Rhodium-catalyzed highly enantioselective addition of arylboronic acids to cyclic aldimines: Practical asymmetric synthesis of cyclic sulfamidates

Article abstract of DOI:10.1055/s-0033-1338418

A highly efficient asymmetric arylation of cyclic N-sulfonyl aldimines with arylboronic acids catalyzed by a rhodium/ sulfur-olefin ligand complex under mild conditions is described. A wide range 4-aryl-3,4-dihydro-1,2,3- benzoxathiazine 2,2-dioxides were obtained in extremely high yields (93-99%) and high enantiomeric purities (97-99% ee).

Full text of DOI:10.1055/s-0033-1338418

SPECIAL TOPIC
▌2125
sRpehciaol tdopiiuc m-Catalyzed Highly Enantioselective Addition of Arylboronic Acids to
Cyclic Aldimines: Practical Asymmetric Synthesis of Cyclic Sulfamidates
Asymmetric Synthesis of Cyclic Sulfamidates
Hui Wang, Ming-Hua Xu*
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, P. R. of China
Fax +86(21)50807388; E-mail: xumh@simm.ac.cn
Received: 21.02.2013; Accepted after revision: 25.03.2013
sulfonyl aldimines remains unexplored. Therefore, the de-
Abstract: A highly efficient asymmetric arylation of cyclic N-sul-
velopment of new catalytic systems capable of efficient
fonyl aldimines with arylboronic acids catalyzed by a rhodium/
synthesis of enantiomerically pure cyclic sulfamidates
would be a highly desirable goal.
sulfur–olefin ligand complex under mild conditions is described. A
wide range 4-aryl-3,4-dihydro-1,2,3-benzoxathiazine 2,2-dioxides
were obtained in extremely high yields (93–99%) and high enantio-
meric purities (97–99% ee).
We recently designed a series of chiral sulfinamide/
sulfoxide-based olefin ligands and used them in rhodium-
catalyzed asymmetric reactions.10,11 Simple linear N-cin-
namylsulfinamide derivatives were found to be elegant
chiral ligands for the 1,2-addition of arylboronic acids to
α-keto esters and α-diketones, and gave a broad range of
aryl α-hydroxy carbonyl compounds with very high enan-
tioselectivities (up to 99% ee).10d Following an extensive
study, we showed that equally simple branched sulfur–
olefin ligands were more effective in promoting asymmet-
ric addition of arylboronic acids to cyclic ketimines, af-
fording a variety of highly enantiomerically enriched (up
to 99% ee) quaternary carbon-containing benzosultams
and benzosulfamidates.10g
Key words: asymmetric catalysis, cyclization, arylation, rhodium,
boron, ligands, sulfamidates, heterocycles
Chiral amines are ubiquitous in nature and commonly oc-
cur as key structural motifs in numerous biologically in-
teresting compounds and pharmaceutical agents.
Consequently, the discovery of efficient techniques for
the asymmetric synthesis of various optically pure amines
continues to be a pivotal subject in modern organic chem-
istry. Cyclic sulfamidates represent an intriguing class of
amine derivatives that contain a sulfonamide functionality
in the ring. They occur widely in pharmaceutical com-
pounds for diverse medicinal uses1 and they can also serve
as versatile building blocks in various organic syntheses.2
In general, cyclic sulfamidates are prepared from amino
alcohols and diols in several steps.2a,3 They can also be
synthesized from alcohols through intramolecular sulfa-
mate ester C−H insertion in the presence of binuclear rho-
dium carboxylate catalysts4 or ruthenium porphyrin
catalysts.5,6 However, methods for creating stereogenic
centers in these heterocycles through asymmetric cataly-
sis are limited because of difficulties in achieving a high
enantioselectivity.5a,5d Among the methods that do exist,
direct asymmetric hydrogenation of the corresponding cy-
clic ketimines is reported to be the most efficient enanti-
oselective route to chiral cyclic sulfamidates.7
Surprisingly, although asymmetric addition to C=N dou-
ble bonds in analogous imine compounds represents an al-
ternative and direct route to chiral sulfamidates, it is only
recently that a few examples of reactions of this type have
been documented.8
In an attempt to broaden the scope of this chemistry, we
surmised that the corresponding cyclic N-sulfonyl ald-
imines might also act as suitable substrates. We present a
detailed survey of the asymmetric addition of such imines
to arylboronic acids in the presence of rhodium catalysts
under mild conditions to give a diversity of chiral cyclic
sulfamidates in extremely high yields and high enantiose-
lectivities (up to 99% ee).
We began by treating the cyclic N-sulfonyl aldimine 1a
with (4-methoxyphenyl)boronic acid (2a) under the con-
ditions previously optimized for the asymmetric arylation
of ketimines in the presence of the simple N-cinnamylsul-
finamide L1 as the chiral ligand (Scheme 1). The reaction
proceeded at room temperature in the presence of dichlo-
rotetrakis(cyclooctene)dirhodium {[Rh(coe)2Cl]2} (1.5
mol%) and ligand L1 (3.3 mol%) in 1.5 M aqueous
potassium fluoride/toluene to give the expected benzo-
sulfamidate 3a in moderate yield and promising enantio-
selectivity (54% ee). To follow up on this encouraging
result, we performed further screening of other sulfur–ole-
fin hybrid ligands with the aim of enhancing the reactivity
and enantioselectivity of the reaction. Interestingly, the
branched-chain sulfinamide ligand L2 gave a much high-
er yield of the product (77%) with a similar enantiomeric
excess (56% ee). Unlike the case of the arylation of cyclic
ketimines,10g the stereocontrol was not affected by the use
of the sterically hindered ligand L3 with an ortho-methyl
substituent on the phenyl ring, but this reaction gave a
lower yield. To our delight, however, marked improve-
The use of commercially available stable arylboronic
acids to replace common organometallic reagents in tran-
sition metal-catalyzed C–C bond-forming reactions has
recently also attracted a considerable degree of attention.9
However, to the best of our knowledge, the asymmetric
addition of arylboronic acids to benzene-fused cyclic N-
SYNTHESIS 2013, 45, 2125–2133
Advanced online publication: 08.05.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1338418; Art ID: SS-2013-C0152-ST
© Georg Thieme Verlag Stuttgart · New York

2126
H. Wang, M.-H. Xu
SPECIAL TOPIC
O
O
O
O
B(OH)2
S
S
O
N
O
NH
[Rh(coe)2Cl]2/L
+
H
KF(1.5 M)/toluene, r.t.
