Synthesis and Optical Resolution of 3,3,3′,3′-Tetramethyl-1,1′-spirobiindane-7,7′-diol

Article abstract of DOI:10.1055/s-0037-1610831

A novel chiral C ₂-symmetric spiro diol, 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-7,7′-diol (TMSIOL), was conveniently prepared via practical seven-step route from Bisphenol A in 45.1% overall yield. l-Menthyl chloroformate is used as optical r

Full text of DOI:10.1055/s-0037-1610831

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–G
paper
A
en
Q. Zhou et al.
Paper
Synthesis
Synthesis and Optical Resolution of 3,3,3′,3′-Tetramethyl-1,1′-
spirobiindane-7,7′-diol
Qiaoxia Zhou
Rihuang Pan
Huanyu Shan
Xufeng Lin*
OH
OH
CHO
OH
OH
0
0
0
0
0-
0
0
3
4-
6
1
1
0-
5
0
7
CHO
OH
Laboratory of Asymmetric Catalysis and Synthesis,
Department of Chemistry, Zhejiang University,
Hangzhou 310027, P. R. of China
OH
lxfok@zju.edu.cn
Bisphenol A
TMSIOL
7 steps
45.1% overall yield
Received: 28.05.2018
Accepted after revision: 30.07.2018
Published online: 04.09.2018
DOI: 10.1055/s-0037-1610831; Art ID: ss-2018-h0371-op
OH
OH
OH
OH
OH
OH
Abstract A novel chiral C2-symmetric spiro diol, 3,3,3′,3′-tetramethyl-
1,1′-spirobiindane-7,7′-diol (TMSIOL), was conveniently prepared via
practical seven-step route from Bisphenol A in 45.1% overall yield.
L-Menthyl chloroformate is used as optical resolving agent for the sepa-
ration of the two enantiomers of TMSIOL.
SpirOH
SPINOL
SBIFOL
O
OH
OH
OH
OH
Key words asymmetric catalysis, chiral ligand, chiral diol, spirobiin-
dane, resolution
O
SBIXOL
TMSIOL
(This work)
Optically active C2-symmetric diols have found many
applications as chiral ligands and also as key cores for pro-
viding a diverse range of excellent supporting chiral ligands
in transition-metal-catalyzed asymmetric reactions, for ex-
ample, bisphosphines, phosphine-oxazolines, bisoxazo-
lines, diamines, and phosphites.1 Recently, chiral diols be-
came also a leading motif in organocatalysts design for
asymmetric synthesis, such as chiral phosphoric acids.2 The
most prominent C2-symmetric diols are BINOL,3 H8-BINOL,4
BIPHENOL,5 TADDOL,6 and VANOL.7 Another prevalent class
of chiral diols is based on the spiro skeletons, such as
SpirOH,8 SPINOL,9 SBIFOL,10 and SBIXOL11 (Figure 1). It
should be noted that the dihedral angles for the axially chi-
ral ligands are a key factor for reactivity and enantioselec-
tivity in asymmetric catalysis.
It is well known that spiro skeleton has been recognized
as a privileged chiral backbone for chiral ligands in asym-
metric catalysis.12 In this context, many outstanding contri-
butions have been made by some research groups, such as
Chan, Sasai, Zhou, van Leeuwen, and Ding groups.13 We also
developed a novel class of chiral spirocyclic phosphoric ac-
ids (SPAs) based on the SPINOL skeleton, and these SPAs
catalysts are now widely applied in over 100 asymmetric
reactions.14 More recently, we developed new types of chi-
Figure 1 Chiral spiro diols
ral phosphine-oxazoline ligands (HMSI-PHOX) and bisphos-
phine ligands (HMSI-PHOS) based on a hexamethyl-1,1′-
spirobiindane backbone, and demonstrated their successful
application in asymmetric reaction.15 Herein, we report the
design, synthesis and optical resolution of a novel chiral C2-
symmetric spiro diol, 3,3,3′,3′-tetramethyl-1,1′-spirobiin-
dane-7,7′-diol (abbreviated as TMSIOL) (Figure 1). We as-
sume that the introduction of double gem-dimethyl substi-
tution in the spiro backbone of SPINOL will remove the ac-
tive benzyl hydrogen and change the dihedral angle of the
conformationally rigid axially chiral diol. Chiral ligands de-
rived from TMSIOL may well keep their stability and im-
prove the enantioselectivity of a reaction in some cases.
We started the synthesis of TMSIOL from commercially
available cheap Bisphenol A ($ 1.5/kg), as shown in Scheme
1. The racemate of tetramethyl-1,1′-spirobiindane-6,6′-diol
(6,6′-TMSIOL) was obtained in 89% yield on a 40 g scale by a
modified acid-catalyzed rearrangement cyclization reac-
tion of Bisphenol A.16 The alkylated product 1 was prepared
in an almost quantitative yield from 6,6′-TMSIOL under
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G

B
Q. Zhou et al.
Paper
Synthesis
general Friedel–Crafts reaction conditions and did not need
any further purification. Then, aldehyde groups were intro-
duced by Duff reaction to afford the corresponding product
2 in 87% yield. The tert-butyl substituents were removed
by the retro-Friedel–Crafts reaction to obtain 3 in 78% yield.
The following esterification with Tf2O gave the bistriflate 4
in 94% yield. The subsequent Pd-catalyzed reduction with
formic acid afforded spiro-bialdehyde 5 in 92% yield. Final-
ly, the rac-TMSIOL was obtained in 91% yield by the Baeyer–
Villiger oxidation rearrangement and subsequent hydroly-
sis. Thus, TMSIOL has been achieved in 7 steps and 45.1%
overall yield from Bisphenol A.
