Synthesis and Application of Hexamethyl-1,1′-spirobiindane-Based Phosphine-Oxazoline Ligands in Ni-Catalyzed Asymmetric Arylation of Cyclic Aldimines

Article abstract of DOI:10.1021/acs.joc.8b00422

With the vastly increasing applications of chiral phosphine-oxazoline (PHOX) hybrid ligands in various transition-metal-catalyzed reactions, novel PHOX ligands bearing innovative backbones are highly valuable and in great demand. This study describes the development of a new type of chiral PHOX ligands based on a hexamethyl-1,1′-spirobiindane scaffold and incorporating both a phosphine and an oxazoline moiety. The optimal ligand provided high yields and excellent enantioselectivities for the Ni-catalyzed asymmetric arylation of cyclic N-sulfonyl imines with arylboronic acids leading to chiral amines.

Full text of DOI:10.1021/acs.joc.8b00422

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Synthesis and Application of Hexamethyl-1,1’-spirobiindane-
based Phosphine-Oxazoline (HMSI-PHOX) Ligands in Ni-
Catalyzed Asymmetric Arylation of Cyclic Aldimines
Weiye Sun, Haorui Gu, and Xufeng Lin
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00422 • Publication Date (Web): 19 Mar 2018
Downloaded from http://pubs.acs.org on March 19, 2018
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The Journal of Organic Chemistry
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Synthesis and Application of Hexamethylꢀ1,1’ꢀspirobiindaneꢀbased
PhosphineꢀOxazoline (HMSIꢀPHOX) Ligands in NiꢀCatalyzed Asymmetric
Arylation of Cyclic Aldimines
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Weiye Sun, Haorui Gu, and Xufeng Lin*
Laboratory of Asymmetric Catalysis and Synthesis, Department of Chemistry, Zhejiang University,
Hangzhou 310027, P. R. China
E-mail: lxfok@zju.edu.cn
Abstract: With the vastly increasing applications of chiral phosphineꢀoxazoline (PHOX) hybrid
ligands in various transitionꢀmetalꢀcatalyzed reactions, novel PHOX ligands bearing innovative
backbones are highly valuable and in great demand. This study describes the development of a new
type of chiral PHOX ligands based on a hexamethylꢀ1,1’ꢀspirobiindane scaffold and incorporating
both a phosphine and an oxazoline moiety. The optimal ligand provided high yields and excellent
enantioselectivities for the Niꢀcatalyzed asymmetric arylation of cyclic Nꢀsulfonyl imines with
arylboronic acids leading to chiral amines.
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INTRODUCTION
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The design and synthesis of novel chiral ligands are always a very important and challenging task in
the development of efficient transitionꢀmetalꢀcatalyzed asymmetric reactions.1 Chiral P, N ligands play a
significant role in transitionꢀmetalꢀcatalyzed asymmetric synthesis due to its characteristics of both
phosphine ligands and nitrogen ligands.2 The chiral phosphineꢀoxazoline (PHOX) ligand, which
coordinates to a metal center with a Nꢀ and a Pꢀatom, is one of the more classic category among P, N
ligands, and has been recognized as one of the most versatile types of chiral inducers in various
transitionꢀmetalꢀcatalyzed reactions.3 The steric and electronic properties can be tailored for a specific
application by variation of the phosphine, the oxazoline ring, and the backbone moiety due to their
modular structure. As pioneering works in this area, Pfaltz, Helmchen, and Williams independently
reported the first synthesis and application of PHOX in 1993.4 After that, various kinds of skeletons
such as biphenyl, hetero aryl, cyclophane, ferrocenyl, Ruthenocenyl, and binaphthyl backbones, also
found successful applications in asymmetric catalysis during the past dacades, and the backbone of the
chiral ligands had remarkable influence on its catalytic performance in many cases.5
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Despite these elegant contributions, the continued innovation of novel and practical backbone of
PHOX is still a highly valuable but very challenging task. On the other hand, the spiro backbone has
been recognized as a privileged structure to provide an excellent platform for chiral ligand and catalyst
diversification6 since the pioneering work of Chan et al. with SpirOP.7 In this context, Zhou group8 and
Ding group9 have developed spirobiindaneꢀbased PHOX and spirononadieneꢀbased PHOX respectively,
which have shown impressive activity in versatile transitionꢀmetalꢀcatalyzed asymmetric
transformations. Inspired by these elegant pioneering studies, we became interested in developing the
hexamethylꢀ1,1’ꢀspirobiindaneꢀPHOX ligands (HMSIꢀPHOX, Scheme 1) with its readily accessible
stable and rigid spiro backbone. The hexamethylꢀ1,1’ꢀspirobiindane motif in HMSIꢀPHOX has one
axially chiral center and can be easily derived from hexamethylꢀ1,1'ꢀspirobiindaneꢀ6,6'ꢀdiol which is
easily prepared from industrially available Bisphenol C. Herein, we report the preliminary results on the
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development of one new type of chiral phosphineꢀoxazoline ligands based on a hexamethylꢀ1,1’ꢀ
spirobiindane backbone (HMSIꢀPHOX, 1) and their application in the Niꢀcatalyzed enantioselective
arylation of cyclic Nꢀsulfonyl imines with arylboronic acids. The reactions proceed smoothly under mild
conditions with excellent enantioselectivities (93ꢀ99% ee), as shown in Scheme 1.
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Scheme 1. Ni/HMSI-PHOX-catalyzed asymmetric arylation of cyclic aldimines
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RESULTS AND DISCUSSION
As illustrated in Scheme 2, the synthesis of enantiopure HMSIꢀPHOX (1) ligands started from
industrially available Bisphenol C. Bisphenol C was firstly converted into hexamethylꢀ1,1'ꢀ
spirobiindaneꢀ6,6'ꢀdiol 5 in 92% yield by acidꢀcatalyzed rearrangement in one step at room temperature
on a large scale by a modified procedure.10 Then the bromination of 5 with Nꢀbromosuccinimide (NBS)
gave the brominated product 6 in 98% yield. The subsequent esterification of 6 with trifluoromethane
sulfonic anhydride afforded the ditriflate 7 in nearly quantitative yield. The Pdꢀcatalyzed selective
reduction with formic acid in DMF furnished spiroꢀdibromide 8 as the key intermediate in 96% yield.
Then, the Pdꢀcatalyzed crossꢀcoupling of 8 with diphenylphosphine oxide afforded compound 9 with
high selectivity despite the moderate conversion.11 The monophosphine 10 was obtained in 92% yield
by reduction of 9 with LiAlH4.12 The Pdꢀcatalyzed reaction of 10 with zinc cyanide to afford cyanide 11
in 65% yield,13 followed by hydrolyzing with dilute H2SO4 to give the acid 12 in 75% yield. The acid 12
was further transformed to the corresponding hydroxyl amides 13a-d as a diastereomer mixture in
quantitative yield by reacting with a variety of enantiopure amino alcohols in the presence of EDCI and
HOBt.14 Finally, the target ligands 1a-d were obtained by cyclization of 13a-d with MsCl in the
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presence of triethylamine.15 To our delight, the two diastereomers of 1a-d, respectively, could all be
readily separated by flash chromatography with high yields (72ꢀ85% for two steps from racemic 12) to
provide the enantiopure phosphineꢀoxazoline ligands based on a hexamethylꢀ1,1’ꢀspirobiindane scaffold
(HMSIꢀPHOX, 1). The absolute configuration of the ligand (Sa,S,S)ꢀ1d was determined by Xꢀray
crystallographic analysis of a single crystal which was obtained from diisopropyl ether (Figure 1).
Scheme 2. Synthesis of HMSI-PHOX ligands
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Figure 1. X-ray crystal structure of the complex of (Sa,S,S)-1d and diisopropyl ether
With the new chiral HMSIꢀPHOX ligands (1) in hand, we next evaluated the enantioselective
arylation of cyclic Nꢀsulfonyl imines with arylboronic acids. Highly efficient transitionꢀmetalꢀcatalyzed
asymmetric addition of arylboron reagents to imines to generate chiral amines is a current topic of
interest,16 and many excellent examples have been reported using Rh17 or Pd18 catalysts. The
development of nickel catalyst which is cheap and abundant remains at the forefront and desirable, only
one nice Niꢀcatalyzed example for such asymmetric transformation has been realized recently by the
group of Zhang.19 To our delight, with the newly synthesized (Ra,S)ꢀ1a (7.5 mol %) as the ligand and
Ni(ClO4)2·6H2O (5 mol %) as the catalyst precursor, the model reaction between 2a and 3a was initially
performed in trifluoroethanol (TFE) at 60 oC to give the desired chiral amine 4a with 97% ee despite in
low yield (Table 1, entry 1). To our delight, when the ligand was replaced with (Ra,S)ꢀ1b, the model
reaction proceeded smoothly to afford the addition product 4a with 99% ee and in 80% yield, indicating
the high efficiency of this novel chiral HMSIꢀPHOX ligand (Table 1, entry 2). After screening of these
new chiral ligands, we found that the chirality at the spiro backbone of 1 had a significant impact on the
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reactivity and asymmetric induction of the catalysis (Table 1, entries 1ꢀ8). The combination of a Ra
configuration of the spiro backbone and the S configuration of the oxazoline moiety was revealed as the
well matched case, such as in (Ra,S)ꢀ1a-c and (Ra,S,S)ꢀ1d. Furthermore, investigation of the substituent
effect of the oxazoline moiety of ligands with a Ra configuration of the spiro backbone on the catalysis
disclosed that the ligand (Ra,S,S)ꢀ1d, bearing two Ph group in the oxazoline moiety, was the best choice
in terms of both reactivity and enantioselectivity (Table 1, entries 1ꢀ4). With the best ligand (Ra,S,S)ꢀ1d,
the corresponding product 4a was afforded in 88% yield and 99% ee (Table 1, entry 4). On the basis of
this result, different nickel and iron salts were exampled instead of Ni(ClO4)2·6H2O to give only low
yield and low enantioselectivity or trace amounts of the product (Table 1, entries 9ꢀ13). Further
evalutation of solvents indicated that the solvent had a remarkable impact on the reactivity and
asymmetric induction of the catalysis (Table 1, entries 14ꢀ18). The experiments showed that
dichloromethane, toluene, chloroform, acetonitrile and ethanol all gave a poor result with low reactivity
and only moderate enantioselectivity, and trifluoroethanol was the best solvent for the Ni/HMSIꢀPHOXꢀ
catalyzed enantioselective arylation reaction. As a comparison, we tested the known spiro ligand (Ra,S)ꢀ
PhꢀBnꢀSIPHOX8 in the Niꢀcatalyzed asymmetric reaction with the model reaction under the current
standard conditions to give the desired product in 85% yield and 97%.