OMe
OMe
1a
2a
3a
O
S
H
N
S
H
N
N
H
S
O
O
49% yield
54% ee
77% yield
L2
62% yield
58% ee
L1
L4
L3
L6
56% ee
H
N
S
H
N
H
N
S
S
O
O
O
95% yield
93% ee
97% yield
L5
94% yield
95% ee
97% ee
Scheme 1 Screening of ligands
Table 1 Asymmetric Addition of Arylboronic Acids to Cyclic
N-Sulfonyl Aldimines Catalyzed by Dichlorotetrakis(cyclooc-
tene)dirhodium and ligand L5
ments in both enantioselectivity (93%) and yield (95%)
were achieved when we used the benzyl-substituted li-
gand L4. The incorporation of a large naphthyl group was
even more beneficial (L5 and L6), the highest enantiose-
lectivity (97% ee) and yield (97%) being observed when
chiral sulfinamide L5 was used as the ligand.
O
O
O
O
S
S
O
N
O
NH
[Rh(coe)2Cl]2/L5
8
7
ArB(OH)2
4
H
Ar
R
H
R
Having performed these optimization studies, we went on
to make a thorough examination of the substrate scope
and generality of the reaction, the results of which are
summarized in Table 1. A wide range of arylboronic acids
with various electronic and steric demands reacted suc-
cessfully with a series of cyclic N-sulfonyl aldimines 1 to
give the corresponding functionalized 3,4-dihydro-1,2,3-
benzoxathiazine 2,2-dioxides 3 in excellent yields and ex-
tremely high enantioselectivities. The electronic proper-
ties of the arylboronic acids did not appear to affect the
reactivity or enantioselectivity of the reaction (entries 1–
11). In addition to the simple aldimine 1a, derivatives
with electron-donating or electron-withdrawing substitu-
ents in various positions on the aromatic ring were all
found to be viable substrates, exhibiting high reactivities
and giving highly optically active cyclic benzosulfami-
dates in excellent yields (entries 12–26). Notably, arylbo-
ronic acids and substrates with high degrees of steric
hindrance also participated in smooth arylation reactions
with excellent enantioselectivities (entries 5 and 10–12).
In view of the high level of enantioselectivity and the ex-
ceptionally mild conditions that are required, this process
represents the most enantioselective and the most conve-
nient route to 3,4-dihydro-1,2,3-benzoxathiazine 2,2-di-
oxides.
5
aq KF (1.5 M)/toluene, r.t.
6
3
1
H
N
S
O
L5
Entrya
R
Ar
Product Yieldb eec
(%)
(%)
1
H
H
H
H
H
H
H
H
H
H
H
4-MeOC6H4
4-Tol
3a
97
96
96
98
99
98
96
98
98
99
99
96
99
98
97
99
99
99
99
99
99
98
99
99
99
99
99
97
2
3b
3c
3d
3e
3f
3
4-ClC6H4
Ph
4
5
1-naphthyl
2-naphthyl
3-MeOC6H4
3-Tol
6
7
3g
3h
3i
8
9
3-ClC6H4
2-MeOC6H4
2-Tol
10
11
12
13
14
3j
3k
3l
5,6-(CH=CH)2 Ph
6-OMe
6-OMe
Ph
3m
3n
4-MeOC6H4
Synthesis 2013, 45, 2125–2133
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Asymmetric Synthesis of Cyclic Sulfamidates
2127
Table 1 Asymmetric Addition of Arylboronic Acids to Cyclic
N-Sulfonyl Aldimines Catalyzed by Dichlorotetrakis(cyclooc-
tene)dirhodium and ligand L5 (continued)
O
O
O
O
S
S
O
N
O
NH
[Rh(coe)2Cl]2/L5
8
7
ArB(OH)2
4
H
Ar
R
H
R
5
aq KF (1.5 M)/toluene, r.t.
6
3
1
H
N
S
Figure 1 X-ray structure of 3z
O
L5
The stereochemical outcome of the reaction can be ratio-
nalized by considering an empirical transition state
model13,14 in which the arylrhodium species has a pre-
ferred conformation with the aryl group positioned trans
to the olefin ligand and the tert-butyl moiety staggered
(Scheme 2). The highly enantioselective formation of the
R-product can be explained by re-face-selective coordina-
tion of the cyclic imine with rhodium, because an unfavor-
able steric interaction between the R group and the
sulfonyl moiety of the imine substrate exists in transition
state A, which is absent in transition state B.
Entrya
R
Ar
Product Yieldb eec
(%)
(%)
15
16
17
18
19
20
21
22
23
24
25
26
6-Me
6-Me
6-Cl
Ph
3o
99
99
93
99
98
99
99
99
96
99
98
98
99
99
99
99
99
99
99
99
97
99
99
99
4-Tol
3p
3q
3r
3s
Ph
6-Cl
4-ClC6H4
3-ClC6H4
4-BrC6H4
Ph
6-Cl
6-Cl
3t
The synthetic utility of the arylation product was exempli-
fied by the conversion of product 3b into cyclic sulfamate
4 by N-methylation (Scheme 3). Such aryl sulfamates
have recently been shown to be highly effective in nickel-
catalyzed Kumada cross-couplings.15 As we had hoped,
the reaction of sulfamate 4 with phenylmagnesium bro-
mide under Du Bois’s conditions15b smoothly gave the bi-
7-OMe
8-OMe
8-OMe
8-Me
8-Me
8-Me
3u
3v
3w
3x
3y
3z
Ph
4-MeOC6H4
Ph
aryl compound
5
in 79% yield with retained
4-Tol
enantioselectivity (99% ee). Additionally, the cross-cou-
pling reaction of cyclic sulfamate 4 and methylmagne-
sium bromide was also successful and gave the chiral
diaryl derivative 6 in 82% yield and 99% ee.
4-BrC6H4
a Reaction conditions: 1 (0.25 mmol), ArB(OH)2 (2.0 equiv),
{[Rh(coe)2Cl]2} (3 mol%), L5 (3.3 mol%), 1.5 M aq KF (1.0 equiv)/
toluene, r.t., 5−6 h.
In summary, we have developed a new, simple, practical,
and enantioselective synthesis of 4-aryl-3,4-dihydro-
1,2,3-benzoxathiazine 2,2-dioxides through the rhodium-
catalyzed asymmetric addition of arylboronic acids with
cyclic aldimines in the presence of a branched chiral N-al-
kenylsulfinamide ligand. This method is general and pro-
vides ready access to a wide range of functionalized
derivatives of 4-aryl-3,4-dihydro-1,2,3-benzoxathiazine
2,2-dioxides in enantiomerically pure form and excellent
b Isolated yield.
c By HPLC on a chiral column.