O
O
O
OMen
separation
(L)-menthyl
chloroformate
OH
OH
Et3N, DMAP, CH2Cl2
97% yield
OMen
O
1:1 mixture of
diastereoisomer 6a and 6b
(
)-TMSIOL
O
O
O
O
O
OMen
+
OMen
O
KOH
EtOH, reflux
O
O
OMen
OMen
6a
35% yield
6b
OH
t-Bu
45% yield
OH
OH
MeSO3H
t-BuOH, MeSO3H
OH
OH
OH
OH
+
r.t.
89%
CH2Cl2
r.t.
96%
OH
(40 g scale)
OH
OH
Bisphenol A
1
6,6' -TMSIOL
t-Bu
t-Bu
(–)-(R)-TMSIOL
(+)-(S)-TMSIOL
97% yield
97% yield
Scheme 2 Optical resolution of rac-TMSIOL
OH
OH
TFA; HMTA
AcOH
CHO
AlCl3, MeNO2
CHO
reflux
87%
CHO
OH
toluene, r.t.
78%
(S)-TMSIOL, were obtained by hydrolysis of 6a and 6b in al-
most quantitative yields, respectively. Absolute configura-
tion of (R)-TMSIOL was confirmed by X-ray diffraction anal-
ysis, which gave the dihedral angle of 77.0° (Figure 3).18 By
comparison, a single crystal of (S)-SPINOL was obtained,
and X-ray diffraction analysis showed the corresponding di-
hedral angle of 69.3° (Figure 4).19 Notably, the dihedral an-
gles of chiral TMSIOL and SPINOL show remarkable differ-
ence. It is well established that double gem-dimethyl sub-
stitution in SPINOL increases the dihedral angle of the
CHO
OH
2
3
t-Bu
OTf
Pd(PPh3)2Cl2, dppp
HCO2H, NEt3
CHO
CHO
CHO
Tf2O, Pyridine
CHO
OTf
DMF, 80 °C
92%
CH2Cl2
94%
r.t.
4
5
1) m-CPBA,CF3CO2H
OH
OH
2) 2 M NaOH, r.t.
91%
(
)-TMSIOL
Scheme 1 Synthesis of rac-TMSIOL
Then, using L-menthyl chloroformate as a resolving
agent, efficient chiral resolution of rac-TMSIOL was accom-
plished, as shown in Scheme 2. Treatment of rac-TMSIOL
with L-menthyl chloroformate in the presence of NEt3 and
4-(N,N-dimethylamino)pyridine (DMAP) gave 6a and 6b as
1:1 diastereoisomer mixture in 97% yield. Menthol ester of
(R)-TMSIOL (6a) was isolated as a white solid by recrystalli-
zation from hexane in 70% yield, based on one diastereo-
mer. Absolute configuration of 6a was confirmed by X-ray
diffraction analysis (Figure 2).17 Another menthol ester of
(S)-TMSIOL 6b was separated as a liquid from mother liquor
of recrystallization by silica gel column in 90% yield, based
on one diastereomer. Pure enantiomers, (R)-TMSIOL and
Figure 2 X-ray single-crystal structure of 6a
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G

C
Q. Zhou et al.
Paper
Synthesis
Figure 3 X-ray single-crystal structure of (R)-TMSIOL
Figure 4 X-ray single-crystal structure of (S)-SPINOL
axially chiral spiro-diol. Thus, chiral ligands derived from
TMSIOL may well improve the enantioselectivity of a reac-
tion in some case.
Ts
Ts
HN
Rh(acac)(C2H4)2 (3 mol %)
(R)-TMSI-PHOP (6 mol %)
N
PhB(OH)2
Ph
H
Additionally, spiro phosphite (R)-TMSI-PHOP was con-
veniently derived from chiral sprio diol (R)-TMSIOL, as
shown in Scheme 3. As a very common oxidation-free relay
for catalytic phosphate ligand, air stable borane complex
(R)-7 was first obtained in good yield by condensation of
chiral spiro diol (R)-TMSIOL with PCl3, followed by treat-
ment with the corresponding lithium phenolate and bo-
rane-tetrahydrofuran complex in one-pot procedure. An
easy and selective method of decomplexation of (R)-7 by
DABCO provided (R)-TMSI-PHOP in 95% yield. Further, the
efficiency of (R)-TMSI-PHOP was tested in the rhodium-
catalyzed asymmetric arylation of imines.20 As shown in
Scheme 4, N-tosylphenylimine 8 was treated with phenyl-
KF (4 eq)
toluene/H2O
Cl
Cl
8
9
10
80% yield, e.r. 87:13
35 °C, 20 h
Scheme 4 Asymmetric arylation of imine
substitution in the spiro backbone of SPINOL increases the
dihedral angle. A spiro phosphite (R)-TMSI-PHOP and its
borane complex were conveniently derived from chiral (R)-
TMSIOL. Further application of novel chiral TMSIOL for the
preparation of new chiral ligands and catalysts in asymmet-
ric catalysis is currently underway.
boronic acid (9) in the presence of
3
mol% of
Rh(acac)(C2H4)2 and 6 mol% of (R)-TMSI-PHOP in aqueous
KF-toluene at 35 °C for 20 hours. The desired chiral diaryl-
methylamine product 10 was obtained in 80% yield with e.r.
87:13.
In summary, we have developed a simple and scalable
route towards a novel C2-symmetric spiro diol (TMSIOL) in 7
steps and 45.1% overall yield from Bisphenol A. L-Menthyl
chloroformate is used as optical resolving agent for the sep-
aration of the two enantiomers of TMSIOL. According to
data from X-ray diffraction analysis of chiral TMSIOL and
SPINOL, dihedral angles of the axially chiral spiro diols
show remarkable difference, and double gem-dimethyl
All reagents and solvents were purchased from commercial sources.
1H NMR and 13C NMR spectra were recorded on Bruker Avance III 400
spectrometer. IR spectra were recorded on Nicolet NEXUS 470 spec-
trometer. HRMS data were measured on Waters GCT Premier and
Bruker Ultraflex. X-ray single crystal diffraction intensity data were
recorded on Rigaku Gemini A Ultra instrument. Optical rotations
were measured on a PerkinElmer Model 341 polarimeter.
