Enantioselective synthesis of cyclic sulfamidates via Pd-catalyzed hydrogenation

Article abstract of DOI:10.1021/ol800591u

Using Pd(CF₃;CO₂)₂/(S,S)-f-binaphane as the catalyst, an efficient enantioselective synthesis of cyclic sulfamidates was developed via asymmetric hydrogenation of the corresponding cyclic imines in 2,2,2-trifluoroethanol at room temperature with high enantioselectivities (up to 99% ee).

Full text of DOI:10.1021/ol800591u

ORGANIC
LETTERS
2008
Vol. 10, No. 10
2071-2074
Enantioselective Synthesis of Cyclic
Sulfamidates via Pd-Catalyzed
Hydrogenation
You-Qing Wang,† Chang-Bin Yu,† Da-Wei Wang,† Xiao-Bing Wang,† and
Yong-Gui Zhou*,†,‡
State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese
Academy of Sciences (CAS), 457 Zhongshan Road, Dalian 116023, China, State Key
Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai 200032, China
ygzhou@dicp.ac.cn
Received March 13, 2008
ABSTRACT
Using Pd(CF3CO2)2/(S,S)-f-binaphane as the catalyst, an efficient enantioselective synthesis of cyclic sulfamidates was developed via asymmetric
hydrogenation of the corresponding cyclic imines in 2,2,2-trifluoroethanol at room temperature with high enantioselectivities (up to 99% ee).
Chiral amines are ubiquitous in natural products and drugs
and serve as building blocks, chiral ligands, and chiral
auxiliaries in asymmetric synthesis.1 Accordingly, the de-
velopment of efficient synthetic methods for chiral amines
is one of the most challenging tasks for organic chemists.
1,2- and 1,3-cyclic sulfamidates have served as useful and
versatile precursors for the synthesis of various chiral amines
possessing heteroatomic functional groups,2 based on the
established ability of this synthon to undergo nucleophilic
displacement.3 Typically, sulfamidates are prepared from
chiral amino alcohols and diols in several steps.2,3 Recently,
the catalytic asymmetric intramolecular amidation of sulf-
amates esters has also been reported to afford chiral cyclic
sulfamidates using chiral Ru(II) porphyrins, Mn(III) Schiff-
(3) (a) Ni, C.; Liu, J.; Zhang, L.; Hu, J. Angew. Chem., Int. Ed. 2007,
46, 786. (b) Bower, J. F.; Szeto, P.; Gallagher, T. Org. Lett. 2007, 9, 3283.
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† Dalian Institute of Chemical Physics.
‡ Shanghai Institute of Organic Chemistry.
(1) For recent reviews, see (a) Enders, D.; Reinhold, U Tetrahedron:
Asymmetry 1997, 8, 1895. (b) Bloch, R. Chem. ReV. 1998, 98, 1407. (c)
Alvaro, G.; Savoia, D. Synlett 2002, 651.
(2) Review: Mele´ndez, R. E.; Lubell, W. D. Tetrahedron 2003, 59, 2581.
10.1021/ol800591u CCC: $40.75
Published on Web 04/22/2008
2008 American Chemical Society

base complexes, and dirhodium complexes with moderate
to good enantioselectivity.4,5 Development of new efficient
methods for the synthesis of sulfamidates is still a challenge.
According to the retrosynthetic analysis, we envisioned that
direct asymmetric hydrogenation of the corresponding cyclic
imines is the most convenient and efficient route to chiral
cyclic sulfamidates (Scheme 1).
functionalized ketones by us9 and other groups,10 and only
activated imines gave high reactivity and enantioselectivity.
In our ongoing efforts toward the development of asymmetric
hydrogenation,9,11 we became interested in exploring the
practical synthesis of enantiopure cyclic sulfamidates via
asymmetric hydrogenation. Herein, we present an efficient
method for the enantioselective synthesis of cyclic sulfam-
idates by the asymmetric hydrogenation of activated imines
2 and 5 using Pd(CF3CO2)2/(S,S)-f-binaphane as catalyst, and
up to 99% ee was obtained.
Scheme 1. Synthesis and Application of Sulfamidates
Cyclic imines (2, 5) can be conveniently prepared from
hydroxy ketones (1, 4) and sulfamoyl chloride by modified
literature procedures12 (Scheme 2).
Scheme 2. Synthesis of Cyclic Activated Imines
The catalytic asymmetric hydrogenation of imines has
drawn much attention since it provides one of the most
efficient routes for the synthesis of chiral amines,6,7 and most
of the catalysts are chiral Ir, Rh, and Ru complexes.6
Recently, chiral palladium complexes8 have been success-
fully applied to asymmetric hydrogenation of imines and
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J.-S.; Che, C.-M. J. Org. Chem. 2004, 69, 3610–3619. (c) Zhang, J.; Chan,
Imine 2a is chosen as a model substrate for the optimiza-
tion of reaction conditions, and the results are shown in Table
1. Based on our previous work on asymmetric hydrogenation
of activated imines,9b,c initial experiments were carried out
in trifluoroethanol (TFE) in the presence of 2.0 mol % of
Pd(CF3CO2)2/(S)-SynPhos. The product was isolated in
quantitative yield with moderate enantioselectivity (44% ee).
Several chiral bisphosphine ligands were examined (entries
1-4, Table 1). Fortunately, up to 97% ee was achieved using
the (S,S)-f-binaphane ligand,13 which was successfully
developed by Zhang for asymmetric hydrogenation of imines.
The absolute configuration of product 3a was assigned by
comparison of rotation sign with literature datum after the
conversion14 of 3a into known N-benzyl derivatives.3a Next,
different solvents were tested, and a strong solvent-dependent
phenomenon was observed. CH2Cl2, THF, and MeOH led
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Org. Lett., Vol. 10, No. 10, 2008