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Table 1. Optimization of reaction parametersa
Entry
Ligand
(Ra,S)ꢀ1a
(Ra,S)ꢀ1b
(Ra,S)ꢀ1c
[M]
Solvent
TFE
Yield [%]b
ee [%]c
97
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Ni(ClO4)2·6H2O
Ni(ClO4)2·6H2O
Ni(ClO4)2·6H2O
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TFE
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TFE
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4
5
(Ra,S,S)ꢀ1d
(Sa,S)ꢀ1a
Ni(ClO4)2·6H2O
Ni(ClO4)2·6H2O
Ni(ClO4)2·6H2O
Ni(ClO4)2·6H2O
Ni(ClO4)2·6H2O
NiCl2·6H2O
TFE
88
<10
<10
<10
trace
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99
ꢀ20
ꢀ5
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TFE
TFE
6
(Sa,S)ꢀ1b
7
(Sa,S)ꢀ1c
TFE
ꢀ65
ꢀꢀꢀ
39
ꢀꢀꢀ
ꢀꢀꢀ
ꢀꢀꢀ
ꢀꢀꢀ
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ꢀꢀꢀ
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8
(Sa,S,S)ꢀ1d
(Ra,S,S)ꢀ1d
(Ra,S,S)ꢀ1d
(Ra,S,S)ꢀ1d
(Ra,S,S)ꢀ1d
(Ra,S,S)ꢀ1d
(Ra,S,S)ꢀ1d
(Ra,S,S)ꢀ1d
(Ra,S,S)ꢀ1d
(Ra,S,S)ꢀ1d
(Ra,S,S)ꢀ1d
TFE
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TFE
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Ni(OAc)2·4H2O
FeCl2·4H2O
TFE
trace
trace
trace
trace
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TFE
Fe(ClO4)2
TFE
Fe(ClO4)3
TFE
Ni(ClO4)2·6H2O
Ni(ClO4)2·6H2O
Ni(ClO4)2·6H2O
Ni(ClO4)2·6H2O
Ni(ClO4)2·6H2O
DCE
toluene
CHCl3
MeCN
EtOH
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7
trace
aReactions conditions: 0.1 mmol 2a, 0.15 mmol 3a, 5 mol % [M], and 7.5 mol % ligand in 1 mL of solvent at 60 C
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at N2 atmosphere for 48 h. bIsolated yields. cDetermined by chiral HPLC analysis.
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With the optimized conditions in hand, the scope of arylboronicacids was firstly examined, and the
results were summarized as shown in Table 2. Notably, excellent enantioselectivity could be achieved in
all case. Arylboronic acids with both electronꢀwithdrawing (Table 2, 4bꢀ4f) and electronꢀdonating
groups (Table 2, 4gꢀ4i) afforded the corresponding products with excellent enantioselectivities (93%ꢀ
99% ee). Meanwhile, the different substitution position on the benzene ring gave excellent
enantioselectivities with all examples, but had significant influence on the yield. The metaꢀ and paraꢀ
substituted arylboronic acids showed outstanding performance in good to excellent yields (76%ꢀ93%),
and orthoꢀsubstituted arylboronic acids disclosed moderate reactivity (51% yield, Table 2, 4d).
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Furthermore, biphenyl, fusedꢀring aryl and hetero aryl boronic acids could also afford their
corresponding products with high yields and excellent enantioselectivities (Table 2, 4jꢀ4l). Besides, the
scope of Nꢀsulfonyl imine derivatives was also examined, and the results were also satisfying because
the substrates possessing methyl, group on the chlorine or brominephenyl ring all gave the
corresponding products in good yields (85%ꢀ94%) with 99% ee (Table 2, 4mꢀ4o). The use of acyclic
imine and alkylboronic acid under the current standard reaction conditions, however, these substrates
showed hydrolyzed or very low reactivity under our conditions, respectively.
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Table 2. Substate scopea
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aReactions conditions: 0.1 mmol of 2, 0.15 mmol of 3, 5 mol % Ni(ClO4)2·6H2O, and 7.5 mol % (Ra,S,S)ꢀ1d in 1 mL
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TFE at 60 C at N2 atmosphere for 48 h. Yields are of isolated products. Enantioselectivity was determined by chiral
HPLC.
CONCLUSION
In summary, a new class of chiral phosphineꢀoxazoline ligands (HMSIꢀPHOX, 1) based on the
hexamethylꢀ1,1’ꢀspirobiindanebackbone has been developed from industrially available Bisphenol C.
The optimal ligand (Ra,S,S)ꢀ1d provided high yields and excellent enantioselectivities for the Niꢀ
catalyzed asymmetric arylation of cyclic Nꢀsulfonyl imines with a broad range of arylboronic acids
leading to optically active amines. Expanding the applications of HMSIꢀPHOX ligands to other
synthetically useful catalytic enantioselective transformations is currently under investigation in our
laboratory.
Experimental Section
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General information. H NMR, C NMR, P NMR and F NMR spectra were measured at 400,
100, 162 and 376 MHz spectrometer, respectively. The chemical shifts were reported relative to internal
standard TMS (0) in CDCl3 or DMSO. Infrared spectra were recorded on an ATRꢀFTIR spectrometer.
HRMS were obtained using EI or ESI ionization. Optical rotation values were measured with
instruments operating at λ = 589 nm, corresponding to the sodium D line at 20 °C. Enantiomeric
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excesses (ee) were determined by chiral highꢀperformance liquid chromatography. Analytical grade
solvents for the column chromatography and commercially available reagents were used as received.
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Synthesis of 3,3,3',3',5,5'-hexamethyl-2,2',3,3'-tetrahydro-1,1'-spirobi[indene]-6,6'-diol (5).10b
A
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500 mL round bottom flask was charged with Bisphenol C (BPC, 50 g, 195 mmol) and methanesulfonic
acid (250 mL). After stirring at room temperature for 3 days, additional 100 mL methanesulfonic acid
was added to the mixture and the solution was allowed to stir for another 1 day. Then the mixture was
directly poured into a large amount of crushed ice and filtered. The filter cake was washed with
saturated NaHCO3 and water. The crude product was recrystallized sequentially with
ethylacetate/petroleum ether and ethanol/water to give the compound 5 (20.1 g, 92% yield) as a white
solid. M.p. 249ꢀ250 oC; 1H NMR (400 MHz, CDCl3) δ 6.91 (s, 2H), 5.84 (s, 2H), 3.93 (s, 2H), 2.29 (d, J
= 13.0 Hz, 2H), 2.20 (s, 6H), 2.15 (d, J = 13.0 Hz, 2H), 1.37 (s, 6H), 1.28 (s, 6H); 13C NMR (100 MHz,
CDCl3) δ 153.2, 150.1, 144.5, 123.5, 122.9, 110.5, 59.4, 57.00 43.1, 31.9, 30.1, 16.0; IR (film): γ = 3515,
2952, 2862, 1615, 1497, 1361, 1313, 858 cmꢀ1; HRMS (GCꢀTOF, EI) m/z calcd for C23H28O2 [M+]
336.2089, found 336.2085.
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Synthesis of 7,7'-dibromo-3,3,3',3',5,5'-hexamethyl-2,2',3,3'-tetrahydro-1,1'-spirobi[indene]-
6,6'-diol (6).20 To a solution of 5 (10.1 g, 30 mmol) in CH2Cl2 (200 mL) was added Nꢀ
bromosuccinimide (NBS, 11.2 g, 63 mmol) slowly and the mixture was stirred at room temperature for
4 hours. Then saturated NaHSO3 (100 mL) was added and the solution was stirred for additional 30
minutes. The organic phase was washed twice with saturated brine and dried over anhydrous Na2SO4.
The solvent was removed under reduced pressure to afford a light yellow solid 6 (14.5 g, 98% yield)
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1
with enough purity for next step without further purification. M.p. 228ꢀ229 C; H NMR (400 MHz,
CDCl3) δ 6.87 (s, 2H), 5.57 (s, 2H), 2.46 (d, J = 13.1 Hz, 2H), 2.31 (s, 6H), 2.25 (d, J = 13.0 Hz, 2H),
1.39 (s, 6H), 1.32 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 149.2, 145.6, 142.7, 124.5, 123.6, 107.1, 60.8,
55.6, 43.1, 32.6, 29.3, 17.1; IR (film): γ = 3506, 2958, 2861, 1610, 1466, 1360, 1313, 864 cmꢀ1; HRMS
(GCꢀTOF, EI) m/z calcd for C23H26Br2O2 [M+] 492.0300, found 492.0302.
