with the
unhindered vinyl phosphates 1a at room
temperature13d,13e (Scheme 1). Yet, the use of
sterically demanding vinyl phosphates, such as
trisubstituted vinyl phosphates 1b, leads to an
reagents.
Scheme
2 Proposed strategy for the synthesis of
tetrasubstituted alkenes via a double Negishi reaction at
room temperature.
Results and discussion
A brief investigation of the reaction between
the bromocyclohexenyl phosphate 6a and 4-
methoxyphenylzinc chloride in the presence of
palladium acetate showed that only the
negligible conversion of the 6a into the
phosphate 7aa was achieved (Table 1, entry 1).
Interestingly, substantially higher conversions
of the phosphate 6a were achieved when the
Buchwald-type ligands were used, while the
bidentate 1,3-bis(diphenylphosphino)propane
(dppp) ligand proved unable to catalyze the
reaction (Table 1, entries 2−7). It is important
to note that all the above-mentioned reactions
were contaminated by the formation of the
increase in the reaction temperature.13g
A
similar phenomenon can be observed in the
case of certain organozinc reagents, whereby
trisubstituted (diphenyl)vinyl phosphates 3
react with organozinc reagents in refluxing
acetonitrile or tetrahydrofuran (THF).12d We
have previously determined that aluminum
chloride decreases the reaction temperature
during the cross-coupling reaction of the
trisubstituted vinyl phosphates
5
with
organozinc reagents to 45 °C.19a,e
undesired
symmetrically
substituted
The apparent inability of trisubstituted
vinyl phosphates to react with organozinc
reagents at ambient temperature conflicts with
reports of the Negishi reaction being
conducted at room temperature.20 During our
recent synthetic efforts to conduct transition-
metal-catalyzed reactions in the pursuit of
organic synthesis19 we decided to investigate
the ability of trisubstituted vinyl phosphate to
react with organozinc reagents at room
temperature. The strategy proposed for the
synthesis of tetrasubstituted alkenes begins
with the preparation of the trisubstituted vinyl
cyclohexadiene 8a (Table 1, note e).
Unfortunately, the cyclohexene 8a could not
be separated from the homocoupling reaction
product, which meant that the yield of the 8a
was not determined. No cyclohexene 8a was
formed during the cross-coupling reaction of
the diethyl phosphate 6b (Table 1, entries 4
and
6).
The
use
of
the
2-
dicyclohexylphosphino-2′,4′,6′-
triisopropylbiphenyl (XPhos) ligand proved
fruitful, as the almost quantitative conversion
of the starting phosphate 6a was observed
(Table 1, entry 8). Reducing the amount of 4-
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methoxyphenylzinc chloride allowed for the
naphthyl- and 2-naphthylzinc chlorides 7ah
and 7ai, although the heteroaromatic
organozinc reagents yielded the products 7aj–
7an in good yields. Aliphatic and alkenyl
substituents 7ao, 7ap, 7aq and 7ar are also
introducible via this method. The scope of the
bromine atom substitution at room
temperature was extended to the cyclic
bromovinyl phosphates 6c–6f. The results
showed that the best isolated yields of the
cyclic phosphates were obtained in the case of
the 4–6-membered carbocycles 7ca, 7da and
7aa, while moderate isolated yields were
provided by the cycloheptene and cyclooctene
derivatives 7ea and7fa.
complete conversion of the phosphate 6a by
avoiding the formation of a symmetrical
product 8a. Moreover, it also allowed for the
almost quantitative isolation of product 7aa.
Similar results were obtained in reactions
carried out at 40 °C and 23 °C (Table 1, entries
9–11).
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Table 1 Optimization of the Negishi reaction between
the phosphates 6a and 6b and 4-methoxyphenylzinc
chloride.
With the phosphates 7 having been
obtained, we optimized the phosphate
substitution reaction. Thus, the starting
compound 7aa was treated with 4-tolylzinc
chloride under different reaction conditions
(Table 2). In accordance with previous reports,
the phosphate 7aa coupled with the
organozinc reagent in the presence of Pd(OAc)2
and the dppp ligand at 60 °C, thereby affording
the product 8b in a 96% yield, although the
same reaction yielded no product when
performed at 45 °C and 23 °C (Table 2, entries
1−3). The use of aluminum chloride as an
additive gave the alkene 8b in an 81% isolated
yield, thereby maintaining the quantitative
conversion. The use of two equivalents of 4-
tolylzinc chloride increased the yield of the
alkene 8b to 86% (Table 2, entries 4−6). The
other tested ligands proved to be less efficient
(Table 2, entries 7 and 8).
Entry
6
Liganda
Temp
(°C)
60
60
60
60
60
60
60
60
60
40
23
7, Conv. (%)
1
2
3
4
5
6
7
8
9
6a
6a
6a
6b
6a
6b
6a
6a
6a
6a
6a
PPh3
SPhos
7aa, 18
7aa, 61 (47b,e
7aa, 83e
)
DavePhos
DavePhos
RuPhos
RuPhos
dppp
XPhos
XPhos
XPhos
XPhos
7ba, 100 (72b)
7aa, 49 (38b,e
)
7ba, 100 (69b)
7aa, −c,e
7aa, 96e
7aa, 100 (91b,d
7aa, 100 (88b,d
7aa, 100 (91b,d
)
)
)
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11
aTypical reaction conditions: A solution of organozinc chloride was added
to a mixture of Pd(OAc)2 (4 mol%) and ligand (8 mol%) in dry THF. The
resultant mixture was stirred at the indicated temperature for 12 h.
bIsolated yield. cFormation of phosphate 7aa was not observed. The
product of biscoupling 8a was formed in this case. d1.2 equiv. of 4-
methoxyphenylzinc chloride was used. eA significant amount of the
symmetrically substituted cyclohexadiene 8a was formed.
The ability of the diphenyl phosphate
6a to provide a trace amount of the phosphate
group substitution product 8a indicates that
this phosphate should be the substrate of
choice when exploring the extent of the
Negishi reactions of the bromovinyl
phosphates 6a and 6c–6f with various
organozinc reagents. In addition to the
electron-neutral substituents 7ab and 7ae, the
developed methodology allowed for the
smooth introduction of the para-substituted
phenyl ring with the electron-donating 7af and
the electron-withdrawing 7ag groups as well as
of the halogen atoms 7ac and 7ad in excellent
isolated yields (Scheme 3). Excellent reactivity
was also observed in the case of the 1-
The reaction conditions developed for
phosphate substitution at room temperature
(Table 2, entry 6) were also applied to other
organozinc reagents (Scheme 4). Uniformly
high isolated yields of the cyclohexenes 8b–8f
were obtained in the case of the substituted
phenyl ring bearing halogen atoms as well as
electron-donating and electron-withdrawing
groups. A similar reactivity pattern was
observed for the 2-furyl- 8h and 2-thienylzinc
chloride 8i as well as for the fused analogues 8j
and 8k. The 2-naphthyl- 8m and 1-naphthylzinc
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chloride 8n also coupled with the phosphate
that the incomplete conversion of the
phosphate 7aa during the reaction with the 1-
naphthylzinc chloride was the result of steric
factors. To verify this hypothesis, we reacted
6aa, although the latter substrate required the
addition of DPEPhos as well as heating to 45 °C
to achieve the complete conversion of the
starting phosphate 7aa. This result indicated
the
phosphate
7aa
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Scheme 3 Substitution of the bromine atom via the Negishi reaction at room temperature.
time periods indicated in the table. bIsolated yield. c2 equiv of 4-tolylzinc
chloride was used.
Table 2 Optimization of the Negishi reaction between the
phosphate 7aa and 4-tolylzinc chloride.
with 2-tolylzinc chloride. The incomplete
conversion of the 7aa was observed when the
reaction was performed in the presence of the
dppp ligand at 23 °C. The use of the DPEPhos
ligand as well as the heating of the reaction
mixture to 45 °C resulted in the complete
conversion of the phosphate 7aa while the
product 8o was isolated in a 96% yield. A
similarly positive result was obtained in
relation to the aliphatic organozinc reagent.
Analogous to the first cross-coupling reaction,
the other cyclic phosphates, namely 7ca, 7da,
7ea and 7fa reacted with 4-methoxyphenylzinc
Entry
Liganda
Additives
Temp
(°C)
60
45
23
45
23
23
45
Conv. (%)
1
2
3
4
5
6
7
8
dppp
dppp
dppp
dppp
dppp
dppp
RuPhos
DPEPhos
−
−
−
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
100 (96b)
0
0
95 (79b)
100 (81b)
100 (86b,c
)
67
74
45
aTypical reaction conditions: A solution of organozinc reagent (1.5 equiv.)
was added to a mixture of Pd(OAc)2 (4 mol%), ligand (4 mol% for the
bidentate ligand, 8 mol% for the monodentate ligand), and phosphate (1.0
equiv.). The resultant mixture was stirred at the temperatures and for the
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chloride at 23 °C, thereby yielding the
corresponding alkenes 8p–8s.
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yield of alkene 8b to 65%. The other
cyclohexene derivatives namely 8l, 8t, 8u, 8w
and 8x with electron-rich or electron-neutral
phenyl groups as well as 2-thienyl and 1-
methyl-2-indolyl moiety were prepared in
similarly high isolated yields. The introduction
of an electron-poor substituent during first
step significantly reduced the isolated yield of
the alkenes 8v and 8y although some
improvement was obtained when the reaction
mixture was heated to 45 °C. The developed
one-pot methodology was also successfully
used for the preparation of the four- and five-
membered cyclic alkenes 8p and 8q.
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Scheme 4 The scope of the phosphate substitution by the
aluminum chloride promoted the Negishi reaction at
room temperature. aThe reaction was catalyzed by
Pd(OAc)2/DPEPhos at 45 °C.
Inspired by the known properties of
the organozinc reagents, we developed a
simple one-pot, two-step procedure for the
preparation of tetrasubstituted cyclic alkenes.
In doing so, we exploited the low stability of
organozinc compounds in an acidic
environment. Thus, the phosphates 6a,6c and
6d
reacted
with
1.2
equiv.
of
aryl/heteroarylzinc chloride under the catalysis
of Pd(OAc)2/XPhos in THF at 23 °C. At the end
of the reaction, the excess organozinc reagent
was quenched with 0.2 equiv of pivalic acid,
while the second Negishi reaction completed
the synthesis of the alkenes 8 in excellent
isolated yields (Scheme 5). It is important to
note, that palladium acetate and the dppp
ligand must be added in order to accomplish
the one-pot synthesis of the cyclic alkene 8b in
high isolated yield. Indeed, performing the
second Negishi reaction without the addition
of palladium acetate and the dppp ligand
inhibited the second reaction and the
formation of alkene 8b was not observed in the
crude reaction mixture. Moreover, the addition
of only the dppp ligand reduced the isolated
Scheme 5 The one-pot, two-step synthesis of 1,2-
disubstituted cyclohexenes. aOnly the dppp ligand was
added during the second cross-coupling reaction. bThe
reaction was performed at 45 °C.
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bond that requires only the separation of the
final product.
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Experimental section
General Information
All reactions were performed under argon atmosphere.
NMR spectra were measured on Varian MercuryPlus 300
(1H, 300.13 MHz; 13C, 75.46 MHz), Agilent 400MR DD2 (1H,
400.13 MHz; 13C, 100.61 MHz) or Bruker Avance III 500
(31P, 202.45 MHz) spectrometer at 298 K. Chemical shifts
of 31P NMR spectra are referenced to the signal of 85%
H3PO4 that was assigned the chemical shift of 0. Mass
spectra were measured on ZAB-SEQ (VG Analytical). The
dry and degassed THF was prepared by PureSolv MD7.
Silica gel (Merck, Silica Gel 60, 40–63 μm or Merck Silica
Gel 60, 63-200 μm) was used for column chromatography.
n-BuLi (2.5 M solution in hexane), and other compounds
were purchased from Sigma-Aldrich, FLuorochem and
Acros Organics. Concentration of BuLi was determined by
titration using menthol and 1,10-phenanthroline before
use.
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Scheme 6 Double Negishi reaction of phosphates 6g and
6h. The reaction was catalyzed by Pd(OAc)2/DPEPhos at
45 °C
a
Using the methodology developed for
the conversion of cyclic bromovinyl phosphates
we also investigated the behavior of acyclic
bromovinyl phosphates. The easily available
acyclic bromovinyl phosphate 6g was smoothly
converted into the trisubstituted vinyl
phosphate 7gs in a 79% isolated yield.
However, the second Negishi reaction gave the
alkene 9a in only a 49% isolated yield. A similar
reactivity pattern was identified in relation to
General procedure for the preparation of phosphates 6
To a solution of HMDS (1.2 equiv) in THF (0.5 mL/mmol)
cooled to 0 °C was dropwise added BuLi (1.2 equiv) and
the reaction mixture was stirred at 0 °C for 10 minutes.
The resultant LiHMDS was cooled to -78 °C and a solution
of α-bromoketone (1.0 equiv) in dry THF (1 mL/mmol) was
dropwise added. The reaction mixture was stirred at -78
°C for 30 minutes followed by addition of diphenyl
chlorophosphate (1.3 equiv) and the mixture was allowed
warmed up to ambient temperature. Then the solution
was stirred at 23 °C for 4 hours, the crude reaction
mixture was quenched with water (5 mL/mmol), water
layer was extracted with diethyl ether (3x10 mL/mmol)
and the organic layer was washed with brine (5 mL/mmol)
and dried over MgSO4. The solvents were evaporated
under reduce pressure and column chromatography
afforded the pure product.
the
asymmetrically
substituted
vinyl
phosphate 6h. In addition, we observed the
formation of the alkene 9b as a single
stereoisomer by 1H NMR spectroscopy.
Conclusions
In conclusion, we have demonstrated that
bromovinyl phosphates can be used as double
electrophilic templates for the synthesis of
tetrasubstituted alkenes by means of a double
Negishi reaction performed at room
temperature. The bromine atom was
substituted by the Pd(OA)2/XPhos ligand, while
the phosphate group smoothly coupled with
the organozinc reagents in the presence of the
Pd(OA)2/dppp catalyst. Both reactions were
performed in dry THF at 23 °C. The bromine
atom and phosphate group substitution can be
combined in a one-pot, two-step procedure in
order to synthesize a tetrasubstituted double
2-Bromocyclohex-1-en-1-yl diphenyl phosphate (6a). L-
selectride (26.7 mL, 26.7 mmol, 1 M in THF) was added to
a solution of cyclohex-2-enone (4.24 g, 24.2 mmol) in THF
(60 mL) cooled to -78 °C. The resultant mixture was stirred
at -78 °C for 1 h. Then diphenyl chlorophosphate (4.1 mL,
19.8 mmol) was added and the reaction mixture was
stirred at 23 °C for 4 h. The crude mixture was quenched
with water (200 mL), water layer was extracted with
diethyl ether (3x200 mL), washed with brine (100 mL) and
the organic layer was dried over MgSO4. The solvents
were evaporated under reduce pressure and column
chromatography (Hexane:EtOAc 6:1, Rf = 0.3) afforded
6.94 g (70 %) of the title compound as a colourless oil. 1H
NMR (500 MHz, CDCl3) δ 7.38−7.33 (m, 4H), 7.31−7.28 (m,
4H), 7.23−7.19 (m, 2H), 2.51 (s, 2H), 2.44 (s, 2H),
1.78−1.71 (m, 2H), 1.71−1.64 (m, 2H). 13C{1H} NMR (126
MHz, CDCl3) δ 150.5 (d, J = 7.6 Hz), 144.5 (d, J = 7,2 Hz),
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129.9, 125.6, 120.3 (d, J = 4.7 Hz), 108.6 (d, J = 10.2 Hz),
2-Bromocyclohept-1-en-1-yl diphenyl phosphate (6e).
