Rhodium-Catalyzed Asymmetric Addition of Organoboronic Acids to Aldimines Using Chiral Spiro Monophosphite-Olefin Ligands: Method Development and Mechanistic Studies

Article abstract of DOI:10.1021/acs.joc.8b01764

The synthesis of a novel type of chiral spiro monophosphite-olefin (SMPO) ligands based on a hexamethyl-1,1′-spirobiindane scaffold was accomplished starting from Bisphenol C. The optimal ligand could serve as an elegant chiral bidentate ligand in the Rh-catalyzed asymmetric 1,2-addition of organoboronic acids to various acyclic/cyclic aldimines, leading to chiral amines with high yields and excellent enantioselectivities. Detailed stereochemical models for enantioselective induction were elucidated through DFT calculations and postulated the origins of the higher enantioselectivity of phosphite-olefin ligands.

Full text of DOI:10.1021/acs.joc.8b01764

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Article
Rhodium-Catalyzed Asymmetric Addition of Organoboronic
Acids to Aldimines Using Chiral Spiro Monophosphite-
Olefin Ligands: Method Development and Mechanistic Studies
Huanyu Shan, Qiaoxia Zhou, Jinglu Yu, Shuoqing Zhang, Xin Hong, and Xufeng Lin
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01764 • Publication Date (Web): 28 Aug 2018
Downloaded from http://pubs.acs.org on August 30, 2018
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The Journal of Organic Chemistry
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RhodiumꢀCatalyzed Asymmetric Addition of Organoboronic Acids to
Aldimines Using Chiral Spiro MonophosphiteꢀOlefin Ligands: Method
Development and Mechanistic Studies
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Huanyu Shan, Qiaoxia Zhou, Jinglu Yu, Shuoqing Zhang, Xin Hong* and Xufeng Lin*
Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China
E-mail: hxchem@zju.edu.cn, lxfok@zju.edu.cn
Abstract: The synthesis of a novel type of chiral spiro monophosphiteꢀolefin (SMPO) ligands based
on a hexamethylꢀ1,1’ꢀspirobiindane scaffold was accomplished starting from Bisphenol C. The
optimal ligand could serve as an elegant chiral bidentate ligand in the Rhꢀcatalyzed asymmetric 1,2ꢀ
addition of organoboronic acids to various acyclic/cyclic aldimines leading to chiral amines with high
yields and excellent enantioselectivities. Detailed stereochemical models for enantioselective
induction were elucidated through DFT calculations and postulated the origins of the higher
enantioselectivity of phosphiteꢀolefin ligands.
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Introduction
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The development of effective chiral ligands for transitionꢀmetalꢀcatalyzed asymmetric reactions has
become one of the most important and challenging goals of research in synthetic chemsitry.1 Chiral
phosphorusꢀbased olefin ligands,2 which combine the strongly coordinating phosphorus atom and the
weakly coordinating olefin into one ligand molecule, have made impressive progress in asymmetric
catalysis since the first demonstration by Grützmacher.3 There have been reported structurally diverse Pꢀ
olefin ligands with various kinds of skeletons, which had remarkable influence on catalytic performance
in some cases.3ꢀ7 These ligands have been used successfully for many asymmetric reactions, including
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hydrogenation, addition, allylic alkylation, amination, and intramolecular hydroacylation. Notably,
Hayashi’s phosphine–olefin4 and Carreira’s phosphoramidite–olefin5 represented the great success of the
promising class of ligands. Recently, Xu developed the first chiral binolꢀ and H8ꢀbinolꢀderived
phosphiteꢀolefin ligands for highly enantioselective catalysis.7 Despite these achievements, the
development of novel Pꢀolefin ligands with excellent catalytic activities continues to be a search focus in
a diverse range of asymmetric transformations. More importantly, the origins of the higher
enantioselectivity of Pꢀolefin ligands in transitionꢀmetalꢀcatalyzed asymmetric reactions are still elusive.
More recently, we developed new types of chiral phosphineꢀoxazoline ligands and bisphosphine
ligands based on a hexamethylꢀ1,1’ꢀspirobiindane backbone, and demonstrated their successful
application in asymmetric catalysis.8
monophosphiteꢀolefin (SMPO) ligands and their application i
Herein, we report the first synthesis of chiral spiro
n
asymmetric reaction, and also elucidate
the mechanism of stereocontrol through DFT calculations and NMR measurements. Importantly, the
origins of the higher enantioselectivity of phosphiteꢀolefin ligands in asymmetric catalysis are postulated
for the first time.
Results and Discussion
Our approach started with Bisphenol C (Scheme 1). Hexamethylꢀ1,1'ꢀspirobiindaneꢀ6,6'ꢀdiol 1 (6, 6’ꢀ
HMSIOL) was obtained in 92% yield by acidꢀcatalyzed rearrangement.8 Then, efficient chiral resolution
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of 1 was accomplished utilizing (ꢀ)ꢀmenthyl chloroformate as a resolving agent. Notably, the two
diastereomers of 2a and 2b were isolated by cycling recrystallization with good yields. Absolute
configurations of 2a and 2b were confirmed by their Xꢀray structures, as shown in Figure 1. Both
enantiomerically pure 6, 6’ꢀHMSIOLs (R)ꢀ1 and (S)ꢀ1 were obtained in 98% yield after hydrolysis.
Then, the new spiro phosphite ligands were synthesized from (R)ꢀ1, as shown in Scheme 2. The Duff
reaction of (R)ꢀ1 with hexamethylenetetramine (HMTA) provided the dialdehydes 3 in 86% yield. The
subsequent esterification with Tf2O afforded triflate 4 in 95% yield. The following Pdꢀcatalyzed
selective reduction with formic acid furnished spiroꢀaldehyde 5 in 96% yield. Then, the BaeyerꢀVilliger
oxidation rearrangement and subsequent hydrolysis gave 7, 7’ꢀHMSIOL 6 in 82% yield. Finally, a oneꢀ
pot, twoꢀstep process afforded spiro monophosphite (SMPP) ligands 7a-d and spiro monophosphiteꢀ
olefin (SMPO) ligands 8a-f in 65ꢀ81% yields.
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Scheme 1. Synthesis and resolution of 6, 6’-HMSIOL
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Scheme 2. Synthesis of chiral ligands
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2a
2b
Figure 1. X-ray crystal structures of 2a and 2b (The ellipsoids are drawn at 50% probability)
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Table 1. Optimization of Reaction Parametersa
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Entry
1d
Ligand
[Rh]
Yield [%]b
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ee [%]c
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(R)ꢀ7a
Rh(acac)(C2H4)2
2d
3d
4d
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(R)ꢀ7b
(R)ꢀ7c
(R)ꢀ7d
(R)ꢀ7a
(R)ꢀ8a
(R)ꢀ8a
(R)ꢀ8b
(R)ꢀ8c
(R)ꢀ8d
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(R)ꢀ8f
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(R)ꢀ8e
(R)ꢀ8e
(R)ꢀ8e
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
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trace
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10
ꢀ57
ꢀ33
ꢀ35
ꢀ64
ꢀ
6d
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80
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[RhCl(C2H4)2]2
Rh(acac)(CO)2
[Rh(COD)Cl]2
Rh(COD)2BF4
aReactions conditions: 0.05 mmol of 9a, 0.1 mmol of 10a, 3 mol % [Rh], 3 mol % ligand, and 0.2 mmol KF in 1 mL
toluene/H2O (1/1) at 35 C for 20 h under N2 atmosphere. Isolated yields. Determined by chiral HPLC analysis.
With 6 mol % ligand.
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b
c
d
Our new ligands were applied to rhodiumꢀcatalyzed asymmetric reactions. First, the efficiency of new
ligands was tested in the Rhꢀcatalyzed asymmetric 1,2ꢀaddition of arylboronic acids to Nꢀ
tosylarylimines. Highly efficient transitionꢀmetalꢀcatalyzed asymmetric addition of arylboron reagents to
Nꢀtosylarylimines is the most versatile method to generate chiral diarylmethylamines.9, 10 Initial
experiments were investigated by the model reaction of Nꢀtosylimine 9a with phenylboronic acid 10a
(Table 1). When the reaction was carried out in the presence of 3 mol % of Rh(acac)(C2H4)2 and 6 mol
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o
% of SMPP 7 under aqueous KFꢀtoluene at 35 C for 20 h, the 1,2ꢀaddition product 11a was obtained
with low yield and enantioselectivity (Table 1, entries 1ꢀ4). The use of 3 mol % of 7a (Table 1, entry 5)
instead of 6 mol % (Table 1, entry 1) gave similar poor result. The use of 6 mol % of SMPO 8a (Table
1, entry 6) instead of 7a (Table 1, entry 1) resulted in no desired adduct. Notably, the use of 3 mol % of
8a (Table 1, entry 7) instead of 6 mol % (Table 1, entry 6) resulted in good yield (83%) and excellent
enantiomeric excess (97%). Furthermore, excellent result could be achieved in all case for the use of 3
mol % of SMPO 8a-f (Table 1, entries 7ꢀ12), and the optimal ligand 8e provided 11a in 85% yield with
99% ee (Table 1, entry 11). Further evalutation of the Rh catalyst precursors indicated that only
[RhCl(C2H4)2]2 gave the comparable result (Table 1, entries 13ꢀ16).
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With the optimized conditions in hand, the scope of substrate was examined, and the result was
summarized as shown in Table 2. Notably, high enantiomeric excess (95ꢀ99%) could be achieved when
a wide variety of Nꢀtosylarylimines with diverse steric and electronic properties were tested to react with
arylboronic acids. The reaction enantiocontrol is not apparently impacted by the electronic nature of the
phenyl ring of either imines or boronic acids. It is noteworthy that sterically encumbered orthoꢀ
substituted arylimines could also be smoothly employed to give excellent enantioselectivity and show
apparently no influence on the yield (Table 2, 11gꢀj). Meanwhile, naphthyl or thiopheneyl Nꢀtosylimine
could afford the corresponding products with high yields and excellent enantioselectivities (Table 2,
11kꢀl). Moreover, various arylboronic acids afforded the corresponding products with high ees (Table 2,
11a’-d’ and 11e’ꢀf’). Interestingly, without changing the catalyst, only simply switching the aryl
acceptor and donor of the substrates could provide both enantiomers of the corresponding product
(Table 2, 11a-f and 11a’-f’).
Furthermore, we tested under the standard conditions the corresponding NꢀNosylarylimine 9m from
paraꢀchlorobenzaldehyde with phenylboronic acid 10a. The corresponding diarylmethylamine product
11m was obtained with 97% ee but low yield (37%). When we tested under the standard conditions the
Nꢀtosyl ketimine 9n from paraꢀfluoroacetophenone with phenylboronic acid 10a, however, no reaction
happened due to its very low reactivity.
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Table 2. Substate Scope for Asymmetric Arylation of N-Tosylaryliminesa
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[a] Reactions conditions: 0.05 mmol of 9, 0.1 mmol of 10, 3 mol % Rh(acac)(C2H4)2, 3 mol % (R)ꢀ8e, and 0.2 mmol
KF in 1 mL toluene/H2O (1/1) at 35 oC for 20 h under N2 atmosphere. Yields are of isolated products.
Enantioselectivity was determined by chiral HPLC.
Newly developed SMPO ligands 8 were also tested in the asymmetric addtion of cyclic Nꢀsulfonyl
aldimines with organoboronic acids.7a, 9, 11 The reaction of cyclic Nꢀsulfonyl aldimine 12a with
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phenylboronic acid 10a was carried out in the presence of rhodium salts and chiral ligands to optimize
the reaction conditions, as shown in Table 3. It was found that both (R)ꢀ8b and (R)ꢀ8e gave the
excellent yield and the best ee value using [RhCl(C2H4)2]2 as the Rh catalyst precursor (Table 3, entries
3 and 6). The complex of (R)ꢀ8b and Rh(acac)(C2H4)2 also gave the good yield and excellent
enantioselectivity (Table 3, entry 8, 87%, 97% ee).
