An Efficient and Modular Route to C 3?-TunePhos-Type Ligands

Article abstract of DOI:10.1055/s-0036-1588421

An efficient and modular synthetic route to the bidentate C ₃?-TunePhos was developed, which allowed tunable steric and electronic effects of the ligands. This novel chemical technology highlights a versatile C ₃?-dibromodiphenyl int

Full text of DOI:10.1055/s-0036-1588421

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–E
paper
A
en
X. Deng et al.
Paper
Synthesis
An Efficient and Modular Route to C3*-TunePhos-Type Ligands
Xu Denga,b
Yu-Qing Guana
O
O
Br
O
O
PR2
PR2
central-to-axial
O
O
Br
Br
Ning-Ning Huoa
Ya-Jing Wangc
Hui Lv*a
I
I
Br
Versatile intermediate
Scalable process
65%
C3*-TunePhos
Xu-Mu Zhang*a,d
R = Ph, 83%
R = Cy, 58%
a College of Chemistry and Molecular Science, Wuhan University, Wuhan,
Hubei 430072, P. R. of China
huilv@whu.edu.cn
xumu@whu.edu.cn
b College of Xiangya Pharmaceutical Sciences, Central South University,
Changsha 410013, P. R. of China
c Hunan University of Chinese Medicine, Changsha 410208, China
d Department of Chemistry, South University of Science and Technology
of China, Shenzhen 518055, P. R. of China
Received: 25.02.2017
Accepted after revision: 17.04.2017
Published online: 11.05.2017
because no ligands is universally efficient for all types of
substrates.11 In 2000, Zhang et al. developed an efficient and
tunable C2-symmetric ligand, namely Cn-TunePhos. We not
only investigated the effect of bite angle on the enantio-
selectivity, but also achieved the optimal ligand choice for a
specific substrate by facile tuning of linking bridge.12
Initially, the synthesis of (R)-Cn-TunePhos was achieved
through functional manipulations of the enantiopure pre-
cursor (R)-MeO-BIPHEP.13 Later, Saito disclosed their de
novo synthetic route to (R)-Cn-TunePhos starting from
DOI: 10.1055/s-0036-1588421; Art ID: ss-2017-h0115-op
Abstract An efficient and modular synthetic route to the bidentate
C3*-TunePhos was developed, which allowed tunable steric and elec-
tronic effects of the ligands. This novel chemical technology highlights
a versatile C3*-dibromodiphenyl intermediate that was accomplished
by in situ Grignard exchange and subsequent Cu(II)-mediated intra-
molecular oxidative radical coupling process. It is worth noting that this
advanced intermediate not only could be easily prepared by a diverse
array of C3*-TunePhos-type ligands, but also could be used to facile syn-
thesis of other novel type of N,S-centered bidentate ligands.
Key words C3*-TunePhos-type ligands, modular route, oxidative cou-
pling
biaryl atropisomeric
backbone
¦θ
Given the tremendous success of BINAP in asymmetric
catalysis,1 design and synthesis of new efficient atropiso-
meric C2-symmetric diphosphine ligands has been a con-
stant research theme in asymmetric catalysis. In fact, both
the aryl phosphorous substituents and the biaryl backbone
are tunable parts in this ligand family.2 Structure variations
on the biaryl backbone led to a diverse set of atropisomeric
C2-symmetric diphosphine ligands in the past two decades,
such as MeO-BIPHEP,3 P-Phos,4 SynPhos,5 SegPhos,6 Difluor-
Phos,2 and other important biaryl phosphine ligands7 (Fig-
ure 1), which found wide applications in asymmetric catal-
ysis.8 Subtle alterations of the electronic and steric proper-
ties of the phosphorous substituents on these C2-symmetric
ligands, such as replacing with bulkier aromatics (p-Tol-
BINAP9 and DTBM-SegPhos6), electronically modified sub-
stituents (p-F-BINAP, Cy-BINAP),9,10 or heteroaromatics (α-
furyl-MeO-BIPHEP),3 also generated new, efficient ligands,
all of which exhibited superior performance in asymmetric
catalysis. Though great achievement has gained for C2-sym-
metric ligands, highly modular ligands are still needed to
counter the challenges posed by the asymmetric catalysis
¦β
P
P
aryl phosphorous
substituent
M
O
O
O
MeO
MeO
PPh2
PPh2
PPh2
PPh2
PPh2
PPh2
O
(S)-BIPHEP
(S)-SegPhos
(S)-BINAP
OMe
O
N
Me
Me
MeO
MeO
PPh2
PPh2
O
O
PPh2
PPh2
O
O
PPh2
PPh2
N
O
OMe
(S)-P-Phos
C3*-TunePhos
(S)-SynPhos
Figure 1 General stereoelectronic tunable features of a C2-symmetric
atropisomeric diphosphane and representative examples. M = transition-
metal center, β = bite angle, θ = dihedral angle.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–E