Prepared according to the general procedure starting
from HMDS (1.20 g, 7.4 mmol), BuLi (3.1 mL, 7.44 mmol,
2.4 M), THF (6 mL), 2-bromocycloheptanone (1.18 g, 6.2
mmol), THF (6 mL), and diphenyl chlorophosphate (1.67
g, 8.1 mmol). Column chromatography (Hexane:EtOAc
6:1, Rf = 0.3) afforded 0.44 g (17 %) of the title compound
as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.38–7.31 (m,
4H), 7.30–7.24 (m, 4H), 7.24–7.17 (m, 2H), 2.71–2.63 (m,
2H), 2.61–2.53 (m, 2H), 1.73–1.61 (m, 6H). 13C{1H} NMR
(101 MHz, CDCl3) δ 150.47 (d, J = 7.6 Hz), 148.44 (d, J = 8.3
Hz), 129.74, 125.49 (d, J = 1.2 Hz), 120.28 (d, J = 5.0 Hz),
112.25 (d, J = 10.2 Hz), 37.21, 32.56, 29.77, 25.44 (d, J =
1.7 Hz), 24.23 (d, J = 0.9 Hz). 31P NMR (202 MHz, CDCl3) δ
-17.87. HRMS (APCI) m/z: [M+H]+ Calcd for C19H20BrO4P
423.0355; Found 423.0347.
34.3, 29.2, 23.7, 22.5. 31P NMR (202 MHz, CDCl3) δ -17.92.
HRMS (APCI) m/z: [M+H]+ Calcd for C18H18BrO4P
409.0199; Found 409.0202.
2-Bromocyclohex-1-en-1-yl diethyl phosphate (6b).
Prepared according to the general procedure starting
from HMDS (2.0 g, 12.4 mmol), BuLi (4.41 mL, 12.4 mmol,
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2.57 M), THF (5 mL). Then
a solution of 2-
bromocyclohexanone (1.83 g, 10.3 mmol) in dry THF (5
mL) was dropwise added to a solution of LiHMDS cooled
to 0 °C. The reaction mixture was stirred at 0 °C for 30
minutes followed by addition of diethyl chlorophosphate
(2.0 mL, 13.8 mmol). Column chromatography
(Hexane:EtOAc 3:1, Rf = 0.3) afforded 1.71 g (53 %) of the
1
title compound as a light yellow oil. H NMR (400 MHz,
CDCl3) δ 4.27–4.16 (m, 4H), 2.53–2.42 (m, 4H), 1.79–1.65
(m, 4H), 1.39–1.30 (m, 6H).13C{1H} NMR (101 MHz, CDCl3)
δ 144.4 (d, J = 6.6 Hz), 107.5 (d, J = 9.8 Hz), 64.5 (d, J = 6.3
Hz), 34.3 (d, J = 0.7 Hz), 29.1 (d, J = 0.9 Hz), 23.8, 22.5, 16.1
(d, J = 7.0 Hz). 31P NMR (202 MHz, CDCl3) δ -6.67. HRMS
(APCI) m/z: [M+H]+ Calcd for C10H18BrO4P 313.0199;
Found 313.0201.
2-Bromocyclooct-1-en-1-yl diphenyl phosphate (6f).
Prepared according to the general procedure starting
from HMDS (1.29 g, 8.0 mmol), BuLi (3.3 mL, 7.92 mmol,
2.4 M), THF (6 mL), 2-bromocyclooctanone (1.37 g, 6.68
mmol), THF (6 mL), and diphenyl chlorophosphate (1.80
mL, 8.68 mmol). Column chromatography (Hexane:EtOAc
6:1, Rf = 0.3) afforded 1.53 g (52 %) of the title compound
2-Bromocyclobut-1-en-1-yl diphenyl phosphate (6c).
Prepared according to the general procedure from HMDS
(1.93 g, 12.0 mmol), BuLi (4.55 mL, 10.92 mmol, 2.4 M),
THF (8 mL), 2-bromocyclobutanone (1.46 g, 9.80 mmol),
THF (10 mL), and diphenyl chlorophosphate (2.7 mL, 13.0
mmol). Column chromatography (Hexane:EtOAc 6:1, Rf =
0.3) afforded 1.104 g (30 %) of the title compound as a
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as a yellow solid, mp = 55.8−58.0 °C. H NMR (500 MHz,
CDCl3) δ 7.34 (t, J = 7.8 Hz, 4H), 7.31–7.27 (m, 4H), 7.23–
7.15 (m, 2H), 2.63–2.58 (m, 2H), 2.58–2.51 (m, 2H), 1.74–
1.60 (m, 4H), 1.52 (s, 4H). 13C{1H} NMR (126 MHz, CDCl3)
δ 150.5 (d, J = 7.5 Hz), 146.0 (d, J = 7.8 Hz), 129.8, 125.5,
120.3 (d, J = 4.9 Hz), 111.1 (d, J = 9.9 Hz), 35.4, 30.9, 28.5,
28.3 (d, J = 2.3 Hz), 26.3, 25.5. 31P NMR (202 MHz, CDCl3)
δ -17.93. HRMS (APCI) m/z: [M+H]+ Calcd for C20H22BrO4P
437.0512; Found 437.0494.
1
colourless oil. H NMR (500 MHz, CDCl3) δ 7.37 (t, J = 7.9
Hz, 1H), 7.32–7.18 (m, 1H), 2.95–2.83 (m, 1H), 2.52–2.41
(m, 1H). 13C{1H} NMR (126 MHz, CDCl3) δ 150.2 (d, J = 7.4
Hz), 140.3 (d, J = 8.0 Hz), 130.0, 125.9, 120.1 (d, J = 4.9 Hz),
90.9 (d, J = 12.9 Hz), 33.6, 28.6. 31P NMR (202 MHz, CDCl3)
δ -18.37. HRMS (APCI) m/z: [M+H]+ Calcd for C16H14BrO4P
380.9886; Found 380.9873.
2-Bromo-1,2-diphenylvinyl diphenyl phosphate (6g).
Prepared according to the general procedure starting
from HMDS (1.19 g, 7,37 mmol), BuLi (3.1 mL, 7.44 mmol,
2.4 M), THF (6 mL), desyl bromide (1.70 g, 6.18 mmol),
THF (6 mL), and diphenyl chlorophosphate (1.66 mL, 8.0
mmol). Column chromatography (Hexane:EtOAc 6:1, Rf =
0.3) afforded 1.83 g (58 %) of the title compound as a
gray solid, mp = 75.0-80.0 and 97.0-97.8 °C. According to
13C NMR the title compound was isolated as a single
stereoisomer. The double bond stereoselectivity was not
determined but by analogy with previous report21 we
reasoned that a trans-stereoisomer is formed. 1H NMR
(500 MHz, CDCl3) δ 7.28 (t, J = 7.7 Hz, 1H), 7.23–7.18 (m,
1H), 7.19–7.13 (m, 1H), 7.13–7.08 (m, 1H). 13C{1H} NMR
(126 MHz, CDCl3) δ 150.5 (d, J = 7.4 Hz), 145.7 (d, J = 8.4
Hz), 137.4, 133.0, 130.3 (d, J = 1.5 Hz), 129.8, 129.7, 129.2,
128.5, 128.2, 128.1, 125.4, 120.2 (d, J = 5.0 Hz), 113.1 (d,
J = 10.0 Hz). 31P NMR (202 MHz, CDCl3) δ -17.88. HRMS
(APCI) m/z: [M+H]+ Calcd for C26H20BrO4P 507.0355;
Found 507.0329.
2-Bromocyclopent-1-en-1-yl diphenyl phosphate (6d). L-
selectride (5.3 mL, 5.3 mmol, 1 M in THF) was added to a
solution of cyclopent-2-enone (0.77 g, 4.80 mmol) in THF
(15 mL) cooled to -78 °C. The resultant mixture was stirred
at -78 °C for 1 h. Then diphenyl chlorophosphate (0.81 mL,
3.9 mmol) was added and the reaction mixture was
stirred at 23 °C for 4 h. The crude mixture was quenched
with conc. NH4Cl solution (50 mL), water layer was
extracted with diethyl ether (3x50 mL), washed with brine
(100 mL) and the organic layer was dried over MgSO4. The
solvents were evaporated under reduce pressure and
column chromatography (Hexane:EtOAc 6:1, Rf = 0.3)
afforded 1.89 g (63 %) of the title compound as a light
yellow oil. 1H NMR (500 MHz, CDCl3) δ 7.36 (t, J = 7.7 Hz,
4H), 7.31–7.24 (m, 4H), 7.21 (t, J = 7.5 Hz, 2H), 2.66–2.50
(m, 4H), 2.02 (p, J = 7.7 Hz, 2H). 13C{1H} NMR (126 MHz,
CDCl3) δ 150.3 (d, J = 7.5 Hz), 146.3 (d, J = 6.5 Hz), 129.9,
125.7, 120.2, 103.3 (d, J = 11.2 Hz), 34.7, 30.3, 20.0. 31P
NMR (202 MHz, CDCl3) δ -19.89. HRMS (APCI) m/z: [M+H]+
Calcd for C17H16BrO4P 395.0042; Found 395.0037.
(Z)-1-Bromo-1-phenylhex-1-en-2-yl diphenyl phosphate
(6h). To a solution of 1,1-dibromohex-1-en-2-yl diphenyl
phosphate (1.273 g, 2.60 mmol), phenylboronic acid (0.44
g, 3.61 mmol), Pd(OAc)2 (11.7 mg) and PPh3 (41.0 mg) in
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toluene (10 mL) was added K3PO4 (3.6 mL, 2M in water)
J = 0.9 Hz), 122.4 (d, J = 8.1 Hz), 113.2, 63.7 (d, J = 6.1 Hz),
55.3, 30.4 (d, J = 0.8 Hz), 28.3 (d, J = 0.7 Hz), 23.0, 22.5,
16.0 (d, J = 7.2 Hz). 31P NMR (202 MHz, CDCl3) δ -6.23.
HRMS (APCI) m/z: [M+H]+ Calcd For C17H25O5P 341.1512;
Found 341.1512.
and the reaction mixture was placed in an oil bath at 45
°C and stirred for 12 h. Column chromatography
(Hexane:EtOAc 6:1, Rf = 0.4) afforded 0.918 g (72%) of
the title compound as an yellow solid, mp = 59−62 °C. 1H
NMR (500 MHz, CDCl3) δ 7.40–7.29 (m, 8H), 7.24–7.19 (m,
2H), 2.41–2.34 (m, 2H), 1.49–1.39 (m, 2H), 1.20–1.07 (m,
2H), 0.73 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3)
δ 150.6 (d, J = 7.4 Hz), 148.3 (d, J = 8.1 Hz), 137.6, 129.8,
129.5 (d, J = 1.6 Hz), 128.7, 128.5, 125.5, 120.2 (d, J = 5.0
Hz), 109.7 (d, J = 10.0 Hz), 31.6, 29.0, 21.9, 13.6. 31P NMR
(202 MHz, CDCl3) δ -18.44. HRMS (APCI) m/z: [M+H]+
Calcd for C24H24BrO4P 487.0668; Found 487.0673.
2-(4-tolyl)cyclohex-1-en-1-yl diphenyl phosphate (7ab).
Prepared according to GP1 starting from phosphate 6a
(213.8 mg, 0.52 mmol), 4-tolylzinc chloride (1.3 mL, 0.65
mmol, 0.5 M), Pd(OAc)2 (4.7 mg) and XPhos (20.0 mg),
hexane:EtOAc (4:1, Rf = 0.3), yield 182.7 mg (83%),
yellow solid, mp = 47−50 °C. 1H NMR (400 MHz, CDCl3) δ
7.27–7.20 (m, 4H), 7.17–7.10 (m, 4H), 7.02 (d, J = 8.3 Hz,
2H), 6.97 (d, J = 8.2 Hz, 4H), 2.56–2.46 (m, 2H), 2.42–2.33
(m, 2H), 2.31 (s, 3H), 1.85–1.75 (m, 2H), 1.75–1.64 (m,
2H). 13C{1H} NMR (101 MHz, CDCl3) δ 150.5 (d, J = 7.5 Hz),
142.5 (d, J = 8.4 Hz), 136.3, 135.9, 129.5, 128.7, 128.2,
125.0, 123.9 (d, J = 8.6 Hz), 120.0 (d, J = 5.1 Hz), 30.6, 28.2,
23.0, 22.4, 21.2. 31P NMR (202 MHz, CDCl3) δ -17.54.
HRMS (APCI) m/z: [M+H]+ Calcd for C25H25O4P 421.1563;
Found 421.1564.
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General procedure for the Negishi reaction of bromovinyl
phosphates 6 (GP1)
Organozinc chloride (1.2 equiv) was added to a solution
of phosphate 6, Pd(OAc)2 (4 mol%) and XPhos (8 mol%) in
THF (1 mL). The resultant mixture was stirred at 23 °C for
12 hours, afterthat the reaction mixture was quenched
with tartaric acid (10 mL, 1M solution in water). The water
layer was extracted with diethyl ether (3x15 mL), the
organic layer was dried over MgSO4 and the solvents were
removed under reduce pressure. The product was
isolated by column chromatography (Hexane:EtOAc 6:1,
Rf = 0.3).
2-(4-Chlorophenyl)cyclohex-1-en-1-yl diphenyl phosphate
(7ac). Prepared according to GP1 starting from phosphate
6a (198.3 mg, 0.48 mmol), 4-chlorophenylzinc chloride
(1.20 mL, 0.58 mmol, 0.48 M), Pd(OAc)2 (4.4 mg) and
XPhos (18.5 mg), hexane:EtOAc (4:1, Rf = 0.3), yield
191.7 mg (90%), yellow solid, mp = 59−65 °C. 1H NMR (400
MHz, CDCl3) δ 7.38–7.29 (m, 1H), 7.29–7.22 (m, 4H), 7.23–
7.10 (m, 6H), 7.02–6.96 (m, 3H), 2.56–2.47 (m, 2H), 2.36–
2.28 (m, 2H), 1.86–1.76 (m, 2H), 1.77–1.66 (m, 3H).