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Table 3. Optimization of Reaction Parametersa
Entry
Ligand
[Rh]
Yield
[%][b]
ee [%][c]
1[d]
2
(R)ꢀ7a
(R)ꢀ8a
(R)ꢀ8b
(R)ꢀ8c
(R)ꢀ8d
(R)ꢀ8e
(R)ꢀ8f
(R)ꢀ8b
(R)ꢀ8b
(R)ꢀ8b
(R)ꢀ8b
[RhCl(C2H4)2]2
[RhCl(C2H4)2]2
[RhCl(C2H4)2]2
[RhCl(C2H4)2]2
[RhCl(C2H4)2]2
[RhCl(C2H4)2]2
[RhCl(C2H4)2]2
85
90
90
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65
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97
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8
Rh(acac)(C2H4)2
Rh(acac)(CO)2
9
[Rh(COD)Cl]2
Rh(COD)2BF4
10
11
[a] Reactions conditions: 0.05 mmol of 12a, 0.1 mmol of 10a, 3 mol % [Rh], 3 mol % ligand, and KF (0.2 mmol) in
o
toluene/H2O (1/1, 1 mL) at 25 C for 20 h under N2 atmosphere. [b] Isolated yields. [c] Determined by chiral HPLC
analysis. [d] With 6 mol % ligand.
Under the optimized conditions (Table 3, entry 3), to our delight, the complex of (R)ꢀ8b and
[RhCl(C2H4)2]2 showed nearꢀperfect performance for such asymmetric transformation, as shown in
Table 4. Notably, a wide range of arylboronic acids with electronꢀwithdrawing or electronꢀdonating
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groups are suitable substrates to afford the corresponding products with high yields (85ꢀ93%) and
excellent enantioselectivities (95%ꢀ98% ee) (Table 4, 13a-13i). Meanwhile, heteroaryl 3ꢀ
thiopheneylboronic acid also be successfully employed (Table 4, 13j, 85% yield and 99% ee). Moreover,
a range of acceptors were also applied in the addition reaction with phenylboronic acid to reveal
excellent results using [Rh(acac)(C2H4)2]2 /(R)ꢀ8b as the catalyst (Table 4, 13k-13p). It is noteworthy
that styrylboronic acid reacted smoothly with various cyclic Nꢀsulfonyl aldimines to afford the
corresponding enantioselective styrylation products7a (Table 4, 13q-13u). However, when we tested
under the standard conditions the more challenging cyclic Nꢀsulfonyl ketimine, such as 4ꢀ
methylbenzo[e][1,2,3]oxathiazine 2,2ꢀdioxide 12h from 2ꢀhydroxyacetophenone, no reaction happened
due to its low reactivity.
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Table 4. Substrate scope for asymmetric addtion of cyclic aldiminesa
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[a] Reactions conditions: 0.05 mmol of 12, 0.1 mmol of 10, 1.5 mol % [RhCl(C2H4)2]2, 3 mol % (R)ꢀ8b, and 0.2
mmol KF in 1 mL toluene/H2O (1/1) at RT for 20 h under N2 atmosphere. Yields are of isolated products.
Enantioselectivity was determined by chiral HPLC. [b] With 3 mol % Rh(acac)(C2H4)2.
Additionally, we have performed NMR measurements7b to investigate the coordination mode of (R)ꢀ
8e to a Rh(I) cation (See Supporting Information for NMR spectra). Upon treatment of (R)ꢀ8e with
Rh(acac)(C2H4)2 (1.1 equiv) in CD2Cl2 at room temperature for 1 hour, the free phosphorus resonance
(31P NMR: δ 119.3 ppm) disappeared with the concomitant formation of new double peaks (δ 133.7
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13
ppm) with the large RhꢀP coupling (JRh−P = 309 Hz). In the H NMR and C spectra, obvious upfield
shifts of the olefinic protons to 5.32 and 4.85 ppm and the olefinic carbons to 58.0 and 57.0 ppm were
observed. All these NMR observations clearly disclose that the (R)ꢀ8e behaves as a Pꢀolefin bidentate
chelating ligand in Rh/(R)ꢀ8e complex.
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We next explored the origins of ligandꢀcontrolled enantioselectivity with DFT calculations at the
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M06/6ꢀ311+G(d,p)ꢀSDDꢀCPCM (toluene) // B3LYP/6ꢀ31G(d)ꢀLANL2DZ level (see Supporting
Information for computational details). Using Nꢀtosylimine (9a) as the model substrate, the
enantioselectivityꢀdetermining transition states for the C−C bond formation step between LnRhPh and
9a are located (Figure 2).12 For the optimal monophosphiteꢀolefin ligand (R)ꢀ8e, TS14, which leads to
the favorable adduct, is 3.0 kcal/mol more favorable than the competing TS15 (Figure 2a).13 This
computed enantioselectivity agrees well with the experimental observations (entry 11, Table 1). The
insertion barrier for TS14 is 13.1 kcal/mol, and that for TS15 is 16.1 kcal/mol, which are surmountable
under the experimental conditions (Figure S2). For the monophosphite ligand (R)ꢀ7a, our calculations
showed that the bisligation is essential to promote the insertion, and the insertion transition states with
only one monophosphite ligand coordination require unsurmountable barriers (Figure S3). TS16 is 0.6
kcal/mol less favorable comparing with TS17 (Figure 2b), which is in line with the reversed trend with
ligand (R)ꢀ7a in experiments (entry 1, Table 1).
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The conformational flexibility of the ligand leads the change of enantioselectivity. Topographic steric
map is applied to elucidate the steric environment of the LnRhPh moiety in the C−C bond formation
transition states (Figure 2).12 For (R)ꢀ8e, the bisꢀligation of phosphine and alkene creates a rigid steric
environment; the topographic steric maps of the LnRhPh moiety in both TS14 and TS15 indicate a
stericꢀdemanding first quadrant (red region), which corresponds to the naphthyl group. Therefore, the
stericꢀdemanding naphthyl group has steric repulsions with the tosyl group in TS15, leading to the
exceptional enantioselectivity. These steric repulsions are also reflected by the orientation of the
naphthyl group of the ligand in TS14 and TS15 (Figure S4). For (R)ꢀ7a, this monophosphite ligand can
rotate around the rhodiumꢀphosphine bond, and the steric environment of the corresponding LnRhPh
moiety is quite flexible. Figure 2b showed the steric environments of the LnRhPh moiety in TS16 and
TS17. Due to the ligand rotation, the stericꢀdemanding spiro backbone of (R)ꢀ7a can avoid the tosyl
group of Nꢀtosylimine in both transition states; TS16 has the stericꢀdemanding red region in the first
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quadrant, while TS17 has the corresponding region in the fourth quadrant. This flexibility of steric
environment results in the significantly diminished enantioselectivity of (R)ꢀ7a and the reversed trend.
To further support our mechanistic rationale that the steric repulsions between tosyl group and naphthyl
group in TS15 are the leading factors that control the enantioselectivity, additional calculations were
performed to clarify the explanation. By replacing the naphthyl group of the ligand with hydrogen, the
computed free energy difference between TS14 and TS15 decreases from +3.0 kcal/mol to ꢀ1.4 kcal/mol
(TS-S25 vs. TS-S26, Figure S6). In addition, similar change was observed when we removed both the
tosyl and naphthyl groups (TS-S27 vs. TS-S28, Figure S6). The optimized structures and relative Gibbs
free energies of the highꢀenergy conformers of the insertion transition states are included in the
Supporting Information (Figure S5).
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Conclusion
In summary, a new class of chiral spiro monophosphiteꢀolefin (SMPO) ligands based on the
hexamethylꢀ1,1’ꢀspiro biindane backbone has been developed. The optimal Pꢀolefin ligand could serve
as an elegant chiral bidentate ligand in the Rhꢀcatalyzed asymmetric 1,2ꢀaddition of organoboronic acids
to acyclic/cyclic aldimines with a broad range of substraes leading to chiral amines with high yields and
excellent enantioselectivities. It has been disclosed that SMPO ligands are capable of coordinating to a
rhodium(I) cation in the bidentate fashion at the phosphorus atom as well as at the olefinic double bond.
Detailed stereochemical models for enantioselective induction of Rh/Pꢀolefin catalyzed asymmetric
reactions were elucidated through DFT calculations, and the origins of the higher enantioselectivity of
phosphiteꢀolefin ligands are postulated.
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The Journal of Organic Chemistry
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Figure 2. DFTꢀcomputed enantioselectivityꢀdetermining transition states and topographic steric maps with (R)ꢀ8e and
(R)ꢀ7a.
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Experimental Section
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General information. All reactions were carried out in ovenꢀdried glassware with magnetic stirring.
All commercially available reagents were purchased and used without further purification, and all
solvents were dried and purified according to standard methods prior to use. NꢀTosylarylimines 910b, 14
and cyclic Nꢀsulfonyl aldimines 1215 were prepared according to the reported procedures. NMR
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spectrums were recorded on 400 NMR spectrometer at 400 MHz for H NMR, 100 MHz for 13C NMR,
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162 MHz for 31P. The chemical shifts were reported in CDCl3 or DMSOꢀd6 with tetramethylsilane
(TMS) as internal standard. The following abbreviations were used to describe peak patterns where
appropriate: br=broad, s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet. Coupling constants were
reported in Hertz (Hz). Infrared spectra were recorded on an ATRꢀFTIR spectrometer. HRMS were
obtained using EI ionization 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 excesses (ee) were
determined by chiral highꢀperformance liquid chromatography. HPLC analysis was performed using
Chiralcel columns (Chiralcel ODꢀH, ADꢀH, ICꢀ3, IFꢀ3 column).
Synthesis of 3,3,3',3',5,5'-Hexamethyl-2,2',3,3'-tetrahydro-1,1'-spirobi[indene]-6,6'-diol (1).8a A 500
mL round bottom flask was charged with Bisphenol C (BPC, 51.2 g, 0.2 mol) and methanesulfonic acid
(160 mL), and then the mixture was stirred at room temperature for 3 days. Additional methanesulfonic
acid (100 mL) was added to the reaction system at the forth day and the reaction was continued to stir
for another 2 days. The mixture was poured directly into the crushed ice and filtered. The filter cake was
washed sequentially with saturated solution of NaHCO3 and hot water. Then, the residue was
recrystallized with ethyl acetate/petroleum ether followed by ethanol/water and dried to afford 6, 6’ꢀ
o
1
HMSIOL (1) as a white solid (20.6 g, 92% yield). mp 249ꢀ250 C; H 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, 150.0, 144.5, 123.5, 122.9, 110.5, 59.4,
57.0, 43.1, 31.9, 30.1, 16.0; IR (film) γ = 3515, 2952, 2862, 1615, 1497, 1411, 1361, 1313, 1288, 1275,
1207, 1149, 1136, 1070, 1014, 886, 858, 758, 668 cmꢀ1; HRMS (EI, GCꢀTOF) m/z: [M+] Calcd for
C23H28O2 336.2089, found 336.2085.
Chiral resolution of 6, 6’-HMSIOL (1).
A solution of 1 (5.05 g, 15 mmol), triethylamine (9.6 mL, 69 mmol) and 4ꢀdimethylꢀaminopyridine
(DMAP) (183 mg, 1.5 mmol) in methylene chloride (50 mL) was treated over 30 minutes with (ꢀ)ꢀ
menthyl chloroformate (7.3 mL, 34.5 mmol). The resulting mixture was stirred at ambient temperature
for 1 h, then the reaction mixture was washed with 1M hydrochloric acid, saturated solution of brine.
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The organic phase was dried with anhydrous sodium sulfate and concentrated in vacuo to afford 2a and
2b as a mixture of diastereomeric diester (1:1). The diastereoisomer mixture of 2a and 2b was
recrystallized from hexane to provide 2b as a colorless solid (2.8 g, ＞99% d.r.). The mother liquor was
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concentrated in vacuo to provide a glassy solid, which was also recrystallized from hexane to give 2a as
a colorless solid (2.0 g, ＞99% d.r.). Furthermore cycling recrystallization of the resulting residue to
provide 2a (1.6 g) and 2b (1.0 g), respectively.
