Formation of trisubstituted buta-1,3-dienes and α,β-unsaturated ketonesviathe reaction of functionalized vinyl phosphates and vinyl phosphordiamidates with organometallic reagents

Article abstract of DOI:10.1039/d0ra07472a

We studied the reactions of vinyl phosphates and vinyl phosphordiamidates containing an ester functional group with organometallic reagents. We found that the functionalized vinyl phosphates were smoothly converted into tri- and tetrasubstituted buta-1,3-

Full text of DOI:10.1039/d0ra07472a

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PAPER
Formation of trisubstituted buta-1,3-dienes and
a,b-unsaturated ketones via the reaction of
functionalized vinyl phosphates and vinyl
phosphordiamidates with organometallic
reagents†
Cite this: RSC Adv., 2020, 10, 35109
a
Petr Oeser,‡a Jakub Koudelka,‡a Hana Dvorakovab and Tomas Tobrman
*
ˇ´
´
´ˇ
We studied the reactions of vinyl phosphates and vinyl phosphordiamidates containing an ester functional
group with organometallic reagents. We found that the functionalized vinyl phosphates were smoothly
converted into tri- and tetrasubstituted buta-1,3-dienes via the reaction with aryllithium reagents.
Moreover, the vinyl phosphordiamidates were converted into a,b-unsaturated ketones using Grignard
reagents. Based on the performed experiments, we proposed a reaction mechanism, which was
confirmed by means of the isolation of key intermediates.
Received 30th July 2020
Accepted 15th September 2020
DOI: 10.1039/d0ra07472a
rsc.li/rsc-advances
Despite considerable progress having been made in relation
to the preparation and application of functionalized Grignard
reagents,10 the preparation of alkenes with functional groups
that react with Grignard reagents using the KTC reaction
remains difficult (Scheme 1). The vinyl phosphates 1 with
a carbonyl group attached to the vinyl unit have been used in
the stoichiometric synthesis of organoselenium11 and organo-
tellurium compounds.12 A methodology for the stoichiometric
Introduction
A Kumada–Tamao–Corriu (KTC) reaction is a representative
example of the traditional cross-coupling reaction of an elec-
trophilic template with an organometallic reagent, as repre-
sented by Grignard reagents. This reaction is frequently used for
the formation of a C–C bond.1 Among the various electrophilic
templates that are suitable for use in a KTC reaction, substrates
containing an activated C–O bond are considered particularly
attractive. The reason behind the popularity of such substrates
is their availability, which is associated with their preparation.
Recent examples of the cross-coupling reactions of ethers,2
tosylates,3 and triates4 with Grignard reagents all illustrate the
KTC reaction potential of compounds with an activated C–O
bond. Using this approach, a wide variety of substances can be
prepared, including substituted alkenes.
The stereoselective synthesis of di-, tri-,5 and tetrasub-
stituted6 double bonds has been the subject of signicant
research attention in recent decades. Vinyl phosphates also play
a key role in the synthesis of substituted alkenes. Unsurpris-
ingly, a number of KTC reactions have been described in which
the reaction of the vinyl phosphates has been catalyzed by iron,7
nickel,8 or palladium9 catalysts in order to prepare the
substituted double bond.
aDepartment of Organic Chemistry, University of Chemistry and Technology, Prague,
´
Technicka 5, 166 28 Prague 6, Czech Republic. E-mail: tomas.tobrman@vscht.cz
bLaboratory of NMR Spectroscopy, University of Chemistry and Technology, Prague,
´
Technicka 5, 166 28 Prague 6, Czech Republic
† Electronic supplementary information (ESI) available. See DOI:
10.1039/d0ra07472a
Scheme 1 General scheme representing the replacement of the
phosphate group of the functionalized vinyl phosphates 1.
‡ These authors contributed equally to the work.
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Table 1 Optimization of the reaction of the vinyl phosphates 2a–c
with phenylmagnesium chloride and phenyllithium
cross-coupling reaction of the functionalized vinyl phosphates
with dialkylcuprates has also been described.13 This method-
ology has been successfully used in the eld of organic
synthesis14 as well as in the total synthesis of naturally occurring
compounds.15 The catalytic reactions of the functionalized vinyl
phosphates represented by the general structure 1 include
reactions with organoaluminum compounds,16 iron-catalyzed
reactions with methylmagnesium halides,17 and nickel-
catalyzed cross-coupling reactions with trimethylsilylme-
thylmagnesium chloride.18 These prior results contrast with
a recent report of the KTC reaction of functionalized vinyl
tosylates being performed in dry acetonitrile at 45 ꢀC.3b The
absence of a general methodology for the KTC reaction of the
functionalized vinyl phosphates 1 with Grignard reagents may
indicate that this type of vinyl phosphate exhibits low stability
in the presence of Grignard reagents. Our review of the litera-
ture indicated that a systematic study of the reactivity of the
functionalized vinyl phosphates 1 with organometallic reagents
has not previously been reported. Thus, based on our earlier
studies of the cross-coupling reactions of vinyl phosphates,19 we
decided to investigate the stability of the functionalized vinyl
phosphates 2a–2c in the presence of Grignard reagents.
Entry
2
M
Workup
3ab (%)
1
2
3
4
5
6
7
8
9
2a
2a
2a
2a
2a
2a
2b
2a
2c
MgCl
MgCl
MgCl
MgCl
MgCl
MgCl
MgCl
Li
NH4Cl
AcOH/MeOH
HCl
H2SO4
H3PO4
H3PO4
H3PO4
H3PO4
H3PO4
27
28
42
40
42
45a
40
51
65
Li
a
b
Six equivalents of phenylmagnesium chloride were used. Isolated
yield.
Results and discussion
yield. A similar reactivity pattern was observed with regard to
the diethyl phosphate with an extended alkyl chain 2d. In this
case, the dienes 3f–3i were obtained in similar isolated yields to
the dienes 3a–3c. The phosphate 2d was also reacted with 2-
methoxyphenyllithium and 2-thienyllithium, as an example of
a heteroaryl reagent, in order to give the dienes 3j and 3k. The
We began our study by synthesizing the vinyl phosphate 2a by
means of the enolization of ethyl acetoacetate, followed by the
reaction of the formed enolate with diethyl chlorophosphate.
The prepared phosphate 2a was mixed with phenylmagnesium
chloride, and then the reaction mixture was stirred for 2 hours
at 23 ꢀC. Aer the reaction mixture was quenched with aqueous
ammonium chloride, the formation of a complex mixture of
products was observed based on analysis of the 1H nuclear
magnetic resonance (1H NMR) spectrum of the mixture.
However, we isolated the trisubstituted diene 3a as a pure
compound in an isolated yield of 27%. This nding was
particularly interesting, as the synthesis of trisubstituted dienes
is generally limited. The palladium-catalyzed coupling of
tosylhydrazones with aryl halides,20 the selective arylation of
vinylarenes,21 and diethyl-phosphite-promoted carbonyl ole-
nation22 are recently reported methods for the synthesis of
substituted buta-1,3-dienes. We observed that the isolated yield
of the diene 3a strongly depended on the reaction workup, with
comparatively higher yields of the alkene 3a being achieved
with hydrochloric acid, sulfuric acid, and phosphoric acid
(Table 1, entries 3–5). The isolated yield of the alkene 3a did not
affect the increased equivalents of phenylmagnesium chloride
or the use of the diphenylphosphate 2b (Table 1, entries 6 and
7). The best isolated yield of the diene 3a was obtained when
phenyllithium was used in combination with the phenyl ester 2c
(Table 1, entry 9).
Optimized reaction conditions were used to evaluate the
scope of the reaction (Scheme 2). The diethyl phosphate 2c
reacted with the aryllithium reagents, thereby affording the
corresponding dienes 3a–3d in a single step and in good iso-
lated yields. 2-Methoxyphenyllithium, as an example of an
Scheme 2 Reaction of the phosphates 2c and 2d with aryllithium
ortho-substituted phenyl, gave the product 3e in a high isolated reagents.
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Scheme 3 Synthesis of trisubstituted a,b-unsaturated ketones via the reaction of the phosphordiamidates 2e–2g with Grignard reagents.
dienes 3f–3k were obtained as an inseparable mixture of the (E)- halides 4b–4f. Almost the same isolated yields of the ketones
and (Z)-stereoisomers and the double-bond geometry was 4h–4m were obtained for the vinyl phosphordiamidate 2f.
determined by means of nuclear Overhauser effect (NOE) Additionally, the 2-thienylmagnesium bromide 4n, benzylmag-
experiments. The use of an alkyllithium reagent, for example, n- nesium chloride 4o, and octylmagnesium chloride 4p reacted
butyllithium, failed to give the expected product. Instead, well with the phosphordiamidate 2f under the tested reaction
a complex reaction mixture was formed, as observed via the 1H conditions. The examination of the reactivity of the variously
NMR spectroscopy of the crude reaction mixture. It is worth substituted vinyl phosphordiamidates was also extended to
noting that all the dienes 3a–3e were stored in a freezer, as a phosphordiamidate with a phenyl substituent rather than an
signicant decomposition was observed when they were stored alkyl group, and the alkenes 4q and 4r were obtained in quan-
at room temperature. However, the tetrasubstituted dienes 3f– titative isolated yields.
3k showed excellent long-term storage stability.
We synthesized the vinyl phosphordiamidates 2e–2g so as to
Table 2 Reaction of the cyclic vinyl phosphordiamidate 2h with
phenyllithium and phenylmagnesium chloride
test their behavior during the developed one-pot synthesis of
the substituted buta-1,3-dienes 3. Surprisingly, the vinyl phos-
phate 2e reacted smoothly with phenylmagnesium chloride to
give the a,b-unsaturated ketone 4a in a high isolated yield
(Scheme 3). a,b-Unsaturated ketones are known for their
medicinal applications,23 and they are also valuable building
blocks in relation to organic synthesis.24 Therefore, signicant
research efforts have been dedicated to identifying a novel
approach to conjugated enones.25 Nickel-catalyzed 1,2-acyl
migration,26 nucleophilic addition to enones,27 the cross-
coupling reaction between acid uorides and vinyl triates,28
and carbonyl group olenations29 are examples of such reac-
tions. The conversion of the vinyl phosphordiamidate 2e into
the ketone 4a observed in our study represents a hitherto
undescribed reaction of phosphordiamidate en route to
becoming a,b-unsaturated ketones. Further investigation in
this regard showed that a signicantly lower isolated yield of the
ketone 4a was obtained with phenyllithium. Uniformly high
yields of the corresponding ketones were obtained with the
other para-, meta-, and ortho-substituted phenylmagnesium
Entry
M
Temp. [ꢀC]
5aa [%]
6a [%]
1
2
3
4
MgCl
MgCl
MgClb
Li
ꢁ78 to 23
ꢁ40
36
24
25
67
33
8
45
0
0 to 23
ꢁ78 to 23
a
Isolated yield. b 10 mol% of CuI was used as a catalyst.