13C{1H} NMR (126 MHz, CDCl3) δ 150.4 (d, J = 7.5 Hz), 143.2
(d, J = 8.3 Hz), 137.2, 132.5, 129.7, 129.6, 128.2, 125.2,
123.1 (d, J = 8.7 Hz), 119.9 (d, J = 5.0 Hz), 30.5, 28.2, 23.0,
22.3. 31P NMR (202 MHz, CDCl3) δ -17.63. HRMS (APCI)
m/z: [M+H]+ Calcd for C24H22ClO4P 441.1017; Found
441.1019.
2-(4-Methoxyphenyl)cyclohex-1-en-1-yl
diphenyl
phosphate (7aa). Prepared according to GP1 starting from
phosphate 6a (132.8 mg, 0.32 mmol), 4-
methoxyphenylzinc chloride (0.79 mL, 0.40 mmol, 0.5 M),
Pd(OAc)2 (2.9 mg) and XPhos (12.3 mg), yield 129.0 mg
(91%), white solid, mp = 74.5−77.0 °C. Large scale
preparation: phosphate 6a (6.73 g, 16.45 mmol), 4-
methoxyphenylzinc chloride (40.3 mL, 19.75 mmol, 0.49
M), Pd(OAc)2 (0.15 g, 0.67 mmol) and XPhos (0.63 g, 1.32
mmol), hexane:EtOAc (4:1, Rf = 0.3), yield 5.08 g (71%).
1H NMR (500 MHz, CDCl3) δ 7.31−7.25 (m, 4H), 7.22 (d, J
= 8 Hz, 2H), 7.20−7.14 (m, 2H), 7.06−7.02 (m, 4H), 6.76 (d,
J = 8 Hz, 2H), 3.81 (s, 3H), 2.56 (s, 2H), 2.40 (s, 2H),
1.88−1.81 (m, 2H), 1.78−1.71 (m, 2H). 13C{1H} NMR (126
MHz, CDCl3) δ 158.3, 150.6 (d, J = 7.4 Hz), 142.5 (d, J = 8.4
Hz), 131.2, 129.6, 129.4, 125.1, 123.6 (d, J = 8.6 Hz), 120.0
(d, J = 5.0 Hz), 113.4, 55.2, 30.7, 28.3, 23.1, 22.5. 31P NMR
(202 MHz, CDCl3) δ -17.55. HRMS (APCI) m/z: [M+H]+
Calcd for C25H25O5P 437.1512; Found 437.1513.
2-(4-fluorophenyl)cyclohex-1-en-1-yl diphenyl phosphate
(7ad). Prepared according to GP1 starting from phosphate
6a (205.1 mg, 0.50 mmol), 4-fluorophenylzinc chloride
(1.4 mL, 0.62 mmol, 0.44 M), Pd(OAc)2 (4.5 mg) and XPhos
(19.1 mg), hexane:EtOAc (4:1, Rf = 0.3), yield 180.3 mg
1
(85%), white solid, mp = 53−54.6 °C. H NMR (400 MHz,
CDCl3) δ 7.28–7.22 (m, 4H), 7.22–7.10 (m, 4H), 7.04–6.96
(m, 4H), 6.90–6.81 (m, 2H), 2.62–2.44 (m, 2H), 2.42–2.26
(m, 2H), 1.86–1.76 (m, 2H), 1.76–1.67 (m, 2H). 13C{1H}
NMR (101 MHz, CDCl3) δ 161.6 (d, J = 246.4 Hz), 150.4 (d,
J = 7.1 Hz), 143.0 (d, J = 9.1 Hz), 134.6, 129.9 (dd, J = 1.0,
8.1 Hz), 129.6, 125.2, 123.1 (d, J = 8.1 Hz), 119.9 (d, J = 5.1
Hz), 114.8 (d, J = 21.2 Hz), 30.6, 28.2, 23.0, 22.3. 31P NMR
(202 MHz, CDCl3) δ -17.57. 19F NMR (471 MHz, CDCl3,
CFCl3) δ -115, 96. HRMS (APCI) m/z: [M+H]+ Calcd for
C24H22FO4P 425.1313; Found 425.1313.
2-(4-Methoxyphenyl)cyclohex-1-en-1-yl diethyl phosphate
(7ba). Prepared according to modified GP1 starting from
phosphate 6b (114.9 g, 0.37 mmol), 4-methoxyphenylzinc
chloride (1.2 mL, 0.6 mmol, 0.5 M), Pd(OAc)2 (3.3 mg) and
RuPhos (13.6 mg), and the reaction mixture was placed in
an oil bath at 60 °C and stirred for 12 h, hexane:EtOAc
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(4:1, Rf = 0.3), yield 86.0 mg (69 %), colourless oil. H
2-(Biphenyl-4-yl)cyclohex-1-en-1-yl diphenyl phosphate
(7ae).Prepared according to GP1 starting from phosphate
6a (216.8 mg, 0.53 mmol), biphenyl-4-ylzinc chloride (1.7
mL, 0.65 mmol, 0.38 M), Pd(OAc)2 (4.8 mg) and XPhos
(20.2 mg), hexane:EtOAc (4:1, Rf = 0.3), yield 221.0 mg
NMR (400 MHz, CDCl3) δ 7.26 (d, J = 8.8 Hz, 2H), 6.85 (d, J
= 8.9 Hz, 2H), 3.94–3.72 (m, 7H), 2.51–2.41 (m, 2H), 2.37–
2.30 (m, 2H), 1.85–1.75 (m, 2H), 1.75–1.66 (m, 2H), 1.17
(dd, J = 7.0, 1.0 Hz, 6H).13C{1H} NMR (101 MHz, CDCl3) δ
158.2, 142.4 (d, J = 8.2 Hz), 131.8 (d, J = 1.6 Hz), 129.5 (d,
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CDCl3) δ -17.89. HRMS (APCI) m/z: [M+H]+ Calcd for
C28H25O4P 457.1563; Found 457.1564.
(87%), off-white solid, mp = 86−90 °C 1H NMR (500 MHz,
CDCl3) δ 7.56 (d, J = 7.7 Hz, 2H), 7.44 (t, J = 7.7 Hz, 4H),
7.37–7.30 (m, 3H), 7.21 (t, J = 7.7 Hz, 4H), 7.09 (t, J = 7.3
Hz, 2H), 6.99 (d, J = 7.9 Hz, 3H), 2.60–2.50 (m, 2H), 2.47–
2.36 (m, 2H), 1.88–1.78 (m, 2H), 1.79–1.69 (m, 2H).
13C{1H} NMR (126 MHz, CDCl3) δ 150.5 (d, J = 7.4 Hz), 143.0
(d, J = 8.4 Hz), 141.0, 139.5, 137.9, 129.6, 128.8, 127.2,
127.0, 126.7, 125.1, 123.6 (d, J = 8.8 Hz), 120.0 (d, J = 5.2
Hz), 30.5, 28.3, 23.1, 22.4. 31P NMR (202 MHz, CDCl3) δ -
17.57. HRMS (APCI) m/z: [M+H]+ Calcd for C30H27O4P
483.1720; Found 483.1719.
2-(6-Methoxynaphthalen-2-yl)cyclohex-1-en-1-yl diphenyl
phosphate (7ai).Prepared according to GP1 starting from
phosphate 6a (194.1 mg, 0.47 mmol), 6-
methoxynaphthalen-2-ylzinc chloride (2.85 mL, 0.57
mmol, 0.2 M), Pd(OAc)2 (4.3 mg) and XPhos (18.1 mg),
hexane:EtOAc (4:1, Rf = 0.3), yield 187.4 mg (81%), white
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solid, mp = 106.0−108.0 °C. H NMR (500 MHz, CDCl3) δ
7.62−7.56 (m, 3H), 7.35 (dd, J = 8.5 Hz, 1.5 Hz, 1H),
7.12−7.00 (m, 8H), 6.90−6.86 (m, 4H), 3.93 (s, 3H),
2.60−2.54 (m, 2H), 2.48−2.42 (m, 2H), 1.88−1.82 (m, 2H),
1.79−1.72 (m, 2H). 13C{1H} NMR (126 MHz, CDCl3) δ 157.6,
150.4 (d, J = 12.7 Hz), 143.0 (d, J = 8.3 Hz), 134.2, 133.5,
129.6, 129.5, 128.8, 127.4, 126.9, 126.4, 125.0, 124.1 (d, J
= 8.9 Hz), 129.9 (d, J = 4.9 Hz), 118.6, 105.6, 55.4, 30.8,
28.3, 23.1, 22.5. 31P NMR (202 MHz, CDCl3) δ -17.51.
HRMS (APCI) m/z: [M+H]+ Calcd for C29H27O5P 487.1669;
Found 487.1670.
2-[4-(N,N-Dimethylamino)phenyl]cyclohex-1-en-1-yl
diphenyl phosphate (7af). Prepared according to GP1
starting from phosphate 6a (219.9 mg, 0.54 mmol), 4-
(N,N-dimethylamino)phenylzinc chloride (1.5 mL, 0.66
mmol, 0.44 M), Pd(OAc)2 (4.8 mg) and XPhos (20.5 mg),
hexane:EtOAc (4:1, Rf = 0.3), yield 195.4 mg (81%),
yellow solid, mp = 50.0−53.0. 1H NMR (500 MHz, CDCl3) δ
7.25–7.20 (m, 4H), 7.16 (d, J = 8.3 Hz, 2H), 7.14–7.09 (m,
2H), 7.03–6.98 (m, 4H), 6.60 (d, J = 8.4 Hz, 2H), 2.92 (s,
6H), 2.51 (s, 2H), 2.36 (s, 2H), 1.82–1.76 (m, 2H), 1.72–
1.67 (m, 2H). 13C{1H} NMR (126 MHz, CDCl3) δ 150.6 (d, J
= 7.5 Hz), 149.4, 141.9 (d, J = 8.4 Hz), 129.5, 129.0, 126.9,
125.0, 123.7 (d, J = 8.6 Hz), 120.1 (d, J = 5.0 Hz), 112.2,
40.6, 30.5, 28.4, 23.2, 22.6. 31P NMR (202 MHz, CDCl3) δ -
17.41. HRMS (APCI) m/z: [M+H]+ Calcd for C26H28NO4P
450.1829; Found 450.1829.
2-(2-Furyl)cyclohex-1-en-1-yl diphenyl phosphate (7aj).
Prepared according to GP1 starting from phosphate 6a
(206.0 mg, 0.50 mmol), 2-furylzinc chloride (1.75 mL, 0.61
mmol, 0.35 M), Pd(OAc)2 (4.5 mg) and XPhos (19.2 mg),
hexane:EtOAc (4:1, Rf = 0.3), yield 138.0 mg (69%),
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colourless oil. H NMR (400 MHz, CDCl3) δ 7.38–7.26 (m,
5H), 7.25–7.15 (m, 6H), 6.50 (d, J = 3.4 Hz, 1H), 6.31 (dd, J
= 3.3, 1.9 Hz, 1H), 2.66–2.55 (m, 2H), 2.55–2.46 (m, 2H),
1.80–1.73 (m, 2H), 1.71–1.63 (m, 2H). 13C{1H} NMR (101
MHz, CDCl3) δ 150.5 (d, J = 7.3 Hz), 142.7 (d, J = 8.5 Hz),
140.7, 129.7 (d, J = 0.6 Hz), 125.4, 120.1, 120.1, 113.9 (d,
J = 9.1 Hz), 111.2, 109.1, 28.5, 25.4, 22.7, 21.7. 31P NMR
(202 MHz, CDCl3) δ -17.69., HRMS (APCI) m/z: [M+H]+
Calcd for C22H21O5P 397.1199; Found 397.1200.
2-(4-Cyanophenyl)cyclohex-1-en-1-yl diphenyl phosphate
(7ag). Prepared according to GP1 starting from phosphate
6a (188.3 mg, 0.46 mmol), 4-cyanophenylzinc chloride
(2.8 mL, 0.56 mmol, 0.2 M), Pd(OAc)2 (4.1 mg) and XPhos
(17.6 mg), hexane:EtOAc (4:1, Rf = 0.3), yield 167.2 mg
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(84%), colourless oil. H NMR (400 MHz, CDCl3) δ 7.43–
7.34 (m, 2H), 7.29–7.24 (m, 7H), 7.21–7.15 (m, 2H), 7.02–
6.98 (m, 3H), 2.60–2.48 (m, 2H), 2.38–2.31 (m, 2H), 1.88–
1.80 (m, 2H), 1.78–1.70 (m, 2H). 13C{1H} NMR (101 MHz,
CDCl3) δ 150.3 (d, J = 7.6 Hz), 144.2 (d, J = 8.2 Hz), 143.6,
131.7, 129.7, 129.0, 125.4, 122.7 (d, J = 8.6 Hz), 119.8 (d,
J = 5.1 Hz), 119.0, 110.3, 30.0, 28.2, 22.8, 22.2. 31P NMR
(202 MHz, CDCl3) δ -17.78. HRMS (APCI) m/z: [M+H]+
Calcd for C25H22NO4P 432.1359; Found 432.1360.
(2-(2-Thienyl)cyclohex-1-en-1-yl) diphenyl phosphate
(7ak).Prepared according to GP1 starting from phosphate
6a (199.1 mg, 0.49 mmol), 2-thienylzinc chloride (0.94 mL,
0.58 mmol, 0.62 M), Pd(OAc)2 (4.4 mg) and XPhos (18.6
mg), hexane:EtOAc (4:1, Rf = 0.3), yield 186.1 mg (93%),
brown oil. 1H NMR (400 MHz, CDCl3) δ 7.34–7.27 (m, 4H),
7.25–7.13 (m, 7H), 7.10 (d, J = 3.7 Hz, 1H), 6.95 (dd, J = 5.1,
3.8 Hz, 1H), 2.70–2.63 (m, 2H), 2.60–2.51 (m, 2H), 1.81–
1.71 (m, 4H). 13C{1H} NMR (126 MHz, CDCl3) δ 150.6 (d, J
= 7.2 Hz), 143.0 (d, J = 7.9 Hz), 139.6, 129.7, 126.2, 125.4,
125.1, 124.9, 120.2 (d, J = 5.2 Hz), 116.2 (d, J = 9.5 Hz),
28.9, 28.6, 22.8, 22.3. 31P NMR (202 MHz, CDCl3) δ -17.77.
HRMS (APCI) m/z: [M+H]+ Calcd for C22H21O4PS 413.0971;
Found 413.0971.