Synthesis of 7,7'-dibromo-3,3,3',3',5,5'-hexamethyl-2,2',3,3'-tetrahydro-1,1'-spirobi[indene]-
6,6'-diyl bis(trifluoromethanesulfonate) (7). The compound 6 (12.3 g, 25 mmol) was dissolved in
CH2Cl2 (150 mL) under nitrogen, and pyridine (8.1 mL, 100 mmol) was added in one portion. After
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cooling to 0 oC, triflic anhydride (10.5 mL, 62.5 mmol) was added dropwise. The resulting mixture was
naturally warmed to room temperature and stirred for 3 hours. The reaction solution was then washed
with aqueous HCl (4 M), saturated NaHCO3 and brine. The organic layer was dried over anhydrous
Na2SO4 and concentrated in vacuum to obtain product 7 (18.6 g, 98% yield) as a yellow solid without
further purification. M.p. 206ꢀ207 oC; 1H NMR (400 MHz, CDCl3) δ 7.02 (s, 2H), 2.55 (d, J = 13.2 Hz,
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2H), 2.45 (s, 6H), 2.30 (d, J = 13.2 Hz, 2H), 1.42 (s, 6H), 1.36 (s, 6H); C NMR (100 MHz, CDCl3) δ
19
153.7, 145.1, 144.5, 132.6, 124.8, 118.5 (d, J = 320.7 Hz), 113.4, 61.3, 54.9, 43.4, 32.4, 28.8, 18.2; F
NMR (376 MHz, CDCl3) δ ꢀ72.18; IR (film): γ = 2962, 2868, 1609, 1555, 1418, 1365, 1318, 846 cmꢀ1;
HRMS (GCꢀTOF, EI) m/z calcd for C25H24Br2F6O6S2 [M+] 755.9285, found 755.9285.
Synthesis of 7,7'-dibromo-3,3,3',3',5,5'-hexamethyl-2,2',3,3'-tetrahydro-1,1'-spirobi[indene] (8).
To a solution of triflate 7 (15.2 g, 20 mmol), bis(triphenylphosphine) palladium dichloride (633.5 mg,
0.9 mmol), and 1,3ꢀbis(diphenylphosphino)propane (dppp, 412.4 mg, 1 mmol) in 180 mL of DMF under
o
nitrogen, triethylamine (33.3 mL, 240 mmol) was added in one portion at 0 C. Then the formic acid
o
(6.0 mL, 160 mmol) was added slowly under the ice bath, and the resulting solution was heated at 80 C
for 2 hours. The reaction system was diluted with water and extracted with ethyl acetate. The organic
phase was washed with 30% aqueous H2O2, 10% aqueous HCl, saturated NaHCO3 and brine, and dried
over anhydrous Na2SO4. After removal of the solvent, the residue was purified by flash chromatography
(ethyl acetate/petroleum ether = 1/50) to give the hexamethyl sprio dibromide 8 (8.9 g, 96% yield).
White solid, m.p. 199ꢀ200 oC; 1H NMR (400 MHz, CDCl3) δ 7.12 (s, 2H), 6.92 (s, 2H), 2.51 (d, J = 13.0
Hz, 2H), 2.32 (s, 6H), 2.23 (d, J = 13.0 Hz, 2H), 1.41 (s, 6H), 1.33 (s, 6H); 13C NMR (100 MHz, CDCl3)
δ 154.9, 142.5, 138.9, 131.9, 122.3, 119.1, 59.8, 55.4, 43.4, 32.6, 28.9, 21.0; IR (film): γ = 2954, 2861,
1602, 1558, 1459, 1360, 1316, 852 cmꢀ1; HRMS (GCꢀTOF, EI) m/z calcd for C23H26Br2 [M+] 460.0401,
found 460.0404.
Synthesis
of
(7'-bromo-3,3,3',3',5,5'-hexamethyl-2,2',3,3'-tetrahydro-1,1'-spirobi[inden]-7-
yl)diphenylphosphine oxide (9). A mixture of dibromide 8 (4.62 g, 10 mmol), diphenylphosphine
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oxide (4.02 g, 20 mmol), palladium acetate (224.5 mg, 1 mmol), 1,4ꢀbis(diphenylphosphino)butane
(dppb, 426.5 mg, 1 mmol), and N,Nꢀdiisopropylethylamine (7.0 mL, 40 mmol) in degassed DMSO (40
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5
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mL) was stirred at 100 C under a dry nitrogen atmosphere for 24 hours. After cooling to room
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temperature, the reaction solution was diluted with water, and the aqueous phase was extracted with
ethyl acetate. The organic layer was washed sequentially with 5% aqueous HCl, saturated NaHCO3 and
brine, and dried over anhydrous Na2SO4, and concentrated under reduced pressure. The resulting residue
was purified by flash chromatography (ethyl acetate/petroleum ether = 1/4) to give the product 9 (2.1 g,
81% yield based of consumable 8). White solid, m.p. 251ꢀ252 oC; 1H NMR (400 MHz, CDCl3) δ 7.46 –
7.27 (m, 10H), 7.12 (s, 1H), 6.87 (s, 1H), 6.80 (d, J = 15.0 Hz, 1H), 6.27 (s, 1H), 3.45 (d, J = 12.2 Hz,
1H), 2.48 (d, J = 13.1 Hz, 1H), 2.24 (dd, J = 20.6, 10.4 Hz, 8H), 1.63 (s, 3H), 1.40 (s, 3H), 1.35 (s, 3H),
1.27 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 156.6, 155.3 (d, J = 10.8 Hz), 151.5 (d, J = 7.0 Hz), 143.6,
137.9, 137.1, 136.1, 135.5 (d, J = 13.2 Hz), 134.6 (d, J = 14.1 Hz), 131.9 (d, J = 3.6 Hz), 131.8 (d, J =
3.9 Hz), 131.4, 130.8 (dd, J = 16.3, 2.5 Hz), 128.1, 128.0, 127.5, 127.4, 126.7 (d, J = 2.7 Hz), 121.6,
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119.2, 59.9 (d, J = 1.6 Hz), 57.0, 55.9, 44.2, 42.8, 33.4, 33.0, 28.8, 28.0, 21.4, 20.9; P NMR (162 MHz,
CDCl3) δ 31.29; IR (film): γ = 2952, 2862, 1607, 1436, 1360, 1203, 1113 cmꢀ1; HRMS (GCꢀTOF, EI)
m/z calcd for C35H36OPBr [M+] 582.1687, found 582.1672.
Synthesis
of
(7'-bromo-3,3,3',3',5,5'-hexamethyl-2,2',3,3'-tetrahydro-1,1'-spirobi[inden]-7-
yl)diphenylphosphane (10). To a stirred solution of phosphine oxide 9 (3.50 g, 6 mmol) in ethylene
glycol dimethyl ether (DME, 40 mL) was added methyltrifluoromethanesulfonate (747 ꢁL, 6.6 mmol) at
room temperature under nitrogen. After 3 hours, the flask was immersed in an ice and lithium aluminum
hydride (6 mL, 15 mmol, 2.5 mol/L in THF) was added dropwise. The resulting mixture was naturally
warmed to room temperature and the mixture was stirred for 5 h, and then quenched by 1 M aqueous
HCl. The organic phase was separated, and the aqueous layer was extracted with ethyl acetate. The
combined extracts were washed by saturated brine and dried over anhydrous Na2SO4, and evaporated
under reduced pressure. The residue was purified by flash chromatography (ethyl acetate/petroleum
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The Journal of Organic Chemistry
ether = 1/50) to afford 10 (3.13 g, 92%) . White solid, m.p. 212ꢀ213 C; 1H NMR (400 MHz, CDCl3) δ
7.23 – 7.14 (m, 6H), 7.07 – 6.99 (m, 4H), 6.97 (s, 1H), 6.87 (s, 1H), 6.72 (d, J = 4.6 Hz, 1H), 6.64 (s,
1H), 2.76 (d, J = 11.9 Hz, 1H), 2.55 (d, J = 13.1 Hz, 1H), 2.31 (d, J = 13.1 Hz, 1H), 2.24 (d, J = 5.8 Hz,
o
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2
3
4
5
6
7
8
13
7H), 1.42 (s, 3H), 1.37 (s, 3H), 1.35 (s, 3H), 1.28 (s, 3H); C NMR (100 MHz, CDCl3) δ 155.3 (d, J =
9
2.9 Hz), 152.9 (d, J = 7.7 Hz), 151.3 (d, J = 24.6 Hz), 144.9 (d, J = 4.1 Hz), 139.3 (d, J = 14.1 Hz),
138.6, 136.7, 136.5 (d, J = 13.5 Hz), 135.7 (d, J = 3.1 Hz), 134.1, 133.8, 133.6, 133.1, 132.9, 131.9,
131.5 (d, J = 20.8 Hz), 128.1 – 128.0 (m), 127.7 – 127.4 (m), 124.1, 121.9, 119.5 (d, J = 2.4 Hz), 59.5 (d,
J = 3.3 Hz), 58.5 (d, J = 5.9 Hz), 55.7, 43.7, 42.9, 33.1, 28.9, 28.2 (d, J = 2.4 Hz), 21.4, 20.9; 31P NMR
(162 MHz, CDCl3) δ ꢀ22.66; IR (film): γ = 2952, 2862, 1585, 1434, 1360, 1313, 1140 cmꢀ1; HRMS
(GCꢀTOF, EI) m/z calcd for C35H36PBr [M+] 566.1738, found 566.1756.