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Scheme 4 Synthesis of tetrasubstituted a,b-unsaturated ketones via
the reaction of the phosphates 2i–2k with organolithium reagents.
Our attempts to prepare enones with a tetrasubstituted
double bond by means of the reaction of the vinyl phos-
phordiamidate 2h with phenylmagnesium chloride proved to
be less effective, with the formation of the ketones 5a and 6
being observed (Table 2, entry 1). Therefore, we tried to opti-
mize the studied reaction in order to obtain only the ketone 5a.
However, the use of phenylmagnesium chloride always gave
a mixture of the ketones 5a and 6, regardless of the reaction
conditions (Table 2, entries 2 and 3). The desired outcome was
ultimately achieved through the reaction between phenyl-
lithium and the phosphordiamidate 2h, and the ketone 5a was
obtained in an isolated yield of 67% (Table 2, entry 4).
The extension of the studied reaction to the cyclic vinyl phos-
phordiamidates 2i and 2j was successful in terms of the prepa-
ration of substituted cyclopentanones and cycloheptanones. In
both cases, the expected ketones 5b, 5c, 5d, and 5e were obtained
in very good isolated yields. Similar results were obtained for the
acyclic phosphordiamidate 2k. Only the use of 2-thienyllithium
proved less effective, and the reaction products 5f and 5i were
obtained in low isolated yields (Scheme 4).
As a result of the performed experiments, we were able to
propose a mechanism for the observed transformations. We
assumed that during the rst step, an organometallic reagent
addition to the ester functional group occurred and formed
a common intermediate 7. The intermediate 7 with a phosphate
group subsequently underwent trans-phosphorylation, with the
resultant elimination forming an unsaturated ketone 4a, which
was obtained in a low isolated yield of 35% when the crude
reaction mixture was quenched at ꢁ78 ꢀC. The resulting ketone
4a reacted with an organolithium reagent to form the corre-
sponding tertiary alcohol, which was then dehydrated by
phosphoric acid to give the diene 3a. This hypothesis was
conrmed by the reaction of the ketone 4a with phenyllithium,
with the subsequent dehydration giving the diene 3a in a 93%
isolated yield. We also veried that ethyl acetoacetate did not
provide the ketone 4a or the diene 3a under the studied
conditions. In the case of the intermediate 7 with phos-
phordiamidate moiety, the trans-phosphorylation reaction is
Scheme 5 Proposed mechanism for the reaction of the vinyl phos-
phate 2c and the vinyl phosphordiamidate 2e with organometallic
reagents.
sluggish and the intermediate 7 was converted into the tertiary
alcohol 8. The formation of this intermediate was conrmed by
means of the hydrolysis of the crude reaction mixture with
water, and the corresponding alcohol 8 was obtained in a 79%
isolated yield. The formation of the ketone 4a was completed by
the alcohol 8 dehydration. This was again conrmed by the
dehydration of the independently prepared alcohol 8 into the
product 4a in a quantitative isolated yield. Alternatively, the
dehydration of the alcohol 8 could be performed using phos-
phoryl chloride in the presence of triethylamine in a similar
isolated yield (Scheme 5).
Conclusion
In conclusion, we studied the reactivity of both vinyl phosphates
and vinyl phosphordiamidates. We found that vinyl phosphates
can be converted into tri- and tetrasubstituted buta-1,3-dienes
via tꢀhe reaction with aryllithium reagents in dry THF at
ꢀ
ꢁ78 C to 23 C. The tetrasubstituted dienes were isolated as
a mixture of the (E)- and (Z)-stereoisomers. In the case of the
vinyl phosphordiamidates, the reaction with Grignard reagents
under the same reaction conditions resulted in the formation of
unsaturated ketones, which were isolated in yields ranging from
24% to 97%. Based on the experimental results, we were able to
propose a mechanism explaining the origins of both products.
Experimental section
Materials and methods
All reactions were performed under argon atmosphere. NMR
spectra were measured on Varian MercuryPlus 300 (1H, 300.13
MHz; 13C, 75.46 MHz), Agilent 400 MR DD2 (1H, 400.13 MHz;
13C, 100.61 MHz) or Bruker Avance III 500 (31P, 202.45 MHz)
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spectrometer at 298 K. Chemical shis of 31P NMR spectra are 1.44–1.38 (m, 2H), 1.32 (td, J ¼ 7.1, 1.2 Hz, 6H), 0.95 (t, J ¼
referenced to the signal of 85% H3PO4 that was assigned the 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 164.1 (d, J ¼ 6.9 Hz),
chemical shi of 0. Mass spectra were measured on ZAB-SEQ 162.0 (d, J ¼ 1.9 Hz), 150.4, 129.3, 125.6, 121.7, 104.1 (d, J ¼ 7.8
(VG Analytical). The dry and degassed THF was prepared by Hz), 64.9 (d, J ¼ 6.4 Hz), 35.0 (d, J ¼ 1.0 Hz), 28.4, 22.0, 16.0 (d, J
PureSolv MD7. Silica gel (Merck, Silica Gel 60, 40–63 mm or ¼ 7.3 Hz), 13.7; HRMS (APCI) m/z: calcd for C17H25O6P [M + H]+
Merck Silica Gel 60, 63–200 mm) was used for column chroma- 357.1462; found 357.1463.
tography. A phosphate 2a was prepared according to a pub-
General procedure for the synthesis of phosphordiamidates
lished procedure.30 n-BuLi (2.5 M solution in hexane), and other 2e–2k (GP2). 1,3-Dicarbonyl compound was added to a suspen-
compounds were purchased from Sigma-Aldrich, FLuorochem sion of sodium hydride (1.25 equiv.) in dry THF (5 mL/1 mmol)
ꢀ
and Acros Organics. Concentration of BuLi was determined by cooled to 0 C. The resultant mixture was stirred for 30 min at
titration using menthol and 1,10-phenanthroline before use.
23 ꢀC followed by addition of bis(N,N-dimethylamino)phos-
General procedure for the synthesis of starting phosphates phoryl chloride (1.0 equiv.). Then the reaction mixture was
2a–2d (GP1). 1,3-Dicarbonyl compound was added to a suspen- stirred for 75 h at 23 ꢀC. The crude reaction mixture was
sion of sodium hydride (1.25 equiv.) in dry THF (5 mL/1 mmol) quenched with saturated aqueous solution of ammonium
ꢀ
cooled to 0 C. The resultant mixture was stirred for 30 min at chloride (1 mL/1 mmol), the organic layer was separated and the
23 ꢀC followed by addition of dialkyl chlorophosphate (1ꢀ.25 water layer was extracted with AcOEt (2 ꢂ 3 mL/1 mmol).
equiv.). Then the reaction mixture was stirred for 2 h at 23 C. Combined organic layers were washed with brine (3 mL/1
The crude reaction mixture was quenched with saturated mmol) dried over MgSO4, the solvents were removed under
aqueous solution of ammonium chloride (1 mL/1 mmol), the reduce pressure and column chromatography (Silica gel) gave
organic layer was separated and the water layer was extracted the product.
with ether (3 ꢂ 3 mL/1 mmol). Combined organic layers were
Ethyl (Z)-3-[(bis(N,N-dimethylamino)phosphoryl)oxy]but-2-enoate
dried over MgSO4, the solvents were removed under reduce (2e). Prepared according to the GP2 from ethyl acetoacetate
pressure and column chromatography (Silica gel) gave the (13.01 g, 100.0 mmol), NaH (4.42 g, 110.0 mmol) and bis(N,N-
product.
dimethylamino)phosphoryl chloride (18.83 g, 110.0 mmol).
Ethyl
(Z)-3-((diphenoxyphosphoryl)oxy)but-2-enoate
(2b). Column chromatography (AcOEt, Rf ¼ 0.33) gave 12.74 g (54%) of
Prepared according to the GP1 from ethyl acetoacetate (0.260 g, the title compound as a yellowish oil. 1H NMR (500 MHz, CDCl3)
2.0 mmol), NaH (0.060 g, 2.50 mmol) and difenyl chlor- d 5.16 (s, 1H), 4.07 (q, J ¼ 7.1 Hz, 2H), 2.69 (d, J ¼ 10.2 Hz, 12H),
ophosphate (0.67 g, 2.5 mmol). Column chromatography 2.11 (s, 3H), 1.20 (dd, J ¼ 7.8, 6.5 Hz, 3H); 13C NMR (126 MHz,
(hexane/AcOEt 3 : 1, Rf ¼ 0.45) gave 0.67 g (93%) of the title CDCl3) d 164.0, 159.7 (d, J ¼ 5.8 Hz), 103.6 (d, J ¼ 7.5 Hz), 59.4, 36.4,
compound as a yellowish oil. 1H NMR (300 MHz, CDCl3) d 7.39– 22.1 (d, J ¼ 2.1 Hz), 14.3; 31P NMR (202 MHz, CDCl3) d 15.02 (s);
7.16 (m, 10H), 5.43 (s, 1H), 4.11 (q, J ¼ 7.1 Hz, 2H), 2.18–2.14 (m, HRMS (ESI) m/z: calcd for C10H21N2O4P [M + Na]+ 287.1131; found
3H), 1.25 (t, J ¼ 7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 163.2 287.1135.
