Catalytic enantioselective allylic amination of olefins for the synthesis of ent -sitagliptin

Article abstract of DOI:10.1055/s-0033-1340079

The presence of nitrogen atoms in most chiral pharmaceutical drugs has motivated the development of numerous strategies for the synthesis of enantiomerically enriched amines. Current methods are based on multistep transformations of functionalized allylic electrophiles to form chiral allylic amines. The enantioselective allylic amination of nonactivated olefins would represent a more direct and more attractive strategy. We report the enantio selective synthesis of ent-sitagliptin through an allylic amination of a nonactivated terminal olefin. Georg Thieme Verlag Stuttgart, New York.

Full text of DOI:10.1055/s-0033-1340079

LETTER
▌2459
lCettaertalytic Enantioselective Allylic Amination of Olefins for the Synthesis of
ent-Sitagliptin
Enantioselective Synthesis of ent-Sitagliptin
Hongli Bao, Liela Bayeh, Uttam K. Tambar*
Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines
Boulevard, Dallas, TX 75390-9038, USA
Fax +1(214)6488856; E-mail: Uttam.Tambar@utsouthwestern.edu
Received: 28.07.2013; Accepted after revision: 10.10.2013
Abstract: The presence of nitrogen atoms in most chiral pharma-
ceutical drugs has motivated the development of numerous strate-
gies for the synthesis of enantiomerically enriched amines. Current
methods are based on multistep transformations of functionalized
allylic electrophiles to form chiral allylic amines. The enantioselec-
tive allylic amination of nonactivated olefins would represent a
more direct and more attractive strategy. We report the enantio-
selective synthesis of ent-sitagliptin through an allylic amination of
Uttam K. Tambar (middle) moved from India to the USA when he
was four years old. He received his A.B. degree from Harvard Uni-
versity in 2000 and his Ph.D. from the California Institute of Technol-
ogy in 2006, under the supervision of Professor Brian Stoltz. After
a nonactivated terminal olefin.
Key words: asymmetric catalysis, aminations, drugs, rearrange-
ments, palladium
completing an NIH Postdoctoral Fellowship at Columbia University
with Professor James Leighton in 2009, Uttam began his independent
research career at UT Southwestern Medical Center in Dallas. He is
currently an assistant professor in the Biochemistry Department and
a W. W. Caruth, Jr. Scholar in Biomedical Research. His research in-
terests include asymmetric catalysis, natural product synthesis, and
Nitrogen atoms are present in more than 80% of pharma-
ceutical drugs approved by the U.S. Food and Drug Ad-
ministration (FDA).1,2 The presence of nitrogen atoms in
small molecules leads to desirable medicinal properties,
including improved solubility under physiological condi-
tions, favorable polar surfaces, and hydrogen-bonding in-
teractions with amino acid residues. As a result, many
powerful chemical methods have been developed for the
incorporation of nitrogen atoms into small molecules,
with profound effects on the discovery of new drugs.3
medicinal chemistry.
Hongli Bao (right) received her B.S. degree in chemistry from the
University of Science and Technology of China in 2002. She obtained
her Ph.D. through the joint program of the Shanghai Institute of Or-
ganic Chemistry and the University of Science & Technology of Chi-
na in 2008 under the supervision of Professor Kuiling Ding and
Professor Tianpa You. She joined the Tambar group in 2009, and she
is interested in developing metal-catalyzed enantioselective [2,3]-re-
arrangements. Hongli is a recipient of the UT Southwestern Chilton
Postdoctoral Fellowship in Biochemistry.
Liela Bayeh (left) received her B.S. degree in Biochemistry from
Baylor University in 2011 and then moved on to UT Southwestern
Medical Center in Dallas to complete her Ph.D. studies. Since joining
the Tambar laboratory in 2012, her research has focused primarily on
asymmetric catalysis and medicinal chemistry.
Chiral amines represent an important subclass of medici-
nally relevant nitrogen-containing molecules.4 For exam-
ple, sitagliptin (1) is an FDA-approved inhibitor of
dipeptidyl peptidase-4 for the treatment of Type II diabe-
tes (Scheme 1).5,6 Several elegant enantioselective meth-
ods have been developed for the synthesis of chiral
amines 4 from allylic alcohols and other allylic electro-
philes, such as allylic halides 3.7
We recently reported a palladium-catalyzed enantioselec-
tive allylic amination of nonactivated terminal olefins
through an ene reaction/[2,3]-rearrangement.10 Here, we
describe the application of this approach to the enantiose-
lective synthesis of ent-sitagliptin (1).
