C O M M U N I C A T I O N S
Table 2. Reaction of 1a-g under Optimized Conditions
for 4e, by X-ray structures of the corresponding rearrangement
products 3b and 3e.
reaction
timea
yield
(%)b
ee
entry
1 (R ))
liganda
(%)c
As an extension of the double asymmetric approach, the reaction
of propargyl 2-chlorophenyl sulfide with diazoacetamides 1a-c,e,f
under the optimized condition was investigated. The reaction
worked well, and a similar level of enantioselectivity could be
achieved with ligand (S,S)-7 for the reaction of sulfide 9a (Table
3). Ligand 8 afforded comparable results, with only one exception
(entry 6). It is noted that the reaction works equally well with
methyl-substituted sulfide 9b (entries 11-14). The absolute con-
figuration of 10d (R ) CH3, R′ ) H) is determined as S by X-ray
structure of the corresponding rearrangement product.
In summary, we have developed a highly stereoselective [2,3]-
sigmatropic rearrangement of sulfur ylide generated through Cu(I)
carbene and allyl and propargyl sulfides by a double asymmetric
induction approach. This approach provides an entry to tertiary
chiral sulfides, which are difficult to access.12
1
2
a (C6H5)
a (C6H5)
(S,S)-7
8
10 h
10 h
70
72
90
92
3
4
5
6
7
8
9
10
11
12
13
14
15
16
b (p-BrC6H4)
b (p-BrC6H4)
b (p-BrC6H4)
c (m,p-Cl2C6H3)
c (m,p-Cl2C6H3)
d (p-NO2C6H4)
d (p-NO2C6H4)
e (CH3)
e (CH3)
e (CH3)
f (CH3CHdCH)
f (CH3CHdCH)
g (PhCHdCH)
g (PhCHdCH)
(S,S)-7
(S,S)-7
8
(S,S)-7
8
(S,S)-7
8
(S,S)-7
(S,S)-7
8
6 h
6 h
6 h
12 h
12 h
48 h
48 h
15 min
15 min
15 min
15 min
15 min
15 min
15 min
82
90
92d
82
>99e
94
53
58
86
90
85
70
39 (58)f
43 (55)f
81
86
95d
67
74
76
82
96e
82
(S,S)-7
8
(S,S)-7
8
82
78
95
85
78
a Refer to the first step only. b Isolated yields for two steps unless
otherwise noted. c Enantiomeric excess values determined by chiral HPLC.
d Isolated yield for the first step. e After single recrystallization of the first
step product. f The yield in parentheses refers to recovered starting diazo
compound.
Acknowledgment. The project is generously supported by
Natural Science Foundation of China (Grant Nos. 20225205 and
20390050).
Supporting Information Available: Experimental procedures,
spectra data for new compounds, X-ray structures, and mechanistic
study. This material is available free of charge via the Internet at http://
pubs.acs.org.
Table 3. Reaction of 1a-c,e,f and Propargyl 2-Chlorophenyl
Sulfide 9a,b under Optimized Conditions
References
(1) (a) Baldwin, J. E.; Hackler, R. E.; Kelley, D. P. J. Am. Chem. Soc. 1968,
90, 4758. (b) Blackburn, G. M.; Ollis, W. D.; Smith, C.; Sutherland, I. O.
J. Chem. Soc., Chem. Commun. 1968, 186. (c) Baldwin, J. E.; Hackler,
R. E.; Kelley, D. P. J. Chem. Soc., Chem. Commun. 1968, 537, 538.
(2) For reviews in the area, see: (a) Trost, B. M.; Melvin, L. S., Jr. Sulfur
Ylides; Academic Press: New York, 1975; Chapter 7. (b) Vedejs, E. Acc.
Chem. Res. 1984, 17, 358. (c) Doyle, M. P.; McKervey, M. A.; Ye, T.
Modern Catalytic Methods for Organic Synthesis with Diazo Compounds;
Wiley-Interscience: New York, 1998. (d) Li, A.-H.; Dai, L.-X.; Aggarwal,
V. K. Chem. ReV. 1997, 97, 2341. (e) Doyle, M. P.; Forbes, D. C. Chem.
ReV. 1998, 98, 911. (f) Hodgson, O. M.; Pierard, F. Y. T. M.; Stupple, P.