(d, J ¼ 1.7 Hz), 156.6 (d, J ¼ 7.2 Hz), 150.4 (d, J ¼ 7.6 Hz), 129.7,
Ethyl
(Z)-3-[(bis(N,N-dimethylamino)phosphoryl)oxy]hex-2-
125.5 (d, J ¼ 1.2 Hz), 120.1 (d, J ¼ 4.9 Hz), 106.7 (d, J ¼ 8.6 Hz), enoate (2f). Prepared according to the GP2 from ethyl 3-oxo-
60.0, 21.5 (d, J ¼ 1.2 Hz), 14.0; HRMS (ESI) m/z: calcd for hexanoate (4.746 g, 30.0 mmol), NaH (1.441 g, 36.0 mmol) and
C
18H20O6P [M + H]+ 363.0992; found 363.0992.
bis(N,N-dimethylamino)phosphoryl chloride (5.373 g, 31.50
Phenyl
(Z)-3-((diethoxyphosphoryl)oxy)but-2-enoate
(2c). mmol). Column chromatography (AcOEt, Rf ¼ 0.32) gave 4.648 g
1
Prepared according to the GP1 from phenyl acetoacetate (53%) of the title compound as a yellowish oil. H NMR (500
(1.780 g, 10.0 mmol), NaH (0.480 g, 12.0 mmol) and diethyl MHz, CDCl3) d 5.24–5.22 (m, 1H), 4.12–4.07 (m, 2H), 2.72 (d, J ¼
chlorophosphate (2.070 g, 12.0 mmol). Column chromatog- 10.2 Hz, 12H), 2.44–2.38 (m, 2H), 1.61–1.54 (m, 2H), 1.26–1.21
raphy (hexane/AcOEt 2 : 1, Rf ¼ 0.21) gave 2.61 g (83%) of the (m, 3H), 0.97–0.92 (m, 3H); 13C NMR (100 MHz, CDCl3) d 164.1,
1
title compound as a yellowish oil. H NMR (300 MHz, CDCl3) 163.5 (d. J ¼ 6.2 Hz), 103.1 (d, J ¼ 7.2 Hz), 59.5, 37.3, 36.6 (d, J ¼
d 7.41–7.38 (m, 2H), 7.26–7.23 (m, 1H), 7.14–7.12 (m, 2H), 5.57 4.3 Hz), 20.0, 14.3, 13.5 (d, J ¼ 1.4 Hz); HRMS (APCI) m/z: calcd
(s, 1H), 4.31–4.25 (m, 4H), 2.30 (s, 3H), 1.38–1.35 (m, 6H); 13C for C12H25N2O4P [M + H]+ 293.1625; found 293.1628.
NMR (75 MHz, CDCl3) d 161.7 (d, J ¼ 1.7 Hz), 160.2 (d, J ¼ 6.3
Ethyl
(Z)-3-((bis(N,N-dimethylamino)phosphoryl)oxy)-3-
Hz), 150.4, 129.2, 125.5, 121.6, 104.3 (d, J ¼ 8.5 Hz), 64.9 (d, J ¼ phenylacrylate (2g). Prepared according to the GP2 from ethyl
6.5 Hz), 21.7 (d, J ¼ 1.2 Hz), 15.9 (d, J ¼ 7.1 Hz); 31P NMR (202 benzoylacetate (3.840 g, 20.0 mmol), NaH (0.960 g, 24.0 mmol)
MHz CDCl3) d ꢁ8.38 (s); HRMS (ESI) m/z: calcd for C14H19O6P and bis(N,N-dimethylamino)phosphoryl chloride (4.120 g, 24.0
[M + Na]+ 337.0812; found 337.0815.
mmol). Column chromatography (AcOEt, Rf ¼ 0.38) gave 3.86 g
1
Phenyl
(Z)-3-[(diethoxyphosphoryl)oxy]hept-2-enoate
(2d). (55%) of the title compound as a yellowish oil. H NMR (500
Prepared according to the GP1 from phenyl 3-oxoheptanoate MHz, CDCl3) d 7.64–7.52 (m, 2H), 7.43–7.42 (m, 3H), 5.81 (s,
(3.524 g, 16.0 mmol), NaH (0.768 g, 19.20 mmol) and diethyl 1H), 4.21 (q, J ¼ 7.1 Hz, 2H), 2.61 (d, J ¼ 10.1 Hz, 12H), 1.34 (t, J
chlorophosphate (2.899 g, 16.80 mmol). Column chromatog- ¼ 7.1 Hz, 3H); 13C NMR (126 MHz, CDCl3) d 164.3 (d, J ¼ 2.1 Hz),
raphy (hexane/AcOEt 3 : 1, Rf ¼ 0.26) gave 4.048 g (71%) of the 158.6 (d, J ¼ 6.7 Hz), 136.0 (d, J ¼ 1.8 Hz), 130.2, 128.3, 127.4,
1
title compound as a yellowish oil. H NMR (300 MHz, CDCl3): 107.1 (d, J ¼ 6.3 Hz), 60.1, 36.6 (d, J ¼ 4.6 Hz), 14.3; 31P NMR
d 7.38–7.35 (m, 2H), 7.23–7.19 (m, 1H), 7.12–7.09 (m, 2H), 5.57 (202 MHz, CDCl3) d 15.23 (s). HRMS (ESI) m/z: calcd for
(s, 1H), 4.29–4.17 (m, 4H), 2.54–2.50 (m, 2H), 1.64–1.58 (m, 2H),
C
15H23N2O4P [M + Na]+ 349.1288; found 349.1294.
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equiv.). Then the crude reaction mixture was stirred for 2 h at
23 ꢀC. The reaction mixture was quenched by phosphoric acid (1
mL/1 mmol, 85 wt%) and the reaction mixture was stirred for
1 h at 60 ꢀC. Then the reaction mixture was cooled to 23 ꢀC,
extracted with ether (2 ꢂ 4 mL mmolꢁ1). The combined organic
phases were washed with water (1 ꢂ 4 mL mmolꢁ1), aqueous
Ethyl
2-((bis(N,N-dimethylamino)phosphoryl)oxy)cyclohex-1-
ene-1-carboxylate (2h). Prepared according to the GP2 from
ethyl 2-oxocyclohexane-1-carboxylate (3.404 g, 20 mmol), NaH
(0.960 g, 24 mmol) and bis(N,N-dimethylamino)phosphoryl
chloride (3.582 g; 21.0 mmol). Column chromatography (AcOEt,
Rf ¼ 0.21) gave 4.578 g (75%) of the title compound as
solution of saturated sodium bicarbonate (1 ꢂ 4 mL mmolꢁ1
)
1
a yellowish oil. H NMR (300 MHz, CDCl3) d 4.16 (qd, J ¼ 7.2,
and brine (1 ꢂ 4 mL mmolꢁ1). The organic layer was dried over
MgSO4, the solvents were removed under reduce pressure and
the product was obtained by column chromatography (Silica
gel).
1,1,3-Triphenylbuta-1,3-diene (3a). Prepared according to the
GP3 from bromobenzene (0.320 g, 2.05 mmol), nBuLi (0.83 mL,
2.0 mmol, 2.4 M) and enol phosphate 2c (0.160 g, 0.5 mmol).
Column chromatography (hexane/toluene 99 : 1, Rf ¼ 0.47) gave
0.092 g (65%) of the title compound as a colorless oil. 1H NMR
(300 MHz, CDCl3) d 7.40–7.15 (m, 15H), 6.74 (d, J ¼ 1.2 Hz, 1H),
5.39 (d, J ¼ 1.4 Hz, 1H), 5.03 (t, J ¼ 1.4 Hz, 1H), in accordance
with literature.22
1.2 Hz, 2H), 2.68 (d, J ¼ 10.1, 12H), 2.48–2.44 (m, 2H), 2.34–2.31
(m, 2H), 1.71–1.56 (m, 4H), 1.28–1.24 (m, 3H); 13C NMR (100
MHz, CDCl3) d 153.6 (d, J ¼ 6.6 Hz), 113.9 (d, J ¼ 7.4 Hz), 111.6
(d, J ¼ 4.7 Hz), 60.0, 36.5 (d, J ¼ 4.3 Hz), 29.3 (d, J ¼ 1.7 Hz), 25.6,
22.3, 21.6, 14.2; 31P NMR (202 MHz, CDCl3): d 14.88; HRMS
(APCI) m/z: calcd for C13H25N2O4P [M + H]+ 305.1625; found
305.1628.
Methyl 2-[(bis(N,N-dimethylamino)phosphoryl)oxy]cyclopent-1-
ene-1-carboxylate (2i). Prepared according to the GP2 from
ethyl 2-oxocyclopentane-1-carboxylate (1.424 g, 10.0 mmol),
NaH (0.480 g, 12.0 mmol) and bis(N,N-dimethylamino)phos-
phoryl chloride (1.791 g; 10.50 mmol). Column chromatography
(AcOEt, Rf ¼ 0.28) gave 2.127 g (77%) of the title compound as
1,1,3-Tris(4-methylphenyl)buta-1,3-diene
(3b).
Prepared
1
according to the GP3 from 4-bromotoluene (0.350 g, 2.05
mmol), nBuLi (0.83 mL, 2.0 mmol, 2.4 M) and enol phosphate 2c
(0.160 g, 0.5 mmol). Column chromatography (hexane, Rf ¼
0.34) gave 0.089 g (55%) of the title compound as a colorless oil.
1H NMR (400 MHz, CDCl3) d 7.37–7.37 (m, 2H), 7.26–7.24 (m,
2H), 7.15–7.08 (m, 6H), 7.05–7.03 (m, 2H), 6.67–6.66 (m, 1H),
5.38–5.37 (m, 1H), 4.97–4.96 (m, 1H), 2.38 (s, 3H), 2.35 (s, 3H),
2.33 (s, 3H); 13C NMR (101 MHz, CDCl3) d 145.0, 144.4, 140.6,
138.1, 137.4, 137.3, 137.2, 136.6, 130.0, 128.9, 128.8, 128.7,
127.9, 127.5, 126.5, 115.9, 21.3, 21.2, 21.1; HRMS (APCI) m/z:
calcd for C25H24 [M + H]+ 325.1951 found 325.1945.
a yellowish oil. H NMR (400 MHz, CDCl3) d 3.69 (s, 3H), 2.72–
2.70 (m, 14H), 2.57–2.57 (m, 2H), 1.93–1.85 (m, 2H); 13C NMR
(100 MHz, CDCl3) d 164.6, 159.6 (d, J ¼ 5.3 Hz), 112.2 (d, J ¼ 7.6
Hz), 50.9, 36.4 (d, J ¼ 4.4 Hz), 33.5 (d, J ¼ 1.9 Hz), 28.7, 19.3; 31
P
NMR (202 MHz, CDCl3): d 15.63; HRMS (APCI) m/z: calcd for
C
11H21N2O4P [M + H]+ ¼ 277.1312; found 277.1315.