B
X. Deng et al.
Paper
Synthesis
Previous work12,13,17
demethylation
m-bromophenol, which features oxidative coupling as the
key step.13 Recently, Zhang14,15 and Chan16,17 have developed
chiral-bridged atropisomeric diphosphine ligands through
a remarkable central-to-axial chirality transfer strategy
(Scheme 1). Though extensive studies have been directed to
the efficient and practical synthesis of Cn-TunePhos, there
were still problems to be circumvented. For instance, most
of the synthetic processes towards atropisomeric C2-sym-
metric ligands involved the tedious resolution procedure to
obtain the enantiopure ligands, which is both time- and
cost-consuming. And all of these processes involved diaryl-
phosphonate as the key intermediate, which were proved to
be quite inefficient for the subsequent arylation, especially
for those with steric bulk and electron-poor substituents.
Moreover, the flexibility of the processes remained to be
improved. Thus, we wondered if we can develop an efficient
and versatile synthetic route towards C3-TunePhos and re-
lated bidentate ligands from a common intermediate. To
this end, C3*-dibromodiphenyl was an excellent choice
since this versatile intermediate could be subjected to the
subsequent arylation through a diverse set of methods,
such as lithiation and cross-coupling reaction, which pro-
vides more possibilities for the synthesis of steric bulk and
electron poor C3-TunePhos, and even other related N,S-cen-
tered bidentate ligands. In turn, we envisaged that C3*-di-
bromodiphenyl could be prepared by regioselective
Grignard exchange18 followed by oxidative coupling reac-
tion using a similar center-to-axial chiral transfer strategy.
Herein we present our efficient and modular synthesis of
bidentate C3*-TunePhos and related bidentate ligands using
C3*-dibromodiphenyl as the key intermediate.
alkylation
O
PPh2
PPh2
MeO
MeO
PPh2
PPh2
HO
HO
PPh2
PPh2
n
O
Cn-TunePhos (n = 1–6)
68% from MeO-BIPHEP
MeO-BIPHEP
J. Org. Chem. 2000, 65, 6223.
O
O
O
alkylation
arylation
Br
Br
PPh2
n
O
PPh2
Br
OH
O
O
EP1095946A1
Cn-TunePhos
(n = 1–6)
oxidative coupling
resolution
5% overall yield
O
O
oxidative
O
O
P(OEt)2
OH
Br
O
O
P(OEt)2
coupling
OH
Mitsunobu
reaction
P(OEt)2
OH
P(OEt)2
O
O
Proc. Natl. Acad. Sci. USA 2004, 101, 5815
arylation
C2*-TunePhos
resolution
25% overall yield
This work
O
Br
Br
O
O
Br
Br
I
I
Br
OH
O
versatile intermediate
Our synthetic endeavors towards C3*-TunePhos com-
menced with the protection of commercially available 3-
bromophenol (1) with N,N-diethylcarbamoyl chloride by
deprotonation with NaH, giving the carbamate 2 in excel-
lent yield. Subsequently, regiospecific lithiation with LDA
followed by quenching with I2 afforded the desired aryl
iodide 3 in good yield.19 Saponification of compound 3 de-
livered the phenol 4 smoothly, which was further converted
to the coupling precursor (R,R)-6 in high yield through
Mitsunobu reaction by reacting with the enantiopure (S,S)-
2,4-pentanediol (5) in the presence of DIAD and PPh3. Up to
this stage, the reactions proceeded uneventfully and we
easily prepared the diiodide (R,R)-6 on gram scale (Scheme 2).