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(R)-3,3,3',3',5,5'-Hexamethyl-2,2',3,3'-tetrahydro-1,1'-spirobi[indene]-6,6'-diyl
bis((1R,2S,5R)-2-
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isopropyl-5-methylcyclohexyl) bis(carbonate) (2a). White solid, 3.6 g, 71% yield, mp 154ꢀ156 oC; [α]D
= ꢀ158.0 (c1.0, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 6.98 (s, 2H), 6.55 (s, 2H), 4.56 (m, 2H), 2.33 (d,
J = 13.1 Hz, 2H), 2.22 (m, 8H), 2.10 (d, J = 11.9 Hz, 2H), 2.03ꢀ1.92 (m, 2H), 1.75 – 1.64 (m, 4H), 1.52
– 1.39 (m, 4H), 1.36 (s, 6H), 1.32 (s, 6H), 1.08 (m, 4H), 0.91 (m, 14H), 0.79 (d, J = 7.0 Hz, 6H); 13C
NMR (101 MHz, CDCl3) δ 153.2 , 149.9, 149.2, 149.2, 128.7, 124.2, 117.1, 79.1, 59.4, 57.1, 47.0, 43.2
, 40.6, 34.1, 31.6, 31.4, 30.3, 26.2, 23.4, 22.0, 20.7, 16.4, 16.1; IR (film) γ= 2955, 2925, 2869, 1756,
1487, 1456, 1254, 1239 cmꢀ1; HRMS (ESI): m/z [M+Na]+ Calcd for C45H64O6Na 723.4601, found
723.4578.
(S)-3,3,3',3',5,5'-Hexamethyl-2,2',3,3'-tetrahydro-1,1'-spirobi[indene]-6,6'-diyl bis((1R,2S,5R) -2-
isopropyl-5-methylcyclohexyl) bis(carbonate) (2b). White solid, 3.8 g, 75% yield, mp 101ꢀ103 oC; [α]D
20
= ꢀ87.4 (c1.0, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 6.99 (s, 2H), 6.55 (s, 2H), 4.55 (m, 2H), 2.32 (d,
J = 13.1 Hz, 2H), 2.23 (d, J = 13.2 Hz, 2H), 2.20 (s, 6H), 2.12 (d, J = 11.8 Hz, 2H), 2.01 (m, 2H), 1.68
(d, J = 12.3 Hz, 4H), 1.53 – 1.39 (m, 4H), 1.36 (s, 6H), 1.32 (s, 6H), 1.16 – 0.97 (m, 4H), 0.91 (m,14H),
0.80 (s, 3H), 0.78 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 153.2, 149.9, 149.2, 128.8, 124.3, 117.2, 79.1,
59.5, 57.1, 47.0, 43.1, 40.6, 34.1, 31.6, 31.4, 30.3, 26.1, 23.3, 22.0, 20.7, 16.3, 16.2; IR (film) γ= 2955,
2927, 2869, 1755, 1486, 1456, 1254, 1239, 1159, 961 cmꢀ1; HRMS (ESI): m/z [M+Na]+ Calcd for
C45H64O6Na 723.4601, found 723.4590.
A solution of 2a (15.7 g, 22.5 mmol) and KOH (6.55 g, 117 mmol, 5.2 equiv.) in ethanol (200 mL)
was heated under reflux for 2 hours, then concentrated in vacuo. The resulting residue was dissolved in
methylene chloride (100 mL), then washed with 1M hydrochloric acid, saturated solution of brine, dried
with anhydrous sodium sulfate and concentrated in vacuo followed by flash chromatography to provide
(R)-1 (7.4 g) in 98 % yield, as a white solid, mp 210ꢀ212 oC, [α]D20 = +30.5 (c1.0, CH2Cl2).
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2b (1.5 g, 2.25 mmol) was also applied to the aboved procedure to give (S)ꢀ1 (0.74 g) in 98% yield,
as a white solid, mp 210ꢀ212 oC, [α]D20 = ꢀ30.4 (c1.0, CH2Cl2).
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Synthesis of (R)-6,6'-Dihydroxy-3,3,3',3',5,5'-hexamethyl-2,2',3,3'-tetrahydro-1,1'-spirobi[indene]-
7,7'-dicarbaldehyde [(R)-3]. (R)ꢀ1 (4.2 g, 12.5 mmol) was dissolved in trifluoroacetic acid (TFA, 150
mL) under nitrogen, and hexamethylenetetramine (HMTA, 10.5 g, 75 mmol) was added in one portion.
The yellow solution was refluxed overnight and glacial acetic acid (150 mL) was added the next day.
The solution then kept refluxing for 3 days. Until the starting diols were converted, 4 M HCl (150 mL)
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was added after cooling to 95 C, and the mixture was stirred overnight. Then after cooling to room
temperature, the mixture was poured into water and finally filtered to give the product (R)ꢀ3 as a yellow
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solid (4.2 g, 86 % yield). mp ＞300 C; [α]D = ꢀ131.0 (c1.0, CH2Cl2); H NMR (400 MHz, CDCl3) δ
12.01 (s, 2H), 9.57 (s, 2H), 7.20 (s, 2H), 2.57 (d, J = 13.5 Hz, 2H), 2.38 (d, J = 13.5 Hz, 2H), 2.26 (s,
6H), 1.37 (s, 6H), 1.35 (s, 6H); 13C NMR (100 MHz, CDCl3) δ194.7, 162.3, 149.6, 141.8, 132.6, 128.0,
113.7, 60.3, 57.8, 43.0, 32.0, 30.1, 15.6; IR (film) γ= 3379, 2966, 2925, 2876, 1636, 1604, 1468, 1393,
1384, 1273, 1162, 1092 cmꢀ1; HRMS (EI, GCꢀTOF) m/z: [M+] Calcd for C25H28O4 392.1988, found
392.1990.
Synthesis of (R)-7,7'-Diformyl-3,3,3',3',5,5'-hexamethyl-2,2',3,3'-tetrahydro-1,1'-spirobi[indene]-6,6'-
diyl bis(trifluoromethanesulfonate) [(R)-4]. To a solution of (R)ꢀ3 (3.92 g, 10 mmol) and pyridine (2.42
mL, 30 mmol) in methylene chloride (60 mL), triflic anhydride (4.21 mL, 25 mmol) was added
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dropwise at 0 C under a nitrogen atmosphere. The mixture was naturally raised to room temperature
and stirred overnight. The reaction was diluted with dichloromethane, washed with 5% HCl aqueous,
saturated solution of brine, saturated solution of NaHCO3, and saturated solution of brine, and dried
over anhydrous Na2SO4. After removal of the solvent, the residue was purified by flash chromatography
on a silica gel column (ethyl acetate/petroleum ether = 1/50) to obtain the product (R)ꢀ4 as a white solid
(6.24 g, 95% yield). mp 160ꢀ162 oC; [α]D20 = ꢀ158.7 (c1.0, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ9.79
(s, 2H), 7.35 (s, 2H), 2.51 (d, J = 12.8 Hz, 2H), 2.45 (s, 6H), 2.42 (d, J = 12.8 Hz, 2H), 1.50 (s, 6H),
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1.40 (s, 6H); C NMR (100 MHz, CDCl3) δ186.5, 153.5, 148.1, 146.2, 130.6, 130.0, 117.4(q, J = 320
Hz), 57.7, 56.5, 42.1, 31.4, 28.0, 15.8; IR (film) γ = 2962, 2870, 1704, 1565, 1455, 1423, 1405, 1215,
1183, 1140, 1048 cmꢀ1; HRMS (EI, GCꢀTOF) m/z: [M+] Calcd for C27H26O8S2F6 656.0973, found
656.0981.
Synthesis
of
(R)-3,3,3',3',5,5'-Hexamethyl-2,2',3,3'-tetrahydro-1,1'-spirobi[indene]-7,7'-
dicarbaldehyde [(R)-5]. Under nitrogen, to a solution of (R)ꢀ4 (6.56 g, 10 mmol), PdCl2(PPh3)2 (280
mg, 0.4 mmol), and 1,3ꢀbis (diphenylphosphino)propane (210 mg, 0.5 mmol) in DMF (100 mL),
triethylamine (17 mL, 120 mmol) was added dropwise at 0 oC followed by the addition of formic acid (3
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o
mL, 80 mmol). Then, the reaction mixture was raised to 80 C and reacted for 1.5 hours. After cooling
to room temperature, the resulting mixture was diluted with ethyl acetateand, and washed sequentially
with water, saturated solution of NaHCO3, and saturated solution of brine. The organic layer was dried
over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by flash
chromatography (ethyl acetate / petroleum ether = 1/30) to afford product (R)ꢀ5 as a yellow solid (3.44
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g, 96% yield). mp 220ꢀ222 C; [α]D = ꢀ181.3 (c1.0, CH2Cl2); H NMR (400 MHz, CDCl3) δ 9.56 (s,
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2H), 7.53 (s, 2H), 7.25 (s, 2H), 2.56 (d, J = 13.2 Hz, 2H), 2.43 (d, J = 13.4 Hz, 2H), 2.41 (s, 6H), 1.45
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(s, 6H), 1.40 (s, 6H); C NMR (100 MHz, CDCl3) δ 189.5, 152.4, 149.1, 137.2, 129.5, 128.4, 128.2,
58.8, 56.2, 42.4, 31.4, 28.6, 20.1; IR (film) γ = 3359, 2963, 2924, 2866, 1681, 1604, 1573, 1460, 1394,
1383, 1311, 1242, 1162cmꢀ1; HRMS (EI, GCꢀTOF) m/z: [M+] Calcd for C25H28O2 360.2089, found
360.2092.
Synthesis of (R)-3,3,3',3',5,5'-Hexamethyl-2,2',3,3'-tetrahydro-1,1'-spirobi[indene]-7,7'-diol [(R)-6].
Under nitrogen atmosphere, to a solution of (R)ꢀ5 (1.44 g, 4 mmol) in methylene chloride (150mL), mꢀ
chloroperbenzoic acid (mꢀCPBA) (3.2 g, 16 mmol, 85% active oxygen content) was added several
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portions at 0 C followed by the addition of trifluoroacetic acid (TFA) (0.6 mL, 8 mmol). The mixture
was naturally raised to room temperature and stirred overnight. The reaction solution was washed with
saturated aqueous solution of Na2SO3, saturated solution of NaHCO3, and brine, and dried over
anhydrous Na2SO4. After removal of the solvent, the residue was redissolved in 40mL methyl alcohol,
1M NaOH aqueous (16 mL, 16 mmol) was added dropwise at 0 oC. Then, the mixture was naturally
raised to room temperature and stirred overnight. After removal of the solvent, the residue was
redissolved in methylene chloride, acidified by 3M HCl aqueous, washed with saturated solution of
brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified
by flash chromatography (ethyl acetate / petroleum ether / glacial acetic acid= 5/100/1) to afford product
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(R)ꢀ6 as a white solid (1.14 g, 82% yield). mp 165ꢀ167 C; [α]D = ꢀ124.8 (c1.0, CH2Cl2); H NMR
(400 MHz, DMSOꢀd6) δ 6.63 (s, 2H), 6.50 (s, 2H), 4.41 (s, 2H), 2.35 (d, J = 13.4 Hz, 2H), 2.30 (m, 8H),
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1.38 (s, 6H), 1.33 (s, 6H); C NMR (100 MHz, DMSOꢀd6) δ 154.0, 152.4, 140.7, 127.1, 116.1, 115.4,
55.9, 53.4, 44.1, 31.9, 29.6, 21.5; IR (film) γ = 3520, 2955, 2925, 2862, 1618, 1585, 1469, 1455, 1447
cmꢀ1; HRMS (EI, GCꢀTOF) m/z: [M+] Calcd for C23H28O2 336.2089, found 336.2089.
General Procedure for Synthesis of Ligands (R)-7/(R)-8. At nitrogen atmosphere, to a solution of
PCl3 (0.25 mL, 0.5 mmol, 2.0 M solution in methylene chloride) in THF (10 mL), Et3N (155 ꢁL, 1.1
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mmol) was added dropwise at 0 C and cooled to ꢀ78 oC. A solution of (R)ꢀ6 (168 mg, 0.5 mmol) in 2
mL THF was added at ꢀ78 oC, the reaction mixture was stirred at this temperature for 2h, naturally raised
up to room temperature and stirred for another 1h. The mixture was cooled to ꢀ78 oC again, and treated
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with lithium phenolates prepared from phenols (0.6 mmol) and butyllithium (0.375 mL, 0.6 mmol, 1.6
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M solution in hexane) in THF (5 mL) at ꢀ30 C. The resulted mixture was warmed slowly to room
temperature and stirred overnight. The solvent was removed in vaccum and the residue was purified by
flash chromatography (ethyl acetate / petroleum ether = 1/100) to afford the corresponding product (R)ꢀ7
or (R)ꢀ8.