Methyl 2-[(bis(N,N-dimethylamino)phosphoryl)oxy]cyclohept-1-
ene-1-carboxylate (2j). Prepared according to the GP2 from
ethyl 2-oxocycloheptane-1-carboxylate (2.558 g, 15.0 mmol),
NaH (0.721 g, 18.0 mmol) and bis(N,N-dimethylamino)phos-
phoryl chloride (2.729 g, 16.0 mmol). Column chromatography
(AcOEt, Rf ¼ 0.25) gave 3.142 g (69%) of the title compound as
a colorless liquid. 1H NMR (300 MHz, CDCl3) d 3.55 (s, 3H),
2.58–2.43 (m, 14H), 2.26–2.26 (m, 2H), 1.59–1.37 (m, 6H); 13C
NMR (100 MHz, CDCl3) d 167.6 (d, J ¼ 1.7 Hz), 158.2 (d, J ¼ 7.3
Hz), 118.7 (d, J ¼ 7.4 Hz), 51.1, 36.1 (d, J ¼ 4.2 Hz), 33.6 (d, J ¼
1,1,3-Tris(4-methoxyphenyl)buta-1,3-diene
(3c).
Prepared
according to the GP3 from 4-bromoanisole (0.38 g, 2.05 mmol),
nBuLi (0.83 mL, 2.0 mmol, 2.4 M) and enol phosphate 2c
(0.160 g, 0.5 mmol). Column chromatography (hexane/AcOEt
20 : 1, Rf ¼ 0.23) gave 0.104 g (56%) of the title compound as
a yellowish oil. 1H NMR (400 MHz, CDCl3) d 7.36–7.33 (m, 2H),
7.29–7.26 (m, 2H), 7.09–7.06 (m, 2H), 6.87–6.84 (m, 2H), 6.80–
6.72 (m, 4H), 6.59–6.57 (m, 1H), 5.31–5.31 (m, 1H), 4.95–4.93
(m, 1H), 3.83 (s, 3H), 3.79 (s, 3H), 3.77 (s, 3H); 13C NMR (101
MHz, CDCl3) d 159.2, 159.1, 158.6, 144.9, 143.6, 136.1, 133.5,
132.7, 131.3, 129.2, 127.8, 126.6, 115.1, 113.5, 113.4, 113.3, 55.3,
55.3, 55.2. HRMS (APCI) m/z: calcd for C25H24O3 [M + H]+
373.1798; found 373.1793.
1.6 Hz), 31.2, 27.4, 25.8 (d, J ¼ 1.4 Hz), 23.9 (d, J ¼ 0.6 Hz); 31
P
NMR (202 MHz, CDCl3): d 14.67; HRMS (APCI) m/z: calcd for
C
13H25N2O4P [M + H]+ 305.1625; found 305.1626.
Ethyl (Z)-3-[(bis(N,N-dimethylamino)phosphoryl)oxy]-2-
methylbut-2-enoate (2k). Prepared according to the GP2 from
ethyl 2-methylacetoacetate (2.88 g, 20 mmol), NaH (0.960 g, 24.0
mmol) and bis(N,N-dimethylamino)phosphoryl chloride
(4.120 g, 24.0 mmol). Column chromatography (AcOEt, Rf ¼
0.33) gave 2.60 g (50%) of the title compound as a yellowish oil.
1H NMR (500 MHz, CDCl3) d 4.17 (q, J ¼ 7.1 Hz, 2H), 2.67 (d, J ¼
10.1 Hz, 12H), 2.11 (s, 3H), 1.83 (s, 3H), 1.27 (t, J ¼ 7.1 Hz, 3H);
13C NMR (126 MHz, CDCl3) d 167.3, 150.0 (d, J ¼ 6.9 Hz), 112.5
(d, J ¼ 7.8 Hz), 60.2, 36.5 (d, J ¼ 3.8 Hz), 18.2 (d, J ¼ 1.6 Hz), 14.7,
14.2; 31P NMR (202 MHz, CDCl3) d 15.08 (s); HRMS (ESI) m/z:
calcd for C11H23N2O4P [M + Na]+ 301.1288; found 301.1289.
General procedure for the synthesis of substituted buta-1,3-
dienes 3 (GP3). n-Butyllithium (4.0 equiv.) was added to a solu-
tion of aryl halide (4.1 equiv.) in dry THF (3 mL/1 mmol) cooled
1,1,3-Tris[(1,10-biphenyl)-4-yl]buta-1,3-diene (3d). Prepared
according to the GP3 from 4-bromobiphenyl (0.48 g, 2.05
mmol), nBuLi (0.83 mL, 2.0 mmol, 2.4 M) and enol phosphate 2c
(0.160 g, 0.5 mmol). Column chromatography (hexane/AcOEt
20 : 1, Rf ¼ 0.57) gave 0.092 g (64%) of the title compound as
1
ꢀ
a white solid, mp ¼ 64.0–66.0 C. H NMR (400 MHz, CDCl3)
d 7.65–7.25 (m, 17H), 6.89 (s 1H), 5.51 (s, 1H), 5.20 (s, 1H); 13C
NMR (101 MHz, CDCl3) d 145.1, 143.9, 142.0, 140.82, 140.80,
140.7, 140.5, 140.3, 139.9, 139.6, 138.9, 130.7, 128.8, 128.71,
128.69, 128.53, 128.48, 127.4, 127.29, 127.22, 127.20, 127.1,
127.04, 127.02, 126.95, 126.8, 126.6, 118.0; HRMS (APCI) m/z:
calcd for C40H30 [M + H]+ 511.2420; found 511.2397.
ꢀ
to ꢁ78 C and the resultant mixture was stirred for 30 min at
ꢁ78 ꢀC followed by addition of enol phosphates 2a–2d (1
35114 | RSC Adv., 2020, 10, 35109–35120
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1,1,3-Tris(2-methoxyphenyl)buta-1,3-diene
RSC Advances
6.0 Hz, 1H, Zminor), 3.83 (s, 3H, Emajor), 3.79 (s, 3H, Zminor), 3.77
(s, 3H, Emajor), 3.76 (s, 3H, Zminor), 3.75 (s, 3H, Emajor), 1.98–1.89
(m, 2H, E and Z), 1.26–1.15 (m, 2H, E and Z), 0.83 (t, J ¼ 6.0 Hz,
3H, Emajor), 0.74 (t, J ¼ 6.0 Hz, 3H, Zminor); 13C NMR (100 MHz,
CDCl3) d 159.1, 158.5, 158.4, 143.9, 136.8, 136.2, 134.6, 133.0,
131.0, 129.3, 129.2, 127.6, 124.4, 113.4, 113.3, 113.1, 113.0, 55.3,
(3e).
Prepared
according to the GP3 from 2-bromoanisole (0.380 g, 2.05 mmol),
nBuLi (0.83 mL, 2.0 mmol, 2.4 M) and enol phosphate 2c
(0.160 g, 0.5 mmol). Column chromatography (hexane/AcOEt
20 : 1, Rf ¼ 0.22) gave 0.132 g (71%) of the title compound as
a yellowish oil. 1H NMR (400 MHz, CDCl3) d 7.30–7.19 (m, 2H),
7.12–7.10 (m, 1H), 7.03–6.87 (m, 4H), 6.84–6.81 (m, 2H), 6.76–
6.72 (m, 1H), 6.70–6.66 (m, 1H), 6.51–6.45 (m, 2H), 5.36–5.35
(m, 1H), 5.21–5.20 (m, 1H), 3.71 (s, 3H), 3.61 (s, 6H); 13C NMR
(101 MHz, CDCl3) d 157.3, 156.3, 156.0, 144.8, 136.0, 133.8,
132.2, 130.8, 130.4, 130.4, 130.1, 129.8, 128.1, 128.0, 127.7,
120.4, 120.3, 119.5, 119.1, 111.8, 109.5, 109.4, 55.8, 55.0, 54.9;
HRMS (APCI) m/z: calcd for C25H24O3 [M + H]+ 373.1798; found
373.1789.
55.2, 55.1, 31.8major, 31.3minor, 22.9minor, 22.3major, 14.0major
,
13.8minor; HRMS (APCI) m/z: calcd for C28H30O3 [M + H]+
415.2268; found 415.2264.
1,1,3-Tris[(1,10-biphenyl)-4-yl]hepta-1,3-diene (3i). Prepared
according to the GP3 from 4-bromobiphenyl (0.287 g, 1.23
mmol), nBuLi (0.49 mL, 2.40 M, 1.17 mmol) and enol phosphate
2d (0.107 g, 0.30 mmol). Column chromatography (hexane /
hexane/EtOAc 30 : 1, Rf ¼ 0.1) gave 0.119 g (72%, E/Z ¼ 86 : 14)
ꢀ
of the title compound as a yellowish solid, mp ¼ 49.0–50.0 C.
(E/Z)-1,1,3-Triphenylhepta-1,3-diene (3f). Prepared according
to the GP3 from bromobenzene (0.320 g, 2.05 mmol), nBuLi
(0.83 mL, 2.0 mmol, 2.4 M) and enol phosphate 2d (0.178 g, 0.5
mmol). Column chromatography (hexane, Rf ¼ 0.35) gave
0.101 g (62%, E/Z ¼ 79 : 21) of the title compound as a yellowish
1H NMR (300 MHz, CDCl3) d 7.65–7.06 (m, 27H, E and Z), 6.85 (s,
1H, Zminor), 6.82 (s, 1H, Emajor), 5.86–5.78 (m, 1H, E and Z), 2.10–
2.01 (m, 2H, E and Z), 1.30–1.23 (m, 2H, E and Z), 0.88 (t, J ¼
7.3 Hz, 3H, Emajor), 0.76 (s, J ¼ 7.3 Hz, 3H, Zminor); 13C NMR (75
MHz, CDCl3) d 144.3, 142.4, 142.0, 141.0, 140.9, 140.8, 140.8,
140.7, 140.4, 139.8, 139.3, 139.3, 139.2, 139.0, 138.5, 138.4,
137.0, 136.6, 132.0, 131.6, 130.8, 130.4, 129.8, 128.8, 128.7,
128.6, 128.6, 128.0, 127.3, 127.2, 127.1, 127.0, 126.9, 126.9,
1
oil. H NMR (300 MHz, CDCl3) d 7.37–7.10 (m, 15H, E and Z),
6.69–6.68 (m, 1H, E and Z), 5.77–5.73 (m, 1H, Emajor), 5.64–5.61
(m, 1H, Zminor), 1.99–1.95 (m, 2H, E and Z), 1.24–1.15 (m, 2H, E
and Z), 0.84 (t, J ¼ 6.0 Hz, 3H, Emajor), 0.72 (t, J ¼ 6.0 Hz, 3H,
126.8, 126.7, 126.4, 126.2, 32.0major
, , ,
31.4minor 22.8minor
Z
minor); 13C NMR (100 MHz, CDCl3) d 145.1, 143.6minor
,
,
,
22.3major, 14.1major, 13.8minor; HRMS (APCI) m/z: calcd for
143.3major
139.7minor
,
141.8major
138.2minor
,
141.6minor
137.3major
,
,
140.4minor
135.6major
,
,
140.3major
131.6major
C
43H36 [M + H]+ 553.2890; found 553.2894.