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Synthesis
of
7'-(diphenylphosphanyl)-3,3,3',3',5,5'-hexamethyl-2,2',3,3'-tetrahydro-1,1'-
spirobi[indene]-7-carbonitrile (11). A mixture of the reduction product 10 (2.84 g, 5 mmol), Zn(CN)2
o
(645.7 mg, 5.5 mmol), and Pd(PPh3)4 (577.8 mg, 0.5 mmol) in DMF (50 mL) was stirred at 130 C for
36 hours under nitrogen. The reaction solution was diluted with ethyl acetate, washed sequentially with
saturated NaHCO3 and brine, and dried over by anhydrous Na2SO4. The solvent was removed in vacuum
to give a product 11 (1.67 g, 65%) for next step without further purification. White solid, m.p. 220ꢀ221
1
oC; H NMR (400 MHz, CDCl3) δ 7.26 (dd, J = 12.3, 4.6 Hz, 1H), 7.23 – 7.15 (m, 5H), 7.06 (s, 1H),
7.02 (s, 1H), 6.97 (td, J = 9.2, 3.9 Hz, 4H), 6.69 (d, J = 4.1 Hz, 1H), 6.41 (s, 1H), 3.06 (dd, J = 13.1, 2.5
Hz, 1H), 2.44 – 2.39 (m, 1H), 2.36 (d, J = 1.8 Hz, 2H), 2.23 (s, 3H), 2.20 (s, 3H), 1.55 (s, 3H), 1.47 (s,
13
3H), 1.36 (s, 3H), 1.29 (s, 3H); C NMR (100 MHz, CDCl3) δ 154.0 (d, J = 3.2 Hz), 153.3 (d, J = 7.6
Hz), 151.2 (d, J = 4.1 Hz), 150.3, 150.1, 139.2 (d, J = 13.5 Hz), 137.6, 137.1, 136.0 (d, J = 2.5 Hz),
135.3 (d, J = 11.2 Hz), 133.9, 133.7, 132.9 (d, J = 19.0 Hz), 131.5, 131.1 (d, J = 19.5 Hz), 128.4, 128.1
(d, J = 6.0 Hz), 127.9 – 127.5 (m), 127.0, 124.3, 117.2, 107.7, 58.4, 58.2 (d, J = 3.0 Hz), 43.6, 43.3, 33.1
31
(d, J = 2.6 Hz), 32.7, 28.6, 27.7 (d, J = 3.3 Hz), 21.5, 20.9; P NMR (162 MHz, CDCl3) δ ꢀ21.87; IR
(film): γ = 2951, 2852, 1721, 1435, 1381, 1262, 1096, 862 cmꢀ1; HRMS (GCꢀTOF, EI) m/z calcd for
C36H36NP [M+] 513.2585, found 513.2584.
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Synthesis
of
7'-(diphenylphosphanyl)-3,3,3',3',5,5'-hexamethyl-2,2',3,3'-tetrahydro-1,1'-
1
2
3
spirobi[indene]-7-carboxylic acid (12). The cyanide 11 (1.03 g, 2 mmol) was added to a solution of
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5
H2O (15 mL), H2SO4 (10 mL), and AcOH (5 mL) under a nitrogen atmosphere, and the suspension was
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allowed to stir at 145 C for 48 hours. The resulting mixture was then cooled to room temperature,
9
diluted with water, and extracted with ethyl acetate. The organic phase was washed with brine and dried
over anhydrous Na2SO4. After removal of the solvent, the residue was purified by flash chromatography
(ethyl acetate/petroleum ether = 1/10) to afford the carboxylic acid 12 (0.80 g, 75%). White solid, m.p.
237ꢀ238 oC; 1H NMR (400 MHz, DMSO) δ 12.13 (s, 1H), 7.30 (d, J = 6.5 Hz, 4H), 7.24 – 7.14 (m, 4H),
7.00 – 6.91 (m, 3H), 6.86 (dd, J = 10.9, 4.1 Hz, 2H), 6.48 (d, J = 4.0 Hz, 1H), 2.74 (d, J = 12.3 Hz, 1H),
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13
2.32 (s, 3H), 2.21 (s, 2H), 2.18 – 2.10 (m, 4H), 1.40 (s, 3H), 1.30 (s, 3H), 1.25 (s, 3H), 1.14 (s, 3H); C
NMR (100 MHz, DMSO) δ 167.79, 153.9 (d, J = 2.8 Hz), 153.3 (d, J = 8.0 Hz), 152.6, 152.3, 147.5 (d,
J = 3.4 Hz), 137.8 (dd, J = 29.7, 14.9 Hz), 136.0, 135.2, 134.4 (d, J = 2.6 Hz), 132.7 (d, J = 11.9 Hz),
132.5 877, 127.6 (d, J = 3.0 Hz), 126.2, 123.7, 58.8 (d, J = 3.5 Hz), 58.7 (d, J = 4.4 Hz), 56.1, 42.5, 42.1,
33.1, 32.2, 28.8, 28.6, 20.9, 20.7; 31P NMR (162 MHz, DMSO) δ ꢀ23.06; IR (film): γ = 2951, 2856,
1694, 1607, 1434, 1360, 1307, 1256 cmꢀ1; HRMS (GCꢀTOF, EI) m/z calcd for C36H37O2P [M+]
532.2531, found 532.2531.
General procedure for synthesis of HMSI-PHOX ligands (1). A solution of acid 12 (532.7 mg,
1.0 mmol), chiral amino alcohol (3.0 mmol), 1ꢀethylꢀ3ꢀ[3ꢀ(dimethylamino)propyl]carbodiimide (EDCI,
575.2 mg, 3.0 mmol) and benzotriazolꢀ1ꢀol (HOBt, 405.4 mg, 3.0 mmol) in DMF (40 mL) was stirred at
room temperature under nitrogen. The mixture was monitored by TLC for a complete conversion. Then
the resulting solution was diluted with water and extracted with ethyl acetate. The organic layer was
washed with saturated brine and dried over anhydrous Na2SO4. After evaporation in vacuum, the crude
product 13 which could be used directly in the next step was obtained. To a solution of amide 13 (1.0
mmol) and 4ꢀdimethlaminopridine (DMAP, 12.2 mg, 0.1 mmol) in CH2Cl2 (30 mL) was added
o
triethylamine (1.1 mL, 8 mmol) and methanesulfonyl chloride (310 ꢁL, 4 mmol) sequentially at 0 C
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The Journal of Organic Chemistry
under a nitrogen atmosphere. Then the resulting mixture was allowed to warm up to room temperature
and stirred overnight. The reaction was quenched with water and extracted with CH2Cl2. The combined
extracts were washed with brine, dried over anhydrous Na2SO4, and evaporated under reduced pressure.
The residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether = 1/20ꢀ
1/10) to give a pair of diastereomers 1 as white solids.
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(S)ꢀ2ꢀ((R)ꢀ7'ꢀ(diphenylphosphanyl)ꢀ3,3,3',3',5,5'ꢀhexamethylꢀ2,2',3,3'ꢀtetrahydroꢀ1,1'ꢀspirobi[inden]ꢀ7ꢀ
20
yl)ꢀ4ꢀisopropylꢀ4,5ꢀdihydrooxazole [(Ra,S)ꢀ1a]: 258 mg, 44% yield; white solid, m.p. 199ꢀ200 oC; [α]D
= +131 (c 0.1, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 7.39 (s, 1H), 7.22 (dd, J = 6.8, 3.4 Hz, 3H), 7.20
– 7.16 (m, 3H), 7.09 (td, J = 7.0, 3.1 Hz, 2H), 7.04 (s, 1H), 6.98 – 6.92 (m, 3H), 6.57 (d, J = 4.4 Hz, 1H),
3.79 – 3.68 (m, 1H), 3.41 (dd, J = 17.7, 9.6 Hz, 1H), 2.84 (t, J = 9.2 Hz, 2H), 2.39 (s, 3H), 2.28 – 2.07
(m, 6H), 1.41 (s, 3H), 1.29 (s, 6H), 1.16 – 1.06 (m, 4H), 0.89 (d, J = 6.6 Hz, 3H), 0.56 (d, J = 6.7 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 163.58, 152.74 (dd, J = 5.1, 3.9 Hz), 150.43 (d, J = 24.7 Hz),
145.92 (d, J = 2.9 Hz), 137.4 (dd, J = 28.6, 14.9 Hz), 135.4, 134.9, 133.6 (d, J = 3.0 Hz), 133.2, 133.0,
132.3 (d, J = 19.0 Hz), 130.4 (d, J = 21.7 Hz), 129.0, 127.0 (d, J = 6.1 Hz), 126.7 (dd, J = 9.8, 5.6 Hz),
124.2, 123.7 (d, J = 2.9 Hz), 122.1, 76.3, 76.0, 75.6, 71.5, 68.7, 57.7 (d, J = 3.5 Hz), 57.0 (d, J = 5.2 Hz),
31
56.3, 42.0, 41.7, 32.6, 31.7, 31.3, 28.1, 27.2, 20.1, 19.1, 17.3; P NMR (162 MHz, CDCl3) δ ꢀ21.49; IR
(film): γ = 2952, 2856, 1640, 1434, 1383, 1358, 1134 cmꢀ1; HRMS (GCꢀTOF, EI) m/z calcd for
C41H46NOP [M+] 599.3317,found 599.3320.