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Phenyl-[(R)-3,3,3',3',5,5'-hexamethyl-2,2',3,3'-tetrahydro-1,1'-spirobiindane-7,7'-diyl]-phosphite
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[(R)-7a]. 148 mg, 65% yield ; white solid, mp 73ꢀ75 C; [α]D20 = +163.3 (c1.0, CH2Cl2); 1H NMR (400
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MHz, CDCl3) δ7.38 – 7.27 (m, 2H), 7.11 (t, J = 7.4 Hz, 1H), 7.06 (m, 2H), 6.83 (s, 1H), 6.79 (s, 1H),
6.79 (s, 1H), 6.54 (s, 1H), 2.39 (d, J = 12.7 Hz, 2H), 2.36 (s, 3H), 2.28 (s, 3H), 2.05 (d, J = 12.5 Hz, 2H),
1.53 (s, 3H), 1.50 (s, 3H), 1.28 (s, 3H), 1.25 (s, 3H);13C NMR (100 MHz, CDCl3) δ 153.3, 153.3, 152.8,
151.4, 151.3, 143.1, 143.1, 141.5, 141.5, 138.8, 138.8, 138.1, 138.1, 137.0, 135.5, 135.5, 128.6, 122.7,
121.6, 121.4, 121.4, 119.6, 119.6, 119.0, 118.76, 118.7, 55.7, 55.3, 54.7, 41.9, 41.3, 31.3, 30.9, 29.2,
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29.0, 20.2, 20.1; P NMR (162 MHz, CDCl3) δ 118.94 ; IR (film) γ = 2959, 2916, 2856, 1613, 1586,
1487, 1474, 1452, 1414, 1362, 1321, 1308, 1291, 1261, 1231,1214, 1162cmꢀ1; HRMS (EI, GCꢀTOF)
m/z: [M+] Calcd for C29H31O3P 458.2011, found 458.2007.
4-Methoxyphenyl-[(R)-3,3,3',3',5,5'-hexamethyl-2,2',3,3'-tetrahydro-1,1'-spirobiindane-7,7'-diyl]-
phosphite [(R)-7b]). 175 mg, 72% yield ; white solid, mp 64ꢀ66 oC; [α]D20 = +145.5 (c 1.0, CH2Cl2); 1H
NMR (400 MHz, CDCl3) δ 6.97 (d, J = 8.9 Hz, 2H), 6.83 (d, J = 6.4 Hz, 2H), 6.82 (s, 1H), 6.80 (s, 1H),
6.77 (s, 1H), 6.57 (s, 1H), 3.79 (s, 3H), 2.38 (d, J = 12.6 Hz, 2H), 2.35 (s, 3H), 2.29 (s, 3H), 2.04 (d, J =
12.2 Hz, 2H), 1.53 (s, 3H), 1.50 (s, 3H), 1.27 (s, 3H), 1.25 (s, 3H); 13C NMR (100 MHz, CDCl3) δ154.8,
153.3, 153.3, 152.8, 144.9, 143.1, 141.6, 141.5, 138.8, 138.1, 137.0, 135.5, 121.6, 121.4, 121.4, 119.7,
119.6, 119.6, 119.5, 119.0, 113.6, 55.6, 55.3, 54.7, 54.6, 41.9, 41.3, 31.3, 31.0, 29.2, 29.0, 20.2, 20.1;
31P NMR (162 MHz, CDCl3) δ 119.32; IR (film) γ = 2959, 2920, 2860, 1611, 1581, 1568, 1502, 1474,
1465, 1450, 1442, 1412, 1360, 1317, 1308, 1289, 1246, 1229, 1201, 1165cmꢀ1; HRMS (EI, GCꢀTOF)
m/z: [M+] Calcd for C30H33O4P 488.2116, found 488.2115.
4-Trifluoromethylphenyl-[(R)-3,3,3',3',5,5'-hexamethyl-2,2',3,3'-tetrahydro-1,1'-spirobiindane-7,7'-
diyl]-phosphite [(R)-7c]. 186 mg, 71% yield; white solid, mp 49ꢀ51 oC; [α]D20 = +161.7 (c 1.0, CH2Cl2);
1H NMR (400 MHz, CDCl3) δ7.55 (d, J = 8.7 Hz, 2H), 7.09 (d, J = 8.4 Hz, 2H), 6.85 (s, 1H), 6.80 (s,
1H), 6.78 (s, 1H), 6.48 (s, 1H), 2.41 – 2.35 (m, 5H), 2.25 (s, 3H), 2.03 (dd, J = 12.5, 2.1 Hz, 2H), 1.53
(s, 3H), 1.50 (s, 3H), 1.27 (s, 3H), 1.26 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 154.2, 153.5, 153.0,
142.7, 142.7, 141.4, 141.3, 138.7, 138.3, 137.3, 135.4, 125.9(q, J = 4Hz), 124.8(q, J = 33Hz), 123.0(q, J
= 272Hz), 121.4, 121.3, 121.3, 119.9, 119.2, 118.9, 118.8, 55.7, 55.4, 54.8, 41.9, 41.4, 31.2, 31.0, 29.2,
29.0, 21.6, 20.2, 20.0, 13.1;31P NMR (162 MHz, CDCl3) δ 117.22; IR (film) γ = 2963, 2916, 2860,
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2357, 2331, 1611, 1583, 1512, 1472, 1444, 1414, 1360, 1321, 1263, 1229, 1169cmꢀ1; HRMS (EI, GCꢀ
TOF) m/z: [M+] Calcd for C30H30F3O3P 526.1885, found 526.1888.
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2-Naphthyl-[(R)-3,3,3',3',5,5'-hexamethyl-2,2',3,3'-tetrahydro-1,1'-spirobiindane-7,7'-diyl]-phosphite
[(R)-7d]. 203 mg, 80% yield; white solid, mp 100ꢀ102 oC; [α]D20 = +89.1 (c1.0, CH2Cl2); 1H NMR (400
MHz, CDCl3) δ7.79 (m, 3H), 7.46 (m, 3H), 7.19 (dd, J = 8.9, 2.3 Hz, 1H), 6.85 (s, 1H), 6.82 (s, 1H),
6.81 (s, 1H), 6.57 (s, 1H), 2.40 (d, J = 12.6 Hz, 2H), 2.37 (s, 3H), 2.26 (s, 3H), 2.06 (dd, J = 12.4, 3.7
Hz, 2H), 1.54 (s, 3H), 1.51 (s, 3H), 1.29 (s, 3H), 1.26 (s, 3H); 13C NMR (100 MHz, CDCl3) δ153.4,
153.3, 152.9, 149.1, 149.1, 143.1, 143.0, 141.6, 141.5, 138.8, 138.8, 138.2, 138.2, 137.1, 135.5, 133.0,
129.3, 128.7, 126.7, 126.2, 125.5, 123.8, 121.5, 121.5, 121.4, 119.7, 119.7, 119.6, 119.1, 114.3,
114.2,63.4, 55.7, 55.4, 54.7, 41.9, 41.4, 31.3, 30.9, 29.3, 29.0, 24.3, 20.2, 20.1; 31P NMR (162 MHz,
CDCl3) δ 118.64 ; IR (film) γ= 2959, 2916, 2860, 1631, 1613, 1598, 1577, 1508, 1461, 1409, 1360,
1319, 1308, 1289, 1263, 1248, 1231, 1212, 1167cmꢀ1; HRMS (EI, GCꢀTOF) m/z: [M+] Calcd for
C33H33O3P 508.2167, found 508.2166.
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(E)-2,4,4,7,7,9-Hexamethyl-12-(2-styrylphenoxy)-4,5,6,7-tetrahydrodiindeno[7,1-de:1',7'-
o
20
fg][1,3,2]dioxaphosphocine [(R)-8a]. 204 mg, 73% yield; white solid, mp 60ꢀ62 C; [α]D = +318
(c0.1, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ7.71 – 7.64 (m, 1H), 7.39 (d, J = 7.3 Hz, 2H), 7.32 (t, J =
7.5 Hz, 2H), 7.28 – 7.18 (m, 3H), 7.15 – 7.03 (m, 3H), 6.83 (s, 1H), 6.77 (s, 1H), 6.74 (s, 1H), 6.51 (s,
1H), 2.40 (dd, J = 12.5, 10.4 Hz, 2H), 2.33 (s, 3H), 2.14 – 1.98 (m, 5H), 1.53 (s, 3H), 1.52 (s, 3H), 1.32
13
(s, 3H), 1.25 (s, 3H); C NMR (100 MHz, CDCl3) δ 153.3, 152.7, 149.0, 148.9, 143.1, 143.0, 141.6,
141.6, 138.7, 138.7, 138.2, 138.1, 137.3, 136.5, 135.6, 128.4, 127.7, 127.5, 127.4, 126.5, 125.6, 125.3,
122.7, 121.6, 121.4, 121.3, 119.6, 119.1, 117.9, 117.7, 55.6, 55.4, 54.9, 41.9, 41.4, 31.3, 31.2, 29.1,
31
29.1, 20.1, 20.0; P NMR (162 MHz, CDCl3) δ 119.16; IR (film) γ = 2963, 2916, 2860, 1616, 1596,
1573, 1485, 1450, 1412, 1360, 1321, 1308, 1289, 1261, 1229, 1208, 1182, 1165cmꢀ1; HRMS (EI, GCꢀ
TOF) m/z: [M+] Calcd for C37H37O3P 560.2480, found 560.2476.
(E)-12-(2-(4-Methoxystyryl)phenoxy)-2,4,4,7,7,9-hexamethyl-4,5,6,7-tetrahydrodiindeno[7,1-de:1',7'-
o
20
fg][1,3,2]dioxaphosphocine [(R)-8b]. 238 mg, 81% yield ; white solid, mp 63ꢀ65 C; [α]D = +140 (c
1
0.1, CH2Cl2); H NMR (400 MHz, CDCl3) δ 7.65 (m, 1H), 7.37 – 7.29 (m, 2H), 7.25 – 7.13 (m, 2H),
7.10 (s, 1H), 6.97 (d, J = 3.7 Hz, 2H), 6.90 – 6.84 (m, 2H), 6.83 (s, 1H), 6.78 (s, 1H), 6.73 (s, 1H), 6.51
(s, 1H), 3.83 (s, 3H), 2.40 (dd, J = 12.5, 10.7 Hz, 2H), 2.33 (s, 3H), 2.13 – 2.00 (m, 5H), 1.53 (s, 3H),
1.52 (s, 3H), 1.33 (s, 3H), 1.25 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.2, 153.3, 152.7, 148.8,
143.1, 141.6, 138.7, 138.1, 137.3, 135.6, 129.4, 128.0, 127.0, 125.0, 122.7, 121.6, 121.4, 119.5, 119.1,
117.9, 112.9, 55.6, 54.9, 54.3, 41.9, 41.4, 31.3, 29.1, 20.1; 31P NMR (162 MHz, CDCl3) δ 119.28 ; IR
(film) γ = 2959, 2916, 2860, 2361, 2335, 2241, 1607, 1579, 1512, 1480, 1450, 1412, 1360, 1319, 1306,
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1248, 1227, 1175cmꢀ1; HRMS (EI, GCꢀTOF) m/z: [M+] Calcd for C38H39O4P 590.2586, found
590.2592.