With the precursor (R,R)-6 in hand, the key oxidative
coupling reaction was then attempted (Table 1). First, sever-
al oxidants were examined. It was found that I2 only afford-
ed the desired product in 10% yield (Table 1 entry 1), while
Fe(acac)3, FeCl3, and CuCl2 also provided the dibromide
(Sax,RR)-7 in low yield (entries 2–4), albeit with minor im-
provements. It is elucidated that the main side product was
the dehalogenated one, which might be attributed to low
solubility of the oxidant in THF thus resulting in low con-
version. The reaction outcomes dissected by way of intro-
O
O
X
X
X = PR2
27% overall yield
can be extended to
N,S-centered
bidentate ligands
Scheme 1 Synthetic endeavors towards Cn-TunePhos
ducing additives. Addition of TMEDA to FeCl3 system result-
ed in negligible effects on the yield (entry 5), whereas the
combination of CuCl2 and TMEDA led to a significant im-
provement (entry 6), partially due to the enhancement of
solubility of CuCl2 in THF and subtle tuning of the oxidation
state of CuCl2. Further improvement was achieved by addi-
tional stabilizing agent, LiCl but not HMPA, delivering the
desired product in acceptable yield (entry 8). In addition,
the concentration also exerted some positive effects on the
yield (entry 9). To this stage, the optimized reaction condi-
tions were established. Notably, this versatile advanced in-
termediate (Sax,RR)-7 could be prepared in gram scale under
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–E

C
X. Deng et al.
Paper
Synthesis
the optimal reaction conditions. Finally, the dibromide
(Sax,RR)-7 was subjected to Li–Br exchange by treatment
with n-BuLi at low temperature, followed by quenching
with R2PCl to deliver the ligands (Sax,RR)-8 and (Sax,RR)-9 in
moderate to good yields (Table 1). Both ligands (Sax,RR)-812
and (Sax,RR)-915 display generally very marked chiral recog-
nition properties in asymmetric hydrogenation. The overall
yield of ligand (Sax,RR)-8 by this route is comparable to that
by Chan’s strategy17 (Scheme 1).
In summary, we have developed an efficient and modu-
lar route to C3*-TunePhos and related ligands, which high-
lights an efficient process involving Grignard exchange and
subsequent Cu(II)-mediated oxidative coupling to give a
versatile C3*-dibromodiphenyl intermediate. It is worth
noting that this advanced intermediate 7 could not only be
the precursor to easily prepare a diverse array of C3*-Tune-
Phos type ligands, but also could be used to the facile syn-
thesis of other novel type of N,S-centered ligands.
O
All reactions were carried out under an argon atmosphere using
flame-dried glassware, unless otherwise noted. CH2Cl2 and 1,2-di-
chloroethane (DCE) were dried over CaH2 and THF was distilled over
Na metal. All reagents were commercially available and used without
further purification, unless indicated otherwise. Reagents were pur-
chased at the highest commercial quality and used without further
purification, unless otherwise stated. Reactions were monitored by
TLC carried out on GF254 plates (0.25 mm layer thickness) using UV
light as visualizing agent and aq ammonium cerium nitrate/ammoni-
um molybdate and H2SO4/EtOH solution (15%) as developing agents.
Flash chromatography was performed with 300–400 mesh silica gel.
b
O
a
Et2N
O
Br
81%
91%
Et2N
O
Br
HO
Br
I
1
2
3
OH OH
O
O
Br
Br
5
c
I
I
Br
OH
84%
d
I
81%
4
6
1H and 13C NMR spectra were recorded on a NMR spectrometer at am-
bient temperature. The residual solvent protons (1H) or the solvent
Scheme 2 Reagents and conditions: (a) N,N-diethylcarbamoyl chloride,
NaH, THF, r.t., 24 h, 91%; (b) LDA, THF, then I2, –78 °C, 0.5 h, 81%; (c) aq
NaOH, THF, reflux, 24 h, 84%; (d) DIAD, PPh3, THF, ultrasound, 0 °C, 1 h,
81%.