(S)ꢀ2ꢀ((S)ꢀ7'ꢀ(diphenylphosphanyl)ꢀ3,3,3',3',5,5'ꢀhexamethylꢀ2,2',3,3'ꢀtetrahydroꢀ1,1'ꢀspirobi[inden]ꢀ7ꢀ
20
yl)ꢀ4ꢀisopropylꢀ4,5ꢀdihydrooxazole [(Sa,S)ꢀ1a]: 244 mg, 41% yield; white solid, m.p. 190ꢀ191 oC; [α]D
= ꢀ182 (c 0.1,CH2Cl2);1H NMR (400 MHz, CDCl3) δ 7.47 (s, 1H), 7.22 (dd, J = 4.0, 2.3 Hz, 3H), 7.17
(d, J = 4.6 Hz, 3H), 7.13 – 7.06 (m, 2H), 7.04 (s, 1H), 7.03 – 6.97 (m, 2H), 6.96 (s, 1H), 6.55 (d, J = 4.5
Hz, 1H), 3.64 – 3.54 (m, 1H), 3.45 (dt, J = 9.8, 6.3 Hz, 1H), 2.97 (dd, J = 9.8, 8.2 Hz, 1H), 2.66 (d, J =
12.6 Hz, 1H), 2.38 (s, 3H), 2.30 – 2.13 (m, 6H), 1.68 (dt, J = 13.0, 6.7 Hz, 1H), 1.38 (s, 3H), 1.32 (s,
3H), 1.29 (s, 3H), 1.08 (s, 3H), 0.87 (d, J = 6.8 Hz, 3H), 0.77 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz,
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CDCl3) δ 164.5, 153.7 (d, J = 2.6 Hz), 153.3 (d, J = 7.6 Hz), 151.7, 151.5, 146.1 (d, J = 2.9 Hz), 138.7 –
138.3 (m), 136.4, 135.7, 134.6 (d, J = 2.6 Hz), 133.6 (dd, J = 26.9, 19.6 Hz), 131.3, 131.1, 130.1, 128.0
(d, J = 6.3 Hz), 127.9 – 127.4 (m), 125.6, 124.5 (d, J = 3.5 Hz), 123.5, 77.3, 77.0, 76.7, 71.1, 68.8, 59.2
(d, J = 3.6 Hz), 58.0 (d, J = 4.3 Hz), 57.4, 42.8, 42.4, 33.3, 32.5 – 32.1 (m), 29.3, 28.9, 21.2 (d, J = 14.4
1
2
3
4
5
6
7
8
9
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Hz), 18.9, 17.7; P NMR (162 MHz, CDCl3) δ ꢀ21.19; IR (film): γ = 2953, 2860, 1646, 1434, 1384,
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1358, 1132 cmꢀ1; HRMS (GCꢀTOF, EI) m/z calcd for C41H46NOP [M+] 599.3317, found 599.3322.
(S)ꢀ2ꢀ((R)ꢀ7'ꢀ(diphenylphosphanyl)ꢀ3,3,3',3',5,5'ꢀhexamethylꢀ2,2',3,3'ꢀtetrahydroꢀ1,1'ꢀspirobi[inden]ꢀ7ꢀ
yl)ꢀ4ꢀphenylꢀ4,5ꢀdihydrooxazole [(Ra,S)ꢀ1b]: 250 mg, 40% yield; white solid, m.p. 67ꢀ68oC; [α]D
=
20
1
+74 (c 0.1, CH2Cl2); H NMR (400 MHz, CDCl3) δ 7.57 (s, 1H), 7.24 – 7.19 (m, 3H), 7.13 – 6.94 (m,
11H), 6.90 (s, 1H), 6.73 (dd, J = 8.0, 6.8 Hz, 3H), 4.83 (t, J = 10.5 Hz, 1H), 4.21 (dd, J = 9.9, 8.3 Hz,
1H), 3.14 – 2.87 (m, 2H), 2.41 (s, 3H), 2.27 (d, J = 12.7 Hz, 2H), 2.19 (d, J = 13.6 Hz, 1H), 2.08 (s, 3H),
1.37 (s, 3H), 1.32 (s, 3H), 1.30 (s, 3H), 1.13 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 166.2, 154.2 (d, J =
2.8 Hz), 153.9 (d, J = 7.4 Hz), 151.7 (d, J = 25.0 Hz), 147.7 (d, J = 3.0 Hz), 141.2, 138.7 (d, J = 13.7
Hz), 137.9 (d, J = 15.6 Hz), 136.6, 136.2, 135.0 (d, J = 2.8 Hz), 134.4, 134.2, 133.2, 133.0, 130.8, 128.0,
128.0, 127.9, 127.8, 127.6, 127.4, 127.0, 125.8, 123.9 (d, J = 3.0 Hz), 123.2, 73.9, 69.7, 58.8 (d, J = 3.4
Hz), 58.56 (d, J = 5.5 Hz), 57.2, 43.2, 42.8, 33.8, 32.4, 29.0, 28.0, 21.2; 31P NMR (162 MHz, CDCl3) δ ꢀ
22.22; IR (film): γ=2950, 2856, 1635, 1434, 1381, 1359, 1266, 1137 cmꢀ1; HRMS (GCꢀTOF, EI) m/z
calcd for C44H44NOP [M+] 633.3161, found 633.3161.
(S)ꢀ2ꢀ((S)ꢀ7'ꢀ(diphenylphosphanyl)ꢀ3,3,3',3',5,5'ꢀhexamethylꢀ2,2',3,3'ꢀtetrahydroꢀ1,1'ꢀspirobi[inden]ꢀ7ꢀ
yl)ꢀ4ꢀphenylꢀ4,5ꢀdihydrooxazole [(Sa,S)ꢀ1b]: 238 mg, 38% yield; white solid, m.p. 38ꢀ39oC; [α]D = ꢀ
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138 (c 0.1, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 7.59 (s, 1H), 7.30 – 7.08 (m, 12H), 7.07 – 6.95 (m,
4H), 6.94 (s, 1H), 6.63 (d, J = 2.3 Hz, 1H), 4.90 – 4.56 (m, 1H), 3.82 – 3.65 (m, 1H), 3.42 – 3.30 (m,
1H), 2.84 – 2.70 (m, 1H), 2.40 (s, 3H), 2.33 – 2.16 (m, 6H), 1.33 (d, J = 6.0 Hz, 6H), 1.26 (s, 3H), 1.15
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(s, 3H); C NMR (100 MHz, CDCl3) δ 165.7, 154.1, 153.3 (d, J = 7.6 Hz), 152.1 (d, J = 25.3 Hz),
146.7, 142.7, 138.6 (d, J = 14.5 Hz), 138.0 (d, J = 15.1 Hz), 136.6, 135.7, 134.7, 134.0, 133.8, 133.4,
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133.2, 130.5, 128.5, 128.0, 128.0, 127.8, 127.8, 127.7, 127.2, 126.6, 126.1, 123.7, 73.9, 68.6, 59.4 (d, J
= 3.7 Hz), 58.4 (d, J = 4.3 Hz), 57.1, 42.9, 42.5, 33.3, 32.4, 29.2, 28.9, 21.4; 31P NMR (162 MHz,
CDCl3) δ ꢀ21.71; IR (film): γ = 2955, 2856, 1641, 1436, 1383, 1356, 1263, 1132 cmꢀ1; HRMS (GCꢀTOF,
EI) m/z calcd for C44H44NOP [M+] 633.3161, found 633.3162.
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(S)ꢀ4ꢀbenzylꢀ2ꢀ((R)ꢀ7'ꢀ(diphenylphosphanyl)ꢀ3,3,3',3',5,5'ꢀhexamethylꢀ2,2',3,3'ꢀtetrahydroꢀ1,1'ꢀ
spirobi[inden]ꢀ7ꢀyl)ꢀ4,5ꢀdihydrooxazole [(Ra,S)ꢀ1c]: 249 mg, 39% yield; white solid, m.p. 57ꢀ58oC;
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[α]D = +106 (c 0.1, CH2Cl2); H NMR (400 MHz, CDCl3) δ 7.46 (s, 1H), 7.23 (dd, J = 7.0, 4.8 Hz,
5H), 7.17 (dd, J = 7.4, 6.1 Hz, 6H), 7.07 (s, 1H), 6.97 (ddd, J = 17.5, 11.6, 6.8 Hz, 5H), 6.64 (d, J = 4.4
Hz, 1H), 4.10 (qd, J = 9.3, 4.1 Hz, 1H), 3.75 (t, J = 8.7 Hz, 1H), 3.04 (dd, J = 13.7, 4.1 Hz, 1H), 2.89 –
2.71 (m, 2H), 2.41 (s, 3H), 2.25 (d, J = 10.8 Hz, 4H), 2.20 – 2.06 (m, 2H), 1.73 (dd, J = 13.6, 10.7 Hz,
1H), 1.37 (s, 3H), 1.31 (d, J = 1.9 Hz, 6H), 1.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 165.6, 154.0 (d,
J = 7.4 Hz), 153.87 151.3, 146.8, 138.6, 138.3, 138.2 (d, J = 3.0 Hz), 136.6, 136.0, 134.8 (d, J = 2.8 Hz),
134.3, 134.1, 133.4, 133.2, 131.6 (d, J = 21.8 Hz), 130.1, 128.7, 128.4, 128.1, 128.0, 127.8 (d, J = 2.0
Hz), 127.8, 126.2, 125.7, 124.2, 123.4, 71.7, 67.2, 58.9 (d, J = 3.6 Hz), 58.0 (d, J = 4.9 Hz), 57.3, 43.0,
42.7, 41.8, 33.6, 32.2, 29.2, 28.4, 21.4, 21.2; 31P NMR (162 MHz, CDCl3) δ ꢀ21.80; IR (film): γ = 2950,
2856, 1646, 1434, 1379, 1359, 1132 cmꢀ1; HRMS (GCꢀTOF, EI) m/z calcd for C45H46NOP [M+]
647.3317, found 647.3313.