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(E)-2,4,4,7,7,9-Hexamethyl-12-(2-(4-(trifluoromethyl)styryl)phenoxy)-4,5,6,7-tetrahydrodiindeno[7,1-
5
6
o
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de:1',7'-fg][1,3,2]dioxaphosphocine [(R)-8c]. 241 mg, 77% yield ; white solid, mp 68ꢀ70 C; [α]D
=
+254 (c 0.1, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ7.67 (d, J = 7.5 Hz, 1H), 7.56 (d, J = 8.3 Hz, 2H),
7.45 (d, J = 8.2 Hz, 2H), 7.33 – 7.22 (m, 2H), 7.18 – 7.10 (m, 2H), 7.03 (d, J = 16.5 Hz, 1H), 6.84 (s,
1H), 6.76 (s, 1H), 6.72 (s, 1H), 6.46 (s, 1H), 2.40 (t, J = 12.9 Hz, 2H), 2.34 (s, 3H), 2.14 – 1.99 (m, 5H),
1.53 (s, 3H), 1.53 (s, 3H), 1.31 (s, 3H), 1.26 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 153.4, 152.8, 149.3,
143.0, 141.6, 140.0, 138.7, 138.2, 137.3, 135.7, 128.1(q, J = 32 Hz), 126.9, 126.7, 125.7, 125.5, 124.4,
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124.2, 123.2(q, J = 272 Hz), 122.7, 121.5, 119.7, 117.9, 55.6, 54.9, 41.9, 41.4, 31.3, 29.3, 29.1, 20.1; P
NMR (162 MHz, CDCl3) δ 119.02; IR (film) γ = 2959, 2925, 2860, 1613, 1573, 1485, 1450, 1414,
1362, 1323, 1261, 1231, 1165 cmꢀ1; HRMS (EI, GCꢀTOF) m/z: [M+] Calcd for C38H36F3O3P 628.2354,
found 628.2354.
(E)-2,4,4,7,7,9-Hexamethyl-12-(2-(2-(naphthalen-1-yl)vinyl)phenoxy)-4,5,6,7-tetrahydrodiindeno[7,1-
o
20
de:1',7'-fg][1,3,2]dioxaphosphocine [(R)-8d]. 207 mg, 68% yield ; white solid, mp 67ꢀ69 C; [α]D
=
+217 (c 0.1, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 7.6 Hz, 1H), 7.82 (m, 4H), 7.60 (d, J =
7.1 Hz, 1H), 7.55 – 7.41 (m, 3H), 7.25 (d, J = 5.1 Hz, 2H), 7.20 – 7.10 (m, 2H), 6.82 (s, 1H), 6.72 (s,
1H), 6.70 (s, 1H), 6.52 (s, 1H), 2.37 (dd, J = 12.8, 3.6 Hz, 2H), 2.30 (s, 3H), 2.11 – 1.96 (m, 5H), 1.52
(s, 3H), 1.48 (s, 3H), 1.24 (s, 3H), 1.20 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 153.3, 152.7, 149.1,
143.0, 141.6, 138.7, 138.1, 137.3, 135.5, 134.1, 132.6, 130.4, 128.0, 127.6, 127.5, 126.9, 125.8, 125.6,
125.0, 124.7, 122.8, 121.5, 119.5, 119.1, 118.1, 117.9, 63.4, 55.5,54.9, 41.9, 41.3, 31.2, 29.3, 24.3, 20.1;
31P NMR (162 MHz, CDCl3) δ 119.12; IR (film) γ = 2959, 2916, 2860, 1609, 1575, 1510, 1482, 1450,
1414, 1360, 1319, 1308, 1287, 1259, 1231, 1223, 1186, 1165 cmꢀ1; HRMS (EI, GCꢀTOF) m/z: [M+]
Calcd for C41H39O3P 610.2637, found 610.2632.
(E)-2,4,4,7,7,9-Hexamethyl-12-(2-(2-(naphthalen-2-yl)vinyl)phenoxy)-4,5,6,7-tetrahydrodiindeno[7,1-
o
20
de:1',7'-fg][1,3,2]dioxaphosphocine [(R)-8e]. 222 mg, 73% yield ; white solid, mp 91ꢀ93 C; [α]D
=
+285 (c 0.1, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ7.86 – 7.71 (m, 5H), 7.59 (m, 1H), 7.51 – 7.40 (m,
2H), 7.30 – 7.19 (m, 4H), 7.18 – 7.07 (m, 1H), 6.83 (s, 1H), 6.78 (s, 1H), 6.75 (s, 1H), 6.54 (s, 1H), 2.41
(t, J = 12.9 Hz, 2H), 2.31 (s, 3H), 2.15 – 2.01 (m, 5H), 1.54 (s, 3H), 1.53 (s, 3H), 1.35 (s, 3H), 1.26 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 153.3, 152.7, 149.0, 148.9, 143.1, 143.0, 141.6, 141.6, 138.7,
138.7, 138.2, 138.1, 137.3, 136.5, 135.6, 128.4, 127.7, 127.4, 127.4, 126.5, 125.6, 125.3, 122.7, 121.6,
121.4, 121.3, 119.6, 119.1, 117.9, 117.7, 55.6, 55.4, 54.9, 41.9, 41.4, 31.3, 31.2, 29.1, 29.1, 20.1, 20.0;
31P NMR (162 MHz, CDCl3) δ 119.17; IR (film) γ = 2963, 2920, 2860, 1613, 1596, 1570, 1478, 1450,
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1414, 1362, 1319, 1308, 1289, 1259, 1229, 1201, 1182, 1162cmꢀ1; HRMS (EI, GCꢀTOF) m/z: [M+]
Calcd for C41H39O3P 610.2637, found 610.2642.
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(E)-12-(2-(2-([1,1'-Biphenyl]-4-yl)vinyl)phenoxy)-2,4,4,7,7,9-hexamethyl-4,5,6,7-
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9
tetrahydrodiindeno[7,1-de:1',7'-fg][1,3,2]dioxaphosphocine [(R)-8f]. 219 mg, 69% yield ; white solid,
mp 78ꢀ80 oC; [α]D20 = +114 (c 0.1, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ7.72 – 7.66 (m, 1H), 7.66 –
7.60 (m, 2H), 7.57 (d, J = 8.3 Hz, 2H), 7.45 (m, 4H), 7.35 (m, 1H), 7.28 – 7.19 (m, 2H), 7.18 – 7.02 (m,
3H), 6.83 (s, 1H), 6.79 (s, 1H), 6.74 (s, 1H), 6.52 (s, 1H), 2.40 (t, J = 12.2 Hz, 2H), 2.33 (s, 3H), 2.16 –
2.00 (m, 5H), 1.53 (s, 3H), 1.53 (s, 3H), 1.34 (s, 3H), 1.26 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
153.3, 152.7, 149.0, 143.1, 141.6, 139.7, 139.2, 138.7, 138.2, 137.4, 135.6, 127.9, 127.4, 126.3, 126.1,
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125.9, 125.3, 122.7, 121.6, 121.4,119.6, 119.1, 118.0, 117.8, 55.6, 54.9, 41.9, 41.4, 31.3, 29.3, 20.1; P
NMR (162 MHz, CDCl3) δ 119.20; IR (film) γ = 2959, 2920, 2860, 1613, 1596, 1573, 1519, 1487,
1450, 1409, 1360, 1317, 1308, 1289, 1261, 1231, 1210, 1182, 1165 cmꢀ1; HRMS (EI, GCꢀTOF) m/z:
[M+] Calcd for C43H41O3P 636.2793, found 636.2796.
General Procedure for Asymmetric Arylation of N-Tosylarylimines. Under a nitrogen
atmosphere, Rh(acac)(C2H4)2 (0.6 mg, 1.5 ꢁmol), and 8e (0.9 mg, 1.5 ꢁmol) were dissolved in toluene
(0.5 mL) in a dry schlenk tube. The mixture was stirred at room temperature for 1 h.Then, aldimine 9
(0.05 mmol), ArB(OH)2 (0.1 mmol), KF (0.2 mmol) and water (0.5 mL) were added sequentially and the
o
reaction mixture was stirred at 35 C for 20 h. The mixture was cooled to room temperature and
concentrated under reduced pressure, and then it was purified by flash chromatography on silica gel
(ethyl acetate/petroleum ether = 1/8) to afford the corresponding product 11.
(R)-N-((4-Chlorophenyl)(phenyl)methyl)-4-methylbenzenesulfonamide (11a).10d 16 mg, 85% yield;
white solid; mp 122ꢀ124 °C; 99% ee; HPLC analysis: Chiralpak ODꢀH (hexane/iꢀPrOH = 93/7, 0.8
20
mL/min, 230 nm), tR (minor) 21.899 min, tR (major) 30.665 min; [α]D = +28.5 (c 0.23, CH2Cl2); 1H
NMR (400 MHz, CDCl3) δ 7.55 (d, J = 8.3 Hz, 2H), 7.21 (m, 3H), 7.16 (m, 4H), 7.09 – 7.01 (m, 4H),
5.53 (d, J = 7.1 Hz, 1H), 5.18ꢀ5.16 (m, 1H), 2.39 (s, 3H); 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; IR (film) γ = 3271,
3063, 3031, 2923, 2871, 2255, 1911, 1806, 1598, 1491 cmꢀ1; HRMS (ESIꢀTOF) m/z: [ MꢀH]ꢀ Calcd for
C20H17ClNO2S 370.0669, found 370.0663.
(S)-N-((4-Chlorophenyl)(phenyl)methyl)-4-methylbenzenesulfonamide (11a’).10d 14 mg, 75% yield;
white solid; mp 121ꢀ123 °C; 99% ee; HPLC analysis: Chiralpak ODꢀH (hexane/iꢀPrOH = 93/7, 0.8
mL/min, 230 nm), tR (major) 21.236 min, tR (minor) 31.081 min;[α]D20 = ꢀ91.7 (c 0.07, CH2Cl2).
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(R)-N-((4-Bromophenyl)(phenyl)methyl)-4-methylbenzenesulfonamide (11b).10d 17 mg, 82% yield;
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3
4
white solid; mp 115ꢀ117 °C; 98% ee; HPLC analysis: Chiralpak ODꢀH (hexane/iꢀPrOH = 80/20, 0.6
20
mL/min, 230 nm), tR (minor) 13.757 min, tR (major) 18.635 min; [α]D = +32.7 (c 0.28, CH2Cl2); 1H
5
6
7
8
NMR (400 MHz, CDCl3) δ 7.54 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.5 Hz, 2H), 7.25 – 7.19 (m, 3H), 7.15
(d, J = 8.1 Hz, 2H), 7.08 – 7.02 (m, 2H), 7.00 (d, J = 8.4 Hz, 2H), 5.51 (d, J = 7.1 Hz, 1H), 5.19 (d, J =
7.1 Hz, 1H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 163.3, 160.9, 143.4, 140.32, 137.3, 136.3,
129.4, 129.2, 129.1, 128.7, 127.8, 127.3, 127.2, 115.5, 115.3, 60.7, 21.5; IR (film) γ = 3269, 3058, 3028,
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2925, 2865, 1890, 1601, 1506, 1491 cmꢀ1; HRMS (ESIꢀTOF) m/z:
[M+Na]+ Calcd for
C20H18BrNO2SNa 438.0140, found 438.0144.
(S)-N-((4-Bromophenyl)(phenyl)methyl)-4-methylbenzenesulfonamide (11b’).10d 15 mg, 72% yield;
white solid; mp 115ꢀ117 °C; 99% ee; HPLC analysis: Chiralpak ODꢀH (hexane/iꢀPrOH = 80/20, 0.6
mL/min, 230nm), tR (major) 13.402 min, tR (minor) 18.244 min; [α]D20 = ꢀ128.8 (c 0.07, CH2Cl2).
(R)-N-((4-Fluorophenyl)(phenyl)methyl)-4-methylbenzenesulfonamide (11c).10f 14 mg, 81% yield;
white solid; mp 116ꢀ117 °C; 98% ee; HPLC analysis: Chiralpak ODꢀH (hexane/iꢀPrOH = 85/15, 0.8
mL/min, 230 nm), tR (minor) 11.156 min, tR (major) 13.678 min; [α]D = ꢀ70.1 (c 0.05, CH2Cl2); 1H
20
NMR (400 MHz, CDCl3) δ 7.55 (d, J = 8.3 Hz, 2H), 7.22ꢀ7.20 (m, 3H), 7.15 (d, J = 8.1 Hz, 2H), 7.10ꢀ
7.05 (m, 4H), 6.91ꢀ6.87 (m, 2H), 5.55 (d, J = 7.1 Hz, 1H), 5.20 (d, J = 7.0 Hz, 1H), 2.38 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 159.0, 143.1, 140.7, 137.4, 132.8, 129.3, 128.6, 128.5, 127.5, 127.3, 127.2,
113.9, 60.8, 55.3, 21.5; IR (film): γ = 3276, 3062, 3030, 3004, 2954, 2930, 2836, 1610, 1586, 1512,
1495 cmꢀ1; HRMS (ESI) m/z: [M+Na]+ Calcd for C20H18FNO2SNa 378.0940, found 378.0948.