2-(Naphthalen-1-yl)cyclohex-1-en-1-yl
diphenyl
phosphate (7ah). Prepared according to GP1 starting from
phosphate 6a (207.7 mg, 0.51 mmol), 1-naphthylzinc
chloride (1.4 mL, 0.62 mmol, 0.44 M), Pd(OAc)2 (4.6 mg)
and XPhos (19.4 mg), hexane:EtOAc (4:1, Rf = 0.3), yield
212.1 mg (92%), colourless oil. 1H NMR (400 MHz, CDCl3)
δ 7.92–7.81 (m, 2H), 7.73 (d, J = 8.1 Hz, 1H), 7.50–7.44 (m,
2H), 7.44–7.35 (m, 1H), 7.35–7.29 (m, 1H), 7.13–6.98 (m,
6H), 6.76–6.68 (m, 2H), 6.68–6.62 (m, 2H), 2.71–2.59 (m,
2H), 2.50–2.35 (m, 2H), 2.01–1.91 (m, 2H), 1.87–1.79 (m,
2H). 13C{1H} NMR (101 MHz, CDCl3) δ 150.2 (d, J = 7.6 Hz),
143.9 (d, J = 8.0 Hz), 137.0 (d, J = 1.4 Hz), 133.7, 131.0,
129.4, 128.3, 127.3, 126.0 (d, J = 1.1 Hz), 126.0, 125.7,
125.6, 125.5, 125.0, 123.0 (d, J = 8.8 Hz), 119.7 (d, J = 9.7
Hz), 119.7, 31.5, 28.0, 23.3, 22.5. 31P NMR (202 MHz,
2-(Benzofuran-2-yl)cyclohex-1-en-1-yl
diphenyl
phosphate (7al). Prepared according to GP1 starting from
phosphate 6a (187.2 mg, 0.46 mmol), 2-benzofuran-2-
ylzinc chloride (1.85 mL, 0.56 mmol, 0.3 M), Pd(OAc)2 (4.1
mg) and XPhos (17.4 mg), hexane:EtOAc (4:1, Rf = 0.3),
yield 149.2 mg (73%), off-white solid, mp = 63.0−64.4 °C.
1H NMR (400 MHz, CDCl3) δ 7.44–7.40 (m, 1H), 7.37–7.27
(m, 5H), 7.26–7.20 (m, 5H), 7.20–7.13 (m, 3H), 6.76 (s,
1H), 2.69–2.60 (m, 4H), 1.85–1.77 (m, 2H), 1.77–1.69 (m,
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2H). 13C{1H} NMR (101 MHz, CDCl3) δ 153.7, 152.6 (d, J =
yellow oil. 1H NMR (500 MHz, CDCl3) δ 7.33 (t, J = 7.7 Hz,
4H), 7.25 (d, J = 7.7 Hz, 4H), 7.18 (t, J = 7.3 Hz, 2H), 2.38 (s,
2H), 1.98 (s, 2H), 1.73–1.63 (m, 2H), 1.59–1.50 (m, 2H),
1.47 (s, 2H), -0.04 (s, 9H). 13C{1H} NMR (101 MHz, CDCl3) δ
150.7 (d, J = 7.4 Hz), 139.5 (d, J = 8.5 Hz), 129.7, 125.2,
121.4 (d, J = 8.7 Hz), 120.2 (d, J = 5.0 Hz), 30.9, 27.8, 23.5,
22.4, 20.9 (d, J = 1.4 Hz), -0.8. 31P NMR (202 MHz, CDCl3)
δ -16.60. HRMS (ESI) m/z: [M+Na]+ Calcd for C22H29O4PSi
439.1465; Found 439.1468.
2.6 Hz), 150.5 (d, J = 7.3 Hz), 145.5 (d, J = 8.2 Hz), 129.8,
128.8, 125.4, 123.9, 122.5, 120.9, 120.1, 120.0, 113.9 (d, J
= 9.0 Hz), 110.9, 105.6, 28.8, 25.6, 22.6, 21.7. 31P NMR
(202 MHz, CDCl3) δ -18.03. HRMS (APCI) m/z: [M+H]+
Calcd for C26H23O5P 447.1356; Found 447.1353.
2-(2-Thianaphthenyl)cyclohex-1-en-1-yl
diphenyl
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phosphate (7am). Prepared according to GP1 starting
from phosphate 6a (197.7 mg, 0.48 mmol), 2-
thianaphthenylzinc chloride (2.1 mL, 0.59 mmol, 0.28 M),
Pd(OAc)2 (4.7 mg) and XPhos (19.9 mg), hexane:EtOAc
(4:1, Rf = 0.3), yield 170.0 mg (76%), brown solid, mp =
57.6−69.5 °C. 1H NMR (500 MHz, CDCl3) δ 7.71 (d, J = 7.6
Hz, 1H), 7.64 (d, J = 7.3 Hz, 1H), 7.32–7.22 (m, 8H), 7.22–
7.17 (m, 4H), 7.14 (t, J = 7.5 Hz, 2H), 2.70 (s, 2H), 2.60 (s,
2H), 1.87–1.72 (m, 4H). 13C{1H} NMR (126 MHz, CDCl3)
150.5 (d, J = 7.3 Hz), 144.9 (d, J = 7.7 Hz), 139.9, 139.2,
129.7, 125.4, 124.0 (d, J = 5.2 Hz), 123.3, 121.9, 121.6,
120.1 (d, J = 5.0 Hz), 116.4 (d, J = 9.4 Hz), 29.0, 28.8, 22.7,
22.2. 31P NMR (202 MHz, CDCl3) δ -17.98. HRMS (APCI)
m/z: [M+H]+ Calcd for C26H23O4PS 463.1127; Found
463.1128.
2-Butylcyclohex-1-en-1-yl diphenyl phosphate (7aq).
Prepared according to GP1 starting from phosphate 6a
(207.9 mg, 0.51 mmol), n-butylzinc chloride (1.3 mL, 0.61
mmol, 0.47 M), Pd(OAc)2 (4.7 mg) and XPhos (19.4 mg),
hexane:EtOAc (4:1, Rf = 0.3), yield 79.9 mg (41%), yellow
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oil. H NMR (500 MHz, CDCl3) δ 7.38 (t, J = 7.7 Hz, 4H),
7.32–7.27 (m, 4H), 7.23 (t, J = 7.4 Hz, 2H), 2.40 (s, 2H),
2.10–1.98 (m, 4H), 1.78–1.68 (m, 2H), 1.64–1.56 (m, 2H),
1.38–1.27 (m, 2H), 1.27–1.16 (m, 2H), 0.87 (t, J = 7.2 Hz,
3H). 13C{1H} NMR (126 MHz, CDCl3) δ 150.7 (d, J = 7.4 Hz),
141.5 (d, J = 8.8 Hz), 129.7, 125.3, 123.7 (d, J = 8.4 Hz),
120.2 (d, J = 4.9 Hz), 29.9, 29.6, 28.04, 27.97, 23.3, 22.7,
22.3, 14.0. 31P NMR (202 MHz, CDCl3) δ -16.79. HRMS
(APCI) m/z: [M+H]+ Calcd for C22H27O4P 387.1720; Found
387.1721.
2-(2,2'-Bithiophen-5-yl)cyclohex-1-en-1-yl
diphenyl
phosphate (7an). Prepared according to GP1 starting from
phosphate 6a (219.2 mg, 0.54 mmol), 2,2’-bithiophen-5-
ylzinc chloride (2.0 mL, 0.66 mmol, 0.33 M), Pd(OAc)2 (4.8
mg) and XPhos (20.4 mg), hexane:EtOAc (4:1, Rf = 0.3),
yield 224.5 (85%), orange solid, mp = 65.7−71.0 °C. 1H
NMR (500 MHz, CDCl3) δ 7.33–7.27 (m, 4H), 7.25–7.22 (m,
4H), 7.19–7.14 (m, 3H), 7.03 (d, J = 3.0 Hz, 1H), 7.01–6.95
(m, 3H), 2.68 (s, 2H), 2.53 (s, 2H), 1.80–1.70 (m, 4H).
13C{1H} NMR (126 MHz, CDCl3) δ 150.6 (d, J = 7.2 Hz), 143.3
(d, J = 7.5 Hz), 138.5, 137.6, 136.7, 129.8, 127.8, 125.6,
125.4, 124.2, 123.4, 123.0, 120.3 (d, J = 4.9 Hz), 120.1 (d,
2-(3,4-Dihydronaphthalen-1-yl)cyclohex-1-en-1-yl
diphenyl phosphate (7ar). Prepared according to GP1
starting from phosphate 6a (221.8 mg, 0.54 mmol), 3,4-
dihydronaphth-1-ylzinc chloride (1.9 mL, 0.67 mmol, 0.35
M), Pd(OAc)2 (4.9 mg) and XPhos (20.6 mg), hexane:EtOAc
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(4:1, Rf = 0.3), yield 232.2 mg (93%), colourless oil. H
NMR (400 MHz, CDCl3) δ 7.23–7.15 (m, 6H), 7.15–7.07 (m,
4H), 7.02 (d, J = 8.1 Hz, 4H), 5.93 (t, J = 4.5 Hz, 1H), 2.68 (s,
2H), 2.57–2.48 (m, 2H), 2.30–2.07 (m, 4H), 1.85 (p, J = 6.2
Hz, 2H), 1.77–1.64 (m, 2H). 13C{1H} NMR (101 MHz, CDCl3)
δ 150.5 (d, J = 7.7 Hz), 143.5 (d, J = 8.4 Hz), 136.2, 135.7
(d, J = 1.6 Hz), 133.6 (d, J = 1.0 Hz), 129.6, 127.6, 127.4 (d,
J = 1.4 Hz), 126.8, 126.5, 125.1, 124.2, 123.2 (d, J = 8.5 Hz),
J = 5.0 Hz), 115.9 (d, J = 9.5 Hz), 28.6, 28.5, 22.8, 22.2. 31
P
NMR (202 MHz, CDCl3) δ -17.92. HRMS (APCI) m/z: [M+H]+
Calcd for C26H23O4PS2 495.0848; Found 495.0850.
120.0 (d, J = 4.9 Hz), 30.0, 28.1, 27.8, 23.2, 23.0, 22.3. 31
P
2-Methylcyclohex-1-en-1-yl diphenyl phosphate (7ao).
Prepared according to GP1 starting from phosphate 6a
(217.6 mg, 0.53 mmol), methylzinc chloride (1.45 mL, 0.64
mmol, 0.44 M), Pd(OAc)2 (4.8 mg) and XPhos (20.3 mg),
hexane:EtOAc (4:1, Rf = 0.3), yield 134.8 mg (74%),
NMR (202 MHz, CDCl3) δ -17.53. HRMS (APCI) m/z: [M+H]+
Calcd for C28H27O4P 459.1720; Found 459.1706.
2-(4-Methoxyphenyl)cyclobut-1-en-1-yl
diphenyl
phosphate (7ca). Prepared according to GP1 starting from
phosphate 6c (205.4 mg, 0.54 mmol), 4-
methoxyphenylzinc chloride (1.5 mL, 0.68 mmol, 0.45 M),
Pd(OAc)2 (4.8 mg) and XPhos (20.5 mg), hexane:EtOAc
(4:1, Rf = 0.3), yield 191.8 mg (87%), off-white solid, mp
= 79−81 °C. 1H NMR (500 MHz, CDCl3) δ 7.40 (t, J = 7.7 Hz,
4H), 7.34–7.29 (m, 6H), 7.26 (t, J = 7.4 Hz, 2H), 6.86 (d, J =
8.4 Hz, 2H), 3.85 (s, 3H), 2.99 (s, 2H), 2.44 (s, 2H). 13C{1H}
NMR (126 MHz, CDCl3) δ 158.8, 150.4 (d, J = 7.3 Hz), 131.7
(d, J = 8.7 Hz), 129.9, 127.6, 125.7, 125.4, 122.2 (d, J = 11.3
Hz), 120.2 (d, J = 5.0 Hz), 113.8, 55.3, 31.2, 21.0. 31P NMR
(202 MHz, CDCl3) δ -17.49. HRMS (APCI) m/z: [M+H]+
Calcd for C23H21O5P 409.1199; Found 409.1180.
1
colourless oil. H NMR (500 MHz, CDCl3) δ 7.34 (t, J = 7.8
Hz, 4H), 7.25 (d, J = 8.1 Hz, 4H), 7.18 (t, J = 7.3 Hz, 2H), 2.31
(s, 2H), 2.00 (s, 2H), 1.72–1.65 (m, 2H), 1.58 (s, 3H). 13C{1H}
NMR (126 MHz, CDCl3) δ 150.7 (d, J = 7.4 Hz), 141.6 (d, J =
9.1 Hz), 129.8, 125.3, 120.1 (d, J = 4.9 Hz), 119.7 (d, J = 7.6
Hz), 30.4, 27.9, 23.4, 22.2, 16.2. 31P NMR (202 MHz, CDCl3)
δ -16.52. HRMS (APCI) m/z: [M+H]+ Calcd for C19H21O4P
345.1250; Found 345.1253.
Diphenyl
phosphate (7ap). Prepared according to GP1 starting from
phosphate 6a (189.9 mg, 0.46 mmol),
2-[(trimethylsilyl)methyl]cyclohex-1-en-1-yl
trimethylsilylmethylzinc chloride (0.82 mL, 0.57 mmol,
0.69 M), Pd(OAc)2 (4.2 mg) and XPhos (17.7 mg),
hexane:EtOAc (4:1, Rf = 0.3), yield 142.6 mg (74%),
2-(4-Methoxyphenyl)cyclopent-1-en-1-yl
diphenyl
phosphate (7da). Prepared according to GP1 starting from
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phosphate 6d (300.9 mg, 0.76 mmol), 4-
128.0, 127.9, 127.4, 127.0, 125.1, 120.0 (d, J = 5.0 Hz). 31
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methoxyphenylzinc chloride (2.1 mL, 0.95 mmol, 0.45 M),
Pd(OAc)2 (6.8 mg) and XPhos (28.9 mg), hexane:EtOAc
(4:1, Rf = 0.3), yield 224.4 mg (70%), off-white solid, mp
= 75.6−77.1 °C. 1H NMR (500 MHz, CDCl3) δ 7.36 (d, J = 8.6
Hz, 2H), 7.32 (t, J = 7.7 Hz, 4H), 7.27–7.16 (m, 6H), 6.75 (d,
J = 8.7 Hz, 2H), 3.79 (s, 3H), 2.89 (t, J = 7.5 Hz, 2H), 2.75–
2.65 (m, 2H), 1.99 (p, J = 7.6 Hz, 2H). 13C{1H} NMR (126
MHz, CDCl3) δ 158.4, 150.5 (d, J = 7.4 Hz), 142.7 (d, J = 7.5
Hz), 129.8, 128.4, 126.8, 125.5, 120.9 (d, J = 9.5 Hz), 120.2
(d, J = 4.9 Hz), 113.5, 55.2, 32.9, 31.3, 19.3. 31P NMR (202
MHz, CDCl3) δ -17.39. HRMS (APCI) m/z: [M+H]+ Calcd for
C24H23O5P 423.1356; Found 423.1333.
NMR (202 MHz, CDCl3) δ -16.89. HRMS (APCI) m/z: [M+H]+
Calcd for C32H25O4P 505.1563; Found 505.1544.