The absolute configuration of the newly created carbon
stereocenter in product 3z was shown to be R by means of
X-ray crystallographic analysis (Figure 1).12
R
NH
R
O
NH
H
O
N
Ar
H
O
S
O
S
O
O
O
Rh
N
S
O
S
Rh
S
O
Ar
O
N
Ar
O
A
B
si-face (unfavorable)
re-face (favorable)
Scheme 2 Proposed transition-state model
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2125–2133

2128
H. Wang, M.-H. Xu
SPECIAL TOPIC
O
O
O
O
S
S
Me
Me
O
NH
O
N
HN
K2CO3, CH3I
DMF
Ni(dppf)Cl2
H
H
H
PhMgBr
benzene
5
3b
4
79% yield
99% ee
Ni(dppf)Cl2
MeMgBr
Et2O
Me
HN
H
6
82% yield
99% ee
Scheme 3 Further transformations of arylation product 3b
(m, 2 H), 7.03–7.11 (m, 2 H), 7.23–7.27 (m, 2 H), 7.32 (t, J = 5.4
Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 54.9, 61.0, 114.3, 118.3, 121.9,
yields under mild conditions, so that it is the most conve-
nient and efficient approach to this class of target com-
pounds. The newly designed sulfur–olefin ligands are
promising and exciting ligands for asymmetric catalysis
124.7, 128.2, 129.2, 129.4, 129.7, 151.0, 159.9.
that should find a wide range of applications in asymmet- HRMS (ESI): m/z [M + Na]+ calcd for C14H13NNaO4S: 314.0463;
found: 314.0466.
ric synthesis.
(4R)-4-(4-Tolyl)-3,4-dihydro-1,2,3-benzoxathiazine 2,2-Diox-
ide (3b)
Commercially available reagents were purchased from J&K Chem-
ical or Sigma-Aldrich and used directly without further purification.
White solid; yield: 66 mg (96%; 99% ee); mp 130 °C.
Toluene was distilled from sodium under nitrogen prior to use; THF
was distilled from benzophenone-ketyl under nitrogen prior to use;
other solvents were dried using standard procedures. Melting points
were determined on a Buchi 510 melting point apparatus and are un-
corrected. IR spectra were recorded on a Thermofisher Nicolet 7600
spectrophotometer. NMR spectra were recorded on a Varian spec-
trometer (300 MHz for 1H, and 100 MHz for 13C). Chemical shifts
are reported on the δ scale in ppm referenced to SiMe4 as an internal
standard for 1H NMR and chloroform-d (δ = 77.16) for 13C NMR.
High-resolution mass spectra were recorded on a MICROMASS Q-
Tof ultima spectrometer. HPLC was performed on a JASCO 2000
instrument. X-ray crystallography was performed on a Bruker
APEX 11.
HPLC: Chiralpak AD-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (85:15); flow = 0.7 mL/min; retention time: 16.1
min, 17.5 min (major).
IR (KBr): 3248, 2922, 1579, 1429, 1367, 1205, 1169, 1097, 891,
850 cm–1.
1H NMR (300 MHz, CDCl3): δ = 2.39 (s, 3 H), 4.78 (s, 1 H), 5.86
(s, 1 H), 6.82 (d, J = 7.5 Hz, 1 H), 7.03–7.11 (m, 2 H), 7.20–7.23
(m, 4 H), 7.32 (t, J = 8.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 21.2, 61.7, 118.7, 122.2, 125.2,
128.6, 128.6, 129.6, 130.1, 134.9, 139.6, 151.4.
HRMS (ESI): m/z [M + Na]+ calcd for C14H13NNaO3S: 298.0514;
found: 298.0531.
4-Aryl-3,4-dihydro-1,2,3-benzoxathiazine 2,2-Dioxides 3; Gen-
eral Procedure
(4R)-4-(4-Chlorophenyl)-3,4-dihydro-1,2,3-benzoxathiazine
2,2-Dioxide (3c)
A soln of cyclic aldimine 1 (0.25 mmol), [Rh(coe)2Cl]2 (2.7 mg,
0.0075 mmol of Rh), ligand L5 (2.5 mg, 0.00825 mmol), and
ArB(OH)2 (0.5 mmol) in toluene was stirred at r.t. for 30 min then
1.5 M aq KF (0.17 mL, 0.25 mmol) was added. The mixture was
stirred at r.t. for 5–6 h then passed through a pad of silica gel with
EtOAc (10 mL). The solvent was removed under vacuum and the
residue was purified by column chromatography (silica gel, PE–
EtOAc, 5:1).
White solid; yield: 71 mg (96%; 99% ee); mp 120 °C.
HPLC: Chiralpak AD-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (85:15); flow = 0.7 mL/min; retention time: 12.2
min, 13.5 min (major).
IR (KBr): 3236, 2922, 1579, 1431, 1371, 1201, 1167, 1092, 903,
849 cm–1.
1H NMR (300 MHz, CDCl3): δ = 4.88 (s, 1 H), 5.88 (s, 1 H), 6.81
(d, J = 5.7 Hz, 1 H), 7.05–7.13 (m, 2 H), 7.28–7.36 (m, 3 H), 7.40–
7.43 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 61.2, 118.9, 121.4, 125.3, 128.4,
129.6, 129.9, 130.2, 135.6, 136.2, 151.4.
(4R)-4-(4-Methoxyphenyl)-3,4-dihydro-1,2,3-benzoxathiazine
2,2-Dioxide (3a)
White solid; yield: 71 mg (97%; 97% ee); mp 112 °C.
HPLC: Chiralpak AD-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (80:20); flow = 0.7 mL/min; retention time: 13.2
min, 16.2 min (major).
HRMS (ESI): m/z [M + Na]+ calcd for C13H10ClNNaO3S:
317.9968; found: 317.9977.
IR (KBr): 3269, 2931, 1612, 1513, 1257, 1168, 1099, 1028, 850,
761 cm–1.
1H NMR (300 MHz, CDCl3): δ = 3.83 (s, 3 H), 4.80 (d, J = 5.7 Hz,
1 H), 5.85 (d, J = 5.7 Hz, 1 H), 6.83 (d, J = 5.7 Hz, 1 H), 6.91–6.95
(4R)-4-Phenyl-3,4-dihydro-1,2,3-benzoxathiazine 2,2-Dioxide
(3d)
White solid; yield: 64 mg (98%; 99% ee); mp 144 °C.
Synthesis 2013, 45, 2125–2133
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Asymmetric Synthesis of Cyclic Sulfamidates
2129
HPLC: Chiralpak IC-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (70/30); flow = 0.6 mL/min; retention time: 11.3
min (major), 12.4 min.