(S)-N-((4-Fluorophenyl)(phenyl)methyl)-4-methylbenzenesulfonamide (11c’).10c 11 mg, 65% yield;
white solid; mp 117ꢀ118°C; 98% ee; HPLC analysis: Chiralpak ODꢀH (hexane/iꢀPrOH = 85/15, 0.8
mL/min, 230 nm), tR (major) 10.973 min, tR (minor) 13.86 min; [α]D20 = +86.7 (c 0.04, CH2Cl2).
(R)-4-Methyl-N-(phenyl(4-(trifluoromethyl)phenyl)methyl)benzenesulfonamide (11d).10b 17 mg, 83%
yield; white solid; mp 124ꢀ125°C; 96% ee; HPLC analysis: Chiralpak ODꢀH (hexane/iꢀPrOH = 85/15,
0.8 mL/min, 230 nm), tR (minor) 10.902 min, tR (major) 16.783 min; [α]D20 = ꢀ32.4 (c 0.23, CH2Cl2); 1H
NMR (400 MHz, CDCl3) δ 7.53 (d, J = 8.3 Hz, 2H), 7.44 (d, J = 8.2 Hz, 2H), 7.29 – 7.20 (m, 5H), 7.12
(d, J = 8.0 Hz, 2H), 7.05 (m, 2H), 5.61 (d, J = 7.2 Hz, 1H), 5.42 (s, 1H), 2.37 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 144.3, 143.6, 139.7, 137.0, 129.7(q, J = 32 Hz), 129.4, 128.9, 128.1, 127.8, 127.3,
127.2, 125.4(q, J = 4 Hz), 61.0, 21.4; IR (film) γ = 3273, 3065, 3033, 2927, 2872, 1620, 1599, 1494,
1452, 1429, 1326, 1291, 1162, 1124 cmꢀ1; HRMS (ESIꢀTOF)m/z: [MꢀH]ꢀ Calcd for C21H17F3NO2S
404.0932, found 404.0938.
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(S)-4-Methyl-N-(phenyl(4-(trifluoromethyl)phenyl)methyl)benzenesulfonamide (11d’).10b 15 mg, 73%
yield; white solid; mp 123ꢀ124 °C; 98% ee; HPLC analysis: Chiralpak ODꢀH (hexane/iꢀPrOH = 85/15,
0.8 mL/min, 230 nm), tR (major) 11.049 min, tR (minor) 17.464 min; [α]D20 = +147.1 (c 0.05, CH2Cl2).
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(R)-4-Methyl-N-(phenyl(p-tolyl)methyl)benzenesulfonamide (11e).10f 13 mg, 77% yield; white solid;
mp 115ꢀ116 °C; 97% ee; HPLC analysis: Chiralpak ODꢀH (hexane/iꢀPrOH = 85/15, 0.8 mL/min, 230
nm), tR (minor) 9.782 min, tR (major) 13.220 min; [α]D20 = +40.5 (c 0.32, CH2Cl2); 1H NMR (400 MHz,
CDCl3) δ 7.56 (d, J = 8.3 Hz, 2H), 7.23 – 7.17 (m, 3H), 7.13 (d, J = 8.0 Hz, 2H), 7.12 – 7.08 (m, 2H),
7.01 (d, J = 8.1 Hz, 2H), 6.97 (d, J = 8.1 Hz, 2H), 5.52 (d, J = 7.0 Hz, 1H), 5.08 (d, J = 7.0 Hz, 1H), 2.38
(s, 3H), 2.28 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 143.2, 140.7, 137.6, 137.4, 129.3, 129.2, 128.5,
127.5, 127.3, 127.3, 127.2, 61.1, 21.5, 21.0; IR (film) γ= 3264, 3085, 3059, 3030, 2951, 2922, 2863,
1599, 1512, 1493, 1448, 1433 cmꢀ1; HRMS (ESIꢀTOF) m/z: [MꢀH]ꢀ Calcd for C21H20NO2S 350.1215,
found 350.1220.
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(S)-4-Methyl-N-(phenyl(p-tolyl)methyl)benzenesulfonamide (11e’). 11 mg, 62% yield; white solid;
mp 116ꢀ117 °C; 95% ee; HPLC analysis: Chiralpak ODꢀH (hexane/iꢀPrOH = 85/15, 0.8 mL/min, 230
nm), tR (major) 9.797 min, tR (minor) 13.419 min; [α]D20 = ꢀ314 (c 0.04, CH2Cl2).
(R)-N-((4-Methoxyphenyl)(phenyl)methyl)-4-methylbenzenesulfonamide (11f).10d 13 mg, 72% yield;
white solid; mp 127ꢀ129 °C; 99% ee; HPLC analysis: Chiralpak ODꢀH (hexane/iꢀPrOH = 85/15, 0.8
mL/min, 230 nm), tR (minor) 14.027 min, tR (major) 21.505 min; [α]D = +19.7 (c 1.0, CH2Cl2); 1H
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NMR (400 MHz, CDCl3) δ7.56 (d, J = 8.3 Hz, 2H), 7.21ꢀ7.19 (m, 3H), 7.17 – 7.07 (m, 4H), 7.02 – 6.96
(m, 2H), 6.77 – 6.70 (m, 2H), 5.51 (d, J = 7.0 Hz, 1H), 5.10 (d, J = 6.9 Hz, 1H), 3.75 (s, 3H), 2.38 (s,
13
3H); C NMR (100 MHz, CDCl3) δ 143.2, 140.2, 137.2, 135.5, 134.0, 130.4, 129.3, 128.9, 128.6,
127.6, 127.5, 127.2, 126.6, 126.1, 125.7, 125.1, 123.4, 58.5, 21.5; IR (film) γ= 3251, 3041, 2922, 2853,
1597, 1507, 1493 cmꢀ1; HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd for C21H21NO3SNa 390.1140, found
390.1142.
(S)-N-((4-Methoxyphenyl)(phenyl)methyl)-4-methylbenzenesulfonamide (11f’).10d 11 mg, 61% yield;
white solid; mp 127ꢀ128°C; 96% ee; HPLC analysis: Chiralpak ODꢀH (hexane/iꢀPrOH = 85/15, 0.8
mL/min, 230 nm), tR (major) 13.811 min, tR (minor) 21.782 min; [α]D20 = ꢀ62.7 (c 0.27, CH2Cl2).
(R)-N-((2-Chlorophenyl)(phenyl)methyl)-4-methylbenzenesulfonamide (11g).10d 15 mg, 82% yield;
white solid; mp 165ꢀ167 °C; 99% ee; HPLC analysis: Chiralpak ADꢀH (hexane/iꢀPrOH = 90/10, 0.8
20
mL/min, 230 nm), tR (minor) 23.301 min, tR (major) 26.716 min; [α]D = ꢀ21.7 (c 0.56, CH2Cl2); 1H
NMR (400 MHz, CDCl3) δ 7.61 (d, J = 8.3 Hz, 2H), 7.35ꢀ7.32(m, 1H), 7.25ꢀ7.19 (m, 4H), 7.18ꢀ7.12 (m,
13
4H), 7.08ꢀ7.06 (m, 2H), 5.91 (d, J = 7.2 Hz, 1H), 5.35 (s, 1H), 2.37 (s, 3H); C NMR (100 MHz,
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CDCl3) δ 143.4, 139.3, 137.5, 137.0, 132.8, 129.9, 129.4, 129.3, 128.8, 128.7, 127.8, 127.3, 127.2,
127.0, 58.6, 21.5; IR (film) γ = 3321, 3063, 3030, 2974, 2924, 1596, 1489, 1471 cmꢀ1; HRMS (ESIꢀ
TOF) m/z: [MꢀH]ꢀ Calcd for C20H17ClNO2S 370.0669, found 370.0670.
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(R)-N-((2-Bromophenyl)(phenyl)methyl)-4-methylbenzenesulfonamide (11h).10c 16 mg, 77% yield;
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white solid; mp 168ꢀ171°C; 98% ee; HPLC analysis: Chiralpak ADꢀH (hexane/iꢀPrOH = 90/10, 0.8
20
mL/min, 230 nm), tR (minor) 24.922 min, tR (major) 27.547 min; [α]D = ꢀ25.7 (c 0.52, CH2Cl2); 1H
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NMR (400 MHz, CDCl3) δ 7.63 (d, J = 8.3 Hz, 2H), 7.43 (d, J = 7.9 Hz, 1H), 7.37ꢀ7.35 (m, 1H), 7.25ꢀ
7.14 (m, 6H), 7.10ꢀ7.03 (m, 3H), 5.91 (d, J = 6.9 Hz, 1H), 5.30 (s, 1H), 2.38 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 143.4, 139.3, 139.0, 136.9, 133.2, 129.6, 129.5, 129.1, 128.7, 127.9, 127.6, 127.4,
127.3, 123.1, 60.6, 21.5; IR (film) γ = 3306, 3063, 3029, 2974, 2924, 2897, 1597, 1494, 1470, 1454 cmꢀ
1; HRMS (ESI) m/z: [MꢀH]ꢀ Calcd for C20H17BrNO2S 414.0164, found 414.0164.
(R)-4-Methyl-N-(phenyl(o-tolyl)methyl)benzenesulfonamide (11i).10c 13 mg, 74% yield; white solid;
mp 134ꢀ136 °C; 98% ee; HPLC analysis: Chiralpak ODꢀH (hexane/iꢀPrOH = 85/15, 0.8 mL/min,
230nm), tR (major) 8.178 min, tR (minor) 10.338 min; [α]D = ꢀ130.1 (c 0.07, CH2Cl2); 1H NMR (400
20
MHz, CDCl3) δ 7.55 (d, J = 8.2 Hz, 2H), 7.22ꢀ7.17 (m, 3H), 7.16ꢀ7.09 (m, 4H), 7.07ꢀ7.05 (m, 4H), 5.79
(d, J = 6.9 Hz, 1H), 5.03 (d, J = 6.9 Hz, 1H), 2.37 (s, 3H), 2.15 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
143.2, 140.0, 138.2, 137.4, 135.5, 130.7, 129.3, 128.6, 127.6, 127.5, 127.2, 127.1, 126.2, 58.1, 21.5,
19.4; IR (film) γ = 3280, 3062, 3028, 2954, 2923, 2869, 1599, 1494 cmꢀ1; HRMS (ESIꢀTOF) m/z: [Mꢀ
H]ꢀ Calcd for C21H20NO2S 350.1215, found 350.1218.
(R)-N-((2-Methoxyphenyl)(phenyl)methyl)-4-methylbenzenesulfonamide (11j).10c 13 mg, 72% yield;
white solid; mp 124ꢀ126 °C; 99% ee; HPLC analysis: Chiralpak ODꢀH (hexane/iꢀPrOH = 90/10, 0.8
20
mL/min, 230nm), tR (major) 14.384 min, tR (minor) 17.569 min; [α]D = +216.8 (c 0.07, CH2Cl2); 1H
NMR (400 MHz, CDCl3) δ 7.51 (d, J = 8.3 Hz, 2H), 7.24 – 7.12 (m, 6H), 7.04 (d, J = 8.1 Hz, 2H), 6.98
– 6.96 (m, 1H), 6.82 – 6.74 (m, 1H), 6.67 (d, J = 8.2 Hz, 1H), 5.81 (d, J = 9.2 Hz, 1H), 5.65 (d, J = 9.2
Hz, 1H), 3.59 (s, 3H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 155.8, 142.3, 140.1, 137.0, 129.1,
128.5, 128.4, 127.6, 127.1, 126.6, 126.5, 126.3, 120.1, 110.6, 58.5, 54.7, 20.9; IR (film) γ = 3286, 3063,
3029, 2939, 2837, 1600, 1494 cmꢀ1; HRMS (ESIꢀTOF) m/z: [MꢀH]ꢀ Calcd for C21H20NO3S 366.1164,
found 366.1168.