A. Chem. Soc. ReV. 2001, 30, 50.
diazo
reaction
timea
yield
(%)b
ee
entry
substrate
sulfide
ligand
(%)c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1a
1a
1b
1b
1c
1c
1e
1e
1f
9a
9a
9a
9a
9a
9a
9a
9a
9a
9a
9b
9b
9b
9b
(S,S)-7
8
(S,S)-7
8
(S,S)-7
8
(S,S)-7
8
(S,S)-7
8
(S,S)-7
8
(S,S)-7
8
5 h
5 h
5 h
5 h
3 h
3 h
15 min
15 min
15 min
15 min
20 h
20 h
2 h
87
85
92
90
86
83
95
88
70
65
77
73
80
82
94
82
91
88
84
50
93
92
91
90
93
90
96
94
(3) (a) Kirmse, W.; Kapps, M. Chem. Ber. 1968, 101, 994. (b) Doyle, M. P.;
Griffin, J. H.; Chinn, M. S.; van Leusen, D. J. Org. Chem. 1984, 49,
1917.
(4) Nishibayashi, Y.; Ohe, K.; Uemura, S. J. Chem. Soc., Chem. Commun.
1995, 1245.
1f
(5) (a) Fukuda, T.; Irie, R.; Katsuki, T. Tetrahedron 1999, 55, 649. (b)
McMillen, D. W.; Varga, N.; Reed, B. A.; King, C. J. Org. Chem. 2000,
65, 2532. (c) Kitagaki, S.; Yanamoto, Y.; Okubo, H.; Nakajima, M.;
Hashimoto, S. Heterocycles 2001, 54, 623. (d) Zhang, X.; Qu, Z.; Ma,
Z.; Shi, W.; Jin, X.; Wang, J. J. Org. Chem. 2002, 67, 5621. (e) Zhang,
X.; Ma, M.; Wang, J. Tetrahedron: Asymmetry 2003, 14, 891. (f) Zhang,
X.; Ma, M.; Wang, J. Chin. J. Chem. 2003, 21, 878.
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Trost, B. M.; Biddlecom, W. G. J. Org. Chem. 1973, 38, 3438.
(7) A controversial issue concerning the asymmetric catalysis in [2,3]-
sigamatropic rearrangement of ylide is whether the rearrangement proceeds
through a metal-associated ylide or a free ylide. See: (a) Doyle, M. P.;
Tamblyn, W. H.; Bagheri, V. J. Org. Chem. 1981, 46, 5094. (b) Aggarwal,
V. K.; Ferrara, M.; Hainz, R.; Spey, S. E. Tetrahedron Lett. 1999, 40,
8923. We have confirmed that the ylide is strongly complexed with the
Cu(I) complex. For the details, see Supporting Information.
1b
1b
1e
1e
2 h
a Refer to the first step only. b Isolated yield for two steps. c Enantiomeric
excess values determined by chiral HPLC.
The optimized reaction condition (sulfide 2d/ligand 7a or 8/CH2-
Cl2/0 °C to room temperature) was then applied to 1b-g. The
results summarized in Table 2 demonstrate that aryldiazoacetamides,
as well as methyl, cinnamoyl, and propenyldiazoacetamide, all
reacted with sulfide 2d smoothly in good yields with good to
excellent enantioselectivity. The ligands 7a and 8 gave comparable
results in most cases. The reaction of aryldiazoacetamides bearing
a p-nitro substituent in the aromatic ring gave slightly low
enantiomeric excess values (Table 2, entries 8 and 9). It is
worthwhile to note that the rearrangement products 3a-g are all
crystalline. Therefore, almost optically pure products of 4a-g could
be obtained by single recrystallization of the rearrangement products
3a-g before removal of the camphor sultam auxiliary (for
examples, entries 4 and 11). The absolute stereochemistry of the
newly formed chiral center was determined to be R for 4b and S
(8) For a report on chiral transition metal auxiliary controlled sulfur ylide
[2,3]-sigmatropic rearrangement, see: Cagle, P. C.; Arif, A. M.; Gladysz,
J. A. J. Am. Chem. Soc. 1994, 116, 3655.
(9) For the preparation of 1a-g, as well as the study with other chiral
auxiliaries, see Supporting Information.
(10) Li, Z.; Conser, K. R.; Jacobsen, E. N. J. Am. Chem. Soc. 1993, 115, 5326.
(11) (a) Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M. M. J. Am.
Chem. Soc. 1991, 113, 726. (b) Lowenthal, R. E.; Masamune, S.
Tetrahedron Lett. 1991, 32, 7373. (c) For a review on C2-symmetric bis-
(oxazoline) ligands in asymmetric catalysis, see: Ghosh, A. K.; Mathi-
vanan, P.; Cappiello, J. Tetrahedron: Asymmetry 1998, 9, 1.
(12) For a recent example of enantioselective construction of C-S bonds with
a quaternary stereocenter, see: Palomo, C.; Oiarbide, M.; Dias, F.; Lo´pez,
R.; Linden, A. Angew. Chem., Int. Ed. 2004, 43, 3307.
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