(S)ꢀ4ꢀbenzylꢀ2ꢀ((S)ꢀ7'ꢀ(diphenylphosphanyl)ꢀ3,3,3',3',5,5'ꢀhexamethylꢀ2,2',3,3'ꢀtetrahydroꢀ1,1'ꢀ
spirobi[inden]ꢀ7ꢀyl)ꢀ4,5ꢀdihydrooxazole [(Sa,S)ꢀ1c]: 246 mg, 38% yield; white solid, m.p. 61ꢀ62oC;
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[α]D = ꢀ125 (c 0.1, CH2Cl2); H NMR (400 MHz, CDCl3) δ 7.42 (s, 1H), 7.29 – 7.23 (m, 2H), 7.23 –
7.14 (m, 7H), 7.07 (dd, J = 10.4, 3.3 Hz, 5H), 7.01 – 6.95 (m, 2H), 6.92 (s, 1H), 6.59 (d, J = 3.9 Hz, 1H),
4.05 – 3.91 (m, 1H), 3.52 (dd, J = 8.3, 6.2 Hz, 1H), 3.12 (t, J = 8.8 Hz, 1H), 2.87 (dd, J = 13.9, 4.3 Hz,
1H), 2.75 (d, J = 12.5 Hz, 1H), 2.39 (s, 3H), 2.29 – 2.17 (m, 3H), 2.15 (s, 3H), 2.04 (dd, J = 13.8, 10.2
Hz, 1H), 1.39 (s, 3H), 1.33 (s, 3H), 1.30 (s, 3H), 1.13 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 164.3,
154.0 (d, J = 2.6 Hz), 153.4 (d, J = 8.1 Hz), 152.2 (d, J = 25.1 Hz), 146.5 (d, J = 3.4 Hz), 138.7 (d, J =
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14.3 Hz), 138.5, 138.2 (d, J = 15.4 Hz), 136.4, 135.7, 134.7 (d, J = 2.7 Hz), 133.9, 133.7, 133.3, 133.2,
130.8 (d, J = 20.9 Hz), 130.1, 129.0, 128.4, 128.0, 128.0, 127.8 – 127.7 (m), 127.6, 126.2, 125.8, 124.1
(d, J = 2.9 Hz), 123.7, 70.5, 66.8, 59.3 (d, J = 3.9 Hz), 58.3 (d, J = 4.2 Hz), 57.0, 42.8, 42.4, 41.1, 33.2,
32.4, 29.2, 28.9, 21.2, 21.1; 31P NMR (162 MHz, CDCl3) δ ꢀ21.96; IR (film): γ = 2950, 2856, 1652,
1434, 1381, 1356, 1132 cmꢀ1; HRMS (GCꢀTOF, EI) m/z calcd for C45H46NOP [M+] 647.3317, found
647.3318.
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(4S,5S)ꢀ2ꢀ((R)ꢀ7'ꢀ(diphenylphosphanyl)ꢀ3,3,3',3',5,5'ꢀhexamethylꢀ2,2',3,3'ꢀtetrahydroꢀ1,1'ꢀspirobi[inden]ꢀ
7ꢀyl)ꢀ4,5ꢀdiphenylꢀ4,5ꢀdihydrooxazole [(Ra,S,S)ꢀ1d]: 258 mg, 36% yield; white solid, m.p. 213ꢀ214oC;
[α]D20 = +94 (c 0.1, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 7.71 (s, 1H), 7.25 – 7.18 (m, 6H), 7.11 (ddd,
J = 12.0, 7.4, 4.6 Hz, 5H), 7.05 – 6.90 (m, 8H), 6.87 (s, 1H), 6.81 (d, J = 4.5 Hz, 1H), 6.64 (s, 1H), 6.62
(s, 1H), 4.62 (d, J = 10.5 Hz, 1H), 4.14 (d, J = 10.5 Hz, 1H), 3.03 (d, J = 12.4 Hz, 1H), 2.45 (s, 3H),
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2.29 – 2.16 (m, 3H), 2.10 (s, 3H), 1.33 (s, 3H), 1.22 (s, 3H), 1.13 (s, 3H), 1.00 (s, 3H); C NMR (100
MHz, CDCl3) δ 165.5, 154.4, 154.4, 154.3, 151.6 (d, J = 24.6 Hz), 148.1 (d, J = 2.9 Hz), 140.4, 139.4,
138.8, 138.7, 137.8, 137.6, 136.7, 136.3, 135.1, 135.0, 133.2, 133.0, 131.1, 130.8 (d, J = 22.0 Hz), 128.4,
128.1, 128.0, 128.0, 127.9, 127.6, 127.4, 127.0, 126.3, 126.0, 124.1 (d, J = 2.9 Hz), 123.1, 89.2, 78.7,
58.7, 58.7, 58.4, 58.4, 57.1, 43.3, 42.9, 34.1, 32.3, 29.1, 27.3, 21.2; 31P NMR (162 MHz, CDCl3) δ ꢀ
22.26; IR (film): γ = 2950, 2852, 1639, 1605, 1454, 1384, 1264, 1136 cmꢀ1; HRMS (GCꢀTOF, EI) m/z
calcd for C50H48NOP [M+] 709.3474, found 709.3478.
(4S,5S)ꢀ2ꢀ((S)ꢀ7'ꢀ(diphenylphosphanyl)ꢀ3,3,3',3',5,5'ꢀhexamethylꢀ2,2',3,3'ꢀtetrahydroꢀ1,1'ꢀspirobi[inden]ꢀ
7ꢀyl)ꢀ4,5ꢀdiphenylꢀ4,5ꢀdihydrooxazole [(Sa,S,S)ꢀ1d]: 256 mg, 36% yield; white solid, m.p. 167ꢀ168oC;
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[α]D = ꢀ43 (c 0.1, CH2Cl2); H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 0.9 Hz, 1H), 7.25 – 7.05 (m,
15H), 6.97 (ddd, J = 11.2, 7.9, 2.8 Hz, 4H), 6.77 – 6.53 (m, 4H), 4.85 (d, J = 9.8 Hz, 1H), 4.67 (d, J =
9.8 Hz, 1H), 2.90 (d, J = 12.5 Hz, 1H), 2.56 (d, J = 12.9 Hz, 1H), 2.41 (d, J = 12.4 Hz, 4H), 2.18 (d, J =
12.5 Hz, 1H), 2.07 (s, 3H), 1.32 (d, J = 11.3 Hz, 9H), 1.13 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 162.2,
154.0 (d, J = 3.0 Hz), 153.3, 153.0, 151.3 (d, J = 8.0 Hz), 145.7 (d, J = 4.2 Hz), 140.2, 138.7, 135.5,
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134.6, 134.0 (d, J = 3.1 Hz), 133.4, 133.2, 131.8, 131.6, 129.6, 129.0 (d, J = 20.1 Hz), 127.3, 127.2,
127.0, 126.9, 126.9, 126.8, 126.6, 126.5, 126.2, 125.9, 125.8, 125.3, 125.2, 123.1, 122.7, 86.9, 77.7,
58.7, 58.7, 54.5, 41.7, 41.4, 32.2, 32.1, 27.7, 27.6, 27.6, 20.3, 20.1; 31P NMR (162 MHz, CDCl3) δ ꢀ
22.33; IR (film): γ = 2951, 2852, 1646, 1605, 1454, 1384, 1260, 1130 cmꢀ1; HRMS (GCꢀTOF, EI) m/z
calcd for C50H48NOP [M+] 709.3474, found 709.3467.
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General Procedure for Asymmetric Arylation. A Schlenk tube was charged with Ni(ClO4)2·6H2O
(1.8 mg, 0.005 mmol), (Ra,S,S)ꢀ1d (5.3 mg, 0.0075 mmol), and TFE (0.5 mL) under a nitrogen
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atmosphere. The mixture was stirred at 60 C for 30 minutes. Then the substrate 2 (0.1 mmol) and aryl
boronic acid 3 (0.15 mmol) were added and the wall of the tube was rinsed with additional 0.5 mL of
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TFE. The reaction mixture was stirred at 60 C for 48 hours monitored by TLC. After cooling to room
temperature, the solution was concentrated under reduced pressure, and the residue was purified by flash
chromatography on silica gel (ethyl acetate/petroleum ether = 1/6) to obtain the corresponding product 4.
(R)ꢀ4ꢀphenylꢀ3,4ꢀdihydrobenzo[e][1,2,3]oxathiazineꢀ2,2ꢀdioxide (4a)21: 23 mg, 88% yield; white solid;
m.p. 131ꢀ132°C; 99% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 90/10, 220 nm,1.0
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mL/min), tR (major) 10.2 min, tR (minor) 11.7 min; [α]D = +28.2 (c 0.10, CH2Cl2); H NMR (400
MHz, CDCl3) δ 7.44 (dd, J = 6.5, 3.7 Hz, 3H), 7.39 – 7.29 (m, 3H), 7.10 (t, J = 7.7 Hz, 2H), 6.83 (d, J =
7.6 Hz, 1H), 5.91 (s, 1H), 4.70 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 150.4, 136.8, 128.7, 128.5,
128.4, 127.8, 127.5, 124.2, 120.9, 117.8, 60.9; IR (film): γ = 3282, 1580, 1423, 1203, 1171, 1101, 846
cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C13H10NO3Sꢀ [MꢀH]ꢀ 260.0381, found 260.0397.