1
carbons (13C) were used as internal standards. H NMR data are pre-
sented as follows: chemical shift in ppm downfield from TMS (multi-
plicity, coupling constant, integration). Standard abbreviations are
used to designate multiplicities. High-resolution mass spectra
(HRMS) was taken on ESITOF (time of flight) mass spectrometer at a
4000 V emitter voltage.
Table 1 Screening of the Coupling Reaction
3-Bromophenyl Diethylcarbamate (2)19
i-PrMgCl
then oxidant
O
O
Br
Br
O
O
Br
Br
I
I
To a suspension of NaH (1.92 g, 80 mmol) in anhyd THF (100 mL) was
added a solution of 3-bromophenol (1; 6.92 g, 40 mmol) in THF (10
mL) dropwise at 0 °C under argon. Upon completion of addition, the
mixture was warmed to r.t. and was stirred at this temperature for
another 3 h. Then, a solution of N,N-diethylcarbamoyl chloride in THF
(10 mL) was added to the reaction mixture dropwise. The resulting
suspension was stirred at r.t. overnight. The reaction was quenched
with aq NH4Cl and the mixture extracted with EtOAc (3 × 50 mL). The
combined organic layers were washed with brine and dried (anhyd
Na2SO4). The solvent was evaporated under vacuum. The crude mix-
ture was purified by chromatography on silica gel eluting with
PE/EtOAc (10:1) to afford the desired product as a white solid; yield:
9.68 g (91%); mp 157–158 °C.
1H NMR (400 MHz, CDCl3): δ = 7.30 (s, 1 H), 7.26 (d, J = 8.5 Hz, 1 H),
7.15 (t, J = 8.5 Hz, 1 H), 7.04 (d, J = 8.5 Hz, 1 H), 3.36–3.33 (m, 4 H),
1.18–1.14 (m, 6 H).
13C NMR (400 MHz, CDCl3): δ = 153.7, 152.4, 130.4, 128.3, 125.4,
122.2, 120.9, 42.6, 42.2, 14.5, 13.6.
THF, –40 to –78 °C
65%
7
6
O
O
PR2
PR2
R2PCl
n-BuLi
–78 °C
8: R = Ph, 83%
9: R = Cy, 58%
Entrya
Oxidant
Additives
Conc. (mol/L)b Yield (%)c
1
2
3
4
5
6
7
8
9
I2
–
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.05
10
33
30
22
28
43
35
54
65
Fe(acac)3
FeCl3
CuCl2
FeCl3
CuCl2
CuCl2
CuCl2
CuCl2
–
–
–
TMEDA
TMEDA
TMEDA/HMPA
TMEDA/LiCl
TMEDA/LiCl
3-Bromo-2-iodophenyl Diethylcarbamate (3)
To a solution of i-Pr2NH (1.54 mL, 11 mmol) in anhyd THF (30 mL) at
–78 °C under argon was added a solution of n-BuLi in THF (4.4 mL, 2.5
M in hexane) dropwise. The mixture was stirred at this temperature
for 45 min. Then, a solution of 3-bromophenyl diethylcarbamate (2;
2.72 g, 10 mmol) in THF (10 mL) was added to the reaction mixture
dropwise. The resulting solution was stirred at –78 °C for 0.5 h. Next,
a solution of I2 (3.05 g, 12 mmol) in THF (10 mL) was added dropwise
a Reactions were carried out in 1 mmol scale with the corresponding oxi-
dant (2.5 equiv) and additive (2.5 equiv).
b The concentration of substrate 6 in THF.
c Isolated yields.
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X. Deng et al.
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and the mixture was stirred at this temperature for another 0.5 h.
Upon completion of the reaction (TLC monitoring), the reaction was
quenched with sat. aq NH4Cl and sat. aq Na2SO3. The aqueous layer
was extracted with EtOAc (3 × 25 mL). The combined organic layers
were washed with brine and dried (anhyd Na2SO4). The solvent was
evaporated under vacuum. The crude mixture was purified by chro-
matography on silica gel eluting with PE/EtOAc (10:1) to afford the
desired product as a white solid; yield: 3.34 g (84%); mp 70–73 °C.
ture was stirred at this temperature for 4 h to give the corresponding
Grignard reagent. The resulting mixture was added to another flask
containing CuCl2 (1.056 g, 8.0 mmol) and TMEDA (1.8 mL, 12 mmol)
in THF (20 mL) at –78 °C dropwise. The mixture was stirred at this
temperature for another 4 h. Upon completion of the reaction (TLC
monitoring), the reaction was quenched with aq 2 M HCl and extract-
ed with EtOAc (3 × 30 mL). The combined organic layers were washed
with brine and dried (anhyd Na2SO4). The solvent was evaporated off
under vacuum. The crude mixture was purified by chromatography
on silica gel eluting with PE/EtOAc (80:1) to afford the dibromide as a
white solid; yield: 0.52 g (60%); mp 157–160 °C.