substituted imines, high enantioselectivities and full conver-
sions were also obtained (94-97% ee, entries 6-8, Table
2). It should be noted that the asymmetric hydrogenation of
2a can be also operated in air with the same enantioselec-
tiVity and actiVity (entry 9, Table 2).
Table 1. Optimization of Reaction Conditionsa
In addition to the five-membered ring imines 2, we also
explored the asymmetric hydrogenation of assorted six-
membered ring benzo-fused imines 5. As summarized in
Table 3, the above Pd catalyst was also effective for a variety
Table 3. Pd-Catalyzed Asymmetric Hydrogenation of Imines 5a
entry
X
R/R′ of 5
Me/H (5a)
Me/6-F (5b)
Me/7-F (5c)
Me/6-Me (5d)
Me/7-Me (5e)
Et/H (5f)
n-C5H11/7-Me (5g)
Ph/H (5 h)
Ph/7-OMe (5i)
Ph/6-Me (5j)
Ph/7-Me (5k)
p-FC6H4/7-Me (5l)
p-MeC6H4/7-Me (5m)
m-MeC6H4/7-Me (5n)
o-MeC6H4/7-Me (5o)
Ph/H (5p)
yield (%)
ee (%)
1
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
92
99
88
99
99
99
97
99
99
99
99
99
99
99
99
99
96
98
(-)-93
(-)-94
(-)-93
(-)-94
(-)-93
(-)-91
(-)-90
(-)-98
(-)-97
(-)-98
(-)-98
(-)-99
(-)-98
(-)-99
(-)-99
(-)-97
(-)-96
(+)-98
2
a 0.25 mmol scale: Pd(CF3CO2)2 2.0 mol %, ligand 2.4 mol %.
b Determined by 1H NMR analysis of the crude product. c ee was determined
by HPLC analysis. d Reaction was run at 60 °C. e Reaction was run at 1000
psi of H2.
3b
4
5
6
7
8
to very low reactivity; TFE was found to be the optimal
solvent, which was in accordance with that in Pd-catalyzed
asymmetric hydrogenation of imines and ketones.9,10a,b The
hydrogen pressure and the reaction temperature had no
apparent effect (entries 8 and 9, Table 1) on the enantio-
selectivity. It is noteworthy that low activity was observed
using the corresponding Ir or Rh/bisphosphine complexes
as the catalysts for asymmetric hydrogenation of 2a.15
Under the optimal reaction conditions, a wide variety of
imines 2 were tested to examine the reaction scope, as shown
in Table 2. Substrates with electron-donating or electron-
withdrawing aryl substituents (94-97% ee, entries 1-5,
Table 2) can be successfully hydrogenated to give the
corresponding cyclic sulfamidates in high ees. For alkyl-
9
10
11
12
13
14
15
16
17
18
NH
NH
NH
4-MeC6H4/H (5q)
3,5-Me2C6H4/H (5r)
a 0.25 mmol scale: Pd(CF3CO2)2 2.0 mol %, (S,S)-f-binaphane 2.4 mol
%, isolated yields, and ee was determined by HPLC or GC. b Conversion
is 92%.
of imines 5 to give the corresponding chiral benzo-fused
oxathiazinanes with 90-99% ee. For the R groups at
4-position of 5, alkyl groups gave 90-94% ee regardless of
the chain length (entries 1-7, Table 3), and aryl groups gave
slightly higher ee (97-99% ee, entries 8-15, Table 3).
Substituents at the 6- or 7-position could be well tolerated.
Furthermore, several nitrogen analogues of 5a, 1H-2,1,3-
benzothiadiazine 2,2-dioxides (5p-5r), prepared conven-
iently from their corresponding o-aminobenzophenones and
sulfamoyl chloride,3l can be successfully hydrogenated to
give the products (6p-r)16 in 96-98% ee (entries 16-18,
Table 3).
To test the practicality of the current method, the asym-
metric hydrogenation of cyclic imine 5 h on a gram scale
(1.037 g, 4.0 mmol of 5 h) was carried out with 0.5 mol %
of Pd catalyst in TFE at room temperature (Scheme 3), and
chiral product 6h was obtained in 97% isolated yield with
98% ee.
Table 2. Pd-Catalyzed Asymmetric Hydrogenation of Imines 2a
entry
R of 2
Ph (2a)
4-FC6H4 (2b)
4-MeC6H4 (2c)
3-MeOC6H4 (2d)
2-MeC6H4 (2e)
Me (2f)
yield (%)
ee (%)
configb
1
2
3
4
5
6
7
8
9c
99
95
96
94
99
99
98
97
95
97
97
96
94
97
97
94
96
97
S-(+)
S-(+)
S-(+)
S-(+)
S-(+)
S-(+)
S-(+)
S-(+)
S-(+)
t-Bu (2g)
n-C6H13 (2 h)
Ph (2a)
a 0.25 mmol scale: Pd(CF3CO2)2 2.0 mol %, (S,S)-f-binaphane 2.4 mol
%, isolated yields, and ee was determined by HPLC or GC. b Absolute
configuration of 3b-i was determined by analogy. c Reaction was run in
air.
(15) For the detailed experiments, see the Supporting Information.
(16) Wright, J. B. J. Org. Chem. 1965, 30, 3960.
Org. Lett., Vol. 10, No. 10, 2008
2073