(R)-4-Methyl-N-(naphthalen-1-yl(phenyl)methyl)benzenesulfonamide (11k).10d 15 mg, 75% yield;
white solid; mp 174ꢀ176 °C; 98% ee; HPLC analysis: Chiralpak ODꢀH (hexane/iꢀPrOH = 85/15, 0.8
20
mL/min, 230 nm), tR (major) 20.424 min, tR (minor) 25.569 min; [α]D = +40.2 (c 0.24, CH2Cl2); 1H
NMR (400 MHz, CDCl3) δ 7.81 (t, J = 7.3 Hz, 2H), 7.73 (d, J = 7.9 Hz, 1H), 7.51 (d, J = 8.2 Hz, 2H),
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7.47 – 7.35 (m, 2H), 7.32 – 7.22 (m, 2H), 7.22 – 7.17 (m, 3H), 7.17 – 7.11 (m, 2H), 7.06 (d, J = 8.2 Hz,
2H), 6.31 (d, J = 7.1 Hz, 1H), 5.17 (d, J = 7.0 Hz, 1H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
143.5, 140.0, 139.5, 137.1, 131.6, 129.4, 129.1, 128.8, 127.9, 127.3, 127.2, 121.6, 60.8, 21.5; IR (film) γ
= 3273, 3062, 3030, 2922, 2870, 1598, 1487 cmꢀ1; HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd for
C24H21NO2SNa 410.1191, found 410.1185.
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(R)-4-Methyl-N-(phenyl(thiophen-2-yl)methyl)benzenesulfonamide (11l).10d 11 mg, 65% yield; white
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solid; mp 131ꢀ132°C; 97% ee; HPLC analysis: Chiralpak ODꢀH (hexane/iꢀPrOH = 90/10, 0.6 mL/min,
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230 nm), tR (minor) 20.599 min, tR (major) 30.087 min; [α]D = +4.7 (c 0.23, CH2Cl2); 1H NMR (400
MHz, CDCl3) δ7.58 (d, J = 8.3 Hz, 2H), 7.25 – 7.21 (m, 3H), 7.20 – 7.10 (m, 5H), 6.84 – 6.82 (m, 1H),
6.67 (d, J = 3.5 Hz, 1H), 5.79 (d, J = 7.4 Hz, 1H), 5.23 (s, 1H), 2.38 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 144.8, 143.3, 140.1, 137.3, 129.4, 128.6, 128.0, 127.2, 127.1, 126.8, 126.2, 125.8, 57.4, 21.5;
IR (film) γ = 3264, 3065, 2968, 2924, 2872, 1654, 1597 cmꢀ1; HRMS (ESIꢀTOF) m/z: [MꢀH]ꢀ Calcd for
C18H16NO2S2 342.0623, found 342.0621.
(R)-4-(((4-Chlorophenyl)(phenyl)methyl)amino)-3-nitrobenzenesulfonic acid (11m).10f 8 mg, 37%
yield; white solid; mp 158ꢀ160°C; 97% ee; HPLC analysis: Chiralpak ODꢀH (hexane/iꢀPrOH = 80/20,
0.8 mL/min, 230nm), tR (minor) 17.390 min, tR (major) 31.308 min; [α]D = ꢀ7.4 (c 0.27, CH2Cl2); 1H
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NMR (600 MHz, acetoneꢀd6) δ 8.20 (d, J = 7.0 Hz, 2H), 8.00 (s, 1H), 7.92ꢀ7.90 (m, 3H), 7.26ꢀ7.21 (m,
8H), 5.78 (d, J = 9.2 Hz, 1H); 13C NMR (151 MHz, acetoneꢀd6) δ 150.6, 148.1, 141.3, 140.8, 133.7,
130.1, 129.4, 129.3, 128.5, 128.4, 124.9, 79.3, 61.8; IR (film): γ = 3269, 1526, 1352, 1164, 1091, 843,
738, 554 cmꢀ1; HRMS (ESI) m/z: [MꢀH]ꢀ Calcd for C19H14ClN2O5S 401.0363, found 401.0378.
General Procedure for Asymmetric Addition of Cyclic Aldimines. Under a nitrogen atmosphere,
[RhCl(C2H4)2]2 (0.3 mg, 0.75 ꢁmol), and 8e (0.9 mg, 1.5 ꢁmol) were dissolved in toluene (0.5 mL) in a
dry schlenk tube. The mixture was stirred at room temperature for 1 h. Then, aldimine 12 (0.05 mmol),
ArB(OH)2 (0.1 mmol), KF (0.2 mmol) and water (0.5 mL) were added sequentially and the reaction
mixture was stirred at RT for 20 h. The mixture was cooled to room temperature and concentrated under
reduced pressure, and then it was purified by flash chromatography on silica gel (ethyl acetate/petroleum
ether = 1/8) to afford the corresponding product 13.
(S)-4-Phenyl-3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide (13a).8a 13 mg, 90% yield; white
solid; mp 133ꢀ134 °C; 98% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 90/10, 0.8 mL/min,
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220 nm), tR (minor) 14.606 min, tR (major) 16.956 min; [α]D = ꢀ25.7 (c 0.10, CH2Cl2); 1H NMR (400
MHz, CDCl3) δ 7.44 – 7.42 (m, 3H), 7.38 – 7.28 (m, 3H), 7.14 – 7.04 (m, 2H), 6.82 (d, J = 7.8 Hz, 1H),
5.90 (s, 1H), 4.77 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 151.5, 137.9, 129.7, 129.6, 129.5, 128.8,
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128.6, 125.3, 122.0, 118.9, 62.0; IR (film) γ = 3286, 3071, 3032, 2963, 2920, 2847, 1613, 1575, 1480,
1448, 1414, 1362, 1261, 1205, 1162 cmꢀ1; HRMS (ESIꢀTOF) m/z: [MꢀH]ꢀ Calcd for C13H10NO3S
260.0381, found 260.0397.
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(S)-4-(4-Chlorophenyl)-3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide(13b).8a 14 mg, 93% yield;
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white solid; mp 140ꢀ142 °C; 96% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 90/10, 0.8
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mL/min, 220 nm), tR (minor) 12.521 min, tR (major) 19.43 min; [α]D = ꢀ16.7 (c 0.10, CH2Cl2); 1H
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NMR (400 MHz, CDCl3) δ 7.46 – 7.39 (m, 2H), 7.38 – 7.27 (m, 3H), 7.13 – 7.09 (m, 1H), 7.07 – 7.05
(m, 1H), 6.81 (d, J = 7.8 Hz, 1H), 5.88 (d, J = 5.0 Hz, 1H), 4.86 (d, J = 3.9 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 151.5, 136.3, 135.6, 130.3, 130.0, 129.7, 128.4, 125.4, 121.5, 119.0, 61.3; IR (film): γ=
3273, 3067, 2925, 2843, 1616, 1596, 1577, 1491, 1448, 1422, 1369, 1293, 1246, 1201, 1171 cmꢀ1;
HRMS (ESIꢀTOF) m/z: [MꢀH]ꢀ Calcd for C13H9ClNO3S 293.9992, found 293.9997.
(S)-4-(4-Bromophenyl)-3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide(13c).8a 15 mg, 91% yield;
white solid; mp 128ꢀ130 °C; 95% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 90/10, 0.8
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mL/min, 220 nm), tR (minor) 13.038 min, tR (major) 20.373 min; [α]D = ꢀ22.4 (c 0.10, 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, 129.0, 127.4, 124.3, 122.8, 120.3, 118.0, 60.3; IR (film) γ = 3277,
2959, 2916, 2847, 1579, 1487, 1450, 1424, 1373, 1293, 1259, 1242, 1201, 1169 cmꢀ1; HRMS (ESIꢀ
TOF) m/z: [MꢀH]ꢀ Calcd for C13H9BrNO3S 337.9487, found 337.9493.
(S)-4-(4-Fluorophenyl)-3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide (13d).11e 12 mg, 87%
yield; white solid; mp 147ꢀ148 °C; 96% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 90/10, 0.8
20
mL/min, 220 nm), tR (minor) 12.066 min, tR (major) 15.876 min; [α]D = ꢀ27.7 (c 0.10, CH2Cl2); 1H
NMR (400 MHz, CDCl3) δ 7.41 – 7.31 (m, 3H), 7.17 – 7.09 (m, 3H), 7.07 – 7.05 (m, 1H), 6.81 (d, J =
7.8 Hz, 1H), 5.90 (d, J = 8.5 Hz, 1H), 4.84 (d, J = 8.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 164.4,
162.0, 151.4, 133.8, 133.7, 130.8, 130.7, 129.9, 128.5, 125.4, 121.7, 119.0, 116.6, 116.4, 61.2; IR (film):
γ= 3273, 3080, 2925, 1607, 1579, 1508, 1482, 1450, 1424, 1369, 1296, 1229, 1201, 1169 cmꢀ1; HRMS
(ESI) m/z: [MꢀH]ꢀ Calcd for C13H9FNO3S 278.0287, found 278.0276.
(S)-4-(4-(Trifluoromethyl)phenyl)-3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide (13e).8a 14mg,
85% yield; white solid; mp 122ꢀ124°C; 98% ee; HPLC analysis: Chiralpak IFꢀ3 (hexane/iꢀPrOH = 95/5,
20
0.6 mL/min, 220 nm), tR (major) 8.37 min, tR (minor) 9.522 min; [α]D = ꢀ24.2 (c 0.10, 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 (m, 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(q, J = 33 Hz), 129.1, 128.4, 127.3, 125.4(q, J = 4 Hz), 124.5, 122.6(q, J = 272 Hz), 120.0,
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118.1, 60.3; IR (film) γ = 3273, 2962, 2925, 2856, 1620, 1581, 1482, 1454, 1424, 1371, 1326, 1259,
1205, 1171 cmꢀ1; HRMS (ESIꢀTOF) m/z: [MꢀH]ꢀ Calcd for C14H9F3NO3S 328.0255, found 328.0268.
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(S)-4-(p-Tolyl)-3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide (13f).8a 13 mg, 93% yield; white
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9
solid; mp 118ꢀ119°C; 97% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 90/10, 0.8 mL/min,
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220 nm), tR (minor) 14.451 min, tR (major) 16.061 min; [α]D = ꢀ21.4 (c 0.10, CH2Cl2); 1H NMR (400
MHz, CDCl3) δ 7.33 – 7.29 (m, 1H), 7.27 – 7.17 (m, 4H), 7.10 – 7.04 (m, 2H), 6.82 (d, J = 7.8 Hz, 1H),
5.86 (s, 1H), 4.74 (s, 1H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 150.5, 138.6, 133.9, 129.1,
128.6, 127.6, 127.6, 124.2, 121.2, 117.8, 60.7, 20.2; IR (film): γ = 3269, 3024, 2963, 2920, 2856, 2357,
2331, 1613, 1579, 1510, 1480, 1450, 1418, 1364, 1291, 1259, 1201, 1169 cmꢀ1; HRMS (ESIꢀTOF) m/z:
[MꢀH]ꢀ Calcd for C14H12NO3S 274.0538, found 274.0540.
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(S)-4-(4-Methoxyphenyl)-3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide (13g).11e 13 mg, 91%
yield; white solid; mp 112ꢀ114 °C; 97% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 90/10, 0.8
mL/min, 220 nm), tR (minor) 24.675 min, tR (major) 41.741 min; [α]D = ꢀ21.7 (c 0.10, CH2Cl2);1H
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NMR (400 MHz, CDCl3) δ 7.37 – 7.29 (m, 1H), 7.29 – 7.21 (m, 2H), 7.11 – 7.05 (m, 2H), 6.97 – 6.90
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(m, 2H), 6.84 (d, J = 7.8 Hz, 1H), 5.86 (s, 1H), 4.69 (s, 1H), 3.83 (s, 3H); C NMR (101 MHz, CDCl3)
δ 160.4, 151.5, 130.1, 129.9, 129.7, 128.6, 125.2, 122.3, 118.8, 114.8, 61.5, 55.4; IR (film) γ = 3273,
2968, 2929, 2834, 1611, 1579, 1512, 1482, 1448, 1418, 1369, 1306, 1259, 1199, 1169 cmꢀ1; HRMS
(ESIꢀTOF) m/z: [MꢀH]ꢀ Calcd for C14H12NO4S 290.0487, found 290.0483.