(Z)-1-(4-methoxyphenyl)-1-phenylhex-1-en-2-yl diphenyl
phosphate (7ht). Prepared according to GP1 starting from
phosphate 6h (0.763 g, 1.57 mmol), 4-methoxyphenylzinc
chloride (4.33 mL, 1.90 mmol, 0.44 M), Pd(OAc)2 (14.0
mg) and XPhos (80.0 mg), hexane:EtOAc (6:1, Rf = 0.3),
yield 0.664 g (82%), yellow solid, mp. = 70-74 °C. 1H NMR
(500 MHz, CDCl3) δ 7.32–7.22 (m, 7H), 7.20–7.10 (m, 6H),
7.04–6.97 (m, 4H), 6.67 (d, J = 8.8 Hz, 2H), 3.73 (s, 3H),
2.51–2.43 (m, 2H), 1.58–1.49 (m, 2H), 1.25–1.16 (m, 2H),
0.76 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ
158.4, 150.6 (d, J = 7.3 Hz), 146.1 (d, J = 9.1 Hz), 140.2,
131.2 (d, J = 2.0 Hz), 131.0, 129.8 (d, J = 1.4 Hz), 129.6,
128.2, 127.1, 125.0, 119.9 (d, J = 5.1 Hz), 113.2, 55.1, 31.7,
29.3, 21.9, 13.7. 31P NMR (202 MHz, CDCl3) δ -17.94.
HRMS (APCI) m/z: [M+H]+ Calcd for C31H31O5P 515.1982;
Found 515.1980.
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2-(4-Methoxyphenyl)cyclohept-1-en-1-yl
diphenyl
phosphate (7ea). Prepared according to GP1 starting from
phosphate 6e (182.8 mg, 0.43 mmol), 4-
methoxyphenylzinc chloride (1.2 mL, 0.54 mmol, 0.45 M),
Pd(OAc)2 (3.9 mg) and XPhos (16.5 mg), hexane:EtOAc
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(4:1, Rf = 0.3), yield 102.3 mg (53%), yellow oil. H NMR
(400 MHz, CDCl3) δ 7.26–7.20 (m, 4H), 7.17–7.10 (m, 4H),
7.00–6.94 (m, 4H), 6.75–6.68 (m, 2H), 3.76 (s, 3H), 2.74–
2.65 (m, 2H), 2.48–2.40 (m, 2H), 1.82–1.65 (m, 7H).
13C{1H} NMR (101 MHz, CDCl3) δ 158.1, 150.5 (d, J = 7.4
Hz), 146.7 (d, J = 9.4 Hz), 133.0 (d, J = 2.0 Hz), 129.6 (d, J =
0.5 Hz), 129.3, 129.3, 129.0 (d, J = 8.7 Hz), 125.0, 119.9 (d,
J = 5.1 Hz), 113.3, 55.2, 33.7, 33.3, 31.4, 26.4, 24.9. 31P
NMR (202 MHz, CDCl3) δ -17.53. HRMS (APCI) m/z: [M+H]+
Calcd for C26H27O5P 451.1669; Found 451.1647.
General procedure for the Negishi reaction of bromovinyl
phosphates 7 (GP2)
A solution of AlCl3 (1 equiv, 0.5M solution in THF) was
added to a mixture of phosphate 7, Pd(OAc)2 (4 mol %)
and dppp (4 mol %) at 23 °C. The resultant mixture was
stirred at 23 °C for 2 minutes and then a solution of
organozinc chloride (2.0 equiv) was added and the
reaction mixture was stirred at 23 °C for 12 hours. Then
the mixture was quenched by tartaric acid (10 mL, 1M
solution in water). The water layer was extracted with
diethyl ether (3x15 mL), the organic layer was dried over
MgSO4 and the solvents were removed under reduce
pressure. The product was isolated by column
chromatography.
2-(4-Methoxyphenyl)cyclooct-1-en-1-yl
diphenyl
phosphate (7fa).
Prepared according to GP1 starting from phosphate 6f
(356.7 mg, 0.82 mmol), 4-methoxyphenylzinc chloride
(2.2 mL, 0.99 mmol, 0.45 M), Pd(OAc)2 (7.3 mg) and XPhos
(31.1 mg), hexane:EtOAc (4:1, Rf = 0.3), yield 137.3 mg
General procedure for one-pot two step synthesis of 1,2-
disubstituted cyclohexenes (GP3)
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(36%), yellow oil. H NMR (400 MHz, CDCl3) δ 7.26–7.20
(m, 4H), 7.16 (d, J = 8.8 Hz, 2H), 7.14–7.09 (m, 2H), 6.98–
6.93 (m, 4H), 6.74 (d, J = 8.8 Hz, 2H), 3.76 (s, 3H), 2.70–
2.62 (m, 2H), 2.48–2.38 (m, 2H), 1.81–1.70 (m, 2H), 1.65–
1.52 (m, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 158.2, 150.5
(d, J = 7.5 Hz), 143.9 (d, J = 8.7 Hz), 131.4, 129.8 (d, J = 1.3
Hz), 129.5, 126.3 (d, J = 8.3 Hz), 125.0 (d, J = 1.1 Hz), 119.9
(d, J = 5.1 Hz), 113.4, 55.1, 32.8, 30.4, 28.9 (d, J = 2.5 Hz),
28.6 (d, J = 1.4 Hz), 26.6, 26.2.31P NMR (202 MHz, CDCl3)
δ -17.51. HRMS (APCI) m/z: [M+H]+ Calcd for C27H29O5P
465.1825; Found 465.1809.
Organozinc chloride (1.2 equiv) was added to a solution
of phosphate 6a, Pd(OAc)2 (4 mol %) and XPhos (8 mol %)
in THF (1 mL). The resultant mixture was stirred at 23 °C
for 12 h, afterthat the residual organozinc chloride was
quenched by addition of a solution of pivalic acid (0.2
equiv) in dry THF (1 mL). Then the crude reaction mixture
was stirred at 23 °C for 5 min, followed by addition of
Pd(OAc)2 (4 mol%) and dppp (4 mol%). The solution was
stirred at 23 °C for 5 min and organozinc chloride (2 equiv)
and AlCl3 (1.2 equiv, 0.5M solution of in THF) were added
and the reaction mixture was stirred at 23 °C for 12 h.
Then the mixture was quenched by tartaric acid (10 mL,
1M solution in water). The water layer was extracted with
diethyl ether (3x15 mL), the organic layer was dried over
MgSO4 and the solvents were removed under reduce
pressure. The product was isolated by column
chromatography.
Diphenyl (1,2,2-triphenylvinyl) phosphate (7gs). Prepared
according to GP1 starting from phosphate 6g (1.06 g, 2.09
mmol), phenylzinc chloride (5.0 mL, 2.50 mmol, 0.5 M),
Pd(OAc)2 (19.0 mg) and XPhos (80.0 mg) in THF (3mL),
hexane:EtOAc (4:1, Rf = 0.3), yield 0.836 g (79%), yellow
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solid, mp = 109.5−110.8 °C. H NMR (500 MHz, CDCl3) δ
7.44 (d, J = 6.8 Hz, 2H), 7.38 (d, J = 7.0 Hz, 2H), 7.28–7.12
(m, 11H), 7.12–7.06 (m, 5H), 7.04–6.99 (m, 2H), 6.81 (d, J
= 8.5 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ 150.5 (d, J
= 7.4 Hz), 143.8 (d, J = 8.8 Hz), 139.6, 139.2, 134.6, 131.2
(d, J = 8.8 Hz), 130.7, 130.5, 129.9, 129.5, 128.7, 128.2,
4-Methoxy-4''-methyl-3',4',5',6'-tetrahydro-1,1':2',1''-
terphenyl (8b). It was prepared according to GP2 starting
from phosphate 7aa (205.2 mg, 0.47 mmol), 4-tolylzinc
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chloride (1.9 mL, 0.95 mmol, 0.5 M), Pd(OAc)2 (4.2 mg),
128.7, 127.0, 126.9, 126.3, 113.1, 55.1, 32.2, 31.9, 23.4.
HRMS (APCI) m/z: [M+H]+ Calcd for C25H24O 341.1900;
Found 341.1887.
dppp (7.8 mg) and AlCl3 (0.94 mL, 0.47 mmol),
hexane:DCM (9:1 → 4:1, Rf = 0.4), yield 112.0 mg (86%),
white solid, mp = 52.0−55.4 °C. The title compound was
also prepared following GP3 starting from phosphate 6a
(496.3 mg, 1.21 mmol), 4-methoxyphenylzinc chloride (3
mL, 1.50 mmol, 0.5 M), Pd(OAc)2 (10.9 mg), XPhos (46.3
mg), PivOH (25 mg), Pd(OAc)2 (10.9 mg), dppp (20.0 mg),
4-tolylzinc chloride (4.9 mL, 2.45 mmol, 0.5 M) and AlCl3
(2.9 mL), 273.6 mg (81%).1H NMR (500 MHz, CDCl3) δ
6.95−6.85 (m, 6H), 6.65 (d, J = 8.5 Hz, 2H), 3.73 (s, 3H),
2.43 (s, 4H), 2.24 (s, 3H), 1.82 (s, 4H). 13C{1H} NMR (126
MHz, CDCl3) δ 157.4, 141.1, 136.5, 135.0, 134.3, 134.0,
130.1, 128.9, 128.4 113.0, 55.1, 32.1, 23.4, 21.1. HRMS
(EI) m/z: [M]+ Calcd for C20H22O 278.1671; Found
278.1662.
4''-Methoxy-3',4',5',6'-tetrahydro-[1,1':2',1''-terphenyl]-
4-carbonitrile (8f). Prepared according to GP2 starting
from phosphate 7aa (204.6 mg, 0.47 mmol), 4-
cyanophenylzinc chloride (4.8 mL, 0.96 mmol, 0.2 M),
Pd(OAc)2 (4.2 mg), dppp (7.7 mg) and AlCl3 (0.94 mL, 0.47
mmol), hexane:EtOAc (20:1, Rf = 0.1), yield 121.1 mg
(89%), yellow oil. 1H NMR (500 MHz, CDCl3) δ 7.38 (d, J =
7.7 Hz, 2H), 7.07 (d, J = 7.6 Hz, 2H), 6.85 (d, J = 7.9 Hz, 2H),
6.65 (d, J = 8.0 Hz, 2H), 3.73 (s, 3H), 2.61–2.29 (m, 4H),
1.83 (s, 4H). 13C{1H} NMR (126 MHz, CDCl3) δ 158.0, 149.3,
137.1, 135.2, 133.0, 131.6, 130.0, 129.9, 119.3, 113.3,
109.1, 55.1, 32.1, 31.4, 23.1. HRMS (APCI) m/z: [M+H]+
Calcd for C20H19NO 290.1539; Found 290.1522.
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4-Chloro-4''-methoxy-3',4',5',6'-tetrahydro-1,1':2',1''-
terphenyl (8c). Prepared according to GP2 starting from
phosphate 7aa (202.4 mg, 0.46 mmol), 4-
chlorophenylzinc chloride (1.93 mL, 0.93 mmol, 0.48 M),
Pd(OAc)2 (4.2 mg), dppp (7.6 mg) and AlCl3 (0.93 mL, 0.46
mmol), hexane:DCM (9:1 → 4:1, Rf = 0.4), yield 116.3 mg
(84%), light yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.07 (d,
J = 8.7 Hz, 2H), 6.91 (d, J = 8.7 Hz, 2H), 6.88 (d, J = 8.9 Hz,
2H), 6.66 (d, J = 8.8 Hz, 2H), 3.73 (s, 3H), 2.41 (s, 4H), 1.82
(s, 4H). 13C{1H} NMR (101 MHz, CDCl3) δ 157.6, 142.5,
135.8, 135.2, 133.2, 131.2, 130.4, 130.0, 127.8, 113.1,
55.1, 32.0, 31.8, 23.2. HRMS (APCI) m/z: [M+H]+ Calcd for
C19H19ClO 299.1197; Found 299.1182.
4''-Methoxy-N,N-dimethyl-3',4',5',6'-tetrahydro-
[1,1':2',1''-terphenyl]-4-amine (8g). Prepared according to
GP2 starting from phosphate 7aa (191.4 mg, 0.44 mmol),
4-N,N-dimethylaminophenylzinc chloride (2 mL, 0.88
mmol, 0.44 M), Pd(OAc)2 (3.9 mg), dppp (7.2 mg) and AlCl3
(0.88 mL, 0.44 mmol). hexane:EtOAc (20:1, Rf = 0.2),
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yield 79.1 mg (59%), yellow solid, mp = 62.5−65.8 °C. H
NMR (400 MHz, CDCl3) δ 6.95 (d, J = 8.8 Hz, 2H), 6.87 (d, J
= 8.9 Hz, 2H), 6.67 (d, J = 8.8 Hz, 2H), 6.51 (d, J = 8.8 Hz,
2H), 3.73 (s, 3H), 2.87 (s, 6H), 2.42 (s, 4H), 1.80 (s, 4H).
13C{1H} NMR (101 MHz, CDCl3) δ 157.2, 148.4, 136.9,
133.9, 132.7, 132.2, 130.1, 129.7, 113.0, 111.9, 55.1, 40.6,
32.1, 31.9, 23.5. HRMS (APCI) m/z: [M+H]+ Calcd for
C21H25NO 308.2009; Found 308.1998.
4-Fluoro-4''-methoxy-3',4',5',6'-tetrahydro-1,1':2',1''-
terphenyl (8d). Prepared according to GP2 starting from
phosphate 7aa (210.9 mg, 0.48 mmol), 4-fluorophenylzinc
chloride (2.2 mL, 0.97 mmol, 0.44 M), Pd(OAc)2 (4.3 mg),
dppp (8.0 mg) and AlCl3 (0.97 mL, 0.48 mmol),
hexane:DCM (9:1 → 4:1, Rf = 0.4), yield 116.2 mg (85%),
white solid, mp = 74.1−75.5 °C. 1H NMR (500 MHz, CDCl3)
δ 6.93 (dd, J = 8.4, 5.7 Hz, 2H), 6.88 (d, J = 8.3 Hz, 2H), 6.79
(t, J = 8.6 Hz, 2H), 6.65 (d, J = 8.3 Hz, 2H), 3.73 (s, 3H), 2.41
(s, 4H), 1.82 (s, 4H). 13C{1H} NMR (126 MHz, CDCl3) δ 160.9
(d, J = 244.4 Hz), 157.6, 140.0 (J = 3.8 Hz), 136.0, 134.8,
133.4, 130.5 (d, J = 7.6 Hz), 130.0, 114.5 (J = 21.4 Hz),
113.1, 55.1, 32.1, 32.0, 23.3. 19F NMR (471 MHz, CDCl3) δ
-117.59. HRMS (APCI) m/z: [M+H]+ Calcd for C19H19FO
283.1493; Found 283.1476.
2-(4'-Methoxy-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-
yl)furan (8h). Prepared according to GP2 starting from
phosphate 7aa (210.0 mg, 0.48 mmol), 2-furylzinc
chloride (2.75 mL, 0.96 mmol, 0.35 M), Pd(OAc)2 (4.3 mg),
dppp (7.9 mg) and AlCl3 (0.96 mL, 0.48 mmol),
hexane:DCM (9:1 → 4:1, Rf = 0.4), yield 89.4 mg (73%),
white solid. mp = 50.4−51.8 °C. 1H NMR (500 MHz, CDCl3)
δ 7.16 (s, 1H), 7.04 (d, J = 8.6 Hz, 2H), 6.85 (d, J = 8.6 Hz,
2H), 6.18–6.12 (m, 1H), 5.45 (d, J = 3.2 Hz, 1H), 3.81 (s,
3H), 2.52 (s, 2H), 2.38 (s, 2H), 1.78 (s, 4H). 13C{1H} NMR
(126 MHz, CDCl3) δ 158.3, 155.2, 140.0, 137.1, 136.0,
129.1, 123.9, 113.8, 110.6, 107.3, 55.2, 33.5, 27.3, 23.1,
22.6. HRMS (APCI) m/z: [M+H]+ Calcd for C17H18O2
255.1380; Found 255.1368.