,
,
131.3minor, 130.4, 129.9, 129.2, 128.2, 128.1, 128.0, 127.9, 127.7,
127.6, 127.5, 127.1, 127.0, 126.7, 126.50, 126.47, 126.4, 126.3,
1,1,3-Tris(2-methoxyphenyl)hepta-1,3-diene (3j). Prepared
according to the GP3 from 2-bromoanisole (0.230 g, 1.23 mmol),
nBuLi (0.49 mL, 2.40 M, 1.17 mmol) and enol phosphate 2d
(0.107 g, 0.30 mmol). Column chromatography (hexane/EtOAc
50 : 1, Rf ¼ 0.14) gave 0.090 g (72%, E/Z ¼ 71 : 29) of the title
compound as a yellowish oil. 1H NMR (300 MHz, CDCl3) d 7.27–
7.12 (m, 3H, E and Z), 6.96–6.36 (m, 10H, E and Z), 5.80 (t, J ¼
6.0 Hz, 1H, Zminor), 5.49 (t, J ¼ 6.0 Hz, 1H), 3.71 (s, 3H, Emajor),
3.68 (s, 3H, Zminor), 3.62 (s, 3H, Zminor), 3.60 (s, 3H, Emajor), 3.59
(s, 3H, Zminor), 3.44 (s, 3H, Emajor), 2.24 (q, J ¼ 7.4 Hz, 2H, Emajor),
1.78 (q, J ¼ 7.4 Hz, 2H, Zminor), 1.46–1.40 (m, 2H, Emajor), 1.25–
1.22 (m, 2H, Zminor), 0.95 (t, J ¼ 7.3 Hz, 3H, Emajor), 0.95 (t, J ¼
7.3 Hz, 3H, Zminor); 13C NMR (100 MHz, CDCl3) d 157.4, 156.3,
156.1, 136.4, 136.1, 134.8, 134.0, 133.9, 132.3, 130.9, 130.8,
130.3, 129.7, 127.7, 127.4, 127.0, 120.3, 119.5, 119.0, 112.1,
31.9major, 31.2minor, 22.7minor, 22.2major, 14.0major, 13.7minor
;
HRMS (APCI) m/z: calcd for C25H24 [M + H]+ 325.1951; found
325.1953.
1,1,3-Tris(4-methylphenyl)hepta-1,3-diene
(3g).
Prepared
according to the GP3 from 4-bromotoluene (0.212 g, 1.23
mmol), nBuLi (0.49 mL, 2.40 M, 1.18 mmol), and enol phos-
phate 2d (0.107 g, 0.30 mmol). Column chromatography
(hexane, Rf ¼ 0.28) gave the title compound 0.056 g (51%, E/Z ¼
83 : 17) as a yellowish oil. 1H NMR (300 MHz, CDCl3) d 7.31–7.24
(m, 3H), 7.14–6.95 (m, 9H), 6.56–6.55 (m, 1H, Zminor), 6.53–6.52
(s, 1H, Emajor), 5.68 (t, J ¼ 6.0 Hz, 1H, Emajor), 5.53 (t, J ¼ 6.0 Hz,
1H, Zminor), 2.37 (s, 3H, Emajor), 2.32 (s, 3H, Zminor), 2.30 (s, 3H,
E
major), 2.29 (s, 3H, Zminor), 2.27 (s, 3H, Emajor), 1.96–1.84 (m, 2H,
109.6, 109.4, 55.9, 55.1, 54.7, 31.3minor, 31.1major, 22.7major
,
E and Z), 1.19–1.09 (m, 2H, E and Z), 0.80 (t, J ¼ 6.0 Hz, 3H,
22.6minor, 14.0major, 13.9minor; HRMS (APCI) m/z: calcd for
E
major), 0.69 (t, J ¼ 6.0 Hz, 3H, Zminor); 13C NMR (75 MHz, CDCl3,
C
28H30O3 [M + H]+ 415.2268; found 415.2277.
only major peaks are reported) d 144.7, 140.7, 138.9, 137.5,
137.2, 136.9, 136.5, 136.1, 130.4, 130.2, 129.7, 129.6, 129.0,
128.9, 128.8, 128.7, 128.7, 128.3, 128.1, 127.5, 126.4, 125.4, 31.9,
22.2, 21.2, 21.1, 21.0, 14.0; HRMS (APCI) m/z: calcd for C28H30
[M + H]+ 367.2420; found 367.2419.
1,1,3-Tris(2-thienyl)hepta-1,3-diene (3k). Prepared according
to the GP3 from thiophene (0.108 g, 1.28 mmol), nBuLi (0.51 mL,
2.40 M, 1.22 mmol), dry THF (3 mL). The reaction mixture was
stirred for 30 min at 0 ꢀC followed by addition of enol phosphate
2d (0.110 g, 0.31 mmol). Column chromatography (hexane, Rf ¼
0.14) gave 0.048 g (45%, E/Z ¼ 93 : 7) of the title compound as
1,1,3-Tris(4-methoxyphenyl)hepta-1,3-diene (3h). Prepared
according to the GP3 from 4-bromoanisole (0.230 g, 1.23 mmol)
1
n
a greenish oil. H NMR (300 MHz, CDCl3) d 7.28–7.26 (m, 1H),
a BuLi (0.49 mL, 2.40 M, 1.17 mmol) and enol phosphate 2d
7.23–7.21 (m, 1H), 7.13–7.12 (m, 1H), 7.09–7.02 (m, 3H), 6.97–
6.87 (m, 3H), 6.69 (d, J ¼ 1.2 Hz, 1H, Emajor), 5.92 (td, J ¼ 7.4,
1.3 Hz, 1H, Emajor), 5.92 (td, J ¼ 7.4, 1.3 Hz, 1H, Zminor), 2.24–
2.18 (m, 2H, Zminor), 2.07–2.01 (m, 2H, Emajor), 1.33–1.23 (m,
2H), 0.87 (t, J ¼ 7.4 Hz, 3H, Emajor), 0.79 (t, J ¼ 7.4 Hz, 3H,
(0.107 g, 0.30 mmol). Column chromatography (hexane/EtOAc
20 : 1, Rf ¼ 0.35) gave 0.063 g (51%, E/Z ¼ 82 : 18) of the title
compound as a yellowish oil. 1H NMR (300 MHz, CDCl3) d 7.31–
7.26 (m, 4H), 7.04–6.65 (m, 8H), 6.54–6.53 (m, 1H, Zminor), 6.48–
6.47 (m, 1H, Emajor), 5.63 (t, J ¼ 6.0 Hz, 1H, Emajor), 5.58 (t, J ¼
Z
minor); 13C NMR (100 MHz, CDCl3) d 146.9minor, 145.9, 145.3,
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141.2minor, 140.2minor, 140.1, 136.2, 131.3, 130.6, 128.5, 127.3, 115.0, 114.9, 114.4, 114.0, 55.3, 30.2; HRMS (APCI) m/z: calcd for
127.1, 126.5, 126.4, 126.2, 125.1, 125.1, 123.7, 123.3, 31.7major
,
C
18H18O3 [M + H]+ 283.1329; found 283.1324.
4,4-Bis(3-(methylthio)phenyl)but-3-en-2-one (4e). Prepared
31.6minor, 22.6minor, 22.2major, 14.0major, 13.8minor; HRMS (APCI)
m/z: calcd for C19H18S3 [M + H]+ 343.0643; found 343.0649.
according to the GP4 from phosphordiamidate 2e (0.130 g, 0.5
General procedure for conversion of phosphorodiamidates mmol) and (3-(methylthio)phenyl)magnesium bromide (2.60
2e–2k to a,b-ketones 4,5 (GP4). Organolithium or Grignard mL, 1.3 mmol). Column chromatography (hexane/AcOEt 6 : 1,
reagent (2.5 equiv.) was added to a solution of phosphordia- Rf ¼ 0.34) gave 0.126 g (80%) of the title compound as
midate 2e–2k in dry THF (10 mL/1 mmol) cooled to ꢁ78 ꢀC. The a yellowish oil. 1H NMR (400 MHz, CDCl3) d 7.35–7.24 (m, 3H),
ꢀ
resultant mixture was warmed to 23 C and stirred for 2 h at 7.19–7.18 (m, 1H), 7.07–7.06 (m, 1H), 7.03–6.96 (m, 3H), 6.55 (s,
23 C. Then the reaction mixture was quenched by phosphoric 1H), 2.47 (s, 3H), 2.45 (s, 3H), 1.92 (s, 3H); 13C NMR (101 MHz,
ꢀ
acid (1 mL/1 mmol, 85 wt%) and the mixture was stirred for 1 h CDCl3) d 200.1, 152.9, 141.1, 139.2, 139.2, 139.1, 128.9, 128.8,
at 60 ꢀC. Then the reaction mixture was cooled to 23 ꢀC and the 128.2, 127.4, 127.1, 126.7, 126.2, 126.1, 125.3, 30.4, 15.7, 15.6;
mixture was extracted with ether (2 ꢂ 4 mL mmolꢁ1). The HRMS (APCI) m/z: calcd for C18H18OS2 [M + H]+ 315.0872; found
combined organic phases were washed with water (1 ꢂ 4 mL 315.0879.
mmolꢁ1), aqueous solution of saturated sodium bicarbonate (1
4,4-Di-o-tolylbut-3-en-2-one (4f). Prepared according to the
ꢂ 4 mL mmolꢁ1) and brine (1 ꢂ 4 mL mmolꢁ1). The organic GP4 from phosphordiamidate 2e (0.130 g, 0.5 mmol) and o-
layer was dried over MgSO4, the solvents were removed under tolylmagnesium chloride (1.30 mL, 1.3 mmol). Column chro-
reduce pressure and column chromatography (Silica gel) gave matography (hexane/AcOEt 6 : 1, Rf ¼ 0.49) gave 0.094 g (75%)
ꢀ
the product.
of the title compound as a yellowish solid, mp ¼ 62.0–65.0 C.