(4R)-4-(3-Tolyl)-3,4-dihydro-1,2,3-benzoxathiazine 2,2-Diox-
ide (3h)
White solid; yield: 67 mg (98%; 98% ee); mp 100 °C.
HPLC: Chiralpak IC-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (80:20); flow = 0.7 mL/min; retention time: 12.7
min (major), 14.4 min.
IR (KBr): 3238, 2922, 1579, 1450, 1365, 1203, 1167, 1103, 893,
845 cm–1.
1H NMR (300 MHz, CDCl3): δ = 4.83 (s, 1 H), 5.90 (s, 1 H), 6.82
(d, J = 7.2 Hz, 1 H), 7.05–7.12 (m, 2 H), 7.31–7.37 (m, 3 H), 7.42–
7.45 (m, 3 H).
IR (KBr): 3257, 2922, 1579, 1429, 1369, 1211, 1169, 1099, 874,
750 cm–1.
1H NMR (300 MHz, CDCl3): δ = 2.37 (s, 3 H), 4.79 (s, 1 H), 5.85
(d, J = 7.2 Hz, 1 H), 6.83 (d, J = 8.1 Hz, 1 H), 7.03–7.14 (m, 4 H),
7.23 (d, J = 7.5 Hz, 1 H), 7.32 (t, J = 7.5 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 21.4, 61.9, 118.8, 122.1, 125.2,
125.8, 128.6, 129.3, 129.4, 129.6, 130.3, 137.8, 139.4, 151.4.
13C NMR (100 MHz, CDCl3): δ = 61.9, 118.8, 122.0, 125.2, 128.5,
128.8, 129.4, 129.5, 129.7, 137.8, 151.4.
HRMS (ESI): m/z [M + Na]+ calcd for C13H11NO3S: 284.0357;
found: 284.0385.
(4R)-4-(1-Naphthyl)-3,4-dihydro-1,2,3-benzoxathiazine 2,2-Di-
oxide (3e)
White solid; yield: 77 mg (99%; 99% ee); mp 140 °C.
HRMS (ESI): m/z [M + Na]+ calcd for C14H13NNaO3S: 298.0514;
found: 298.0541.
HPLC: Chiralpak AD-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (80:20); flow = 0.7 mL/min; retention time: 10.1
min, 12.1 min (major).
(4R)-4-(3-Chlorophenyl)-3,4-dihydro-1,2,3-benzoxathiazine
2,2-Dioxide (3i)
White solid; yield: 72 mg (98%; 99% ee); mp 106 °C.
HPLC: Chiralpak IC-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (80:20); flow = 0.7 mL/min; retention time: 13.3
min, 17.5 min (major).
IR (KBr): 3276, 2924, 1583, 1454, 1371, 1192, 1171, 1103, 839,
760 cm–1.
1H NMR (300 MHz, CDCl3): δ = 4.25 (s, 1 H), 6.65 (s, 1 H), 6.86
(d, J = 7.8 Hz, 1 H), 7.04–7.13 (m, 2 H), 7.31–7.37 (m, 1 H), 7.42–
7.58 (m, 4 H), 7.93–7.96 (m, 2 H), 8.02(s, 1 H).
IR (KBr): 3234, 2922, 1579, 1427, 1371, 1200, 1169, 1099, 858,
760 cm–1.
1H NMR (300 MHz, CDCl3): δ = 4.97 (s, 1 H), 5.86 (s, 1 H), 6.82
(d, J = 6.6 Hz, 1 H), 7.05 (d, J = 6.9 Hz, 1 H), 7.12 (t, J = 5.4 Hz, 1
H), 7.25 (d, J = 8.4 Hz, 1 H), 7.33–7.37 (m, 2 H), 7.39–7.43 (m, 2
H).
13C NMR (100 MHz, CDCl3): δ = 59.0, 119.1, 122.1, 122.7, 125.3,
125.4, 126.5, 127.4, 128.1, 128.3, 129.3, 129.7, 130.5, 134.2, 151.5.
HRMS (ESI): m/z [M + Na]+ calcd for C17H13NNaO3S: 334.0514;
found: 334.0498.
13C NMR (100 MHz, CDCl3): δ = 61.3, 119.0, 121.2, 125.4, 127.1,
(4R)-4-(2-Naphthyl)-3,4-dihydro-1,2,3-benzoxathiazine 2,2-Di-
oxide (3f)
128.4, 129.0, 129.8, 130.0, 130.7, 135.2, 139.6, 151.4.
HRMS (ESI): m/z [M – H]– calcd for C13H9ClNO3S: 293.9992;
found: 293.9980.
White solid; yield: 76 mg (98%; 99% ee); mp 132 °C.
HPLC: Chiralpak IC-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (70:30); flow = 0.7 mL/min; retention time: 11.6
min (major), 17.6 min.
(4R)-4-(2-Methoxyphenyl)-3,4-dihydro-1,2,3-benzoxathiazine
2,2-Dioxide (3j)
White solid; yield: 72 mg (99%; 99% ee); mp 111 °C.
IR (KBr): 3265, 2922, 1579, 1452, 1358, 1190, 1167, 1099, 879,
758 cm–1.
1H NMR (300 MHz, CDCl3): δ = 4.94 (s, 1 H), 6.07 (s, 1 H), 6.84
(d, J = 7.4 Hz, 1 H), 7.08 (t, J = 7.5 Hz, 2 H), 7.32–7.37 (m, 2 H),
7.54–7.60 (m, 2 H), 7.85–7.92 (m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 62.1, 118.9, 122.0, 125.2, 125.3,
127.0, 127.2, 127.8, 128.1, 128.6, 128.8, 129.7, 129.8, 133.1, 133.5,
134.8, 151.5.
HPLC: Chiralpak IC-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (70:30); flow = 0.7 mL/min; retention time: 11.7
min (major), 14.7 min.
IR (KBr): 3284, 2922, 1603, 1425, 1373, 1200, 1171, 1103, 820,
756 cm–1.
1H NMR (300 MHz, CDCl3): δ = 3.68 (s, 3 H), 5.72 (d, J = 7.5 Hz,
1 H), 5.91 (d, J = 7.5 Hz, 1 H), 6.68 (d, J = 5.7 Hz, 1 H), 6.96–7.09
(m, 4 H), 7.25–7.30 (m, 1 H), 7.33–7.36 (m, 1 H), 7.41–7.46 (m, 1
H).
HRMS (ESI): m/z [M + Na]+ calcd for C17H13NNaO3S: 334.0514;
found: 334.0510.