3,3,3′,3′-Tetramethyl-1,1′-spirobiindene-6,6′-diol (6,6′-TMSIOL)
MeSO3H (440 mL) was added to a flask containing Bisphenol A (100 g,
438 mmol), and the mixture was stirred at r.t. for 3 days. Then the
mixture was poured onto 400 g crushed ice, stirred to r.t. and filtered.
The filter residue was washed with hot water. To a boiling saturated
solution of the crude product in EtOH, hot water was added slowly
BH3
OH
DABCO
O
O
O
1) PCl3,NEt3
P
OPh
P OPh
OH
2)
PhOLi
O
95% yield
3) BH3 ⋅ THF
76% yield
(R) -TMSIOL
(R)-7
(R)-TMSI-PHOP
Scheme 3 Synthesis of spiro phosphite
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G

D
Q. Zhou et al.
Paper
Synthesis
until no more precipitation was observed. The product 6,6′-TMSIOL
was collected by filtration as a white solid after drying in an oven
(105 °C); yield: 40 g (89%); mp 176–178 °C.
6,6′-Dihydroxy-3,3,3′,3′-tetramethyl-1,1′-spirobiindene-7,7′-dicarb-
aldehyde (3)
To a solution of compound 2 (2.0 g, 4.2 mmol) and AlCl3 (10.0 g, 75
mmol) in toluene (30 mL) was added MeNO2 (20 mL) at 0 °C. The reac-
tion mixture was stirred overnight at r.t. under an atmosphere of N2.
Then, aq 3 M HCl was added slowly at 0 °C to quench the reaction. The
resulting mixture was stirred at r.t. for 24 h and extracted with EtOAc.
The combined organic extracts were washed with H2O and sat. brine,
dried (Na2SO4), and concentrated under reduced pressure. The resi-
due was purified by flash column chromatography with 100% CH2Cl2.
The solid was washed with hexane to give the product 15 as a yellow
powder; yield: 1.2 g (78%); mp 219–220 °C.
IR (film): 3376, 3020, 2953, 2861, 1607, 1492, 1467, 1383, 1149,
1117, 1096, 856, 820, 668, 649 cm–1
.
1H NMR (400 MHz, acetone-d6): δ = 7.96 (s, 2 H), 7.05 (d, J = 8.2 Hz, 2
H), 6.71 (dd, J = 8.2, 2.4 Hz, 2 H), 6.22 (d, J = 2.3 Hz, 2 H), 3.04 (s, 2 H),
2.34 (d, J = 13.0 Hz, 2 H), 2.21 (d, J = 13.0 Hz, 2 H), 1.37 (s, 6 H), 1.31 (s,
6 H).
13C NMR (100 MHz, acetone-d6): δ = 157.77, 152.93, 143.94, 123.29,
115.35, 111.22, 60.58, 58.25, 43.43, 32.21, 30.90.
HRMS (EI, GC-TOF): m/z [M+] calcd for C21H24O2: 308.1776; found:
308.1779.
IR (film): 2961, 2867, 1659, 1604, 1579, 1454, 1392, 1285, 1181,
1165, 1151 cm–1
.
The analytical and spectral data were in complete agreement with the
previously published data.16
1H NMR (400 MHz, CDCl3): δ = 11.72 (s, 2 H), 9.58 (s, 2 H), 7.35 (d,
J = 8.6 Hz, 2 H), 6.94 (d, J = 8.6 Hz, 2 H), 2.62 (d, J = 13.5 Hz, 2 H), 2.43
(d, J = 13.5 Hz, 2 H), 1.39 (s, 6 H), 1.37 (s, 6 H).
5,5′-Di-tert-butyl-3,3,3′,3′-tetramethyl-1,1′-spirobiindene-6,6′-
diol (1)
13C NMR (101 MHz, CDCl3): δ = 194.28, 163.97, 152.08, 142.55,
132.07, 118.97, 114.37, 60.20, 58.04, 43.01, 32.01, 30.11.
To a solution of 6,6′-TMSIOL (10.0 g, 32.5 mmol) in CH2Cl2 (100 mL)
was added t-BuOH (10 mL, 109 mmol). The resulting mixture was
stirred at r.t. and MeSO3H (15 mL) was added slowly. The reaction was
allowed to proceed 4 h at r.t. Then, the reaction was quenched by add-
ing H2O. The mixture was evaporated under reduced pressure to re-
move CH2Cl2. The resulting mixture was filtered and the solid was
washed with H2O to give product 1 as a white powder after drying in
an oven (105 °C); yield: 13 g (96%); mp 283–284 °C.
HRMS (EI, GC-TOF): m/z [M+] calcd for C23H24O4: 364.1675; found:
364.1679.
7,7′-Diformyl-3,3,3',3′-tetramethyl-1,1′-spirobiindene-6,6′-diyl
Bis(trifluoromethanesulfonate) (4)
To a solution of compound 3 (2 g, 5.5 mmol) and pyridine (2.4 mL, 30
mmol) in CH2Cl2 (30 mL) was added Tf2O (3.8 mL) at 0 °C. The result-
ing mixture was stirred at r.t. for 24 h under an atmosphere of N2.
Then, aq 1 M HCl was added to quench the reaction. The mixture was
extracted with CH2Cl2, the combined organic extracts were washed
with H2O and sat. brine, dried (Na2SO4), and concentrated under re-
duced pressure. The residue was purified by flash column chromatog-
raphy with 100% CH2Cl2 to give the product 4 as a pale yellow pow-
der; yield: 3.25 g (94%); mp 114–115 °C.