4,4-Diphenylbut-3-en-2-one (4a). Prepared according to the 1H NMR (400 MHz, CDCl3) d 7.28–7.03 (m, 8H), 6.31 (s, 1H), 2.35
GP4 from phosphordiamidate 2e (0.130 g, 0.5 mmol) and phe- (s, 3H), 2.10 (s, 3H), 1.85 (s, 3H); 13C NMR (101 MHz, CDCl3)
nylmagnesium chloride (0.70 mL, 1.3 mmol). Column chro- d 200.2, 153.8, 140.3, 139.4, 135.7, 135.6, 132.3, 131.3, 130.6,
matography (hexane/AcOEt 9 : 1, Rf ¼ 0.42) gave 0.087 g (78%) 130.1, 129.9, 128.7, 128.4, 125.8, 125.8, 29.9, 21.0, 19.9; HRMS
of the title compound as a yellowish oil. 1H NMR (300 MHz, (APCI) m/z: calcd for C18H18O [M + H]+ 251.1430; found
CDCl3) d 7.43–7.39 (m, 3H), 7.36–7.28 (m, 5H), 7.25–7.20 (m, 251.1432.
2H), 6.58 (s, 1H), 1.88 (s, 3H), in accordance with literature.31
4-Octyldodec-3-en-2-one (4g). Prepared according to the GP4
4,4-Bis(4-chlorophenyl)but-3-en-2-one (4b). Prepared according from phosphordiamidate 2e (0.13 g, 0.5 mmol) and octylmag-
to the GP4 from phosphordiamidate 2e (0.130 g, 0.5 mmol) and nesium chloride (0.6 mL, 1.3 mmol). Column chromatography
4-chlorophenylmagnesium chloride (1.30 mL, 1.3 mmol). (hexane/AcOEt 6 : 1, Rf ¼ 0.41) gave 0.124 g (84%) of the title
Column chromatography (hexane/AcOEt 9 : 1, Rf ¼ 0.24) gave compound as a yellowish oil. 1H NMR (400 MHz, CDCl3) d 6.01
0.116 g (80%) of the title compound as a yellowish oil. 1H NMR (s, 1H), 2.55–2.51 (m, 2H), 2.16 (s, 3H), 2.12–2.08 (m, 2H), 1.46–
(400 MHz, CDCl3) d 7.40–7.38 (m, 2H), 7.32–7.30 (m, 2H), 7.21– 1.25 (m, 24H), 0.90–0.85 (m, 6H); 13C NMR (101 MHz, CDCl3)
7.19 (m, 2H), 7.15–7.12 (m, 2H), 6.56 (s, 1H), 1.99 (s, 3H); 13C d 198.4, 163.8, 122.9, 38.7, 32.4, 31.92, 31.88, 31.85, 30.0, 29.44,
NMR (101 MHz, CDCl3) d 199.3, 151.5, 139.1, 137.0, 136.0, 135.2, 29.42, 29.3, 29.2, 28.6, 27.8, 22.67, 22.66, 14.12, 14.11; HRMS
131.1, 129.8, 129.0, 128.9, 127.7, 31.0; HRMS (APCI) m/z: calcd (APCI) m/z: calcd for C20H38O [M + H]+ 295.2995; found
for C16H12Cl2O1 [M + H]+ 291.0338; found 291.0329.
4,4-Bis(4-uorophenyl)but-3-en-2-one (4c). Prepared according
295.2984.
1,1-Diphenylhex-1-en-3-one (4h). Prepared according to the
to the GP4 from phosphordiamidate 2e (0.130 g, 0.5 mmol) and GP4 from phosphordiamidate 2f (0.149 g; 0.51 mmol) and
4-uorophenylmagnesium chloride (1.30 mL, 1.3 mmol). phenylmagnesium chloride (0.65 mL, 1.28 mmol). Column
Column chromatography (hexane/AcOEt 9 : 1, Rf ¼ 0.33) gave chromatography (hexane/AcOEt 20 : 1, Rf ¼ 0.23) gave 0.101 g
1
0.105 g (81%) of the title compound as a yellowish oil. 1H NMR (79%) of the title compound as a yellowish oil. H NMR (300
(400 MHz, CDCl3) d 7.28–7.24 (m, 2H), 7.20–7.17 (m, 2H), 7.13– MHz, CDCl3) d 7.41–7.29 (m, 8H), 7.21–7.18 (m, 2H), 6.58 (s,
7.09 (m, 2H), 7.05–7.01 (m, 2H), 6.53 (s, 1H), 1.96 (s, 3H); 13C 1H), 2.22 (t, J ¼ 7.3 Hz, 2H), 1.59–1.46 (m, 2H), 0.79 (t, J ¼ 7.4 Hz,
NMR (101 MHz, CDCl3) d 199.5, 163.6 (d, J ¼ 251.5 Hz), 163.1 (d, 3H), in accordance with literature.32
J ¼ 250.5 Hz), 151.8, 136.8 (d, J ¼ 3.1 Hz), 134.6 (d, J ¼ 3.5 Hz),
1,1-Bis(4-chlorophenyl)hex-1-en-3-one (4i). Prepared according
131.5 (d, J ¼ 8.1 Hz), 130.4 (d, J ¼ 9.1 Hz), 127.2 (d, J ¼ 6.1 Hz), to the GP4 from phosphordiamidate 2f (0.146 g; 0.50 mmol) and
115.7 (d, J ¼ 5.1 Hz), 115.5 (d, J ¼ 6.1 Hz), 30.6; HRMS (APCI) m/ 4-chlorophenylmagnesium chloride (1.30 mL, 1.25 mmol).
z: calcd for C16H12F2O1 [M + H]+ 259.0929; found 259.0929.
Column chromatography (hexane/AcOEt 20 : 1, Rf ¼ 0.31) gave
4,4-Bis(3-methoxyphenyl)but-3-en-2-one (4d). Prepared accord- 0.121 g (76%) of the title compound as a yellowish oil. 1H NMR
ing to the GP4 from phosphordiamidate 2e (0.130 g, 0.5 mmol) (300 MHz, CDCl3) d 7.37–7.35 (m, 2H), 7.32–7.29 (m, 2H), 7.21–
and 3-methoxyphenylmagnesium bromide (1.30 mL, 1.3 mmol). 7.19 (m, 2H), 7.12–7.10 (m, 2H), 6.57 (s, 1H), 2.33 (t, J ¼ 7.3 Hz,
Column chromatography (hexane/AcOEt 6 : 1, Rf ¼ 0.32) gave 2H), 1.61–1.51 (m, 2H), 0.85 (t, J ¼ 7.4 Hz, 3H); 13C NMR (100
0.112 g (79%) of the title compound as a yellowish oil. 1H NMR MHz, CDCl3) d 201.2, 150.8, 139.1, 136.9, 135.6, 134.7, 130.8,
(400 MHz, CDCl3) d 7.34–7.30 (m, 1H), 7.26–7.22 (m, 1H), 6.97– 129.6, 128.7, 128.6, 126.4, 45.6, 17.6, 13.7; HRMS (APCI) m/z:
6.80 (m, 5H), 6.75–6.74 (m, 1H), 6.56 (s, 1H), 3.80 (s, 3H), 3.78 (s, calcd for C18H16Cl2O [M + H]+ 319.0651; found 319.0650.
3H), 1.89 (s, 3H); 13C NMR (101 MHz, CDCl3) d 200.4, 159.6,
159.5, 153.5, 142.0, 140.2, 129.5, 129.4, 128.0, 122.1, 121.0, to the GP4 from phosphordiamidate 2f (0.146 g; 0.50 mmol) and
1,1-Bis(4-uorophenyl)hex-1-en-3-one (4j). Prepared according
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4-uorophenylmagnesium bromide (1.30 mL, 1.25 mmol). 125.5, 44.9, 17.9, 13.7; HRMS (APCI) m/z: calcd for C14H14OS2 [M
Column chromatography (hexane/AcOEt 20 : 1, Rf ¼ 0.24) gave + H]+ 263.0559; found 263.0551.
0.110 g (77%) of the title compound as a yellowish oil. 1H NMR
2-Benzyl-1-phenylhept-2-en-4-one (4o). Prepared according to
(300 MHz, CDCl3) d 7.27–7.24 (m, 2H), 7.18–7.14 (m, 2H), 7.10– the GP4 from phosphordiamidate 2f (0.146 g; 0.50 mmol) and
7.00 (m, 4H), 6.53 (s, 1H), 2.30 (t, J ¼ 7.3 Hz, 2H), 1.60–1.51 (m, benzylmagnesium chloride (1.30 mL, 1.26 mmol). Column
2H), 0.84 (t, J ¼ 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 201.5, chromatography (hexane/AcOEt 50 : 1, Rf ¼ 0.28) gave 0.088 g
1
163.5 (d, J ¼ 250.4 Hz), 162.9 (d, J ¼ 248.6 Hz) 151.2, 137.1 (d, J ¼ (63%) of the title compound as a yellowish oil. H NMR (300
3.5 Hz), 134.6 (d, J ¼ 3.5 Hz), 131.3 (d, J ¼ 8.3 Hz), 130.2 (d, J ¼ MHz, CDCl3) d 7.33–7.22 (m, 8H), 7.12–7.09 (m, 2H), 6.09 (s,
8.4 Hz), 126.1, 115.5 (d, J ¼ 10.9 Hz), 115.3 (d, J ¼ 10.8 Hz), 45.5, 1H), 3.94 (s, 2H), 3.33 (s, 2H), 2.46 (t, J ¼ 7.3 Hz, 2H), 1.68–1.62
17.6, 13.7; HRMS (APCI) m/z: calcd for C18H16F2O [M + H]+ (m, 2H), 0.94 (t, J ¼ 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3)
287.1242; found 287.1243.
d 201.3, 157.6, 138.9, 137.8, 129.3, 129.1, 128.5, 128.4, 126.6,
1,1-Bis(3-methoxyphenyl)hex-1-en-3-one
(4k).