13C NMR (100 MHz, CDCl3): δ = 55.7, 60.3, 112.1, 118.3, 121.3,
(4R)-4-(3-Methoxyphenyl)-3,4-dihydro-1,2,3-benzoxathiazine
2,2-Dioxide (3g)
122.7, 124.5, 124.9, 126.8, 129.2, 131.0, 151.1, 157.2.
HRMS (ESI): m/z [M – H]+ calcd for C14H12NO4S: 290.0487;
found: 290.0496.
White solid; yield: 70 mg (96%; 99% ee); mp 112 °C.
HPLC: Chiralpak IC-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (80:20); flow = 0.7 mL/min; retention time: 17.6
min (major), 19.7 min.
(4R)-4-(2-Tolyl)-3,4-dihydro-1,2,3-benzoxathiazine 2,2-Diox-
ide (3k)
White solid; yield: 68 mg (99%; 99% ee); mp 114 °C.
IR (KBr): 3236, 2920, 1589, 1427, 1373, 1259, 1201, 1171, 862,
750 cm–1.
1H NMR (300 MHz, CDCl3): δ = 3.79 (s, 3 H), 5.00 (s, 1 H), 5.84
(s, 1 H), 6.83–6.87 (m, 2 H), 6.91–6.97 (m, 2 H), 6.99–7.03 (d, J =
7.4 Hz, 1 H), 7.06–7.11 (t, J = 7.5 Hz, 1 H), 7.29–7.37 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 55.4, 61.9, 114.4, 115.0, 118.7,
120.9, 121.9, 125.2, 128.5, 129.7, 130.5, 139.1, 151.3, 160.2.
HPLC: Chiralpak IC-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (80:20); flow = 0.7 mL/min; retention time: 10.2
min (major), 12.1 min.
IR (KBr): 3253, 2922, 1579, 1406, 1363, 1205, 1169, 1097, 854,
752 cm–1.
1H NMR (300 MHz, CDCl3): δ = 2.47, (s, 3 H), 4.77 (s, 1 H), 6.17
(s, 1 H), 6.83 (d, J = 7.8 Hz, 1 H), 7.03–7.06 (m, 1 H), 7.09–7.14
(m, 2 H), 7.19–7.24 (m, 1 H), 7.28–7.36 (m, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C14H13NNaO4S: 314.0463;
found: 314.0478.
13C NMR (100 MHz, CDCl3): δ = 19.1, 58.3, 118.8, 121.9, 125.2,
126.9, 128.2, 128.5, 129.3, 129.4, 131.2, 135.8, 137.3, 151.6.
© Georg Thieme Verlag Stuttgart · New York
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HRMS (ESI): m/z [M – H]– calcd for C14H12NO3S: 274.0538;
found: 274.0525.
(4R)-6-Methyl-4-(4-tolyl)-3,4-dihydro-1,2,3-benzoxathiazine
2,2-Dioxide (3p)
White solid; yield: 72 mg (99%; 99% ee); mp 171 °C.
(1R)-1-Phenyl-1,2,7,8,9,10-hexahydronaphtho[1,2-e][1,2,3]ox-
athiazine 3,3-Dioxide (3l)
HPLC: Chiralpak AD-3 column (250 mm); detection: 220 nm;
hexane–i-PrOH (90:10); flow = 0.7 mL/min; retention time: 22.7
min, 23.7 min (major).
Light-yellow solid; yield: 75 mg (96%; 99% ee); mp 184 °C.
HPLC: Chiralpak IC-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (85:15); flow = 0.7 mL/min; retention time: 21.3
min, 23.1 min (major).
IR (KBr): 3296, 1593, 1456, 1419, 1200, 1082, 955, 835 cm–1.
1H NMR (300 MHz, CDCl3): δ = 4.91 (s, 1 H), 6.35 (s, 1 H), 7.24–
7.28 (m, 3 H), 7.30–7.37 (m, 5 H), 7.39–7.45 (m, 1 H), 7.85 (d, J =
8.1 Hz, 1 H), 7.90 (d, J = 8.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 60.6, 114.1, 118.6, 124.2, 125.5,
127.3, 128.2, 128.8, 129.0, 129.2, 130.0, 131.2, 131.3, 138.5, 150.1.
HRMS (ESI): m/z [M – H]– calcd for C17H12NO3S: 310.0538;
IR (KBr): 3261, 2924, 1487, 1421, 1365, 1201, 1174, 1107, 850,
793 cm–1.
1H NMR (300 MHz, CDCl3): δ = 2.20 (s, 3 H), 2.39 (s, 3 H), 4.82
(d, J = 6.3 Hz, 1 H), 5.81 (d, J = 6.3 Hz, 1 H), 6.60 (s, 1 H), 6.93 (d,
J = 6.6 Hz, 1 H), 7.09–7.12 (m, 1 H), 7.21–7.26 (m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 20.7, 21.3, 61.8, 118.5, 121.7,
128.7, 128.7, 130.1, 130.3, 135.0, 135.1, 139.5, 149.4.
HRMS (ESI): m/z [M + Na]+ calcd for C15H15NNaO3S: 312.0670;
found: 312.0684.
found: 310.0524.
(4R)-6-Chloro-4-phenyl-3,4-dihydro-1,2,3-benzoxathiazine 2,2-
Dioxide (3q)
(4R)-6-Methoxy-4-phenyl-3,4-dihydro-1,2,3-benzoxathiazine
2,2-Dioxide (3m)
White solid; yield: 72 mg (99%; 99% ee); mp 148 °C.
White solid; yield: 69 mg (93%; 99% ee); mp 158 °C.
HPLC: Chiralpak AD-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (80:20); flow = 0.7 mL/min; retention time: 9.4 min
(major), 10.6 min.
IR (KBr): 3278, 2924, 1612, 1493, 1429, 1369, 1201, 1171, 1036,
849, 764 cm–1.
1H NMR (300 MHz, CDCl3): δ = 3.64 (s, 3 H), 4.79 (s, 1 H), 5.84
(s, 1 H), 6.29 (d, J = 2.1 Hz, 1 H), 6.84–6.87 (m, 1 H), 6.99 (d, J =
6.6 Hz, 1 H), 7.35 (t, J =2.7 Hz, 2 H), 7.42–7.44 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 55.7, 62.1, 113.2, 115.2, 119.8,
122.8, 128.8, 129.5, 129.6, 137.8, 145.3, 156.5.
IR (KBr): 3288, 1473, 1427, 1367, 1207, 1169, 1113, 845, 781
cm–1.