We were interested in developing an alternative approach
for the preparation of chiral amines 4 by direct conversion
of nonfunctionalized olefins 2 through an allylic amina-
tion in the presence of a chiral catalyst.8 Unsaturated hy-
drocarbons such as 2 are ideal substrates for chemical
synthesis because they are inexpensive and abundant
components of petrochemical feedstocks.9 However, ole-
fins are also challenging substrates for asymmetric catal-
ysis, because it is difficult to achieve selective
transformation of a single C–H bond into a C–N bond in
the presence of several sterically and electronically simi-
lar C–H bonds.
Several elegant approaches to sitagliptin have been re-
ported in the literature.6 Most notably, researchers at Mer-
ck developed multiple enantioselective routes to this
compound.6a–d,6g In our retrosynthetic analysis of ent-sita-
gliptin (Scheme 2), we surmised that the target molecule
1 might be obtained from β-amino acid 5. This intermedi-
ate might, in turn, be generated from the allylic amine de-
rivative
6
through
a
series of functional-group
interconversions. Enantiomerically enriched allylic amine
6 is a suitable retron for our recently developed catalytic
enantioselective allylic amination of nonactivated olefins.
The analysis therefore suggested that 1-but-3-en-1-yl-
SYNLETT 2013, 24, 2459–2463
Advanced online publication: 22.10.2013
DOI: 10.1055/s-0033-1340079; Art ID: ST-2013-S0710-L
© Georg Thieme Verlag Stuttgart · New York
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6

2460
H. Bao et al.
LETTER
X = OH, halide, OAc, OCO2R4
X
R1
3
F
F
chiral
metal
catalyst
F
R2
R3
NH2
O
R1
N
N
R1
N
nitrogen
source
N
N
2
1
4
nonactivated
olefin
(petrochemical
feedstock)
this
work
ent-sitagliptin
(pharmaceutical
drug)
CF3
chiral
amine
Scheme 1 Strategies for the conversion of nonactivated olefins into chiral allylic amines
ment, the discovery of which was inspired by the seminal
reports of Sharpless, Kresze, and Katz and their respective
co-workers on the conversion of olefins into racemic
allylic amines.11 In the first step, a nonactivated olefin 2a
reacts with sulfurdiimide reagent 8 through a hetero-ene
reaction. The resulting zwitterion 9a is subjected to a
palladium-catalyzed enantioselective [2,3]-rearrangement
to give the desired allylic amine 11a.
F
Ph
O2S
F
F
F
NH
O
NH2
O
N
OH
N
N
F
F
N
5
1
CF3
ent-sitagliptin
O2
S
As a model system for our first step in the synthesis of ent-
sitagliptin (7 → 6, Scheme 2), we selected but-3-en-1-yl-
benzene (2b), which lacked the three fluoride substituents
in the aromatic ring of olefin 7 (Scheme 3). We expected
that our carefully optimized conditions for the palladium-
catalyzed generation of allylic amines 11a with aliphatic
substitution at the homoallylic position would also be suit-
able for the conversion of aryl alkene 2b into the allylic
amine 11b with aromatic substitution at the homoallylic
position. To our dismay, however, in the presence of 10
mol% palladium(II) trifluoroacetate and 12 mol% of li-
gand 10a, the allylic amine 11b was generated in only 4%
enantiomeric excess (Table 1, entry 2).
F
F
enantioselective
allylic
amination
F
F
Ph HN
O2S
Ph
F
F
S
N
6
7
Scheme 2 Retrosynthetic analysis of sitagliptin
2,4,5-trifluorobenzene (7) would be a suitable starting
point for our synthetic efforts.