Scheme 3
.
Asymmetric Hydrogenation of 5h on a Gram Scale
Scheme 4
.
Oxathiazinane Ring-Opening Reactions Using
LiAlH4
To demonstrate the utility of the current methodology, the
nucleophilic ring opening of these sulfamidate heterocycles
were carried out to synthesize enantiopure amino alcohol
and 2-(amino(phenyl)methyl)phenol. The chiral amino al-
cohols and 2-aminomethyl phenols are important building
blocks in organic synthesis and as well as structural units of
agricultural and pharmaceuticals agents.17 With LiAlH4 as
the nucleophilic reagent, 3a and 5 h were converted to
ꢀ-amino alcohol 7 and 2-[amino(phenyl)methyl]phenol 8,18
respectively, without the loss of the optical purity (Scheme
4).
can be hydrogenated using Pd(CF3CO2)2/(S,S)-f-binaphane/
TFE as the catalyst with high enantioselectivity. The present
method provides a new efficient route to the synthesis of
enantiopure cyclic sulfamidates.
In conclusion, three series of cyclic imines, readily
synthesized from hydroxyketones and sulfamoyl chloride,
Acknowledgment. Financial support from the National
Natural Science Foundation of China (20532005 & 20060608)
and the Chinese Academy of Sciences.
(17) (a) Kunieda, T.; Ishizuka, T. In Studies in Natural Products
Chemistry; Atta-urRahman, Ed.; Elsevier, NY, 1993; Vol. 12, p 411. (b)
Golebiowski, A.; Jurczak, J. Synlett 1993, 241. (c) Ohfune, Y. Acc. Chem.
Res. 1992, 25, 360. (d) Yokomatsu, T.; Yuasa, Y.; Shibuya, S. Heterocycles
1992, 33, 1051. (e) Reetz, M. T. Angew. Chem., Int. Ed. 1991, 30, 1531.
(18) There are only few examples for ring-opening of 1,2,3-benzoxa-
thiazole 2,2-dioxides with N-Ts substituents: (a) Andersen, K. K.; Bray,
D. D.; Chumpradit, S.; Clark, M. E.; Habgood, G. J.; Hubbard, C. D.;
Young, K. M J. Org. Chem. 1991, 56, 6508. (b) Andersen, K. K.; Kociolek,
M. G J. Org. Chem. 1995, 60, 2003.
Supporting Information Available: Experimental pro-
cedures and full spectroscopic data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL800591U
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Org. Lett., Vol. 10, No. 10, 2008