1H NMR (300 MHz, CDCl3): δ = 4.86 (s, 1 H), 5.85 (s, 1 H), 6.80
(d, J = 2.7 Hz, 1 H), 7.01 (d, J = 9.0 Hz, 1 H), 7.27–7.35 (m, 3 H),
7.46 (t, J = 3.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 61.6, 120.2, 123.5, 128.2, 128.6,
129.6, 129.8, 130.4, 136.9, 149.9.
HRMS (ESI): m/z [M – H]– calcd for C14H12NO4S: 290.0487;
found: 290.0504.
HRMS (ESI): m/z [M – H]– calcd for C13H9ClNO3S: 293.9992;
found: 294.0000.
(4R)-6-Methoxy-4-(4-methoxyphenyl)-3,4-dihydro-1,2,3-ben-
zoxathiazine 2,2-Dioxide (3n)
(4R)-6-Chloro-4-(4-chlorophenyl)-3,4-dihydro-1,2,3-benzoxa-
thiazine 2,2-Dioxide (3r)
Colorless oil; yield: 82 mg (99%; 99% ee).
Colorless oil; yield: 79 mg (98%; 97% ee).
HPLC: Chiralpak IC-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (70:30); flow = 0.7 mL/min; retention time: 17.3
min (major), 23.9 min.
IR (KBr): 3269, 2939, 1612, 1489, 1254, 1171, 1030, 852 cm–1.
HPLC: Chiralpak IC-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (80:20); flow = 0.7 mL/min; retention time: 9.1
min, 11.8 min (major).
1H NMR (300 MHz, CDCl3): δ = 3.62 (s, 3 H), 3.80 (s, 3 H), 5.05
(d, J = 7.8 Hz, 1 H), 5.76 (d, J = 7.8 Hz, 1 H), 6.29 (d, J = 3.0 Hz, 1
H), 6.79–6.84 (m, 1 H), 6.91 (t, J = 9.0 Hz, 3 H), 7.24 (d, J = 9.0 Hz,
2 H).
13C NMR (100 MHz, CDCl3): δ = 57.3, 57.5, 63.4, 115.1, 116.6,
117.1, 121.5, 125.1, 131.6, 132.1, 147.1, 158.3, 162.1.
IR (KBr): 3276, 2920, 1597, 1473, 1427, 1371, 1203, 1167, 1111,
849, 777 cm–1.
1H NMR (300 MHz, CDCl3): δ = 5.21 (s, 1 H), 5.82 (s, 1 H), 6.77
(m, 1 H), 6.99 (d, J = 6.6 Hz, 1 H), 7.27–7.31 (m, 3 H), 7.42–7.44
(m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 61.0, 120.4, 123.1, 128.2, 129.9,
130.1, 130.2, 130.7, 135.4, 136.0, 149.9.
HRMS (ESI): m/z [M + Na]+ calcd for C15H15NNaO5S: 344.0569;
found: 344.0577.
HRMS (ESI): m/z [M + Na]– calcd for C13H9Cl2NNaO3S: 351.9578;
found: 351.9586.
(4R)-6-Methyl-4-phenyl-3,4-dihydro-1,2,3-benzoxathiazine 2,2-
Dioxide (3o)
White solid; yield: 68 mg (99%; 99% ee); mp 168 °C.
(4R)-6-Chloro-4-(3-chlorophenyl)-3,4-dihydro-1,2,3-benzoxa-
thiazine 2,2-Dioxide (3s)
White solid; yield: 81 mg (98%; 99% ee); mp 178 °C.
HPLC: Chiralpak AD-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (80:20); flow = 0.7 mL/min; retention time: 10.5
min (major), 11.9 min.
HPLC: Chiralpak IC-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (80:20); flow = 0.7 mL/min; retention time: 10.6
min, 13.6 min (major).
IR (KBr): 3278, 2922, 1487, 1425, 1365, 1198, 1173, 1111, 858,
700 cm–1.
IR (KBr): 3244, 3207, 1473, 1439, 1367, 1207, 1165, 1109, 849,
783 cm–1.
1H NMR (300 MHz, CDCl3): δ = 4.99 (s, 1 H), 5.81 (s, 1 H), 6.79–
6.80 (m, 1 H), 7.02 (d, J = 6.6 Hz, 1 H), 7.22–7.25 (m, 1 H), 7.30–
7.34 (m, 2 H), 7.39–7.46 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 60.7, 120.0, 122.4, 126.5, 127.7,
128.5, 129.7, 129.7, 130.3, 130.5, 135.1, 138.4, 149.4.
1H NMR (300 MHz, CDCl3): δ = 2.19 (s, 3 H), 4.84 (s, 1 H), 5.83
(s, 1 H), 6.58 (s, 1 H), 6.91 (d, J = 8.7 Hz, 1 H), 7.10 (d, J = 8.4 Hz,
1 H), 7.32–7.35 (m, 2 H), 7.42–7.44 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 20.6, 61.8, 118.4, 121.5, 128.5,
128.7, 129.3, 129.4, 130.2, 134.9, 137.8, 149.3.
HRMS (ESI): m/z [M – H]– calcd for C14H12NO3S: 274.0538;
found: 274.0521.
Synthesis 2013, 45, 2125–2133
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Asymmetric Synthesis of Cyclic Sulfamidates
2131
HRMS (ESI): m/z [M + Na]+ calcd for C13H9Cl2NNaO3S:
351.9578; found: 351.9563.
H), 6.84 (d, J = 8.1 Hz, 1 H), 6.90–7.01 (m, 3 H), 7.28 (d, J = 8.4
Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 57.3, 58.0, 63.5, 113.5, 116.5,
121.5, 125.3, 126.5, 131.9, 132.0, 143.0, 150.6, 162.1.
HRMS (ESI): m/z [M + Na]+ calcd for C15H15NNaO5S: 344.0569;
found: 344.0575.
(4R)-4-(4-Bromophenyl)-6-chloro-3,4-dihydro-1,2,3-benzoxa-
thiazine 2,2-Dioxide (3t)
White solid; yield: 93 mg (98%; 99% ee); mp 185 °C.
HPLC: Chiralpak IC-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (80:20); flow = 0.7 mL/min; retention time: 12.2
min, 13.5 min (major).
(4R)-8-Methyl-4-phenyl-3,4-dihydro-1,2,3-benzoxathiazine 2,2-
Dioxide (3x)
IR (KBr): 3255, 2922, 1647, 1473, 1423, 1375, 1211, 1171, 1109,
White solid; yield: 68 mg (99%; 99% ee); mp 142 °C.
852, 777 cm–1.
HPLC: Chiralpak IC-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (80:20); flow = 0.7 mL/min; retention time: 8.2 min
(major), 9.0 min.