Prepared 126.2, 125.6 46.5, 43.5, 36.8, 17.5, 13.8; HRMS (APCI) m/z: calcd
according to the GP4 from phosphordiamidate 2f (0.146 g; 0.50 for C20H22O [M + H]+ 279.1743; found 279.1738.
mmol) and 3-methoxyphenylmagnesium bromide (1.30 mL,
6-Octyltetradec-5-en-4-one (4p). Prepared according to the GP4
1.25 mmol). Column chromatography (hexane/AcOEt 20 : 1, Rf from phosphordiamidate 2f (0.148 g; 0.51 mmol) and octyl-
¼ 0.18) gave 0.129 g (83%) of the title compound as a yellowish magnesium chloride (0.63 mL, 1.26 mmol). Column chroma-
1
oil. H NMR (300 MHz, CDCl3) d 7.32–7.22 (m, 2H), 6.95–6.71 tography (hexane/AcOEt 30 : 1, Rf ¼ 0.44) gave 0.147 g (90%) of
(m, 6H), 6.55 (s, 1H), 3.78 (s, 3H), 3.77 (s, 3H), 2.21 (t, J ¼ 7.3 Hz, the title compound as a colorless oil. 1H NMR (300 MHz, CDCl3)
2H), 1.56–1.47 (m, 2H), 0.79 (t, J ¼ 7.3 Hz, 3H); 13C NMR (75 d 5.99 (s, 1H), 2.55–2.51 (m, 2H), 2.39 (t, J ¼ 7.3 Hz, 2H), 2.12–
MHz, CDCl3) d 202.6, 159.4, 159.4, 152.4, 142.2, 140.2, 129.3, 2.08 (m, 2H), 1.64–1.58 (m, 2H), 1.44–1.25 (m, 24H), 0.94–0.86
127.0, 121.9, 120.9, 114.9, 114.5, 114.1, 114.0, 55.3, 55.2, 44.9, (m, 9H); 13C NMR (75 MHz, CDCl3) d 200.9, 163.3, 122.6, 46.4,
17.8, 13.7; HRMS (APCI) m/z: calcd for C20H22O3 [M + H]+ 38.7, 32.5, 31.9, 31.8, 30.0, 29.5, 29.4, 29.4, 29.3, 29.2, 28.7, 27.8,
311.1642; found 311.1645.
22.7, 22.6, 17.7, 14.1, 13.8; HRMS (APCI) m/z: calcd for C22H42O
1,1-Bis(3-(methylthio)phenyl)hex-1-en-3-one (4l). Prepared [M + H]+ 323.3308; found 323.3310.
according to the GP4 from phosphordiamidate 2f (0.146 g; 0.50
1,3,3-Triphenylprop-2-en-1-one (4q). Prepared according to the
mmol) and (3-(methylthio)phenyl)magnesium bromide (1.40 GP4 from phosphordiamidate 2g (0.160 g; 0.50 mmol) and
mL, 1.25 mmol). Column chromatography (hexane/AcOEt phenylmagnesium chloride (0.70 mL, 1.30 mmol). Column
30 : 1, Rf ¼ 0.11) gave 0.122 g (71%) of the title compound as chromatography (hexane/AcOEt 9 : 1, Rf ¼ 0.32) gave 0.129 g
a yellowish oil. 1H NMR (300 MHz, CDCl3) d 7.30–7.18 (m, 5H), (97%) of the title compound as a yellow oil. 1H NMR (400 MHz,
7.05–6.94 (m, 3H), 6.54 (s, 1H), 2.46 (s, 3H), 2.46 (s, 3H), 2.45 (s, CDCl3) d 7.92–7.90 (m, 2H), 7.48–7.46 (m, 1H), 7.41–7.36 (m,
3H), 2.24 (t, J ¼ 7.3 Hz, 2H), 1.57–1.48 (m, 2H), 0.81 (t, J ¼ 7.4 Hz, 7H), 7.28–7.26 (m, 3H), 7.19–7.12 (m, 2H), 7.12 (s, 1H), in
3H); 13C NMR (75 MHz, CDCl3) d 202.2, 151.9, 141.4, 139.3, accordance with literature.33
138.9, 138.8, 128.8, 128.6, 127.2, 127.16, 127.13, 126.5, 126.2,
126.1, 125.2, 45.1, 17.7, 15.7, 15.7, 13.7; HRMS (APCI) m/z: calcd to the GP4 from phosphordiamidate 2g (0.160 g; 0.50 mmol)
for C20H22OS2 [M + H]+ 343.1185; found 343.1188.
and 2-tolylmagnesium chloride (1.30 mL, 1.30 mmol). Column
1-Phenyl-3,3-di-o-tolylprop-2-en-1-one (4r). Prepared according
1,1-Di-o-tolylhex-1-en-3-one (4m). Prepared according to the chromatography (hexane/AcOEt 9 : 1, Rf ¼ 0.35) gave 0.144 g
GP4 from phosphordiamidate 2f (0.146 g; 0.50 mmol) and o- (95%) of the title compound as a yellow oil. 1H NMR (400 MHz,
tolylmagnesium chloride (1.30 mL, 1.25 mmol). Column chro- CDCl3) d 7.90–7.88 (m, 2H), 7.50–7.46 (m, 1H), 7.40–7.36 (m,
matography (hexane/AcOEt 30 : 1, Rf ¼ 0.28) gave 0.103 g (74%) 2H), 7.25–7.06 (m, 8H), 6.98 (s, 1H), 2.36 (s, 3H), 2.09 (s, 3H); 13
C
of the title compound as a yellowish oil. 1H NMR (300 MHz, NMR (101 MHz, CDCl3) d 192.0, 154.9, 141.1, 139.6, 138.3, 135.8,
CDCl3) d 7.26–7.06 (m, 8H), 6.33 (s, 1H), 2.33 (s, 3H), 2.19 (t, J ¼ 135.7, 132.6, 131.2, 130.3, 129.9, 129.6, 128.5, 128.4, 128.3,
7.3 Hz, 2H), 2.10 (s, 3H), 1.54–1.49 (m, 2H), 0.79 (t, J ¼ 7.4 Hz, 128.0, 128.0, 125.9, 125.5, 21.0, 20.1; HRMS (APCI) m/z: calcd for
3H); 13C NMR (75 MHz, CDCl3) d 202.3, 152.7, 140.7, 139.5,
C
23H20O [M + H]+ 313.1587; found 313.1591.
135.7, 135.6, 131.2, 131.1, 130.4, 129.8, 129.8, 128.3, 128.2,
2-(Diphenylmethylene)cyclohexan-1-one (5a). Prepared accord-
125.7, 125.6, 44.8, 20.9, 19.9, 17.7, 13.7; HRMS (APCI) m/z: calcd ing to the GP4 from bromobenzene (0.196 g, 1.25 mmol), nBuLi
for C20H22O [M + H]+ 279.1743; found 279.1746.
(0.50 mL, 1.20 mmol), phosphordiamidate 2h (0.152 g, 0.50
1,1-Di(thiophen-2-yl)hex-1-en-3-one (4n). Prepared according mmol). Column chromatography (hexane/AcOEt 20 : 1, Rf ¼
to the GP4 from phosphordiamidate 2f (0.146 g; 0.50 mmol) and 0.17) gave 0.088 g, (67%) of the title compound as a white solid,
2-thienylmagnesium bromide (1.30 mL, 1.26 mmol). Column mp ¼ 130.0–131.0 ꢀC. 1H NMR (400 MHz, CDCl3) d 7.34–7.22 (m,
chromatography (hexane/AcOEt 20 : 1, Rf ¼ 0.38) gave 0.098 g 6H), 7.14–7.11 (m, 2H), 7.06–7.04 (m, 2H), 2.65–2.59 (m, 4H),
1
(75%) of the title compound as a brownish oil. H NMR (300 2.01–1.96 (m, 2H), 1.83–1.78 (m, 2H); 13C NMR (100 MHz,
MHz, CDCl3) d 7.48–7.46 (m, 1H), 7.38–7.36 (m, 1H), 7.15–7.12 CDCl3) d 206.9, 144.2, 142.2, 140.8, 138.9, 129.9, 129.0, 128.0,
(m, 1H), 7.10–7.08 (m, 2H), 7.03–7.00 (m, 1H), 6.61 (d, J ¼ 127.7, 127.3, 45.0, 34.1, 26.6, 26.3; HRMS (APCI) m/z: calcd for
1.7 Hz, 1H), 2.28 (td, J ¼ 7.3, 1.8 Hz, 2H), 1.62–1.49 (m, 2H), 0.83
C
19H18O [M + H]+ 263.1430; found 263.1434.
2-(Diphenylmethylene)cyclopentan-1-one
(td, J ¼ 7.4, 1.8 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 201.2,
(5b).
Prepared
145.0, 138.6, 138.2, 129.9, 129.6, 128.1, 127.9, 127.7, 126.9, according to the GP4 from bromobenzene (0.198 g, 1.26 mmol),
nBuLi (0.50 mL, 1.20 mmol), phosphordiamidate 2i (0.138 g,
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0.50 mmol). Column chromatography (hexane/AcOEt 20 : 1, Rf (s, 3H), 1.82 (s, 3H); 13C NMR (101 MHz, CDCl3) d 207.9, 145.1,
¼ 0.08) gave 0.085 g (68%) of the title compound as a yellow oil. 141.7, 141.1, 137.7, 129.8, 129.7, 128.4, 128.3, 128.1, 127.7, 30.2,
1H NMR (300 MHz, CDCl3) d 7.34–7.31 (m, 6H), 7.21–7.17 (m, 18.7; HRMS (APCI) m/z: calcd for C17H16O [M + H]+ 237.1274;
2H), 7.14–7.10 (m,2H), 2.82 (t, J ¼ 7.0 Hz, 2H), 2.38 (t, J ¼ 7.7 Hz, found 237.1266.
2H), 1.98–1.88 (m, 2H), in accordance with literature.34
4,4-Bis(4-methoxyphenyl)-3-methylbut-3-en-2-one
(5h).