IR (film): 3537, 2954, 2866, 1615, 1499, 1464, 1409, 1361, 1250,
1167, 1116, 889, 852, 741 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.05 (s, 2 H), 5.40 (s, 2 H), 3.04 (s, 2 H),
2.29 (d, J = 13.0 Hz, 2 H), 2.09 (d, J = 13.0 Hz, 2 H), 1.43 (s, 6 H), 1.35 (s,
18 H), 1.28 (s, 6 H).
13C NMR (101 MHz, CDCl3): δ = 153.68, 149.14, 144.01, 135.07,
119.72, 111.78, 59.59, 56.69, 43.22, 34.65, 31.81, 30.47, 29.77.
HRMS (EI, GC-TOF): m/z [M+] calcd for C29H40O2: 420.3038; found:
IR (film): 2961, 2870, 1704, 1649, 1600, 1470, 1428, 1365, 1250,
1216, 1140, 869, 841, 805 cm–1
.
420.3034.
1H NMR (400 MHz, CDCl3): δ = 9.88 (s, 2 H), 7.52 (d, J = 8.4 Hz, 2 H),
7.30 (d, J = 8.4 Hz, 2 H), 2.53–2.41 (m, 4 H), 1.51 (s, 6 H), 1.43 (s, 6 H).
5,5′-Di-tert-butyl-6,6′-dihydroxy-3,3,3′,3′-tetramethyl-1,1′-spiro-
biindene-7,7′-dicarbaldehyde (2)
13C NMR (101 MHz, CDCl3): δ = 186.57, 154.89, 151.81, 149.98,
128.90, 123.35, 118.56 (q, J = 319 Hz), 59.18, 57.28, 43.22, 32.43,
29.01.
HRMS (EI, GC-TOF): m/z [M+] calcd for C25H22F6O8S2: 628.0660; found:
628.0655.
A solution of hexamethylenetetraamine (HMTA; 10.8 g, 77 mmol) and
compound 1 (5.2 g, 12.4 mmol) in trifluoroacetic acid (150 mL) was
refluxed for 24 h under an atmosphere of N2. Then, AcOH (150 mL)
was added and the mixture was refluxed for 72 h. Aq 6 M HCl (150
mL) was added, and after refluxing for 24 h, H2O (300 mL) was added,
and the reaction mixture was refluxed for further 24 h and cooled to
r.t. The precipitate was collected by filtration, washed with H2O, and
dried to give 2 as a yellow powder; yield: 5.0 g (87%); mp 226–227 °C.
3,3,3′,3′-Tetramethyl-1,1′-spirobiindene-7,7′-dicarbaldehyde (5)
To a solution of compound 4 (628 mg, 1 mmol), Pd(PPh3)2Cl2 (59 mg,
0.084 mmol), dppp (40 mg, 0.96 mmol), and NEt3 (3.34 mL, 24 mmol)
in DMF was added HCO2H (0.95 mL, 15.5 mmol) at 0 °C. The resulting
mixture was stirred at 80 °C for 24 h under an atmosphere of N2.
Then, the mixture was cooled to r.t. and quenched with aq 1 M HCl.
The mixture was extracted with EtOAc, the combined organic ex-
tracts were washed with H2O and sat. brine, and dried (Na2SO4). The
solvent was removed in vacuo and the residue was purified by flash
column chromatography (PE/EtOAc 15:1) to give the product 5 as a
white powder; yield: 305 mg (92%); mp 203–204 °C.
IR (film): 2956, 2925, 2869, 1685, 1637, 1606, 1465, 1430, 1391,
1363, 1303, 1283, 1253, 1201, 1186, 1163 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 12.55 (s, 2 H), 9.60 (s, 2 H), 7.30 (s, 2
H), 2.56 (d, J = 13.5 Hz, 2 H), 2.39 (d, J = 13.5 Hz, 2 H), 1.42 (s, 18 H),
1.37 (s, 6 H), 1.35 (s, 6 H).
13C NMR (101 MHz, CDCl3): δ = 195.17, 163.72, 149.48, 141.37,
139.25, 128.91, 114.19, 77.35, 77.03, 76.71, 60.32, 57.56, 43.19, 35.07,
32.06, 30.13, 29.31.
IR (film): 3788, 3351, 2962, 2861, 2754, 1700, 1685, 1589, 1451,
HRMS (EI, GC-TOF): m/z [M+] calcd forC31H40O4: 476.2927; found:
1394, 1305, 1241, 807 cm–1
.
476.2927.
1H NMR (400 MHz, CDCl3): δ = 9.58 (s, 2 H), 7.73 (dd, J = 7.4, 1.4 Hz, 2
H), 7.50–7.39 (m, 4 H), 2.58 (d, J = 13.2 Hz, 2 H), 2.47 (d, J = 13.2 Hz, 2
H), 1.48 (s, 6 H), 1.42 (s, 6 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G

E
Q. Zhou et al.
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Synthesis
13C NMR (101 MHz, CDCl3): δ = 190.28, 153.41, 152.39, 130.89,
HRMS (ESI): m/z [M + Na]+ calcd for C43H60O6Na: 695.4288; found:
129.34, 128.45, 128.40, 59.35, 58.05, 43.62, 32.46, 29.58.
695.4262.
HRMS (EI, GC-TOF): m/z [M+] calcd for C23H24O2: 332.1776; found:
332.1773.
6b
Yield: 2.83 g (45%); liquid; [α]D20 –205.0 (c 1.00, acetone).
IR (film): 2995, 2868, 1760, 1462, 1234 cm–1
.
3,3,3′,3′-Tetramethyl-1,1′-spirobiindane-7,7′-diol (TMSIOL)
To a solution of 5 (2 g, 6 mmol) in CH2Cl2 was added trifluoroacetic
acid (0.9 mL) at 0 °C. The resulting solution was stirred for 10 min at 0
°C under an atmosphere of N2. Subsequently, m-CPBA (4.28 g) was
added. The mixture was stirred for 20 min. Then, the reaction was al-
lowed to proceed overnight and quenched by adding sat. aq Na2SO3.
The mixture was extracted with EtOAc, the combined organic ex-
tracts were washed with H2O and sat. brine, and dried (Na2SO4). The
solvent was removed in vacuo and the residue was dissolved in MeOH
(10 mL), and aq 3 M NaOH (20 mL) was added slowly. The mixture
was stirred overnight at r.t. Then, aq 3 M HCl was added until pH 7.