(S)-4-([1,1'-Biphenyl]-4-yl)-3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide (13h).8a 15 mg, 87%
yield; white solid; mp 171ꢀ173°C; 97% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 95/5, 0.6
mL/min, 220 nm), tR (minor) 31.744 min, tR (major) 38.366 min; [α]D = ꢀ15.2 (c 0.10, CH2Cl2); 1H
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NMR (400 MHz, CDCl3) δ 7.64 (d, J = 8.2 Hz, 2H), 7.62 – 7.57 (m, 2H), 7.48 – 7.44 (m, 2H), 7.43 –
7.37 (m, 3H), 7.36 – 7.32 (m, 1H), 7.13 – 7.07 (m, 2H), 6.88 (d, J = 7.7 Hz, 1H), 5.94 (s, 1H), 4.82 (s,
1H); 13C NMR (100 MHz, CDCl3) δ151.5, 142.6, 140.0, 136.7, 129.8, 129.3, 129.0, 128.6, 128.1,
127.9, 127.2, 125.3, 122.0, 118.9, 61.7; IR (film) γ = 3273, 3062, 3028, 2959, 2925, 2847, 1577, 1482,
1450, 1422, 1373, 1291, 1265, 1244, 1203, 1171 cmꢀ1; HRMS (ESIꢀTOF) m/z: [MꢀH]ꢀ Calcd for
C19H14NO3S 336.0694, found 336.0705.
(S)-4-(Benzo[d][1,3]dioxol-5-yl)-3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide (13i).8a 13 mg,
88% yield; white solid; mp 123ꢀ125°C; 97% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 95/5,
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0.6 mL/min, 220 nm), tR (major) 47.45 min, tR (minor) 50.304 min; [α]D = ꢀ18.7 (c 0.10, CH2Cl2); 1H
NMR (400 MHz, CDCl3) δ 7.34 – 7.31 (m, 1H), 7.16 – 7.07 (m, 1H), 7.05 (d, J = 8.3 Hz, 1H), 6.88 –
6.82 (m, 3H), 6.73 (d, J = 0.9 Hz, 1H), 6.00 (s, 2H), 5.81 (d, J = 8.3 Hz, 1H), 4.78 (d, J = 8.3 Hz, 1H);
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13C NMR (100 MHz, CDCl3) δ 151.4, 148.6, 148.5, 131.5, 129.8, 128.6, 125.3, 123.0, 122.0, 118.9,
108.8, 108.7, 101.7, 61.8; IR (film) γ = 3273, 3084, 2899, 2774, 1611, 1575, 1504, 1489, 1450, 1424,
1364, 1287, 1250, 1233, 1199, 1167 cmꢀ1; HRMS (ESIꢀTOF) m/z: [MꢀH]ꢀ Calcd for C14H10NO5S
304.0280, found 304.0286.
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(R)-4-(Thiophen-3-yl)-3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide (13j).11e 11 mg, 85% yield;
white solid; mp 124ꢀ126 °C; 99% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 90/10, 0.8
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mL/min, 220 nm), tR (minor) 17.529 min, tR (major) 18.087 min; [α]D = ꢀ17.9 (c 0.23, CH2Cl2); 1H
NMR (400 MHz, CDCl3) δ 7.43 – 7.37 (m, 2H), 7.37 – 7.30 (m, 1H), 7.14 – 7.10 (m, 1H), 7.07 – 6.99
(m, 2H), 6.93 (d, J = 7.8 Hz, 1H), 6.04 (d, J = 7.8 Hz, 1H), 4.84 (d, J = 7.4 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 151.1, 138.0, 129.9, 128.2, 127.9, 126.6, 125.9, 125.3, 121.7, 118.9, 56.9; IR (film) γ =
3264, 3105, 3054, 1577, 1478, 1448, 1420, 1392, 1371, 1287, 1276, 1257, 1205, 1188, 1167 cmꢀ1;
HRMS (ESIꢀTOF) m/z: [MꢀH]ꢀ Calcd for C11H8NO3S2 265.9946, found 365.9943.
(S)-6-Fluoro-4-phenyl-3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide (13k). 12 mg, 89% yield;
white solid; mp 154ꢀ157 °C; 96% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 90/10, 0.8
mL/min, 220 nm), tR (minor) 6.522 min, tR (major) 7.006 min; [α]D = ꢀ58.7 (c 1.0, CH2Cl2); 1H NMR
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(400 MHz, CDCl3) δ7.51 – 7.43 (m, 3H), 7.53 – 7.33 (m, 2H), 7.08– 7.04(m, 2H), 6.55 – 6.52 (m, 1H),
5.87 (s, 1H), 4.72 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 160.4, 157.9, 147.4, 147.4, 137.1, 129.9,
129.7, 128.7, 123.8, 123.7, 120.5, 120.4, 117.0, 116.8, 115.1, 114.9, 61.9, 61.9; IR (film) γ = 3276,
3067, 3028, 2925, 2852, 1626, 1592, 1482, 1454, 1420, 1373, 1343, 1291, 1255, 1235, 1207, 1160 cmꢀ1;
HRMS(ESIꢀTOF) m/z: [MꢀH]ꢀ Calcd for C13H9FNO3S 278.0287, found 278.0292.
(S)-6-Chloro-4-phenyl-3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide (13l).11e 14 mg, 92% yield;
white solid; mp 161ꢀ163 °C; 97% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 90/10, 0.8
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mL/min, 220 nm), tR (minor) 10.209 min, tR (major) 10.952 min; [α]D = ꢀ67.4 (c 1.0, CH2Cl2); 1H
NMR (400 MHz, CDCl3) δ 7.51 – 7.43 (m, 3H), 7.39 – 7.27 (m, 3H), 7.02 (d, J = 8.8 Hz, 1H), 6.80 (d, J
= 1.8 Hz, 1H), 5.85 (s, 1H), 4.77 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 149.0, 136.0, 129.5, 128.9,
128.7, 127.7, 127.3, 122.6, 119.3, 60.7; IR (film) γ = 3273, 3080, 3058, 3028, 2959, 2925, 2852, 1605,
1500, 1474, 1454, 1424, 1366, 1261, 1203, 1184, 1167 cmꢀ1; HRMS(ESIꢀTOF) m/z: [MꢀH]ꢀ Calcd for
C13H9ClNO3S 293.9992, found 293.9994.
(S)-6-Bromo-4-phenyl-3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide (13m).11e 16 mg, 91%
yield; white solid; mp 152ꢀ154 °C; 98% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 90/10, 0.8
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mL/min, 220 nm), tR (minor) 10.422 min, tR (major) 11.065 min; [α]D = ꢀ78.8 (c 1.0, CH2Cl2);; 1H
NMR (400 MHz, CDCl3) δ 7.52 – 7.41 (m, 4H), 7.39 – 7.30 (m, 2H), 6.97 – 6.94 (m, 2H), 5.86 (s, 1H),
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4.78 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 149.5, 136.0, 131.8, 130.2, 128.9, 128.7, 127.7, 123.0,
119.6, 117.0, 60.6. IR (film) γ = 3277, 3032, 2959, 2920, 1472, 1454, 1422, 1396, 1366, 1336, 1302,
1261, 1244, 1199, 1184, 1165 cmꢀ1; HRMS (ESIꢀTOF) m/z: [MꢀH]ꢀ Calcd for C13H9BrNO3S 337.9487,
found 337.9486.
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(S)-6-Methyl-4-phenyl-3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide (13n).11e 13 mg, 94%
yield; white solid; mp 171ꢀ173°C; 98% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 90/10, 0.8
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mL/min, 220 nm), tR (minor) 17.436 min, tR (major) 19.206 min; [α]D = ꢀ32.7 (c 1.0, CH2Cl2); 1H
NMR (400 MHz, CDCl3) δ 7.45 – 7.42 (m, 3H), 7.35 – 7.32 (m, 2H), 7.19 – 7.08 (m, 1H), 6.97 (d, J =
8.4 Hz, 1H), 6.60 (s, 1H), 5.86 (s, 1H), 4.65 (s, 1H), 2.21 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 149.5,
138.1, 135.1, 130.4, 129.6, 129.5, 128.8, 128.6, 121.5, 118.6, 62.0, 20.7; IR (film) γ =3273, 3062, 3024,
2959, 2925, 2852, 1489, 1457, 1416, 1364, 1291, 1257, 1195, 1177 cmꢀ1; HRMS (ESIꢀTOF) m/z: [Mꢀ
H]ꢀ Calcd for C14H12NO3S 274.0538, found 274.0530.
(S)-6-Methoxy-4-phenyl-3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide (13o).11e 13 mg, 92%
yield; white solid; mp 148ꢀ150 °C; 97% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 90/10, 0.8
mL/min, 220 nm), tR (minor) 11.844 min, tR (major) 12.627 min; [α]D = ꢀ60.1 (c 1.0, CH2Cl2);; 1H
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NMR (400 MHz, CDCl3) δ7.46 – 7.39 (m, 3H), 7.38 – 7.29 (m, 2H), 6.99 (d, J = 9.0 Hz, 1H), 6.86 –
6.83 (m, 1H), 6.29 – 6.28 (m, 1H), 5.84 (s, 1H), 4.79 (s, 1H), 3.64 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ156.5, 145.3, 137.8, 129.6, 129.5, 128.8, 122.8, 119.8, 115.2, 113.3, 62.1, 55.7; IR (film) γ = 3265,
3067, 3028, 3002, 2963, 2933, 2834, 2353, 2335, 1611, 1581, 1491, 1422, 1366, 1281, 1250, 1171 cmꢀ1;
HRMS (ESIꢀTOF) m/z: [MꢀH]ꢀ Calcd for C14H12NO4S 290.0487, found 290.0492.
(S)-6-(tert-Butyl)-4-phenyl-3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide (13p). 14 mg, 86%
yield; white solid; mp 161ꢀ162 °C; 97% ee; HPLC analysis: Chiralpak ICꢀ3 (hexane/iꢀPrOH = 90/10, 0.8
mL/min, 220 nm), tR (minor) 7.494 min, tR (major) 8.43 min; [α]D = ꢀ67.2 (c 1.0, CH2Cl2);; 1H NMR
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(400 MHz, CDCl3) δ 7.48 – 7.40 (m, 3H), 7.38 – 7.31 (m, 3H), 6.99 (d, J = 8.7 Hz, 1H), 6.79 (d, J = 1.5
Hz, 1H), 5.89 (d, J = 8.4 Hz, 1H), 4.75 (d, J = 8.3 Hz, 1H), 1.16 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
149.4, 148.3, 138.0, 129.5, 129.4, 128.8, 126.8, 125.4, 121.0, 118.3, 62.2, 34.4, 31.2; IR (film) γ = 3269,
3062, 3032, 2963, 2864, 1495, 1457, 1418, 1364, 1293, 1272, 1248, 1199, 1177 cmꢀ1; HRMS (ESIꢀ
TOF) m/z: [MꢀH]ꢀ Calcd for C17H18NO3S 316.1008, found 316.1005.
(S,E)-4-Styryl-3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide (13q).11g 13 mg, 87% yield;
colorless oil; 95% ee; HPLC analysis: Chiralpak ODꢀH (hexane/iꢀPrOH = 80/20, 0.8 mL/min, 254 nm),
tR (minor) 21.236 min, tR (major) 24.565 min; [α]D = +5.7 (c 1.0, CH2Cl2); 1H NMR (400 MHz,
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CDCl3) δ7.47 – 7.42 (m, 2H), 7.41 – 7.30 (m, 4H), 7.25 – 7.15 (m, 2H), 7.06 (d, J = 8.2 Hz, 1H), 6.87
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