In an initial report, we described a catalytic enantioselec-
tive intermolecular allylic amination of nonactivated ter-
minal olefins that are substituted with aliphatic
substituents (2a → 11a, Scheme 3).10 This transformation
proceeds through a two-step ene reaction/[2,3]-rearrange-
Although we still do not known why terminal olefins with
aromatic substitution in the homoallylic position do not
behave well under our previously optimized conditions,
Pd(TFA)2 (10 mol%)
ligand 10a (12 mol%)
PhSO2
R
SNHSO2Ph
N
–15 °C to 4 °C
MeOH, 2–7 d
11a
8
R = aliphatic
61–97% yield
91–98% ee
H
N
PhSO2N
S
NSO2Ph
PhSO2
N
R
S
SO2Ph
Et2O
4 °C, 12 h
R
2a, R = aliphatic
2b, R = Ph
9
(purified by filtration)
Pd(TFA)2 (10 mol%)
ligand 10a (12 mol%)
PhSO2
SNHSO2Ph
Me Me
N
O
O
4 °C
Ph
MeOH, 2 d
11b
R = Ph
91% yield
4% ee
N
N
10a
Ph
Ph
Scheme 3 Allylic aminations of alkene substrates
Synlett 2013, 24, 2459–2463
© Georg Thieme Verlag Stuttgart · New York

LETTER
Enantioselective Synthesis of ent-Sitagliptin
2461
Table 1 Optimization of Enantioselective Allylic Amination
PhSO2N
S
8
NSO2Ph
H
PhSO2
Ph
SNHSO2Ph
N
N
conditions
N
Ph
PhSO2
Ph
S
SO2Ph
Et2O, 4 °C, 12 h
9b
11b
2b
(purified by filtration)
Entry
Metal catalyst (10 mol%) Ligand (mol%)
Solvent (0.13 M)
Temp (°C)
Time (d)
Yielda
ee (%)
1
2
–
–
–
4
4
0.5
2
< 5
91
71
75
60
63
73
80
94
94
–
Pd(TFA)2
Pd(OAc)2
Pd(OAc)2
Pd2(dba)3
PdCl2(MeCN)2
Pd(acac)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
10a (12)
10a (12)
10b (12)
10b (12)
10b (12)
10b (12)
10b (12)
10b (12)
10b (20)
CH2Cl2
MeOH
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DCE
4
3
4
0.5
0.5
2
19
79
0
4
4
5
4
6
4
2
6
7
4
2
0
8
4
2
85
91
93
9
4
2
10
DCE
–15
7
Me Me
O
O
O
O
N
N
N
N
t-Bu
t-Bu
10a
10b
Ph
Ph
a Isolated yield for two steps.
we decided to reoptimize all the conditions for the palla- derivatives 11 (Table 2).13 This reaction tolerated both
dium-catalyzed [2,3]-rearrangement step with the model electron-withdrawing and electron-donating substituents.
substrate but-3-en-1-ylbenzene (2b) (Table 1). We con- In all cases, the allylic amination products 11 were isolat-
firmed that zwitterion 9b did not undergo a thermal ed in synthetically useful yields and enantiomeric excess-
[2,3]-rearrangement in the absence of a palladium catalyst es.
at 4 °C (Table 1, entry 1). As discussed above, treatment
of zwitterion 9b with ligand 10a under our previously op-
timized conditions resulted in an almost racemic product
(entry 2). After surveying other bisoxazoline and bisoxa-
zolinyl-pyridine ligands with palladium(II) acetate, we
found that bisoxazoline 10b was a more effective ligand
Next, we used our new reaction conditions in an enantio-
selective allylic amination of 1-but-3-en-1-yl-2,4,5-triflu-
orobenzene (7) as a step in our synthesis of ent-sitagliptin
(Scheme 4). To our delight, aryl alkene 7 was smoothly
converted into the desired allylic amine derivative 6 by a
hetero-ene reaction followed by a palladium-catalyzed en-
antioselective [2,3]-rearrangement. Treatment of the re-
sulting allylic amination product 6 with methanolic
than bisoxazoline 10a (entries 3 and 4), giving the desired
product in 75% yield and 79% ee (entry 4).12 We also ex-
amined a series of palladium sources (entries 5–8), among
potassium carbonate gave the allylic sulfonamide 12 in
which palladium(II) trifluoroacetate proved to be the most
78% yield (three steps) and 93% ee. Hydroboration and
promising (entry 8). We were now able to isolate the de-
extensive oxidation of olefin 12 gave the β-amino acid 5.