The mixture was extracted with EtOAc (3 ×), the combined organic
layers were washed with H2O and sat. brine, and dried (Na2SO4). The
solvent was removed in vacuo and the residue was purified by flash
column chromatography (PE/EtOAc 10:1) to give the product TMSIOL
as a white powder; yield: 1.7 g (91%); mp 190–192 °C.
1H NMR (400 MHz, CDCl3): δ = 7.19 (t, J = 7.8 Hz, 2 H), 6.97 (dd,
J = 17.3, 7.8 Hz, 4 H), 4.26 (td, J = 10.8, 4.4 Hz, 2 H), 2.46 (d, J = 13.2 Hz,
2 H), 2.25 (d, J = 13.2 Hz, 2 H), 1.90–1.75 (m, 2 H), 1.69–1.57 (m, 6 H),
1.42–1.17 (m, 16 H), 1.00–0.60 (m, 24 H).
13C NMR (101 MHz, CDCl3): δ = 153.16, 151.18, 146.12, 137.85,
127.34, 118.95, 118.29, 77.46, 55.78, 54.48, 45.87, 43.12, 39.26, 33.03,
31.41, 30.13, 28.50, 24.75, 22.13, 20.93, 19.79, 15.32. HRMS (ESI): m/z
[M + Na]+ calcd for C43H60O6Na: 695.4288; found: 695.4262.
(R)-TMSIOL
To a solution of 6a (672 mg, 1 mmol) in EtOH (10 mL) was added KOH
(560 mg, 10 mmol). The mixture was refluxed for 1 h and cooled to
r.t. Aq 3 M HCl was added until the solution was acidic. The mixture
was extracted with EtOAc, and the combined organic layers were
washed with H2O and sat. brine, and dried (Na2SO4). The solvent was
removed in vacuo and the residue was purified by flash column chro-
matography (PE/EtOAc 100:1) to give the product (R)-TMSIOL as a
white powder; yield: 300 mg (97%); mp 180–181 °C; [α]D20 –130.1 (c
1.00, acetone).
IR (film): 3805, 3746, 3195,2 983, 2925, 1748, 1683, 1585, 1469,
1456, 1360, 1304, 1242, 1201, 1175 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.21 (m, 2 H), 6.83 (d, J = 7.5 Hz, 2 H),
6.66 (d, J = 8.0 Hz, 2 H), 4.43 (s, 2 H), 2.39 (d, J = 13.4 Hz, 2 H), 2.33 (d,
J = 13.4 Hz, 2 H), 1.41 (s, 6 H), 1.36 (s, 6 H).
13C NMR (101 MHz, CDCl3): δ = 154.08, 152.71, 130.36, 130.07,
115.41, 114.59, 77.37, 77.05, 76.74, 55.56, 54.14, 44.26, 31.94, 29.68.
(S)-TMSIOL
(S)-TMSIOL was obtained by the above same procedure from 6b (672
mg, 1 mmol); yield: 300 mg (97%); white powder; mp 180–181 °C;
[α]D20 +130.0 (c 1.00, acetone).
HRMS (EI, GC-TOF): m/z [M+] calcd for C21H24O2: 308.1776; found:
308.1778.
Chiral Resolution of TMSIOL
Compound [(R)-7]
To a solution of TMSIOL (2.876 g, 9.35 mmol) and NEt3 (3.23 mL, 22.4
mmol) in CH2Cl2 (140 mL) were added L-menthyl chloroformate (3.53
g, 21.57 mmol) and DMAP (122 mg, 1 mmol) at 0 °C. The reaction
mixture was stirred overnight at r.t. under an atmosphere of N2. Aq 1
M HCl was added to quench the reaction. The mixture was extracted
with EtOAc, the combined organic layers were washed with H2O and
sat. brine, and dried (Na2SO4). The solvent was removed in vacuo to
give 6a and 6b as 1:1 diastereoisomer mixture in 97% yield (6.11 g) as
light yellow oil, which was dissolved in hexane (20 mL) and cooled to
–18 °C to give a white solid (2.42 g) (95% dr). The latter was recrystal-
lized from hexane once to give the diastereomerically pure isomer 6a
(2.2 g) as colorless crystals. The diastereomerically pure isomer 6b
(2.83 g) was obtained by column chromatography (PE/EtOAc 100:1)
from the mother liquor.
To a solution of (R)-TMSIOL (1.54 g, 5 mmol) and NEt3 (1.72 mL, 12
mmol) in THF (30 mL) was added PCl3 (2.75 mL) at –78 °C. Then, the
mixture was stirred for 30 min under an atmosphere of N2. The reac-
tion was allowed to proceed for 3 h at r.t. Then, the mixture was
cooled to –78 °C, and a solution of lithium phenolate (6 mmol) in THF,
which was prepared from phenol (563 mg, 6 mmol) and n-BuLi (2
M/THF, 2 mL, 5 mmol) in THF (7 mL), was added The resulting mix-
ture was stirred overnight at r.t.. A 1 M solution of BH3·THF (20 mL, 20
mmol) in hexane was added at 0 °C. The resulting mixture was stirred
2 h at r.t. and then H2O was added at 0 °C to quench the reaction. The
mixture was extracted with EtOAc, the combined organic layers were
washed with H2O and sat. brine, and dried (Na2SO4). The solvent was
removed in vacuo and the residue was purified by flash column chro-
matography (PE/EtOAc 50:1) to give the product (R)-7 as a white
powder; yield: 1.65 g (73%); mp 200–201 °C; [α]D20 +164.7 (c 1.00, ac-
etone).
6a
Yield: 2.2 g (35%); colorless crystals; mp 84–85 °C; [α]D20 –60.9 (c
1.00, acetone).