The spectral data of 3 were consistent with that reported in the litera-
ture.20
1H NMR (400 MHz, CDCl3): δ = 7.47 (dd, J = 8.1, 1.5 Hz, 1 H), 7.22 (t, J =
8.1 Hz, 1 H), 7.08 (dd, J = 8.1, 1.5 Hz, 1 H), 3.52 (q, J = 7.1 Hz, 2 H), 3.38
(q, J = 7.1 Hz, 2 H), 1.31 (t, J = 7.1 Hz, 3 H), 1.22 (t, J = 7.1 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 153.4, 152.8, 130.6, 130.0, 129.7,
121.8, 99.9, 42.5, 42.2, 14.5, 13.4.
The spectral data of (Sax,RR)-7 were consistent with that reported in
the literature.15
1H NMR (400 MHz, CDCl3): δ = 7.41 (d, J = 8.0 Hz, 2 H), 7.25 (t, J = 8.0
Hz, 2 H), 7.10 (d, J = 8.0 Hz, 2 H), 4.53 (m, 2 H), 1.79 (m, 2 H), 1.34 (d, J
= 6.4 Hz, 6 H).
13C NMR (400 MHz, CDCl3): δ = 158.6, 132.2, 130.2, 127.2, 125.0,
117.5, 76.7, 40.9, 22.4.
3-Bromo-2-iodophenol (4)
To a solution of 3-bromo-2-iodophenyl diethylcarbamate (3; 3.96 g,
10 mmol) in EtOH (100 mL) was added powdered NaOH (4.0 g, 100
mmol) in two portions. The mixture was heated to reflux for 24 h.
Upon completion of the reaction (TLC monitoring), the reaction was
cooled to r.t. and quenched with aq 2 M HCl. The aqueous layer was
extracted with EtOAc (3 × 30 mL). The combined organic layers were
washed with brine and dried (anhyd Na2SO4). The solvent was evapo-
rated off under vacuum. The crude mixture was purified by chroma-
tography on silica gel eluting with PE/EtOAc (8:1) to afford the desired
product as a white solid; yield: 2.66 g (89%); mp 85–87 °C.
(Sax)-[6,6′-(2R,4R-Pentadioxy)]-(2,2′)-bis(diphenylphosphino)-
(1,1′)-biphenyl] [(Sax,RR)-8]
To a solution of (S)-[6,6′-(2R,4R-pentadioxy)]-(2,2′)-dibromo-(1,1′)-
biphenyl [(Sax,RR)-7] (412 mg, 1.0 mmol) in anhydrous THF (20 mL) at
–78 °C under argon was added a solution of n-BuLi in THF (1.25 mL,
2.5mmol) dropwise. The mixture was stirred at this temperature for 1
h. Then a solution of Ph2PCl (550 mg, 2.5mmol) in THF (2 mL) was
added to the mixture dropwise. The mixture was stirred at this tem-
perature for another 2 h and then slowly warmed to the room tem-
perature. Upon the completion of the reaction by TLC, the reaction
was quenched with saturated aqueous NH4Cl solution and was ex-
tracted with EtOAc (3 × 30 mL). The combined organic layers were
washed with saturated brine and dried over anhydrous Na2SO4. The
solvent was evaporated under vacuum. The crude mixture was puri-
fied by chromatography on silica gel eluting with PE/EtOAc (100:1),
affording the title compound as a white foam; yield: 0.52 g (83%).
The spectral data of compound 4 were consistent with that reported
in the literature.19
1H NMR (400 MHz, CDCl3): δ = 7.20 (dd, J = 8.1, 1.5 Hz, 1 H), 7.12 (t, J =
8.1 Hz, 1 H), 6.92 (dd, J = 8.1, 1.5 Hz, 1 H), 5.54 (br s, 1 H).
13C NMR (400 MHz, CDCl3): δ = 156.6, 130.8, 129.6, 125.0, 13.3, 94.4.
3,3′-(2R,4R)-Pentane-2,4-diylbis(oxy)bis(1-bromo-2-iodoben-
zene) (6)
The spectral data were consistent with that reported in the litera-
ture.17
1H NMR (400 MHz, CDCl3): δ = 1.25 (d, J = 6.4 Hz, 6 H), 1.74 (t, J = 3.9
Hz, 2 H), 4.22–4.66 (m, 2 H), 6.67 (d, J = 7.4 Hz, 2 H), 6.92 (d, J = 8.0 Hz,
6 H), 7.05–7.21 (m, 12 H), 7.26–7.27 (m, 6 H), 7.44–7.46 (m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 22.1, 40.9, 75.6, 118.6, 127.9, 128.1,
128.1, 128.2, 128.6, 128.6, 128.6, 129.1, 133.5, 133.7, 133.8, 133.9,
134.1, 134.2, 135.8, 136.0, 136.2, 137.7, 137.7, 137.8, 138.6, 138.6,
138.7, 138.8, 138.9, 139.0, 158.1, 158.2, 158.2.