(R)ꢀ4ꢀ(4ꢀchlorophenyl)ꢀ3,4ꢀdihydrobenzo[e][1,2,3]oxathiazineꢀ2,2ꢀdioxide (4b)19: 28 mg, 93% yield;
white solid; m.p. 139ꢀ140°C; 99% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 90/10, 220
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nm,1.0 mL/min), tR (major) 7.3 min, tR (minor) 9.8 min; [α]D = +8.5 (c 0.20, CH2Cl2); 1H NMR (400
MHz, CDCl3) δ 7.45 – 7.27 (m, 5H), 7.15 – 7.03 (m, 2H), 6.80 (d, J = 7.8 Hz, 1H), 5.88 (d, J = 8.4 Hz,
1H), 4.86 (d, J = 8.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 151.4, 136.29, 135.6, 130.2, 130.0, 129.7,
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128.4, 125.4, 121.4, 119.0, 61.2; IR (film): γ = 3274, 1581, 1425, 1202, 1170, 1092, 849 cmꢀ1; HRMS
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(ESIꢀTOF) m/z calcd for C13H9ClNO3Sꢀ [MꢀH]ꢀ 293.9992, found 293.9997.
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white solid; m.p. 104ꢀ105°C; 99% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 95/5, 220
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nm,1.0 mL/min), tR (minor) 8.8 min, tR (major) 11.5 min; [α]D = +16.6 (c 0.28, CH2Cl2); H NMR
(400 MHz, CDCl3) δ 7.45 – 7.32 (m, 4H), 7.28 – 7.23 (m, 1H), 7.11 (ddd, J = 23.4, 11.7, 4.6 Hz, 2H),
6.83 (d, J = 7.8 Hz, 1H), 5.87 (s, 1H), 4.79 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 151.4, 139.6, 135.3,
130.8, 130.0, 129.8, 129.0, 128.4, 127.1, 125.4, 121.2, 119.0, 61.4; IR (film): γ = 3276, 1581, 1425,
1203, 1172, 1101, 857cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C13H9ClNO3Sꢀ [MꢀH]ꢀ 293.9992, found
293.9997.
(S)ꢀ4ꢀ(2ꢀchlorophenyl)ꢀ3,4ꢀdihydrobenzo[e][1,2,3]oxathiazineꢀ2,2ꢀdioxide (4d)21: 15 mg, 51% yield;
light yellow solid; m.p. 114ꢀ115°C; 93% ee; HPLC analysis: Chiralpak IFꢀ3 (hexane/iꢀPrOH = 90/10,
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220 nm,1.0 mL/min), tR (major) 6.2 min, tR (minor) 7.6 min; [α]D = +29.8 (c 0.08, CH2Cl2); 1H NMR
(400 MHz, CDCl3) δ 7.51 – 7.45 (m, 1H), 7.44 – 7.29 (m, 4H), 7.15 – 7.05 (m, 2H), 6.78 (d, J = 7.7 Hz,
1H), 6.30 (s, 1H), 5.09 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 151.4, 134.9, 134.0, 131.3, 130.9, 130.8,
129.8, 127.8, 127.6, 125.4, 121.1, 118.9, 59.6; IR (film): γ = 3280, 1581, 1427, 1374, 1203, 1172, 1101,
847cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C13H9ClNO3Sꢀ [MꢀH]ꢀ 293.9992, found 293.9999.
(R)ꢀ4ꢀ(4ꢀbromophenyl)ꢀ3,4ꢀdihydrobenzo[e][1,2,3]oxathiazineꢀ2,2ꢀdioxide (4e)19: 31 mg, 91% yield;
white solid; m.p. 126ꢀ127°C; 99% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 90/10, 220
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nm,1.0 mL/min), tR (major) 7.6 min, tR (minor) 10.2 min; [α]D = +10.2 (c 0.23, CH2Cl2); 1H NMR
(400 MHz, CDCl3) δ 7.61 – 7.55 (m, 2H), 7.35 (td, J = 7.9, 0.8 Hz, 1H), 7.25 – 7.20 (m, 2H), 7.11 (ddd,
J = 9.1, 6.8, 1.0 Hz, 2H), 6.81 (d, J = 7.8 Hz, 1H), 5.88 (s, 1H), 4.70 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 150.4, 135.8, 131.6, 129.5, 128.9, 127.4, 124.3, 122.8, 120.3, 117.9, 60.3; IR (film): γ= 3276,
1581, 1426, 1371, 1203, 1170, 1099, 849 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C13H9BrNO3Sꢀ [MꢀH]ꢀ
337.9487, found 337.9493.
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(R)ꢀ4ꢀ(4ꢀ(trifluoromethyl)phenyl)ꢀ3,4ꢀdihydrobenzo[e][1,2,3]oxathiazineꢀ2,2ꢀdioxide (4f)19: 25 mg, 76%
yield; light yellow solid; m.p. 119ꢀ120°C; 98% ee; HPLC analysis: Chiralpak IFꢀ3 (hexane/iꢀPrOH =
90/10, 220 nm,0.8 mL/min), tR (minor) 5.9 min, tR (major) 6.8 min; [α]D20 = +34.3 (c 0.07, CH2Cl2); 1H
NMR (400 MHz, CDCl3) δ 7.64 (d, J = 8.2 Hz, 2H), 7.43 (d, J = 8.1 Hz, 2H), 7.30 (dd, J = 11.5, 4.2 Hz,
1H), 7.12 – 7.00 (m, 2H), 6.73 (d, J = 7.7 Hz, 1H), 5.91 (s, 1H), 4.72 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 150.5, 140.6, 130.8 (d, J = 32.8 Hz), 129.1, 128.3, 127.3, 125.4 (d, J = 3.7 Hz), 124.4, 122.6
(d, J = 272.4 Hz), 120.0, 118.1, 60.3; 19F NMR (376 MHz, CDCl3) δ ꢀ62.80 (s, 3F); IR (film): γ = 3274,
1582, 1427, 1326, 1205, 1171, 853 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C14H9F3NO3Sꢀ [MꢀH]ꢀ
328.0255, found 328.0268.
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(R)ꢀ4ꢀ(pꢀtolyl)ꢀ3,4ꢀdihydrobenzo[e][1,2,3]oxathiazineꢀ2,2ꢀdioxide (4g)21: 24 mg, 87% yield; white solid;
m.p. 120ꢀ121°C; 93% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 95/5, 220 nm,1.0 mL/min),
tR (major) 16.0 min, tR (minor) 17.4 min; [α]D20 = +18.7 (c 0.12, CH2Cl2); 1H NMR (400 MHz, CDCl3)
δ 7.31 (t, J = 7.7 Hz, 1H), 7.27 – 7.17 (m, 4H), 7.07 (dd, J = 15.6, 8.0 Hz, 2H), 6.82 (d, J = 7.8 Hz, 1H),
5.86 (s, 1H), 4.73 (s, 1H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 150.4, 138.6, 133.9, 129.1,
128.6, 127.64, 127.5, 124.1, 121.2, 117.7, 60.7, 20.2; IR (film): γ = 3276, 1580, 1424, 1370, 1203, 1170,
1100, 850 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C14H12NO3Sꢀ [MꢀH]ꢀ 274.0538, found 274.0540.
(R)ꢀ4ꢀ(mꢀtolyl)ꢀ3,4ꢀdihydrobenzo[e][1,2,3]oxathiazineꢀ2,2ꢀdioxide (4h)21: 25 mg, 91% yield; white
solid; m.p. 83ꢀ84°C; 99% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 95/5, 220 nm,1.0
20
mL/min), tR (major) 15.0 min, tR (minor) 17.4 min; [α]D = +12.1 (c 0.31, CH2Cl2); 1H NMR (400
MHz, CDCl3) δ 7.32 (dd, J = 12.2, 4.8 Hz, 2H), 7.27 – 7.20 (m, 1H), 7.09 (ddd, J = 15.0, 10.9, 2.6 Hz,
13
4H), 6.82 (d, J = 7.8 Hz, 1H), 5.85 (s, 1H), 4.72 (s, 1H), 2.37 (s, 3H); C NMR (100 MHz, CDCl3) δ
151.5, 139.4, 137.8, 130.3, 129.7, 129.4, 129.3, 128.6, 125.8, 125.2, 122.1, 118.8, 62.0, 21.4; IR (film):
γ = 3277, 1581, 1421, 1370, 1198, 1170, 1101, 879 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C14H12NO3Sꢀ
[MꢀH]ꢀ 274.0538, found 274.0541.