Coupling of amino acid 5 with amine 13, and subsequent
deprotection of the sulfonamide gave ent-sitagliptin (1).
sired product in 80% yield and 85% ee. By screening sev-
eral solvents,12 we identified 1,2-dichloroethane as the
optimal medium for the reaction (entry 9). Finally, by
lowering the reaction temperature to –15 °C and increas-
ing the loading of ligand 10b to 20 mol%, we generated
allylic amination product 11b in 94% isolated yield (two
In conclusion, our synthesis of ent-sitagliptin highlights
the potential utility of enantioselective allylic amination
as an economically efficient and environmentally benign
alternative for the production of pharmaceutical drugs.
We expect that this method will be useful for the synthesis
of other nitrogen-containing pharmaceutical agents from
inexpensive and abundant nonactivated olefins.
steps) and 93% ee (entry 10).
Having identified the optimal conditions, we then con-
verted a series of 4-arylbut-1-ene substrates 2 into the cor-
responding enantiomerically enriched allylic amine
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 2459–2463

2462
H. Bao et al.
LETTER
Table 2 Substrate Scope of Enantioselective Allylic Amination
Pd(TFA)2 (10 mol%)
Ligand 10b (20 mol%)
PhSO2N
S
8
NSO2Ph
H
PhSO2
R
SNHSO2Ph
N
N
N
R
PhSO2
S
SO2Ph
DCE, –15 °C
4–7 d
Et2O
R
4 °C, 12 h
2
11
R = aromatic
O
O
9
R = aromatic
(purified by
filtration)
N
N
10b
t-Bu
t-Bu
Entry
1
Olefin
Product
Yielda
94
ee (%)
93
PhSO2
SNHSO2Ph
N
PhSO2
SNHSO2Ph
F
F
N
2
3
4
5
89
79
83
84
90
90
95
81
PhSO2
F3C
F3C
SNHSO2Ph
N
PhO2S
PhO2S
SNHSO2Ph
SNHSO2Ph
N
N
MeO
MeO
MeO
MeO
a Isolated yield for two steps.
O2
F
F
F
F
Ph
O2S
S
F
F
Ph HN
O2S
Ph
F
F
a, b
c
NH
F
S
N
12
7
6
78% yield, 93% ee
(3 steps)
F
F
F
Ph
O2S
F
NH2
O
F
d, e
f, g
NH
O
N
N
N
N
OH
HN
N
N
F
N
ent-sitagliptin
40% yield
(4 steps)
(1)
CF3
⋅HCl
5
CF3
13
Scheme 4 Enantioselective synthesis of ent-sitagliptin. Reaction conditions: (a) 8, Et2O, 4 °C, 12 h; (b) Pd(TFA)2 (10 mol%), ligand 10h
(20 mol%), DCE, –15°C, 7 d; (c) K2CO3, MeOH, H2O, 16 h; (d) 9-BBN, THF, then aq NaOH, H2O2; (e) CrO3, H5IO6, MeCN, 0 °C; (f) 13,
1H-1,2,3-benzotriazol-1-ol, EDC, DIPEA, DMF; (g) MsOH, TFA, PhSMe, 40 °C.
Acknowledgment
References and Notes
Financial support was provided by the W. W. Caruth, Jr. Endowed
Scholarship, the Robert A. Welch Foundation (Grant I-1748), the
National Institutes of Health (1R01GM102604-01), a Chilton Foun-
dation Fellowship (H.B.), a University of Texas System Chemistry
and Biology Training Grant (L.B.), and a Sloan Research Fellow-
ship (U.K.T.).
(1) (a) Henkel, T.; Brunne, R. M.; Müller, H.; Reichel, F.
Angew. Chem. Int. Ed. 1999, 38, 643. (b) Hili, R.; Yudin, A.
K. Nat. Chem. Biol. 2006, 2, 284.
(2) The structures of more than 1400 FDA-approved small-
molecule drugs were downloaded from DrugBank
(http://www.drugbank.ca/) and analyzed manually for the
presence of N atoms. See Supporting Information.