1H NMR (300 MHz, CDCl3): δ = 5.02 (d, J = 6.3 Hz, 1 H), 5.80 (d,
J = 6.6 Hz, 1 H), 6.77 (d, J = 2.1 Hz, 1 H), 6.99 (d, J = 6.6 Hz, 1 H),
7.22 (d, J = 6.3 Hz, 2 H), 7.30 (dd, J = 1.8, 6.6 Hz, 1 H), 7.59 (d, J =
6.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 61.1, 120.4, 123.0, 124.2, 128.1,
130.1, 130.5, 130.7, 132.9, 135.9, 149.9.
IR (KBr): 3269, 2922, 1631, 1433, 1365, 1207, 1149, 879, 719
cm–1.
1H NMR (300 MHz, CDCl3): δ = 2.30 (s, 3 H), 4.81 (s, 1 H), 5.88
(s, 1 H), 6.63 (d, J = 8.1 Hz, 1 H), 6.97 (t, J = 7.5 Hz, 1 H), 7.16 (d,
J = 7.2 Hz, 1 H), 7.32–7.35 (m, 2 H), 7.40–7.43 (m, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C13H9BrClNNaO3S:
395.9073; found: 395.9077.
13C NMR (100 MHz, CDCl3): δ = 15.6, 62.0, 121.8, 124.6, 126.1,
128.2, 128.8, 129.4, 129.5, 131.1, 138.2, 150.2.
HRMS (ESI): m/z [M – H]– calcd for C14H12NO3S: 274.0538;
found: 274.0531.
(4R)-7-Methoxy-4-phenyl-3,4-dihydro-1,2,3-benzoxathiazine
2,2-Dioxide (3u)
Light-yellow solid; yield: 72 mg (99%; 99% ee); mp 181 °C.
HPLC: Chiralpak AD-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (80:20); flow = 0.7 mL/min; retention time: 16.8
min (major), 20.3 min.
(4R)-8-Methyl-4-(4-tolyl)-3,4-dihydro-1,2,3-benzoxathiazine
2,2-Dioxide (3y)
White solid; yield: 71 mg (98%; 99% ee); mp 174 °C.
IR (KBr): 3205, 2920, 1626, 1427, 1367, 1200, 1151, 1090, 953,
798 cm–1.
1H NMR (300 MHz, CDCl3): δ = 3.79 (s, 3 H), 4.79–4.81 (m, 1 H),
5.82 (d, J = 6.3 Hz, 1 H), 6.55–6.56 (m, 1 H), 6.63–6.72 (m, 2 H),
7.32–7.35 (m, 2 H), 7.42–7.44 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 55.5, 61.4, 103.3, 112.1, 113.7,
128.6, 129.1, 129.3, 129.4, 137.9, 152.1, 160.3.
HPLC: Chiralpak AD-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (85:15); flow = 0.7 mL/min; retention time: 11.2
min, 14.5 min (major).
IR (KBr): 3249, 2925, 1462, 1408, 1369, 1200, 1149, 872, 795
cm–1.
1H NMR (300 MHz, CDCl3): δ = 2.25 (s, 3 H), 2.38 (s, 3 H), 4.87
(s, 1 H), 5.84 (s, 1 H), 6.64 (d, J = 5.7 Hz, 1 H), 6.96 (t, J = 6.0 Hz,
1 H), 7.15 (d, J = 6.3 Hz, 1 H), 7.22 (d, J = 6.6 Hz, 4 H).
HRMS (ESI): m/z [M – H]– calcd for C14H12NO4S: 290.0487;
found: 290.0500.
13C NMR (100 MHz, CDCl3): δ = 15.5, 21.2, 61.7, 122.0, 124.4,
126.1, 128.0, 128.6, 130.0, 130.9, 135.1, 139.4, 149.9.
HRMS (ESI): m/z [M + Na]+ calcd for C15H15NNaO3S: 312.0670;
found: 312.0654.
(4R)-8-Methoxy-4-phenyl-3,4-dihydro-1,2,3-benzoxathiazine
2,2-Dioxide (3v)
White solid; yield: 72 mg (99%; 99% ee); mp 144 °C.
HPLC: Chiralpak AD-H column (250 mm); detection: 220 nm; hex-
ane–i-PrOH (80:20); flow = 0.7 mL/min; retention time: 16.9 min,
19.4 min (major).
(4R)-4-(4-Bromophenyl)-8-methyl-3,4-dihydro-1,2,3-benzoxa-
thiazine 2,2-Dioxide (3z)
White solid; yield: 87 mg (98%; 99% ee); mp 182 °C.
IR (KBr): 3236, 2922, 1581, 1442, 1365, 1209, 1157, 1082, 870
cm–1.
1H NMR (300 MHz, CDCl3): δ = 3.89 (s, 3 H), 4.81 (s, 1 H), 5.91
(s, 1 H), 6.38 (d, J = 7.8 Hz, 1 H), 6.90 (d, J = 8.1 Hz, 1 H), 7.02 (t,
J = 8.1 Hz, 1 H), 7.34–7.37 (m, 2 H), 7.42–7.45 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 56.2, 62.1, 111.8, 119.6, 123.0,
124.8, 128.8, 129.4, 129.5, 138.0, 141.3, 148.8.
HPLC: Chiralpak IC-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (80:20); flow = 0.7 mL/min; retention time: 11.1
min (major), 14.1 min.
IR (KBr): 3286, 2922, 1597, 1412, 1367, 1200, 1155, 1011, 868,
775 cm–1.
1H NMR (300 MHz, CDCl3): δ = 2.26 (s, 3 H), 4.97 (s, 1 H), 5.83
(s, 1 H), 6.61 (d, J = 5.7 Hz, 1 H), 6.98 (t, J = 5.7 Hz, 1 H), 7.17–
7.19 (m, 1 H), 7.21–7.24 (m, 2 H), 7.53–7.57 (m, 2 H).
HRMS (ESI): m/z [M – H]– calcd for C14H12NO4S: 290.0487;
found: 290.0503.
13C NMR (100 MHz, CDCl3): δ = 15.5, 61.3, 121.2, 123.6, 124.7,
125.9, 128.3, 130.5, 131.3, 132.5, 137.1, 150.0.
HRMS (ESI): m/z [M + Na]+ calcd for C14H12BrNNaO3S:
375.9619; found: 375.9604.
(4R)-8-Methoxy-4-(4-methoxyphenyl)-3,4-dihydro-1,2,3-ben-
zoxathiazine 2,2-Dioxide (3w)
White solid; yield: 77 mg (96%; 97% ee); mp 191 °C.
Crystal data: C14H12BrNO3S: T = 100 K, wavelength: 0.71073 Å.