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(R)ꢀ4ꢀ(benzo[d][1,3]dioxolꢀ5ꢀyl)ꢀ3,4ꢀdihydrobenzo[e][1,2,3]oxathiazineꢀ2,2ꢀdioxide (4i)19: 27 mg, 88%
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3
yield; white solid; m.p. 127ꢀ128°C; 95% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 90/10,
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5
20
220 nm,1.0 mL/min), tR (minor) 17.3 min, tR (major) 18.1 min; [α]D = +21.0 (c 0.10, CH2Cl2); 1H
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7
8
NMR (400 MHz, CDCl3) δ 7.32 (t, J = 7.7 Hz, 1H), 7.17 – 6.98 (m, 2H), 6.92 – 6.79 (m, 3H), 6.73 (s,
9
13
1H), 6.00 (s, 2H), 5.80 (t, J = 8.2 Hz, 1H), 4.73 (d, J = 8.3 Hz, 1H); C NMR (100 MHz, CDCl3) δ
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151.4, 148.6, 148.5, 131.5, 129.7, 128.6, 125.2 , 122.9 , 122.0, 118.8, 108.8, 108.7, 101.6, 61.8; IR
(film): γ = 3277, 1580, 1423, 1370, 1202, 1170, 1096, 836 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for
C14H10NO5Sꢀ [MꢀH]ꢀ 304.0280, found 304.0286.
(R)ꢀ4ꢀ([1,1'ꢀbiphenyl]ꢀ4ꢀyl)ꢀ3,4ꢀdihydrobenzo[e][1,2,3]oxathiazineꢀ2,2ꢀdioxide (4j)19: 31 mg, 92%
yield; white solid; m.p. 167ꢀ168°C; 99% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 90/10,
20
220 nm,1.0 mL/min), tR (major) 12.5 min, tR (minor) 14.4 min; [α]D = +17.0 (c 0.10, CH2Cl2); 1H
NMR (400 MHz, CDCl3) δ 7.64 (d, J = 8.2 Hz, 2H), 7.62 – 7.54 (m, 2H), 7.46 (dd, J = 10.3, 4.7 Hz,
2H), 7.38 (ddd, J = 24.0, 11.4, 6.0 Hz, 4H), 7.10 (dd, J = 14.8, 7.9 Hz, 2H), 6.89 (d, J = 7.7 Hz, 1H),
13
5.95 (d, J = 8.5 Hz, 1H), 4.77 (d, J = 8.4 Hz, 1H); C NMR (100 MHz, CDCl3) δ 151.5, 142.5, 140.0,
136.7, 129.82, 129.2, 128.9, 128.6, 128.1, 127.9, 127.1, 125.3, 121.9, 118.9, 61.7; IR (film): γ = 3278,
1580, 1423, 1371, 1204, 1170, 1100, 851 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd forC19H14NO3Sꢀ [MꢀH]ꢀ
336.0694, found 336.0705
(R)ꢀ4ꢀ(naphthalenꢀ2ꢀyl)ꢀ3,4ꢀdihydrobenzo[e][1,2,3]oxathiazineꢀ2,2ꢀdioxide (4k)21: 28 mg, 90% yield;
white solid; m.p. 138ꢀ139°C; 98% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 90/10, 220
20
nm,1.0 mL/min), tR (major) 11.4 min, tR (minor) 18.3 min; [α]D = ꢀ48.3 (c 0.10, CH2Cl2); 1H NMR
(400 MHz, CDCl3) δ 7.94 – 7.81 (m, 4H), 7.61 – 7.50 (m, 2H), 7.40 – 7.30 (m, 2H), 7.17 – 7.03 (m,
13
2H), 6.85 (d, J = 7.8 Hz, 1H), 6.09 (d, J = 11.3 Hz, 1H), 4.79 (s, 1H); C NMR (100 MHz, CDCl3) δ
151.5, 134.9, 133.5, 133.1, 129.8, 129.7, 128.8, 128.6, 128.1, 127.9, 127.2, 127.0, 125.3, 125.2, 122.0,
118.9, 62.2; IR (film): γ = 3276, 1580, 1421, 1365, 1204, 1171, 1099, 865 cmꢀ1; HRMS (ESIꢀTOF) m/z
calcd for C17H12NO3Sꢀ [MꢀH]ꢀ 310.0538, found 310.0544.
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(S)ꢀ4ꢀ(thiophenꢀ3ꢀyl)ꢀ3,4ꢀdihydrobenzo[e][1,2,3]oxathiazineꢀ2,2ꢀdioxide (4l)19: 22 mg, 82% yield; white
solid; m.p. 130ꢀ131°C; 95% ee; HPLC analysis: Chiralpak IFꢀ3 (hexane/iꢀPrOH = 90/10, 220 nm,0.8
mL/min), tR (minor) 9.9 min, tR (major) 12.9 min; [α]D20 = +59.2 (c 0.07, CH2Cl2); 1H NMR (400 MHz,
CDCl3) δ 7.40 (ddd, J = 4.3, 3.9, 2.3 Hz, 2H), 7.37 – 7.30 (m, 1H), 7.12 (td, J = 7.7, 1.0 Hz, 1H), 7.05
(dd, J = 8.3, 0.8 Hz, 1H), 7.01 (dd, J = 4.9, 1.4 Hz, 1H), 6.94 (d, J = 7.8 Hz, 1H), 6.04 (d, J = 8.7 Hz,
1H), 4.79 (d, J = 8.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 151.1, 138.0, 129.8, 128.2, 127.9, 126.6,
125.9 , 125.2, 121.6, 118.8, 56.9; IR (film): γ = 3275, 1580, 1423, 1368, 1195, 1170, 1100, 863 cmꢀ1;
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ꢀ
HRMS (ESIꢀTOF) m/z calcd for C11H8NO3S2 [MꢀH]ꢀ 265.9946, found 265.9943.
(R)ꢀ6ꢀmethylꢀ4ꢀphenylꢀ3,4ꢀdihydrobenzo[e][1,2,3]oxathiazineꢀ2,2ꢀdioxide (4m)21: 26 mg, 94% yield;
white solid; m.p. 125ꢀ126°C; 99% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 95/5, 220
20
nm,1.0 mL/min), tR (major) 20.1 min, tR (minor) 21.9 min; [α]D = +57.0 (c 0.10, CH2Cl2); 1H NMR
(400 MHz, CDCl3) δ 7.49 – 7.42 (m, 1H), 7.39 – 7.31 (m, 1H), 7.12 (dd, J = 8.4, 1.9 Hz, 1H), 6.97 (d, J
= 8.4 Hz, 1H), 6.60 (s, 1H), 5.86 (s, 1H), 4.65 (s, 1H), 2.21 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
148.4, 137.0, 134.0, 129.3, 128.5, 128.4, 127.8, 127.5, 120.4, 117.5, 60.9, 19.7; IR (film): γ = 3276,
1488, 1422, 1370, 1176, 1109, 856 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C14H12NO3Sꢀ [MꢀH]ꢀ
274.0538, found 274.0530.
(R)ꢀ6ꢀchloroꢀ4ꢀphenylꢀ3,4ꢀdihydrobenzo[e][1,2,3]oxathiazineꢀ2,2ꢀdioxide (4n)21: 26 mg, 88% yield;
white solid; m.p. 137ꢀ138°C; 99% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 98/2, 220
20
nm,0.8 mL/min), tR (major) 34.6 min, tR (minor) 40.7 min; [α]D = +33.9 (c 0.22, CH2Cl2); 1H NMR
(400 MHz, CDCl3) δ 7.46 (d, J = 2.9 Hz, 3H), 7.38 – 7.28 (m, 3H), 7.04 (d, J = 8.8 Hz, 1H), 6.81 (d, J =
1.3 Hz, 1H), 5.86 (s, 1H), 4.71 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 148.9, 135.9, 129.5, 128.9 (d, J =
1.5 Hz), 128.6, 127.7, 127.2, 122.5, 119.2, 60.7; IR (film): γ = 3279, 1473, 1426, 1371, 1204, 1169,
1111, 847 cmꢀ1; HRMS (ESIꢀTOF) m/z calcd for C13H9ClNO3Sꢀ [MꢀH]ꢀ 293.9992, found 293.9994.
(R)ꢀ6ꢀbromoꢀ4ꢀphenylꢀ3,4ꢀdihydrobenzo[e][1,2,3]oxathiazineꢀ2,2ꢀdioxide (4o)19: 29 mg, 85% yield;
white solid; m.p. 154ꢀ155°C; 99% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 98/2, 220
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nm,0.8 mL/min), tR (major) 40.3 min, tR (minor) 45.3 min; [α]D = +37.8 (c 0.23, CH2Cl2); 1H NMR
(400 MHz, CDCl3) δ 7.52 – 7.41 (m, 4H), 7.33 (dd, J = 6.3, 3.2 Hz, 2H), 6.96 (dd, J = 11.0, 5.4 Hz, 2H),
5.87 (s, 1H), 4.75 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 150.5, 137.0, 132.8, 131.2, 129.9, 129.7,
128.7, 124.0, 120.7, 118.0, 61.7; IR (film): γ = 3266, 1471, 1417, 1368, 1200, 1167, 1111, 845 cmꢀ1;
HRMS (ESIꢀTOF) m/z calcd for C13H9BrNO3Sꢀ [MꢀH]ꢀ 337.9487, found 337.9486.
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ASSOCIATED CONTENT
Supporting Information
This Supporting Information is available free of charge via the Internet at http://pubs.acs.org.
1
13
19
copies of H, C, F NMR and HPLC traces; crystallographic data for the complex of (Sa,S,S)ꢀ1d and
diisopropyl ether (CIF).
Accession Codes
CCDC 1814373 contains the supplementary crystallographic data for this paper. These data can be
obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
* lxfok@zju.edu.cn.
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
We appreciate the National Natural Science Foundation of China (21572200) and the Fundamental
Research Funds for the Central Universities (2017QNA3013) for financial support.
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