4-Methoxy-3',4',5',6'-tetrahydro-1,1':2',1'':4'',1'''-
2-(4'-Methoxy-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-
quaterphenyl (8e). Prepared according to GP2 starting
from phosphate 7aa (195.8 mg, 0.45 mmol), 4-
biphenylzinc chloride (2.4 mL, 0.91 mmol, 0.38 M),
Pd(OAc)2 (4.0 mg), dppp (7.4 mg) and AlCl3 (0.90 mL, 0.45
mmol), hexane:DCM (9:1 → 4:1, Rf = 0.4), yield 140.9 mg
(92%), white solid, mp = 88.8−93.0 °C. 1H NMR (500 MHz,
CDCl3) δ 7.55 (d, J = 7.0 Hz, 2H), 7.44–7.31 (m, 4H), 7.29
(t, J = 7.4 Hz, 1H), 7.06 (d, J = 8.2 Hz, 2H), 6.95 (d, J = 8.6
Hz, 2H), 6.66 (d, J = 8.6 Hz, 2H), 3.72 (s, 3H), 2.53–2.42 (m,
4H), 1.85 (s, 4H). 13C{1H} NMR (126 MHz, CDCl3) δ 157.6,
143.2, 140.9, 138.1, 136.2, 134.7, 133.9, 130.1, 129.5,
yl)thiophene (8i). Prepared according to GP2 starting from
phosphate 7aa (200.1 mg, 0.46 mmol), 2-thienylzinc
chloride (1.5 mL, 0.93 mmol, 0.62 M), Pd(OAc)2 (4.1 mg),
dppp (7.6 mg) and AlCl3 (0.92 mL, 0.46 mmol),
hexane:DCM (9:1 → 4:1, Rf = 0.4), yield 99.0 mg (80%),
white solid, mp = 61.0−64.0 °C. 1H NMR (500 MHz, CDCl3)
δ 6.85 (d, J = 8.5 Hz, 2H), 6.81−6.78 (m, 1H), 6.68 (d, J = 3
Hz, 1H), 3.81 (s, 3H), 2.59−2.53 (m, 2H), 2.44−2.38 (m,
2H), 1.87−1.76 (m, 4H). 13C{1H} NMR (126 MHz, CDCl3) δ
158.6, 145.7, 136.5, 136.3, 130.0, 126.7, 125.9, 124.8,
124.1, 114.0, 55.2, 33.9, 31.3, 23.2, 23.0. HRMS (APCI)
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m/z: [M+H]+ Calcd for C17H18OS 271.1151; Found
0.2 M), Pd(OAc)2 (4.2 mg), dppp (7.6 mg) and AlCl3 (0.93
mL, 0.46 mmol), hexane:DCM (9:1 → 2:1, Rf = 0.3), yield
159.9 mg (100%), yellow solid, mp = 71.9−75.8 °C. 1H NMR
(500 MHz, CDCl3) δ 7.57 (d, J = 9.0 Hz, 1H), 7.47 (s, 1H),
7.43 (d, J = 8.5 Hz, 1H), 7.09–7.00 (m, 3H), 6.95 (d, J = 8.2
Hz, 2H), 6.61 (d, J = 8.3 Hz, 2H), 3.88 (s, 3H), 3.68 (s, 3H),
2.54 (s, 2H), 2.48 (s, 2H), 1.86 (s, 4H). 13C{1H} NMR (126
MHz, CDCl3) δ 157.5, 157.3, 139.6, 136.3, 134.5, 134.2,
132.8, 130.2, 129.3, 128.9, 128.8, 127.0, 125.3, 118.3,
113.1, 105.5, 55.3, 55.1, 32.19, 32.15, 23.5, 23.4. HRMS
(APCI) m/z: [M+H]+ Calcd for C24H24O2 345.1849; Found
345.1837.
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271.1142.
2-(4'-Methoxy-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-
yl)benzofuran (8j). Prepared according to GP2 starting
from phosphate 7aa (195.3 mg, 0.45 mmol), 2-
benzofurylzinc chloride (3 mL, 0.90 mmol, 0.3 M),
Pd(OAc)2 (4.0 mg), dppp (7.4 mg) and AlCl3 (0.89 mL, 0.45
mmol), hexane:DCM (9:1 → 4:1, Rf = 0.4), yield 84.0 mg
(62%), white solid, mp = 72.0−76.0 °C. 1H NMR (500 MHz,
CDCl3) δ 7.33 (d, J = 7.5 Hz, 1H), 7.27 (d, J = 7.4 Hz, 1H),
7.14 (t, J = 7.5 Hz, 1H), 7.11–7.06 (m, 3H), 6.84 (d, J = 8.6
Hz, 2H), 5.86 (s, 1H), 3.82 (s, 3H), 2.62 (s, 2H), 2.45 (s, 2H),
1.88–1.77 (m, 4H). 13C{1H} NMR (126 MHz, CDCl3) δ 158.5,
157.4, 153.6, 139.6, 136.6, 129.1, 128.9, 124.0, 123.3,
122.3, 120.5, 113.8, 110.7, 104.0, 55.3, 33.7, 27.6, 23.0,
22.6. HRMS (APCI) m/z: [M+H]+ Calcd for C21H20O2
305.1536; Found 305.1530.
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1-(4'-Methoxy-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-
yl)naphthalene (8n). Prepared according to modified GP2
starting from phosphate 7aa (208.1 mg, 0.48 mmol), 1-
naphthylzinc chloride (2.2 mL, 0.97 mmol, 0.44 M),
Pd(OAc)2 (4.3 mg), DPEPhos (10.3 mg), AlCl3 (0.95 mL,
0.48 mmol) and the reaction mixture was placed in an oil
bath at 45 °C and stirred for 12 h, hexane:DCM (9:1 → 4:1,
Rf = 0.4), yield 149.9 mg (100%), yellow oil. 1H NMR (500
MHz, CDCl3) δ 7.93 (d, J = 8.2 Hz, 1H), 7.76 (d, J = 7.8 Hz,
1H), 7.60 (d, J = 8.2 Hz, 1H), 7.45–7.37 (m, 2H), 7.26 (t, J =
7.6 Hz, 1H), 7.07 (d, J = 7.0 Hz, 1H), 6.88 (d, J = 8.5 Hz, 2H),
6.46 (d, J = 8.5 Hz, 2H), 3.59 (s, 3H), 2.61–2.48 (m, 3H),
2.40–2.28 (m, 1H), 2.03–1.83 (m, 4H). 13C{1H} NMR (126
MHz, CDCl3) δ 157.4, 142.4, 136.0, 135.8, 133.7, 133.6,
131.6, 128.8, 128.3, 126.5, 126.2, 125.9, 125.52, 125.50,
125.3, 54.9, 33.1, 31.8, 23.6, 23.3. HRMS (APCI) m/z:
[M+H]+ Calcd for C23H22O 315.1743; Found 315.1733.
2-(4'-Methoxy-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-
yl)thianaphthene (8k). Prepared according to GP2 starting
from phosphate 7aa (204.0 mg, 0.47 mmol), 2-
benzothiophenylzinc chloride (3.4 mL, 0.95 mmol, 0.28
M), Pd(OAc)2 (4.2 mg), dppp (7.7 mg) and AlCl3 (0.93 mL,
0.47 mmol), hexane:DCM (9:1 → 4:1, Rf = 0.4), yield
116.3 mg (78%), white solid. mp = 88.2−91.4 °C. 1H NMR
(500 MHz, CDCl3) δ 7.58 (dd, J = 12.1, 7.9 Hz, 2H), 7.21 (t,
J = 7.4 Hz, 1H), 7.16 (t, J = 7.5 Hz, 1H), 7.10 (d, J = 8.6 Hz,
2H), 6.95 (s, 1H), 6.82 (d, J = 8.6 Hz, 2H), 3.80 (s, 3H), 2.61
(s, 2H), 2.44 (s, 2H), 1.90–1.75 (m, 4H). 13C{1H} NMR (126
MHz, CDCl3) δ 158.8, 146.0, 139.8, 139.4, 138.6, 135.8,
130.1, 127.1, 123.8, 123.6, 123.0, 121.8, 121.4, 113.9,
55.2, 34.0, 31.3, 23.2, 23.0. HRMS (APCI) m/z: [M+H]+
Calcd for C21H20OS 321.1308; Found 321.1295.
4-Methoxy-2''-methyl-3',4',5',6'-tetrahydro-1,1':2',1''-
terphenyl (8o). Prepared according to modified GP2
starting from phosphate 7aa (203.1 mg, 0.47 mmol), 2-
tolylzinc chloride (2.4 mL, 0.96 mmol, 0.4 M), Pd(OAc)2
(4.2 mg), DPEPhos (10.0 mg) and AlCl3 (0.93 mL, 0.47
mmol) and the reaction mixture was placed in an oil bath
at 45 °C and stirred for 12 h, hexane:DCM (4:1, Rf = 0.4),
6-nButyl-4'-methoxy-2,3,4,5-tetrahydro-1,1'-biphenyl (8l).
Prepared according to GP2 starting from phosphate 7aa
(197.5 mg, 0.45 mmol), n-butylzinc chloride (1.93 mL, 0.91
mmol, 0.47 M), Pd(OAc)2 (4.1 mg), dppp (7.5 mg) and AlCl3
(0.91 mL, 0.46 mmol), hexane:DCM (9:1 → 4:1, Rf = 0.4),
yield 100.8 mg (91%), colorless oil. The title compound
was also prepared according to GP3 starting from
phosphate 6a (153.2 mg, 0.37 mmol), 4-
methoxyphenylzinc chloride (1.01 mL, 0.48 mmol, 0.48
M), Pd(OAc)2 (3.4 mg), XPhos (14.3 mg), PivOH (7.6 mg),
Pd(OAc)2 (3.4 mg), dppp (6.2 mg), n-butylzinc chloride (1.6
mL, 0.75 mmol, 0.47 M) and AlCl3 (0.75 mL, 0.38 mmol),
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yield 125.0 mg (96%), white solid, mp = 37.8–38.5 °C. H
NMR (400 MHz, CDCl3) δ 7.06–6.95 (m, 4H), 6.90 (d, J =
8.8 Hz, 2H), 6.59 (d, J = 8.8 Hz, 2H), 3.69 (s, 3H), 2.59–2.47
(m, 1H), 2.41–2.20 (m, 3H), 2.05 (s, 3H), 1.90–1.76 (m,
4H).13C{1H}NMR (101 MHz, CDCl3) δ 157.4, 143.7, 135.9,
134.9, 134.3, 134.0, 129.7, 129.4, 129.2, 126.0, 125.2,
112.7, 55.0, 32.4, 31.3, 23.5, 23.2, 19.5. HRMS (APCI) m/z:
[M+H]+ Calcd for C20H22O 279.1743; Found 279.1755.
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1-Methoxy-4-(2-(4-tolyl)cyclobut-1-en-1-yl)benzene (8p).
Prepared according to GP2 starting from phosphate 7ca
(181.3 mg, 0.44 mmol), 4-tolylzinc chloride (1.78 mL, 0.89
mmol, 0.5 M), Pd(OAc)2 (4.0 mg), dppp (7.3 mg) and AlCl3
(0.89 mL, 0.45 mmol), hexane:DCM (9:1 → 4:1, Rf = 0.4),
100.8 mg (91%). H NMR (500 MHz, CDCl3) δ 7.38 (t, J =
7.7 Hz, 4H), 7.32–7.27 (m, 4H), 7.23 (t, J = 7.4 Hz, 2H), 2.40
(s, 2H), 2.10–1.98 (m, 4H), 1.78–1.68 (m, 2H), 1.64–1.56
(m, 2H), 1.38–1.27 (m, 2H), 1.27–1.16 (m, 2H), 0.87 (t, J =
7.2 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ 157.7, 137.2,
133.3, 132.2, 129.4, 113.3, 55.2, 34.0, 32.7, 30.7, 28.8,
23.7, 23.2, 22.7, 14.1. HRMS (APCI) m/z: [M+H]+ Calcd for
C17H24O 245.1900; Found 245.1891.
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yield 97.3 mg (88%), white solid, mp = 74.0−75.0 °C. H
NMR (500 MHz, CDCl3) δ 7.47 (d, J = 8.6 Hz, 2H), 7.41 (d, J
= 8.0 Hz, 2H), 7.13 (d, J = 7.9 Hz, 2H), 6.85 (d, J = 8.6 Hz,
2H), 3.82 (s, 3H), 2.73 (s, 4H), 2.35 (s, 3H). 13C{1H} NMR
(126 MHz, CDCl3) δ 158.9, 137.4, 137.0, 136.7, 133.7,
129.3, 129.0, 127.4, 125.9, 113.7, 55.3, 26.8, 26.7, 21.4, in
accordance with reference.19b
2-Methoxy-6-(4'-methoxy-3,4,5,6-tetrahydro-[1,1'-
biphenyl]-2-yl)naphthalene (8m). Prepared according to
GP2 starting from phosphate 7aa (202.6 mg, 0.46 mmol),
6-methoxy-2-naphthylzinc chloride (4.65 mL, 0.93 mmol,
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1-Methoxy-4-(2-(4-tolyl)cyclopent-1-en-1-yl)benzene
4''-chloro-3',4',5',6'-tetrahydro-[1,1':2',1''-terphenyl]-4-ol
(8u). Prepared according to modified GP3 starting from
phosphate 6a (116.1 mg, 0.28 mmol), 4-chlorophenylzinc
chloride (0.71 mL, 0.34 mmol, 0.48 M), Pd(OAc)2 (2.5 mg),
XPhos (10.8 mg), PivOH (5.7 mg), Pd(OAc)2 (2.5 mg), dppp
(4.6 mg), (4-((tert-butyldimethylsilyl)oxy)phenyl)zinc
chloride (1.72 mL, 0.57 mmol, 0.33 M) and AlCl3 (0.68 mL,
0.34 mmol) and the reaction mixture was stirred at 23 °C
for 12 h Then the mixture was quenched by tartaric acid
(10 mL, 1M solution in water). The water layer was
extracted with diethyl ether (3x15 mL), the organic layer
was dried over MgSO4 and the solvents were removed
under reduce pressure. The crude product was dissolved
in THF (5 mL) and TBAF (0.3 mL, 1M in THF) was added.
The resultant mixture was stirred for 1 h at 23 °C. Then
the crude reaction mixture was diluted with ether (30
mL), the organic phase was washed with HCl (2 mL, 1M
aqueous solution), water (1x10 mL) and brine (1x10 mL).