(3) (a) Jiang, L.; Buchwald, S. L. In Metal-Catalyzed Cross-
Coupling Reactions: de Meijere A., Diederich F; Wiley-
VCH: Weinheim, 2004, 2nd ed., Vol. 2, 699. (b) Hartwig, J.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnoIufproig
m
iotSrat
ungIifoop
r
t
Synlett 2013, 24, 2459–2463
© Georg Thieme Verlag Stuttgart · New York

LETTER
F. In Handbook of Organopalladium Chemistry for Organic
Enantioselective Synthesis of ent-Sitagliptin
2463
6761. (d) Lafrance, M.; Roggen, M.; Carreira, E. M. Angew.
Chem. Int. Ed. 2012, 51, 3470; and references therein.
(8) (a) Johannsen, M.; Jørgensen, K. A. Chem. Rev. 1998, 98,
1689. (b) Ramirez, T. A.; Zhao, B.; Shi, Y. Chem. Soc. Rev.
2012, 41, 931. (c) Collet, F.; Lescot, C.; Dauban, P. Chem.
Soc. Rev. 2011, 40, 1926. (d) Zalatan, D. N.; Du Bois, J. Top.
Curr. Chem. 2010, 292, 347.
Synthesis; Negishi, E., Ed.; Wiley-Interscience: New York,
2002. (c) Davies, H. M. L.; Long, M. S. Angew. Chem. Int.
Ed. 2005, 44, 3518. (d) Beccalli, E. M.; Broggini, G.;
Martinelli, M.; Sottocornola, S. Chem. Rev. 2007, 107, 5318.
(e) Surry, D. S.; Buchwald, S. L. Chem. Sci. 2011, 2, 27.
(f) Collet, F.; Dodd, R. H.; Dauban, P. Chem. Commun.
2009, 5061. (g) Davies, H. M. L.; Manning, J. R. Nature
2008, 451, 417.
(9) Handbook of Metathesis; Vol. 2; Grubbs, R. H., Ed.; Wiley-
VCH: Weinheim, 2003.
(4) Farina, V.; Reeves, J. T.; Senanayake, C. H.; Song, J. J.
Chem. Rev. 2006, 106, 2734.
(5) For reviews on sitagliptin, see: (a) Aschner, P.; Kipnes, M.
S.; Lunceford, J. K.; Sanchez, M.; Mickel, C.; Williams-
Herman, D. E. Diabetes Care 2006, 29, 2632.
(10) Bao, H.; Tambar, U. K. J. Am. Chem. Soc. 2012, 134, 18495.
(11) (a) Sharpless, K. B.; Hori, T. J. Org. Chem. 1976, 41, 176.
(b) Sharpless, K. B.; Hori, T.; Truesdale, L. K.; Dietrich, C.
O. J. Am. Chem. Soc. 1976, 98, 269. (c) Kresze, G.;
Münsterer, H. J. Org. Chem. 1983, 48, 3561. (d) Katz, T. J.;
Shi, S. J. Org. Chem. 1994, 59, 8297. (e) Bruncko, M.;
Khuong, T.-A. V.; Sharpless, K. B. Angew. Chem. Int. Ed.
1996, 35, 454.
(b) Thornberry, N. A.; Weber, A. E. Curr. Top. Med. Chem.
2007, 7, 557. (c) Miller, S. A.; St. Onge, E. L. Ann.
Pharmacother. 2006, 40, 1336. (d) Desai, A. A. Angew.
Chem. Int. Ed. 2011, 50, 1974.
(12) For a more complete account of the optimization of the
reaction parameters, see Table S1 in the Supporting
Information.
(6) For recent syntheses of sitagliptin, see: (a) Hansen, K. B.;
Balsells, J.; Dreher, S.; Hsiao, Y.; Kubryk, M.; Palucki, M.;
Rivera, N.; Steinhuebel, D.; Armstrong, J. D. III.; Askin, D.;
Grabowski, E. J. J. Org. Process Res. Dev. 2005, 9, 634.
(b) Clausen, A. M.; Dziadul, B.; Cappuccio, K. L.; Kaba,
M.; Starbuck, C.; Hsiao, Y.; Dowling, T. M. Org. Process
Res. Dev. 2006, 10, 723. (c) Hansen, K. B.; Hsiao, Y.; Xu,
F.; Rivera, N.; Clausen, A.; Kubryk, M.; Krska, S.; Rosner,
T.; Simmons, B.; Balsells, J.; Ikemoto, N.; Sun, Y.; Spindler,
F.; Malan, C.; Grabowski, E. J. J.; Armstrong, J. D. III.