Crystal system: orthorhombic, space group: P212121; unit cell di-
mensions: a = 9.6530(3) Å, b = 12.3548(4) Å, c = 24.1314(9) Å,
V = 2877.93(17) Å3, Z = 8, ρcalcd = 1.635 g/cm3; F; (000) = 1424.
The final anisotropic full-matrix least-squares refinement on F2
with 368 variables converged at R1 = 3.97% (4343), for the ob-
served data and wR2 = 7.49% (6611) for all data. The goodness-of-
HPLC: Chiralpak IC-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (70:30); flow = 0.7 mL/min; retention time: 23.8
min (major), 28.0 min.
IR (KBr): 3299, 2920, 1614, 1479, 1410, 1267, 1200, 1155, 1082,
876, 789 cm–1.
1H NMR (300 MHz, CDCl3): δ = 3.80 (s, 3 H), 3.81 (s, 3 H), 5.01
(d, J = 8.7 Hz, 1 H),5.83 (d, J = 8.7 Hz, 1 H), 6.37 (d, J = 8.1 Hz, 1
© Georg Thieme Verlag Stuttgart · New York
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SPECIAL TOPIC
fit was 0.998. Data were corrected for absorption effects by using
the multi-scan method (SADABS).12
References
(1) (a) Liu, Y. G.; Xiao, W. B.; Wong, M. K.; Che, C. M. Org.
Lett. 2007, 9, 4107. (b) Alig, B.; Müller, K. H.; Franken,
E.-M.; Görgens, U.; Voerste, A. WO2010072310, 2010.
(c) Kim, S. J.; Jung, M. H.; Yoo, K. H.; Cho, J. H.; Oh, C. H.
Bioorg. Med. Chem. Lett. 2008, 18, 5815. (d) Kim, S. J.;
Park, H. B.; Lee, J. S.; Jo, N. H.; Yoo, K. H.; Baek, D.; Kang,
B.-w.; Cho, J. H.; Oh, C. H. Eur. J. Med. Chem. 2007, 42,
1176. (e) Petry, S.; Baringhaus, K. H.; Hölder, S.; Mueller,
G. WO2002011722, 2002.
(2) For a review, see: (a) Meleńdez, R. E.; Lubell, W. D.
Tetrahedron 2003, 59, 2581. For selected examples, see:
(b) Brodsky, B. H.; Du Bois, J. J. Am. Chem. Soc. 2005, 127,
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Chiral Aryl Amines 5 and 6; General Procedure
A 10-mL Schlenk flask was charged with cyclic sulfamate 4 (0.4
mmol) under N2, then 5 mol% of Ni(dppp)Cl2 in benzene (4 mL)
was added from a syringe. The resulting red suspension was treated
with a 0.5–2 M soln of RMgX (0.8 mmol, 2 equiv) in Et2O, and mix-
ture was stirred at 55 °C for 15 h. The mixture was then cooled to
25 °C and the reaction was quenched by the addition of MeOH (500
μL). The resulting mixture was stirred vigorously for 5 min and then
transferred to a recovery flask. All volatiles were removed by con-
centration under reduced pressure to give an oily residue that was
treated with anhyd 2 M methanolic HCl (2 mL). The resulting or-
ange solution was stirred at 55 °C for 6 h then cooled to 25 °C and
poured carefully into a separatory funnel containing sat. aq
NaHCO3 (10 mL). The organic phase was separated and collected,
and the aqueous solution was extracted with EtOAc (3 × 15 mL).
The organic phases were combined, washed with sat. aq NaCl (10
mL), dried (MgSO4), filtered, and concentrated under reduced pres-
sure to give a residue that was purified by chromatography (silica
gel, PE–EtOAc, 4:1).
(R)-1-Biphenyl-2-yl-N-methyl-1-(4-tolyl)methanamine (5)
Light-yellow oil; yield: 91 mg (79%; 99% ee).
HPLC: Chiralpak IC-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (99:1); flow = 0.5 mL/min; retention time: 12.7 min
(major), 14.1 min.
IR (KBr): 3338, 3022, 2947, 1597, 1475, 1438, 1124, 804, 752, 702
cm–1.
1H NMR (300 MHz, CDCl3): δ = 2.29 (s, 3 H), 2.29 (s, 3 H), 4.80
(s, 1 H), 7.03–7.06 (m, 4 H), 7.18–7.28 (m, 4 H), 7.35–7.42 (m, 4
H), 7.60–7.63 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 21.0, 34.8, 64.1, 126.4, 126.9,
127.0, 127.4, 127.8, 127.9, 128.9, 129.4, 129.9, 136.2, 140.7, 141.2,
141.4, 141.9.
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and aziridination, see: (a) Barman, D. N.; Nicholas, K. M.
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HRMS (EI): m/z [M]+ calcd for C21H21N: calcd 287.1674; found:
287.1663.
(R)-N-Methyl-1-(2-tolyl)-1-(4-tolyl)methanamine (6)
Light-yellow oil; yield: 74 mg (82%; 99% ee).
HPLC: Chiralpak AY-H column (250 mm); detection: 220 nm;
hexane–i-PrOH (97:3); flow = 0.7 mL/min; retention time: 7.3 min,
8.0 min (major).
IR (KBr): 3356, 2952, 2922, 1739, 1662, 1460, 1377, 1111, 814,
748 cm–1.
1H NMR (300 MHz, CDCl3): δ = 2.28 (s, 3 H), 2.30 (s, 3 H), 2.41
(s, 3 H), 4.84 (s, 1 H), 7.08–7.12 (m, 3 H), 7.13–7.15 (m, 1 H), 7.19–
7.23 (m, 2 H), 7.24–7.25 (m, 1 H), 7.57 (d, J = 5.7 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 19.6, 21.1, 35.1, 64.9, 126.1,
126.2, 126.6, 127.9, 129.0, 130.5, 135.7, 136.5, 139.8, 141.4.
(7) Wang, Y.-Q.; Yu, C.-B.; Wang, D.-W.; Wang, X.-B.; Zhou,
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HRMS (EI): m/z [M]+ calcd for C16H19N: calcd 225.1517; found:
225.1505.
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Acknowledgment
(9) Boronic Acids: Preparation and Applications in Organic
Synthesis and Medicine; Hall, D. G., Ed.; Wiley-VCH:
Weinheim, 2005.
We thank the National Natural Science Foundation of China
(20972172 and 21021063) for financial support.
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Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
n
nfomartit
Synthesis 2013, 45, 2125–2133
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
(e) Wang, H.; Zhu, T.-S.; Xu, M.-H. Org. Biomol. Chem.
Asymmetric Synthesis of Cyclic Sulfamidates
2133
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2125–2133