The organic phase was dried over MgSO4, concentrated
under reduce pressure and the product was isolate by
column chromatography, hexane:EtOAc (9:1 → 6:1, Rf =
0.5), 67.9 mg (84%), colourless oil. 1H NMR (500 MHz,
CDCl3) δ 7.06 (d, J = 8.5 Hz, 2H), 6.90 (d, J = 8.5 Hz, 2H),
6.83 (d, J = 8.6 Hz, 2H), 6.58 (d, J = 8.6 Hz, 2H), 4.48 (s, 1H),
2.40 (s, 4H), 1.81 (s, 4H). 13C{1H} NMR (126 MHz, CDCl3) δ
153.6, 142.5, 136.1, 135.2, 133.4, 131.3, 130.4, 130.2,
127.8, 114.7, 32.1, 31.8, 23.2. HRMS (APCI) m/z: [M-H]-
Calcd for C18H17ClO 283.0895; Found 283.0898.
(8q). Prepared according to GP2 starting from phosphate
7da (105.7 mg, 0.25 mmol), 4-tolylzinc chloride (1.0 mL,
0.50 mmol, 0.5 M), Pd(OAc)2 (2.2 mg), dppp (4.1 mg) and
AlCl3 (0.50 mL, 0.25 mmol), hexane:DCM (9:1 → 4:1, Rf =
0.4), yield 65.1 mg (98%), white solid, mp = 50.0−54.0 °C.
1H NMR (500 MHz, CDCl3) δ 7.12 (d, J = 8.0 Hz, 2H), 7.09
(d, J = 7.6 Hz, 2H), 7.02 (d, J = 7.8 Hz, 2H), 6.75 (d, J = 8.1
Hz, 2H), 3.77 (s, 3H), 2.86 (t, J = 7.4 Hz, 4H), 2.30 (s, 3H),
2.01 (p, J = 7.4 Hz, 2H). 13C{1H} NMR (126 MHz, CDCl3) δ
158.2, 136.2, 136.2, 136.0, 135.8, 131.0, 129.3, 128.8,
128.0, 113.4, 55.2, 39.2, 39.0, 22.0, 21.2. HRMS (APCI)
m/z: [M+H]+ Calcd for C19H20O 265.1587; Found 265.1578.
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1-(4-Methoxyphenyl)-2-(4-tolyl)cyclohept-1-ene (8r). It
was prepared according to GP2 starting from phosphate
7ea (28.0 mg, 0.062 mmol), 4-tolylzinc chloride (0.25 mL,
0.13 mmol, 0.5 M), Pd(OAc)2 (0.6 mg), dppp (1.0 mg) and
AlCl3 (0.13 mL, 0.07 mmol), hexane:DCM (9:1 → 4:1, Rf =
0.4), yield 14.5 mg (80%), white solid, mp = 68.4−70.1 °C.
1H NMR (500 MHz, CDCl3) δ 6.92–6.83 (m, 6H), 6.63 (d, J =
8.6 Hz, 2H), 3.72 (s, 3H), 2.70–2.59 (m, 4H), 2.23 (s, 3H),
1.89 (p, J = 5.8 Hz, 2H), 1.77–1.63 (m, 4H). 13C{1H} NMR
(126 MHz, CDCl3) δ 157.3, 142.4, 140.2, 140.0, 137.8,
134.7, 130.0, 128.9, 128.3, 113.0, 55.1, 36.9, 32.8, 26.7,
21.1. HRMS (APCI) m/z: [M+H]+ Calcd for C21H24O
293.1900; Found 293.1885.
1-(4-Methoxyphenyl)-2-(4-tolyl)cyclooct-1-ene
(8s).
Prepared according to GP2 starting from phosphate 7fa
(49.7 mg, 0.11 mmol), 4-tolylzinc chloride (0.43 mL, 0.22
mmol, 0.5 M), Pd(OAc)2 (1.0 mg), dppp (1.8 mg) and AlCl3
(0.21 mL, 0.11 mmol). hexane:DCM (9:1 → 4:1, Rf = 0.4),
yield 6.0 mg (18%), colourless oil. 1H NMR (400 MHz,
CDCl3) δ 6.95–6.89 (m, 6H), 6.63 (d, J = 9.2 Hz, 2H), 3.72
(s, 3H), 2.67–2.58 (m, 4H), 2.22 (s, 3H), 1.81–1.57 (m, 8H).
13C{1H} NMR (101 MHz, CDCl3) δ 157.3, 141.6, 137.3,
137.0, 136.9, 134.8, 130.1, 129.0, 128.3, 112.9, 55.0, 34.2,
34.1, 29.8, 29.7, 26.9, 26.8, 21.1. HRMS (APCI) m/z:
[M+H]+ Calcd for C22H26O 307.2056; Found 307.2037.
6'-(thiophen-2-yl)-2',3',4',5'-tetrahydro-[1,1'-biphenyl]-4-
carbonitrile (8v). Prepared according to GP3 starting from
phosphate 6a (108.5 mg, 0.27 mmol), 4-cyanophenylzinc
chloride (1.33 mL, 0.32 mmol, 0.24 M), Pd(OAc)2 (2.4 mg),
XPhos (10.0 mg), PivOH (5.5 mg), Pd(OAc)2 (2.4 mg), dppp
(4.4 mg), 2-thienylzinc chloride (1.07 mL, 0.54 mmol, 0.5
M) and AlCl3 (0.64 mL, 0.32 mmol), hexane:DCM (9:1 →
2:1, Rf = 0.8), 40.0 mg (57%), white solid, mp = 120−124
1
°C. H NMR (500 MHz, CDCl3) δ 7.53 (d, J = 8.3 Hz, 2H),
7.23 (d, J = 8.3 Hz, 2H), 7.05 (dd, J = 5.2, 1.2 Hz, 1H), 6.77
(dd, J = 5.1, 3.6 Hz, 1H), 6.56 (dd, J = 3.7, 1.2 Hz, 1H), 2.57–
2.50 (m, 2H), 2.43–2.33 (m, 2H), 1.87–1.76 (m, 4H).
13C{1H} NMR (126 MHz, CDCl3) δ 149.3, 144.5, 135.1,
132.2, 129.8, 129.1, 126.3, 125.8, 124.6, 119.1, 110.2,
32.8, 31.9, 22.9, 22.7. HRMS (APCI) m/z: [M-H]- Calcd for
C17H15NS 264.0852; Found 264.0853.
2-(2-(6-Methoxynaphthalen-2-yl)cyclohex-1-en-1-
yl)thiophene (8t). Prepared according to GP3 starting
from phosphate 6a (160.1 mg, 0.39 mmol), 2-thienylzinc
chloride (0.76 mL, 0.47 mmol, 0.62 M), Pd(OAc)2 (3.5 mg),
XPhos (14.9 mg), PivOH (8.0 mg), Pd(OAc)2 (3.5 mg), dppp
(6.4 mg), 6-methoxy-2-naphthylzinc chloride (3.91 mL,
0.78 mmol, 0.2 M) and AlCl3 (0.78 mL, 0.39 mmol),
hexane:DCM (9:1 → 4:1, Rf = 0.4), 100.0 mg (80%), light
yellow solid, mp = 99.5−101.8 °C. 1H NMR (500 MHz,
CDCl3) δ 7.72–7.67 (m, 2H), 7.63 (s, 1H), 7.24 (dd, J = 8.4,
1.5 Hz, 1H), 7.18–7.13 (m, 2H), 6.99–6.95 (m, 1H), 6.78–
6.75 (m, 1H), 6.70 (d, J = 3.5 Hz, 1H), 3.96 (s, 3H), 2.69–
2.61 (m, 2H), 2.58–2.50 (m, 2H), 1.98–1.83 (m, 4H).13C{1H}
NMR (126 MHz, CDCl3) δ 157.6, 145.5, 139.5, 136.6,
133.5, 129.5, 129.2, 128.2, 127.3, 127.1, 126.8, 125.9,
125.1, 124.2, 118.6, 105.7, 55.3, 33.9, 31.4, 23.2, 23.1.
HRMS (APCI) m/z: [M+H]+ Calcd for C21H20OS 321.1308;
Found 321.1295.
1-methyl-2-(2-(thiophen-2-yl)cyclohex-1-en-1-yl)-1H-
indole (8w). Prepared according to GP3 starting from
phosphate 6a (105.7 mg, 0.26 mmol), 2-thienylzinc
chloride (0,63 mL, 0.32 mmol, 0.5 M), Pd(OAc)2 (2.3 mg),
XPhos (9.9 mg), PivOH (5.3 mg), Pd(OAc)2 (2.3 mg), dppp
(4.2 mg), 2-(N-methylindol)zinc chloride (1.4 mL, 0.53
mmol, 0.38 M) and AlCl3 (0.62 mL, 0.31 mmol),
hexane:DCM (100:0 → 9:1, Rf = 0.2), 62.9 mg (83%), white
solid, mp = 79−82 °C. 1H NMR (500 MHz, CDCl3) δ 7.61 (d,
J = 7.8 Hz, 1H), 7.29–7.26 (m, 1H), 7.22–7.16 (m, 1H), 7.11
(t, J = 7.2 Hz, 1H), 6.99 (dd, J = 5.1, 1.1 Hz, 1H), 6.77 (dd, J
= 5.0, 3.8 Hz, 1H), 6.70 (d, J = 3.7 Hz, 1H), 6.38 (s, 1H), 3.36
(s, 3H), 2.69 (s, 2H), 2.43 (s, 2H), 1.91–1.79 (m, 4H). 13C{1H}
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NMR (126 MHz, CDCl3) δ 144.3, 141.7, 137.1, 132.0,
(m, 3H), 7.03–6.94 (m, 4H), 6.81–6.75 (m, 2H), 6.58–6.51
(m, 2H), 3.69 (s, 3H), 2.44–2.32 (m, 2H), 2.28 (s, 3H), 1.35–
1.11 (m, 4H), 0.76 (t, J = 7.1 Hz, 3H), in accordance with
ref.19e
128.4, 126.2, 126.1, 125.4, 124.7, 121.1, 120.5, 119.4,
109.6, 100.2, 34.0, 30.5, 29.7, 23.0, 22.8. HRMS (APCI)
m/z: [M+H]+ Calcd for C19H19NS 294.1311; Found
294.1317.
ASSOCIATED CONTENT
2-(4'-methyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-
Supporting Information. The Supporting Information is
available free of charge via the Internet at
yl)thiophene (8x). Prepared according to GP3 starting
from phosphate 6a (126.6 mg, 0.31 mmol), 4-tolylzinc
chloride (0.79 mL, 0.37 mmol, 0.47 M), Pd(OAc)2 (2.8 mg),
XPhos (11.8 mg), PivOH (6.3 mg), Pd(OAc)2 (2.8 mg), dppp
(5.1 mg), 2-thienylzinc chloride (1.25 mL, 0.63 mmol, 0.50
M) and AlCl3 (0.74 mL, 0.37 mmol), hexane:DCM (100:0
→ 9:1, Rf = 0.5), 63.0 mg (80%), white solid, mp = 46−48
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http://pubs.acs.org.
Experimental
procedures,
characterizations of new compounds, NMR spectra data.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
1
°C. H NMR (500 MHz, CDCl3) δ 7.10 (d, J = 7.8 Hz, 2H),
7.03 (d, J = 8.0 Hz, 2H), 6.99 (dd, J = 5.2, 1.2 Hz, 1H), 6.77
(dd, J = 5.1, 3.6 Hz, 1H), 6.65 (dd, J = 3.7, 1.2 Hz, 1H), 2.60–
2.50 (m, 2H), 2.43–2.37 (m, 3H), 2.34 (s, 3H), 1.86–1.75
(m, 4H). 13C{1H} NMR (126 MHz, CDCl3) δ 145.6, 141.2,
136.7, 136.3, 129.2, 128.7, 126.6, 125.9, 124.8, 124.0,
33.8, 31.4, 23.2, 23.0, 21.3. HRMS (APCI) m/z: [M+H]+
Calcd for C17H18S 255.1202; Found 255.1204.
This work was supported from the grant of
specific university research
– grant No
A2_FCHT_2020_023 and the Grant Agency of
the Czech Republic (Grant No 18-12150S).
6'-(1-methyl-1H-indol-2-yl)-2',3',4',5'-tetrahydro-[1,1'-
biphenyl]-4-carbonitrile (8y). Prepared according to
modified GP3 starting from phosphate 6a (137.1 mg, 0.34
mmol), 4-cyanophenylzinc chloride (1.68 mL, 0.40 mmol,
0.24 M), Pd(OAc)2 (3.0 mg), XPhos (12.8 mg), PivOH (6.9
mg), Pd(OAc)2 (3.0 mg), dppp (5.5 mg), 2-(N-
methylindol)zinc chloride (1.8 mL, 0.68 mmol, 0.38 M)
and AlCl3 (0.80 mL, 0.40 mmol), hexane:DCM (9:1 → 2:1,
Rf = 0.5), 39.5 mg (38%), white solid, mp = 122−124 °C. 1H
NMR (500 MHz, CDCl3) δ 7.51 (d, J = 7.8 Hz, 1H), 7.35 (d, J
= 8.4 Hz, 2H), 7.14–7.09 (m, 4H), 7.08–7.04 (m, 1H), 6.27
(s, 1H), 3.22 (s, 3H), 2.57–2.51 (m, 2H), 2.50–2.44 (m, 2H),
1.95–1.83 (m, 4H). 13C{1H} NMR (126 MHz, CDCl3) δ 147.8,
141.3, 137.5, 136.9, 131.7, 129.1, 128.6, 127.9, 121.2,
120.2, 119.6, 118.9, 109.9, 109.4, 101.0, 32.9, 30.9, 30.3,
23.0, 22.7. HRMS (APCI) m/z: [M+H]+ Calcd for C22H20N2
313.1699; Found 313.1703.
References
1. Selected recent reviews: (a) Biffis, A.; Centomo, P.; Del Zotto
A.; Zecca, M., Pd Metal Catalysts for Cross-Couplings and Related
Reactions in the 21st Century: A Critical Review. Chem. Rev. 2018,
118, 2249−2295; (b) Cahiez, G.; Moyeux, A., Cobalt-Catalyzed
Cross-Coupling Reactions. Chem. Rev. 2010, 110, 1435−1462. (c)
Cherney, A. H.; Kadunce, N. T.; Reisman, S. E., Enantioselective
and Enantiospecific Transition-Metal-Catalyzed Cross-Coupling
Reactions of Organometallic Reagents To Construct C–C Bonds.
Chem. Rev. 2015, 115, 9587−9652.
2. Selected recent reviews: (a) Moselage, M.; Li J.; Ackermann, L.,
Cobalt-Catalyzed C–H Activation, ACS Catalysis 2016, 6, 498−525.
(b) Ruiz-Castillo, P.; Buchwald, S. L., Applications of Palladium-
Catalyzed C-N Cross-Coupling Reactions, Chem. Rev. 2016, 116,
12564−12649. (c) Shang, M.; Sun, S.-Z.; Wang, H.-L.; Wang, M.-
M.; Dai, H.-X., Recent Progress on Copper-Mediated Directing-
Group-Assisted C(sp2)–H Activation. Synthesis 2016, 48,
4381−4399. (d) Wang, C., Manganese-Mediated C–C Bond
Formation via C–H Activation: From Stoichiometry to Catalysis.