IR (film): 3370, 2968, 2924, 2416, 1591, 1489, 1456, 1315, 1200,
1168, 1124, 968, 940, 886, 747 cm–1
.
IR (film): 2995, 2867, 1760, 1462, 1234 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.33–7.22 (m, 4 H), 7.12 (dt, J = 14.1,
6.9 Hz, 3 H), 7.04–6.95 (m, 2 H), 6.84 (d, J = 8.5 Hz, 2 H), 2.43 (dd,
J = 12.7, 4.1 Hz, 2 H), 2.06 (dd, J = 26.3, 12.7 Hz, 2 H), 1.56 (d, J = 3.3
Hz, 6 H), 1.28 (d, J = 1.7 Hz, 6 H), 0.52 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 154.99, 154.62, 150.58, 150.52,
143.31, 142.97, 142.83, 139.57, 138.86, 129.56, 129.12, 125.42,
122.15, 122.11, 121.63, 121.60, 121.10, 120.81, 120.56, 120.53, 57.45,
56.15, 55.63, 42.96, 42.67, 32.60, 32.57, 30.01, 29.99.
1H NMR (400 MHz, CDCl3): δ = 7.20 (dd, J = 8.1, 7.5 Hz, 2 H), 7.04–6.92
(m, 4 H), 4.26 (td, J = 10.9, 4.4 Hz, 2 H), 2.46 (d, J = 13.2 Hz, 2 H), 2.23
(d, J = 13.2 Hz, 2 H), 2.02 (dd, J = 7.0, 4.6 Hz, 2 H), 1.65–1.55 (m, 6 H),
1.47–1.28 (m, 14 H), 1.26–1.17 (m, 2 H), 0.99–0.75 (m, 18 H), 0.62 (d,
J = 6.9 Hz, 6 H).
13C NMR (101 MHz, CDCl3): δ = 154.07, 152.19, 147.19, 138.48,
128.22, 119.55, 119.12, 56.88, 55.53, 46.77, 44.10, 40.48, 34.07, 32.48,
31.26, 29.54, 25.20, 22.99, 22.00, 20.98, 16.14.
31P NMR (162 MHz, CDCl3): δ = 105.44 (br).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G

F
Q. Zhou et al.
Paper
Synthesis
HRMS (ESI): m/z [M + Na]+ calcd for C27H30BO3PNa: 467.1923; found:
467.1930.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1609623.
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Phenyl [(R)-3,3,3′,3′-Tetramethyl-1,1′-spirobiindane-7,7′-di-
yl]phosphite [(R)-TMSI-PHOP]
In a three-necked flask, a mixture of (R)-7 (444 mg, 1 mmol), DABCO
(112 mg, 1 mmol), and hexane (10 mL) was stirred for 2 h at 40 °C.
Then, the mixture was filtered, and the filtrate was concentrated un-
der reduced pressure. The residue was purified by flash column chro-
matography (PE/EtOAc 50:1) to give the product (R)-TMSI-PHOP as a
white power; yield: 410 mg (95%); mp 100–102 °C; [α]D20 +145.4 (c
1.00, acetone).
References
(1) (a) Ojima, I. Catalytic Asymmetric Synthesis; Wiley-VCH: Wein-
heim, 2000. (b) Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H. Compre-
hensive Asymmetric Catalysis;1V–o.3l Springer: Berlin, 1999. (c) Brunel,
J. M. Chem. Rev. 2005, 105, 857. (d) McCarthy, M.; Guiry, P. J. Tet-
rahedron 2001, 57, 3809. (e) Whitesell, J. K. Chem. Rev. 1989, 89,
1581.
IR (film): 3355, 2972, 1583, 1460, 1212, 1050, 880, 808, 758, 690 cm–1
.
(2) (a) Akiyama, T.; Itoh, J.; Fuchibe, K. Adv. Synth. Catal. 2006, 348,
999. (b) Akiyama, T. Chem. Rev. 2007, 107, 5744. (c) Terada, M.
Chem. Commun. 2008, 44, 4097. (d) Adair, G.; Mukherjee, S.;
List, B. Aldrichimica Acta 2009, 41, 31. (e) Yu, J.; Shi, F.; Gong, L.-
Z. Acc. Chem. Res. 2011, 44, 1156. (f) Parmar, D.; Sugiono, E.;
Raja, S.; Rueping, M. Chem. Rev. 2014, 114, 9047.
1H NMR (400 MHz, CDCl3): δ = 7.29–7.14 (m, 3 H), 7.13–6.86 (m, 7 H),
6.68 (d, J = 7.9 Hz, 1 H), 2.34 (d, J = 12.7 Hz, 2 H), 2.00 (d, J = 12.5 Hz, 2
H), 1.47 (d, J = 11.0 Hz, 6 H), 1.22 (d, J = 8.3 Hz, 6 H).
31P NMR (162 MHz, CDCl3): δ = 118.84.
13C NMR (101 MHz, CDCl3): δ = 154.44, 153.99, 152.34, 152.25,
144.46, 144.41, 142.85, 142.78, 142.71, 139.39, 129.72, 129.08,
129.06, 128.19, 123.84, 121.97, 121.88, 121.82, 120.01, 119.99,
119.77, 119.68, 119.35, 77.37, 77.05, 76.74, 57.05, 56.39, 55.45, 43.09,
42.51, 32.43, 32.09, 30.31, 30.09.
HRMS (EI, GC-TOF): m/z [M+] calcd for C27H27O3P: 430.1698; found.
430.1725.
(3) (a) Brunel, J. M. Chem. Rev. 2007, 107, PR1. (b) Chen, Y.; Yekta, S.;
Yudin, A. K. Chem. Rev. 2003, 103, 3155. (c) Brunel, J. M. Chem.
Rev. 2005, 105, 857. (d) Noyori, R.; Takaya, H. Acc. Chem. Res.