To a solution of 3-bromo-2-iodophenol (4; 2.48 g, 8.3 mmol) in anhyd
THF (40 mL) at 0 °C under argon were added (2S,4S)-2,4-pentanediol
(5; 417 mg, 4.0 mmol) and PPh3 (2.19 g, 8.3 mmol) successively. The
mixture was stirred at this temperature for 15 min and then DIAD
(1.63g, 8.3 mmol) was added to the reaction mixture dropwise. The
resulting solution was ultrasonicated in ice-bath for 1 h. Upon com-
pletion of the reaction (TLC monitoring), Et2O was added to dilute the
suspension and the insolubles were filtered off. The filtrate was evap-
orated under vacuum and the crude mixture was purified by chroma-
tography on silica gel eluting with PE/EtOAc (6:1) to afford the desired
product as a white solid; yield: 2.34 g (88%); mp 71–73 °C.
31P NMR (162 MHz, CDCl3): δ = –11.1.
1H NMR (400 MHz, CDCl3): δ = 7.11 (dd, J = 8.0, 1.4 Hz, 2 H), 6.98 (t, J =
7.6 Hz, 2 H), 6.56 (dd, J = 8.2, 1.2 Hz, 2 H), 4.77 (m, 2 H), 2.09 (m, 2 H),
1.39 (d, J = 6.4 Hz, 6 H).
13C NMR (400 MHz, CDCl3): δ = 157.6, 129.9, 129.1, 124.1, 110.7, 95.1,
72.5, 44.0, 19.4.
(Sax)-[6,6′-(2R,4R-Pentadioxy)]-(2,2′)-bis(dicyclhexylphosphino)-
(1,1′)-biphenyl] [(Sax,RR)-9]
The procedure described above for compound (Sax,RR)-8 but with
Cy2PCl as the chlorophoshine provide (Sax,RR)-9 as a white foam;
yield: 0.57 g (58%).
The spectra data of (Sax,RR)-9 were in consistent with that reported in
HRMS (ESI): m/z calcd for C17H17Br2I2O2 [M + H]+: 666.7659; found:
666.7643.
the literature.15
1H NMR (400 MHz, CDCl3): δ = 7.16 (d, J = 7.8 Hz, 2 H), 7.02 (d, J = 7.5
Hz, 2 H), 6.88 (d, J = 7.9 Hz, 2 H), 4.37 (dt, J = 6.4, 4.1 Hz, 2 H), 1.96 (d,
J = 11.7 Hz, 2 H), 1.70–0.80 (m, 50 H).
(S)-[6,6′-(2R,4R-Pentadioxy)]-(2,2′)-dibromo-(1,1′)-biphenyl
[(Sax,RR)-7]18
13C NMR (100 MHz, CDCl3): δ = 22.1, 26.6, 27.0, 27.3, 27.8, 27.9, 28.6,
29.5, 30.2, 30.7, 32.2, 35.5, 40.6, 74.5, 116.9, 125.9, 126.6, 136.2,
157.7.
To a solution of 6 (1.332 g, 2.0 mmol) in anhyd THF (20 mL) and LiCl
(0.127 g, 3 mmol) at –40 °C under argon were added a solution of iso-
propylmagnesium bromide in THF (2.5 mL, 2 M) dropwise. The mix-
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31P NMR (162 MHz, CDCl3): δ = –11.4 (s).
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Funding Information
We are grateful for the financial support by a grant from Wuhan Uni-
versity (203273463), ‘111’ Project of the Ministry of Education of Chi-
na and the National Natural Science Foundation of China (Grant No.
21302193, 21372179, 21432007, 21402145).
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(10) Kumobayashi, H.; Miura, T.; Sayo, N.; Saito, T.; Zhang, X. Synlett
2001, 1055.
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6223.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1588421.
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(13) Yokozawa, T.; Sayo, N.; Saito, T.; Ishizaki, T. Patent
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–E