Synlett 2013, 24, 1606−1613.
2-(4-Methoxyphenyl)-1,1,2-triphenylethene
(9a).
Prepared according to GP2 starting from phosphate 7gs
(205.9 mg, 0.41 mmol), 4-methoxyphenylzinc chloride
(1.71 mL, 0.82 mmol, 0.48 M), Pd(OAc)2 (3.7 mg), dppp
(6.7 mg) and AlCl3 (0.82 mL, 0.41 mmol), hexane:DCM (9:1
→ 4:1, Rf = 0.4), 72.0 mg (49%). 1H NMR (500 MHz, CDCl3)
δ 7.14–7.06 (m, 9H), 7.06–6.99 (m, 6H), 6.93 (d, J = 8.7 Hz,
2H), 6.63 (d, J = 8.7 Hz, 2H), 3.73 (s, 3H). 13C{1H} NMR (126
MHz, CDCl3) δ 158.1, 144.1, 144.0, 140.6, 140.1, 136.1,
132.5, 131.4, 131.4, 131.4, 127.7, 127.6, 126.4, 126.3,
113.1, 55.1, in accordance with ref.22
3. Selected recent reviews: (a) Meng, G.; Shi, S.; Szostak, M.,
Cross-Coupling of Amides by N–C Bond Activation. Synlett 2016,
27, 2530−2540. (b) Pound, S. M.; Watson, M. P., Asymmetric
synthesis via stereospecific C–N and C–O bond activation of alkyl
amine and alcohol derivatives. Chem. Commun. 2018, 54,
12286−12301. (c) Wang, Q.; Su, Y.; Li, L.; Huang, H., Transition-
metal catalysed C–N bond activation, Chem. Soc. Rev. 2016, 45,
1257−1272.
4. Selected recent reviews: (a) Cheng, H.-G.; Chen, H.; Liu, Y.
Zhou, Q., The Liebeskind–Srogl Cross-Coupling Reaction and its
Synthetic Applications. Asian J. Org. Chem. 2018, 7, 490−508. (b)
Pan, F.; Shi, Z.-J., Recent Advances in Transition-Metal-Catalyzed
C–S Activation: From Thioester to (Hetero)aryl Thioether. ACS
Catalysis 2014, 4, 280−288. (c) Prokopcová, H.; Kappe, C. O., The
Liebeskind–Srogl C−C Cross-Coupling Reaction. Angew. Chem.
Int. Ed. 2009, 48, 2276−2286.
(Z)-1-methoxy-4-(1-phenyl-2-(p-tolyl)hex-1-en-1-
yl)benzene (9b). Prepared according to modified GP2
starting from phosphate 7ht (87.7 mg, 0.17 mmol), 4-
tolylzinc chloride (0.73 mL, 0.37 mmol, 0.40 M), Pd(OAc)2
(1.5 mg), DPEPhos (3.7 mg) and AlCl3 (0.34 mL, 0.17
mmol), hexane:DCM (9:1 → 4:1, Rf = 0.4), 22.0 mg (36%).
1H NMR (300 MHz, CDCl3) δ 7.37–7.29 (m, 2H), 7.27–7.19
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Page 16 of 17
1
2
3
4
5
6
7
8
9
5. Selected recent reviews: (a) Bisz, E.; Szostak, M., Iron-
13. (a) Cahiez, G.; Avedissian, H., Highly Stereo- and
Chemoselective Iron-Catalyzed Alkenylation of
Catalyzed C−O Bond Activation: Opportunity for Sustainable
Catalysis. ChemSusChem 2017, 10, 3964−3981. (b) Gooßen, L. J.;
Gooßen, K.; Stanciu, C., C(aryl)-O Activation of Aryl Carboxylates
in Nickel-Catalyzed Biaryl Syntheses. Angew. Chem. Int. Ed. 2009,
48, 3569−3571. (c) Tobisu, M.; Chatani, N., Cross-Couplings Using
Aryl Ethers via C–O Bond Activation Enabled by Nickel Catalysts.
Acc. Chem. Res. 2015, 48, 1717−1726. (d) Tobisu, M.; Chatani, N.,
Nickel-Catalyzed Cross-Coupling Reactions of Unreactive
Phenolic Electrophiles via C–O Bond Activation. Topics Curr.
Chem. 2016, 374, 41.
Organomagnesium Compounds. Synthesis, 1998, 1199−1205. (b)
Cahiez, G.; Gager, O.; Habiak, V., Iron-Catalyzed Alkenylation of
Grignard Reagents by Enol Phosphates. Synthesis, 2008,
2636−2644. (c) Cahiez, G.; Habiak, V.; Gager, O., Efficient
Preparation of Terminal Conjugated Dienes by Coupling of Dienol
Phosphates with Grignard Reagents under Iron Catalysis. Org.
Lett., 2008, 10, 2389−2392. (d) Fiorito, D.; Folliet, S.; Liu, Y.;
Mazet, C., A General Nickel-Catalyzed Kumada Vinylation for the
Preparation of 2-Substituted 1,3-Dienes. ACS Catalysis 2018, 8,
1392−1398. (e) Gauthier, D.; Beckendorf, S.; Gøgsig, T. M.;
Lindhardt, A. T.; Skrydstrup, T., A Ligand Free and Room
Temperature Protocol for Pd-Catalyzed Kumada−Corriu
Couplings of Unactivated Alkenyl Phosphates. J. Org. Chem.
2009, 74, 3536−3539. (f) Karlström, A. S. E.; Itami, K.; Bäckvall, J.-
E., Nickel-Catalyzed Cross-Coupling of Dienyl Phosphates with
Grignard Reagents in the Synthesis of 2-Substituted 1,3-Dienes.
J. Org. Chem., 1999, 64, 1745−1749. (g) You, W.; Li, Y.; Brown, M.
K., Stereoselective Synthesis of All-Carbon Tetrasubstituted
Alkenes from In Situ Generated Ketenes and Organometallic
Reagents. Org. Lett., 2013, 15, 1610−1613.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
6. Aggarwal, V. K.; Humphries, P. S.; Fenwick, A., A Formal
Asymmetric
Synthesis
of
(+)-Anatoxin-a Using
an
Enantioselective Deprotonation Strategy on an Eight-Membered
Ring. Angew. Chem. Int. Ed. 1999, 38, 1985−1986.
7. Fuwa, H.; Ishigai, K.; Hashizume, K., Sasaki, M., Total Synthesis
and Complete Stereostructure of Gambieric Acid A. J. Am. Chem.
Soc. 2012, 134, 11984−11987.
8. Fuwa, H.; Naito, S.; Goto, T.; Sasaki, M., Total Synthesis of (+)-
Neopeltolide. Angew. Chem. Int. Ed. 2008, 47, 4737−4739.
14. Lindhardt, A. T.; Gøgsig, T. M.; Skrydstrup, T., Studies on the
1,2-Migrations in Pd-Catalyzed Negishi Couplings with JosiPhos
Ligands. J. Org. Chem. 2009, 74, 135−143.
9. Fuwa, H.; Sakamoto, K.; Muto, T.; Sasaki, M., Concise synthesis
of the C15–C38 fragment of okadaic acid, a specific inhibitor of
protein phosphatases
1 and 2A. Tetrahedron 2015, 71,
6369−6383.
15. (a) Ebran, J.-P.; Hansen, A. L.; Gøgsig, T. M.; Skrydstrup, T.,
Studies on the Heck Reaction with Alkenyl Phosphates:ꢀ Can the
1,2-Migration Be Controlled? Scope and Limitations, J. Am.
Chem. Soc., 2007, 129, 6931−6942. (b) Hansen, A. L.; Ebran, J.-P.;
Ahlquist, M.; Norrby, P.-O.; Skrydstrup, T., Heck Coupling with
Nonactivated Alkenyl Tosylates and Phosphates: Examples of
Effective 1,2-Migrations of the Alkenyl Palladium(II)
Intermediates. Angew. Chem. Int. Ed. 2006, 45, 3349−3353.
10. Selected recent reviews: (a) Fuwa, H., Palladium-Catalyzed
Synthesis of N- and O-Heterocycles Starting from Enol
Phosphates. Synlett 2011, 6−29. (b) Han, F.-S., Transition-metal-
catalyzed Suzuki–Miyaura cross-coupling reactions: a remarkable
advance from palladium to nickel catalysts. Chem. Soc. Rev. 2013,
42, 5270−5298. (c) Li, B.-J.; Yu, D.-G.; Sun, C.-L.; Shi, Z.-J.,
Activation of “Inert” Alkenyl/Aryl C-O Bond and Its Application in
Cross-Coupling Reactions. Chem.Eur. J. 2011, 17, 1728−1759. (d)
Li, W.-N.; Wang, Z.-L., Kumada–Tamao–Corriu cross-coupling
reaction of O-based electrophiles with Grignard reagents via C–
O bond activation. RSC Adv. 2013, 3, 25565−25575.
16. Hu, X.-H.; Yang, X.-F.; Loh, T.-P. Selective Alkenylation and
Hydroalkenylation of Enol Phosphates through Direct C−H
Functionalization. Angew. Chem. Int. Ed. 2015, 54, 15535−15539.
17. Ackermann, L.; Barfüsser, S.; Pospech, J., Palladium-Catalyzed
Direct Arylations, Alkenylations, and Benzylations through C−H
Bond Cleavages with Sulfamates or Phosphates as Electrophiles.
Org. Lett. 2010, 12, 724-726.
11. (a) Nicolaou, K. C.; Yu, R.; Shi, L.; Cai, Q.; Lu, M.; Heretsch, P.,
General Synthetic Approach to Functionalized Dihydrooxepines.
Org. Lett. 2013, 15, 1994−1997. (b) Takai, K.; Oshima, K.; Nozaki,
H., Carbon-carbon bond formation by cross-coupling of enol
phosphates with organoaluminium compounds catalyzed by
palladium(O) complex. Tetrahedron Lett. 1980, 21, 2531−2534.
18. (a) Lagerlund, O.; Mantel, M. L. H.; Larhed, M.,
Aminocarbonylations of alkenyl phosphates, chlorides,
bromides, and triflates with Mo(CO)6 as a solid CO source.
Tetrahedron 2009, 65, 7646−7652. (b) Takeuchi, R.; Akiyama, Y.,
Iridium complex-catalyzed carbonylation of allylic phosphates, J.
Organomet. Chem. 2002, 651, 137−145.
12. (a) Fuwa, H.; Sasaki, M., Synthesis of 2-Substituted Indoles
and Indolines via Suzuki−Miyaura Coupling/5-endo-trig
Cyclization Strategies. J. Org. Chem. 2009, 74, 212−221 (b)
Hansen, A. L.; Ebran, J.-P.; Gøgsig, T. M.; Skrydstrup, T., Direct
synthesis of 1,1-diarylalkenes from alkenyl phosphates via
nickel(0)-catalysed Suzuki–Miyaura coupling. Chem. Commun.
2006, 4137−4139. (c) Hansen, A. L.; Ebran, J.-P.; Gøgsig, T. M.;
Skrydstrup, T., Investigations on the Suzuki−Miyaura and Negishi
Couplings with Alkenyl Phosphates:ꢀ Application to the Synthesis
of 1,1-Disubstituted Alkenes. J. Org. Chem. 2007, 72, 6464−6472.
(d) Nakatsuji, H.; Ashida, Y.; Hori, H.; Sato, Y.; Honda, A.; Taira,
M.; Tanabe, Y., (E)- and (Z)-stereodefined enol phosphonates
derived from β-ketoesters: stereocomplementary synthesis of
fully-substituted α,β-unsaturated esters. Org. Biomol. Chem.
2015, 13, 8205−8210. (e) Nan, Y.; Yang, Z., Nickel-catalyzed cross-
couplings of cyclohexenyl phosphate and arylboronic acids.
Tetrahedron Lett. 1999, 40, 3321−3324.
19. (a) Kotek, V.; Polák, P.; Dvořáková, H.; Tobrman, T., Aluminum
Chloride Promoted Cross-Coupling of Trisubstituted Enol
Phosphates with Organozinc Reagents En Route to the
Stereoselective Synthesis of Tamoxifen and Its Analogues. Eur. J.
Org. Chem. 2016, 5037−5044. (b) Polák, P.; Tobrman, T., Novel
Selective Approach to Terminally Substituted [n]Dendralenes,
Eur. J. Org. Chem. 2019, 957−968. 21. (c) Polák, P.; Čejka, J.;
Tobrman, T., Formal Transition-Metal-Catalyzed Phosphole C-H
Activation for the Synthesis of Pentasubstituted Phospholes. Org
Lett. 2020, 22, 2187−2190. (d) Čubiňák, M.; Eigner, V.; Tobrman,
T., Bench-Stable Sulfoxide-Based Boronates: Preparation and
Application in a Tandem Suzuki Reaction. Adv. Synth. Catal. 2018,
360, 4604−4614. (e) Kotek, V.; Dvořáková, H.; Tobrman, T.,
Modular and Highly Stereoselective Approach to All-Carbon
Tetrasubstituted Alkenes. Org. Lett. 2015, 17, 608−611.
ACS Paragon Plus Environment

Page 17 of 17
The Journal of Organic Chemistry
1
2
3
20. (a) Gong, H.; Sinisi, R.; Gagné, M. R., A Room Temperature
Negishi Cross-Coupling Approach to C-Alkyl Glycosides. J. Am.
Chem. Soc. 2007, 129, 1908−1909. (b) Hadei, N.; Kantchev, E. A.
B.; O'Brie, C. J.; Organ, M. G., The First Negishi Cross-Coupling
Reaction of Two Alkyl Centers Utilizing a Pd−N-Heterocyclic
Carbene (NHC) Catalyst. Org. Lett. 2005, 7, 3805−3807. (c) Hadei,
N.; Kantchev, E. A. B.; O'Brien, C. J.; Organ, M. G., Room-
Temperature Negishi Cross-Coupling of Unactivated Alkyl
Bromides with Alkyl Organozinc Reagents Utilizing a Pd/N-
Heterocyclic Carbene Catalyst. J. Org. Chem. 2005, 70,
8503−8507. (d) Zhou, J.; Fu, G. C., Cross-Couplings of Unactivated
Secondary Alkyl Halides:ꢀ Room-Temperature Nickel-Catalyzed
Negishi Reactions of Alkyl Bromides and Iodides. J. Am. Chem.
Soc. 2003, 125, 14726−14727.
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
21. Muraki, T.; Yokoyama, M.; Togo, H., Iodophosphoryloxylation
of carbon-carbon multibonds and its application to glycals. J. Org.
Chem. 2000, 65, 4679−4684.
22. Xue, F.; Zhao, J.; Hor, T. S. A.; Hayashi, T., Nickel-Catalyzed
Three-Component Domino Reactions of Aryl Grignard Reagents,
Alkynes, and Aryl Halides Producing Tetrasubstituted Alkenes. J.
Am. Chem. Soc. 2015, 137, 3189−3192.
ACS Paragon Plus Environment