2-(Bis(4-methoxyphenyl)methylene)cyclopentan-1-one
(5c). Prepared according to the GP4 from 4-bromoanisole (0.240 g,
Prepared according to the GP4 from 4-bromoanisole (0.237 g, 1.3 mmol), nBuLi (0.52 mL, 1.25 mmol), phosphordiamidate 2k
1.26 mmol), nBuLi (0.50 mL, 1.20 mmol), phosphordiamidate 2i (0.140 g, 0.50 mmol). Column chromatography (hexane/AcOEt
(0.140 g, 0.51 mmol). Column chromatography (hexane/AcOEt 6 : 1, Rf ¼ 0.55) gave 0.072 g (49%) of the title compound as
1
ꢀ
9 : 1, Rf ¼ 0.15) gave 0.115 g (74%) of the title compound as a white solid, mp ¼ 58.0–61.0 C. H NMR (400 MHz, CDCl3)
a yellow oil. 1H NMR (400 MHz, CDCl3) d 7.14–7.12 (m, 2H), d 7.10–7.07 (m, 2H), 7.02–7.00 (m, 2H), 6.88–6.80 (m, 4H), 3.82
7.06–7.04 (m, 2H), 6.86–6.83 (m, 4H), 3.82 (s, 6H), 2.81 (t, J ¼ (s, 3H), 3.81 (s, 3H), 2.00 (s, 3H), 1.80 (s, 3H); 13C NMR (101
7.0 Hz, 2H), 2.37 (t, J ¼ 7.7 Hz, 2H), 1.91 (p, J ¼ 7.3 Hz, 2H); 13
C
MHz, CDCl3) d 207.9, 160.0, 159.1, 145.6, 136.3, 134.6, 133.8,
NMR (100 MHz, CDCl3) d 206.6, 159.7, 159.4, 148.2, 134.6, 132.6, 131.4, 131.4, 113.7, 113.4, 55.3, 30.2, 19.0; HRMS (APCI) m/z:
132.5, 131.6, 131.3, 113.2, 113.1, 55.3, 55.1, 40.0, 33.5, 20.7; calcd for C19H20O3 [M + H]+ 297.1485; found 297.1489.
HRMS (APCI) m/z: calcd for C20H20O3 [M + H]+ 309.1485; found
3-Methyl-4,4-di(thiophen-2-yl)but-3-en-2-one (5i). Prepared
309.1489.
according to the GP4 from thiophene (0.110 g, 1.30 mmol),
2-(Diphenylmethylene)cycloheptan-1-one
(5d).
Prepared nBuLi (0.52 mL, 1.25 mmol), phosphordiamidate 2k (0.140 g,
according to the GP4 from bromobenzene (0.200 g, 1.28 mmol), 0.50 mmol). Column chromatography (hexane/AcOEt 9 : 1, Rf ¼
nBuLi (0.51 mL, 1.22 mmol), phosphordiamidate 2j (0.160 g, 0.52) gave 0.029 g (24%) of the title compound as a yellow oil. 1H
0.52 mmol). Column chromatography (hexane/AcOEt 20 : 1, Rf NMR (400 MHz, CDCl3) d 7.41–7.39 (m, 2H), 7.06–7.05 (m, 2H),
¼ 0.15) gave 0.120 g (83%) of the title compound as a white 6.99–6.98 (m, 2H), 2.17 (s, 3H), 1.91 (s, 3H); 13C NMR (101 MHz,
solid, mp ¼ 79.5–81.5 ꢀC. 1H NMR (400 MHz, CDCl3) d 7.37–7.19 CDCl3) d 207.2, 143.2, 142.7, 139.8, 130.3, 129.9, 129.5, 128.5,
(m, 8H), 7.11–7.08 (m, 2H), 2.50–2.47 (m, 2H), 2.39–2.36 (m, 127.6, 127.2, 127.0, 29.5, 19.3; HRMS (APCI) m/z: calcd for
2H), 1.92–1.88 (m, 2H), 1.72–1.61 (m, 4H); 13C NMR (100 MHz,
CDCl3) d 211.2, 142.5, 141.8, 141.5, 140.9, 128.9, 128.6, 128.3,
C
13H12OS2 [M + H]+ 249.0402; found 249.0406.
Phenyl(3,4,5,6-tetrahydro-[1,10-biphenyl]-2-yl)methanone
128.1, 127.22, 127.20, 43.4, 30.3, 29.3, 29.2, 24.2; HRMS (APCI) (6). Phenylmagnesium chloride (0.78 mL, 1.53 mmol) was
m/z: calcd for C20H20O [M + H]+ 277.1587; found 277.1586.
2-(Bis(4-methoxyphenyl)methylene)cycloheptan-1-one
added to a mixture of CuI (0.029 g, 10 mol%) in dry ether (5 mL)
(5e). cooled to 0 ꢀC. The resultant mixture was stirred for 1 h at 0 ꢀC
Prepared according to the GP4 from 4-bromoanisole (0.240 g, followed by addition of phosporodiamidate 2h (0.156 g, 0.51
1.28 mmol), nBuLi (0.51 mL, 1.22 mmol), phosphordiamidate 2j mmol). Then the mixture was stirred for 3 h at 23 ꢀC. The crude
(0.152 g, 0.50 mmol). Column chromatography (hexane/AcOEt reaction mixture was quenched with saturated aqueous solu-
9 : 1, Rf ¼ 0.24) gave 0.152 g (90%) of the title compound as tion of ammonium chloride (2 mL), diluted with ether (30 mL)
a yellow oil. 1H NMR (400 MHz, CDCl3) d 7.12–7.10 (m, 2H), and the organic layer was washed with water (30 mL) and brine
7.00–6.98 (m, 2H), 6.88–6.86 (m, 2H), 6.77–6.74 (m, 2H), 3.81 (s, (30 mL). The organic phase was dried over MgSO4 and the
3H), 3.76 (s, 3H), 2.50–2.41 (m, 2H), 2.40–2.38 (m, 2H), 1.90–1.86 solvents were removed under reduce pressure. Column chro-
(m, 2H), 1.71–1.60 (m, 4H); 13C NMR (100 MHz, CDCl3) d 211.7, matography (Silica gel, hexane/AcOEt 20 : 1, Rf ¼ 0.28) gave
1
158.7, 158.7, 141.4, 141.4, 134.4, 133.6, 130.4, 13.99, 113.0, 0.062 g (46%) of the title compound as a white solid. H NMR
113.4, 55.19, 55.1, 43.4, 30.5, 29.4, 29.3, 24.3; HRMS (APCI) m/z: (300 MHz, CDCl3) d 7.69–7.66 (m, 2H), 7.32–7.31 (m, 1H), 7.23–
calcd for C22H24O3 [M + H]+ 337.1798; found 337.1802.
7.19 (m, 2H), 7.09–6.99 (m, 5H), 2.53–2.45 (m, 4H), 1.91–1.82
2-(Di(thiophen-2-yl)methylene)cycloheptan-1-one (5f). Prepared (m, 4H), in accordance with literature.35
according to the GP4 from thiophene (0.104 g, 1.23 mmol),
(Z)-4-Hydroxy-4,4-diphenylbut-2-en-2-yl bis(N,N-dimethyla-
nBuLi (0.49 mL, 1.17 mmol), phosphordiamidate 2j (0.156 g, mino)phosphordiamidate (8). Phenylmagnesium chloride (6.58
0.51 mmol). Column chromatography (hexane/AcOEt 20 : 1, Rf mL, 12.50 mmol) was added to a solution of phosphordiami-
ꢀ
¼ 0.28) gave 0.059 g (40%) of the title compound as an orange dated 2e (1.320 g, 5.0 mmol) cooled to ꢁ78 C. The resultant
1
oil. H NMR (400 MHz, CDCl3) d 7.36–7.35 (m, 1H), 7.26–7.24 reaction mixture was stirred for 2 h at 23 ꢀC. Then the reaction
(m, 1H), 7.04–6.99 (m, 2H), 6.93–6.88 (m, 2H), 2.53–2.46 (m, mixture was quenched with water (20 mL), the organic layer was
4H), 1.86–1.67 (m, 6H); 13C NMR (100 MHz, CDCl3) d 211.4, separated and the water layer was extracted with ether (2 ꢂ 40
145.1, 142.4, 141.6, 128.0, 127.8, 126.8, 126.7, 126.4, 126.3, mL). Combined organic layers were washed with water (30 mL),
124.7, 42.7, 30.9, 28.4, 28.3, 23.7; HRMS (APCI) m/z: calcd for brine (10 mL), dried over MgSO4 and concentrated under reduce
C
16H16OS2 [M + H]+ 289.0715; found 289.0719.
pressure. Column chromatography (Silica gel, hexane/AcOEt
3-Methyl-4,4-diphenylbut-3-en-2-one (5g). Prepared according 20 : 1, Rf ¼ 0.53) gave 1.480 g (79%) of the title compound as
1
to the GP4 from bromobenzene (0.20 g, 1.3 mmol), nBuLi (0.52 a white solid, mp ¼ 74.0–77.0 C. H NMR (500 MHz, CDCl3)
ꢀ
mL, 1.25 mmol), phosphordiamidate 2k (0.140 g, 0.50 mmol). d 7.59–7.57 (m, 4H), 7.30–7.27 (m, 4H), 7.18–7.15 (m, 2H), 6.22
Column chromatography (hexane/AcOEt 20 : 1, Rf ¼ 0.37) gave (s, 1H), 5.74 (s, 1H), 2.42 (d, J ¼ 10.1 Hz, 12H), 2.05 (s, 3H); 13
C
0.084 g (71%) of the title compound as an yellowish oil. 1H NMR NMR (126 MHz, CDCl3) d 148.8, 145.5 (d, J ¼ 7.6 Hz), 128.1,
(400 MHz, CDCl3) d 7.37–7.26 (m, 6H), 7.18–7.10 (m, 4H), 1.98 126.4, 126.2, 122.7 (d, J ¼ 6.6 Hz), 75.8, 36.2 (d, J ¼ 4.7 Hz), 21.8;
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31P NMR (202 MHz, CDCl3) d 15.12 (s); HRMS (ESI) m/z: calcd for 10 (a) P. Knochel, W. Dohle, N. Gommermann, F. F. Kneisel,
C
20H27N2O3P [M + Na]+ 397.1652; found 397.1660.
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Conflicts of interest
There are no conicts to declare.
Acknowledgements
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