J. Am. Chem. Soc. 2009, 131, 8798. (d) Steinhuebel, D.; Sun,
Y.; Matsumura, K.; Sayo, N.; Saito, T. J. Am. Chem. Soc.
2009, 131, 11316. (e) Zeng, L. L.; Ding, Y. J.; Zhang, G. C.;
Song, H. R.; Hu, W. H. Chin. Chem. Lett. 2009, 20, 1397.
(f) Liu, F.; Yu, W.; Ou, W.; Wang, X.; Ruan, L.; Li, Y.;
Peng, X.; Tao, X.; Pan, X. J. Chem. Res. 2010, 34, 230.
(g) Savile, C. K.; Janey, J. M.; Mundorff, E. C.; Moore, J. C.;
Tam, S.; Jarvis, W. R.; Colbeck, J. C.; Krebber, A.; Fleitz, F.
J.; Brands, J.; Devine, P. N.; Huisman, G. W.; Hughes, G. J.
Science 2010, 329, 305. (h) Davies, S. G.; Fletcher, A. M.;
Lv, L.; Roberts, P. M.; Thomson, J. E. Tetrahedron Lett.
2012, 53, 3052. (i) Fistikci, M.; Gundogdu, O.; Aktas, D.;
Secen, H.; Sahin, M. F.; Altundas, R.; Kara, Y. Tetrahedron
2012, 68, 2607.
(13) N-[(1S)-1-Benzylprop-2-en-1-yl]-N-
{[(phenylsulfonyl)amino]sulfanyl}benzenesulfonamide
(11b); Typical Procedure
A 0.5 M solution of diimide 8 (685 mg, 2 mmol) in Et2O (4
mL) was cooled to 0 °C and treated with but-3-en-1-
ylbenzene (6 mmol, 3 equiv), and the mixture was stirred at
4 °C for 12 h. The ene adduct 9, which formed as a white
precipitate, was purified by vacuum filtration at r.t., washed
with Et2O (20–40 mL), and dried under vacuum. The ene
adduct 9 was then suspended in DCE (5 mL) and the
suspension was cooled to –20 °C then treated with a Pd–
ligand complex in DCE (10 mL). The Pd–ligand complex
was prepared by mixing Pd(TFA)2 (10 mol%) and ligand
10b (20 mol%) in DCE (10 mL), and stirring for 30 min at
50 °C. The ene adduct-containing mixture was warmed to
–15 °C and stirred for 7 d. Purification by flash
chromatography [hexanes–EtOAc (20:1 to 5:1)] gave a clear
oil; yield: 887 mg (94%, two steps); [α]D23 = +93.0 (c 1.0,
CH2Cl2). The enantiomeric excess of the product was
determined to be 93% by comparison with a sample of the
racemate. IR (thin film): 3234, 1447, 1352, 1165, 1088, 806
cm–1. 1H NMR (500 MHz, CDCl3, 50 °C): δ = 7.90 (d,
J = 7.5 Hz, 2 H), 7.59 (t, J = 7.5 Hz, 1 H), 7.52 (t, J = 7.5 Hz,
4 H), 7.37 (m, 2 H), 7.18–7.10 (m, 6 H), 6.95 (s, 1 H), 6.10
(7) For excellent discussions on the synthesis of allylic amines
by means of catalytic asymmetric allylic amination from
functionalized substrates, see: (a) Hartwig, J. F.; Stanley, L.
M. Acc. Chem. Res. 2010, 43, 1461. (b) Trost, B. M.; Zhang,
T.; Sieber, J. D. Chem. Sci. 2010, 1, 427. (c) Evans, P. A.;
Robinson, J. E.; Nelson, J. D. J. Am. Chem. Soc. 1999, 121,
(br s, 1 H), 5.07 (m, 2 H), 4.80 (m, 1 H), 3.23 (m, 2 H). 13
C
NMR (100 MHz, CDCl3, 50 °C): δ = 140.9, 139.6, 137.8,
133.4, 133.3, 129.6, 129.4, 129.1, 28.6, 127.9, 127.3, 126.7,
118.9, 68.2, 39.9. HRMS (ESI): m/z [M + Na]+ calcd for
[C22H22N2O4S3Na]+: 497.0634; found: 497.0645.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 2459–2463

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