1990, 23, 345. (e) Berthod, M.; Mignani, G.; Woodward, G.;
Lemaire, M. Chem. Rev. 2005, 105, 1801. (f) Rueping, M.;
Kuenkel, A.; Atodiresei, I. Chem. Soc. Rev. 2011, 40, 4539.
(4) Cramer, N.; Laschat, S.; Baro, A. Organometallics 2006, 25, 2284.
(5) (a) Hua, Z.; Vassar, V. C.; Ojima, I. Org. Lett. 2003, 5, 3831.
(b) Shi, C.; Chien, C. W.; Ojima, I. Chem. Asian J. 2011, 6, 674.
(6) (a) Seebach, D.; Beck, A. K.; Heckel, A. Angew. Chem. Int. Ed.
2001, 40, 92. (b) Seebach, D.; Pichota, A.; Beck, A. K.; Pinkerton,
A. B.; Litz, T.; Karjalainen, J.; Gramlich, V. Org. Lett. 1999, 1, 55.
(7) (a) Wulff, W.; Desai, A. Synthesis 2010, 3670. (b) Bao, J.; Wulff,
W. D.; Rheingold, A. L. J. Am. Chem. Soc. 1993, 115, 3814.
(8) (a) Cram, D. J.; Steinberg, H. J. Am.Chem. Soc. 1954, 76, 2753.
(b) Hardeggar, E.; Maeder, E.; Semarne, H. M.; Cram, D. J. J. Am.
Chem. Soc. 1959, 81, 2729. (c) Chan, A. S. C.; Hu, W.; Pai, C.-C.;
Lau, C.-P. J. Am. Chem. Soc. 1997, 119, 9570. (d) Srivastava, N.;
Mital, A.; Kumar, A. J. Chem. Soc., Chem. Commun. 1992, 493.
(9) (a) Birman, V. B.; Rheingold, A. L.; Lam, K.-C. Tetrahedron: Asym-
metry 1999, 10, 125. (b) Li, Z.; Liang, X.; Wu, F.; Wan, B. Tetrahe-
dron: Asymmetry 2004, 15, 665.
(10) Cheng, X.; Hou, G.-H.; Xie, J.-H.; Zhou, Q.-L. Org. Lett. 2004, 6,
2381.
(11) (a) Wu, S.; Zhang, W.; Zhang, Z.; Zhang, X. Org. Lett. 2004, 6,
3565. (b) Zhang, W.; Wang, C.-J.; Gao, W.; Zhang, X. Tetrahedron
Lett. 2005, 46, 6087. (c) Zhang, W.; Wu, S.; Zhang, Z.; Yennawar,
H.; Zhang, X. Org. Biomol. Chem. 2006, 4, 4474.
(12) (a) Xie, J.-H.; Zhou, Q.-L. Acc. Chem. Res. 2008, 41, 581.
(b) Bajracharya, G. B.; Arai, M. A.; Koranne, P. S.; Suzuki, T.;
Takizawa, S.; Sasai, H. Bull. Chem. Soc. Jpn. 2009, 82, 285.
(c) Ding, K.; Han, Z.; Wang, Z. Chem. Asian J. 2009, 4, 32. (d) Xie,
J.-H.; Zhou, Q.-L. Acta Chim. Sinica 2014, 72, 778. (e) Liu, Y.; Li,
W.; Zhang, J. Natl. Sci. Rev. 2017, 4, 326.
(S)-N-[(4-Chlorophenyl)phenylmethyl]-4-methylbenzenesulfon-
amide (10)
Under a N2, Rh(acac)(C2H4)2 (0.6 mg, 1.5 μmol), and (R)-TMSI-PHOP
(1.4 mg, 3 μmol) were dissolved in toluene (0.5 mL) in a dry Schlenk
tube. The mixture was stirred at r.t. for 1 h. Then, (E)-N-(4-chloroben-
zylidene)-4-methylbenzenesulfonamide (8; 15 mg, 0.05 mmol),
PhB(OH)2 (12 mg, 0.1 mmol), KF (12 mg, 0.2 mmol), and H2O (0.5 mL)
were added sequentially and the reaction mixture was stirred at
35 °C for 20 h. The mixture was cooled to r.t. and concentrated under
reduced pressure. The residue was purified by flash chromatography
on silica gel (EtOAc/PE 1:8) to afford the product 10 as a white pow-
der; yield: 15 mg (80%); mp 119–120 °C; e.r. = 87:13; [α]D20 –28.0 (c
0.25, CH2Cl2).
HPLC analysis: Chiralpak OD-H (hexane/i-PrOH (93:7), 0.8 mL/min,
230 nm); tR (major) = 21.455 min, tR (minor) = 30.599 min.
IR (film): 3271, 3063, 3031, 2923, 2871, 1911, 1806, 1598, 1491 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.55 (d, J = 8.3 Hz, 2 H), 7.24–7.12 (m, 7
H), 7.10–7.01 (m, 4 H), 5.53 (d, J = 7.1 Hz, 1 H), 5.18–5.15 (m, 1 H),
2.39 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 143.5, 140.1, 139.0, 137.2, 133.4,
129.4, 128.8, 128.7, 128.6, 127.9, 127.3, 127.2, 60.8, 21.5.
HRMS (ESI): m/z [M – H]– calcd for C20H18ClNO2S: 370.0669; found:
370.0665.
(13) (a) Chan, A. S. C.; Hu, W. H.; Pai, C. C.; Lau, C. P. J. Am. Chem. Soc.
1997, 119, 9570. (b) Arai, M. A.; Kuraishi, M.; Arai, T.; Sasai, H.
J. Am. Chem. Soc. 2001, 123, 2907. (c) Fu, Y.; Xie, J.-H.; Hu, A. G.;
Zhou, H.; Wang, L. X.; Zhou, Q.-L. Chem. Commun. 2002, 480.
(d) Zoraida, F.; Beentjes, M. S.; Batema, G. D.; Dieleman, C. B.;
van Strijdonck, G. P. F.; Joost, N. H. R.; Paul, C. J. K.; Jan, F.; Kees,
G.; van Leeuwen, P. W. N. M. Angew. Chem. Int. Ed. 2003, 42,
1284. (e) Xie, J-H.; Duan, H-F.; Fan, B-M.; Cheng, X.; Wang, L-X.;
Zhou, Q-L. Adv. Synth. Catal. 2004, 346, 625. (f) Han, Z. B.; Wang,
Funding Information
We appreciate the National Natural Science Foundation of China
(21572200) and the Fundamental Research Funds for the Central Uni-
versities (2017QNA3013) for financial support.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G

G
Q. Zhou et al.
Paper
Synthesis
Z.; Zhang, X. M.; Ding, K. L. Angew. Chem. Int. Ed. 2009, 48, 5345.
(g) Li, J.; Chen, G.; Wang, Z.; Zhang, R.; Zhang, X. M.; Ding, K.
Chem. Sci. 2011, 2, 1141. (h) Wang, X. M.; Meng, F. Y.; Wang, Y.;
Han, Z. B.; Chen, Y. J.; Liu, L.; Wang, Z.; Ding, K. L. Angew. Chem.
Int. Ed. 2012, 51, 9276.
Chem. Soc. 2016, 138, 16561. For a recent review focusing on
SPAs, see: (t) Rahman, A.; Lin, X. Org. Biomol. Chem. 2018, 16,
4753.
(15) (a) Sun, W.; Gu, H.; Lin, X. J. Org. Chem. 2018, 83, 4034.
(b) Chang, S.; Wang, L.; Lin, X. Org. Biomol. Chem. 2018, 16,
2239.
(14) For recent examples from our group, see: (a) Xu, F.; Huang, D.;
Han, C.; Shen, W.; Lin, X.; Wang, Y. J. Org. Chem. 2010, 75, 8677.
(b) Huang, D.; Xu, F.; Lin, X.; Wang, Y. G. Chem. Eur. J. 2012, 18,
3148. (c) Li, X.; Zhao, Y.; Qu, H.; Mao, Z.; Lin, X. Chem. Commun.
2013, 49, 1401. (d) Huang, D.; Li, X.; Xu, F.; Li, L.; Lin, X. ACS
Catal. 2013, 3, 2244. (e) Li, X.; Chen, D.; Gu, H.; Lin, X. Chem.
Commun. 2014, 50, 7538. (f) Shen, X.; Wang, Y.; Wu, T.; Mao, Z.;
Lin, X. Chem. Eur. J. 2015, 21, 9039. (g) Lou, H.; Wang, Y.; Jin, E.;
Lin, X. J. Org. Chem. 2016, 81, 2019. (h) Xie, E.; Rahman, A.; Lin,
X. Org. Chem. Front. 2017, 4, 1407. For selected examples by
other groups, see: (i) Čorić, I.; Müller, S.; List, B. J. Am. Chem. Soc.
2010, 132, 17370. (j) Xing, C.; Liao, Y.; Ng, J.; Hu, Q. J. Org. Chem.
2011, 76, 4125. (k) Xu, B.; Zhu, S.-F.; Xie, X.-L.; Shen, J.-J.; Zhou,
Q.-L. Angew. Chem. Int. Ed. 2011, 50, 11483. (l) Rubush, D. M.;
Morges, M. A.; Rose, B. J.; Thamm, D. H.; Rovis, T. J. Am. Chem.
Soc. 2012, 134, 13554. (m) Chen, Z.; Wang, B.; Wang, Z.; Zhu, G.;
Sun, J. Angew. Chem. Int. Ed. 2013, 52, 2027. (n) Wu, J.; Wang, Y.;
Drljevic, A.; Rauniyar, V.; Phipps, R.; Toste, F. D. Proc. Natl. Acad.
Sci. U S A 2013, 110, 13729. (o) Wang, S.-G.; You, S.-L. Angew.
Chem. Int. Ed. 2014, 53, 2194. (p) Zhang, Y.; Zhao, J.; Jiang, F.;
Sun, S.; Shi, F. Angew. Chem. Int. Ed. 2014, 53, 13912. (q) Gobé,
V.; Guinchard, X. Chem. Eur. J. 2015, 21, 8511. (r) Rong, Z.;
Zhang, Y.; Chua, R. H. B.; Pan, H.; Zhao, Y. J. Am. Chem. Soc. 2015,
137, 4944. (s) Li, S.; Zhang, J.; Li, X.; Cheng, D.; Tan, B. J. Am.
(16) (a) Fisher, C. H.; Furlong, R. W.; Grant, M. J. Am. Chem. Soc. 1936,
58, 820. (b) Molteni, V.; Rhodes, D.; Rubins, K.; Hansen, M.;
Bushman, F. D.; Siegel, J. S. J. Med. Chem. 2000, 43, 2031.
(c) Chen, W.-F.; Lin, H.-Y.; Dai, S. A. Org. Lett. 2004, 6, 2341.
(17) CCDC 1843734 contains the supplementary crystallographic
data for compound 6a reported in this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/getstructures.
(18) CCDC 1845549 contains the supplementary crystallographic
data for (R)-TMSIOL reported in this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/getstructures.
(19) CCDC 1854445 contains the supplementary crystallographic
data for (S)-SPINOL reported in this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/getstructures.
(20) For reviews, see: (a) Marques, C. S.; Burke, A. J. ChemCatChem
2011, 3, 635. (b) Tian, P.; Dong, H.-Q.; Lin, G.-Q. ACS Catal. 2012,
2, 95. (c) Chen, D.; Xu, M.-H. Chin. J. Org. Chem. 2017, 37, 1589.
For selected examples, see: (d) Duan, H.-F.; Jia, Y.-X.; Wang, L.-X.;
Zhou, Q.-L. Org. Lett. 2006, 8, 2567. (e) Wang, Z.-Q.; Feng, C.-G.;
Xu, M.-H.; Lin, G.-Q. J. Am. Chem. Soc. 2007, 129, 5336.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G