補助本校教師出席國際學術會議報告
99 年 6 月 27 日
報告人姓名 林文偉
會議時間 99/6/22 - 99/6/25
會議
名稱
發表論
文題目
服務單位
及職稱
師大化學系
助理教授
會議地點 中國北京
第十一屆 Tetrahedron Symposuim
Pyrrolidine-Type Organocatalysts Bearing Sulfone Moieties in Asymmetric
Michael Addition Reactions
報告內容：
一、參加會議經過
六月二十二日下午抵達會場後即為 poster section ，也有機會和北京大學席振峰教授及大
會秘書長姚祝軍教授進行研究交流和討論。
六月二十三日至六月二十五日間除了參加會議，進行學術交流和討論外，也有機會可以聆聽
國際著名學者發表演說其重大的發現。
六月二十六日中午在北京搭機，下午返抵國門。
二、參加會議心得
此會議（Tetrahedron Symposuim）乃國際間極為重視的大型研討會，邀請的學者皆為
在有機催化和合成上有傑出貢獻的知名教授。透過參與此研討會，不僅可以更快的掌握到這
些學者們現今最新的傑出研究成果，也有機會可以進行研究交流和討論，對於現今正在進行
的計畫（綠色催化化學之子計畫四: 有機催化劑的發展(B)）中，特別是有機催化劑的開發
和應用上，受益匪淺。
此外，透過交流和討論，除了在研究主題上，瞭解並吸收到國外學者們如何有效的整合
資源和結合研究團隊能量的經驗，對現在正在進行的整合型研究計畫，有很大的幫助。
三、建議事項
此次會議可以得知國外的研究風氣十分鼎盛，學術能量也十分充足，應多鼓勵校內師長或研
究生多加參與。
四、攜回資料
論文集一本
五、論文內容
五、論文內容：
Asymmetric organocatalysis of carbon-carbon bond formation is of importance in
organic synthesis. Among them, the most successful development of chiral
organocatalysts for the asymmetric Michael reaction includes pyrrolidine-type
organocatalysts bearing H-bond functions,1 bulky groups,2 salt moieties,3 and
phosphine oxide function.4
Recently,
we
have
developed
a
new
type
of
organocatalyst,
(S)-2-((naphthalen-2-ylsulfonyl)methyl)pyrrolidine, prepared in three steps from
(S)-N-Boc-2-[((4-toluenesulfonyl)oxy)methyl]pyrrolidine in 62% overall yield. It
shows very high catalytic activity toward the direct asymmetric Michael reaction of
cyclohexanone and nitroolefins. All the corresponding adducts can be furnished in
90–99% yields and with up to 98% ee and over 99:1 dr on water in the presence of
this catalyst (15 mol %) without any additive (Scheme 1).5
O
NO 2
+
Ar
3a
4a-m
O
15 mol% 2b
NO 2
H2 O
10 o C,12-24 h
5a-m
up to 99% yield
(>99:1 dr, 98% ee)
O O
S
N
H
Ar
2b
Scheme 1.
A series of new type of organocatalysts 1a-b and 2a-b bearing a pyrrolidine and a
sulfide or sulfone moiety were easily prepared, and the remarkable effects of sulfone
moiety and Ar group of catalysts 1 or 2 were shown (Scheme 2 and Table 1). After
careful optimization of the reaction condition, the enantioselectivity of 5a can be up to
98% (Table 2).
S Ar
1) NaSAr
2) TFA
OTs
N
H
1a: Ar = Ph
1b: Ar = 2-naphthalenyl (68%)
Ar
O
N
Boc
S
1) NaSAr
2) mCPBA
3) TFA
O
N
H
2a : Ar = Ph
2b: Ar = 2-naphthalenyl (62%)
Scheme 2.
Table 1. Screening of catalysts 1a, 1b, 2a and 2b for the Michael addition of
cyclohexanone (3a) to β-nitrostyrene (4a).a
O
O
Ph
NO2 15 mol% cat.
+
neat
Ph
3a
NO2
5a
4a
Entry
Cat.
Time [h]
Yield [%]b
syn/antic
ee [%] synd
1
1a
1.5
60
92/8
23
2
1b
1
97
97/3
65
3
2a
2
90
90/10
64
4
2b
2.5
97
97/3
94
a
Unless stated otherwise, the reaction was performed with cyclohexanone (3a) (5.0
equiv) and β-nitrostyrene (4a) (0.2 mmol) at 27 oC. b Yield of analytically pure
isolated product. c Determined by 1H NMR analysis of the crude product. d
Determined by HPLC using a Chiralpak AS-H column.
Table 2. Optimization of reaction condition for the Michael addition of
cyclohexanone (3a) to β-nitrostyrene (4a) catalyzed by organocatalyst 2b.a
O
O
NO2
+
NO2
solvent
Ph
3a
Ph
15 mol% 2b
4a
5a
Entry
Solvent
Time [h]
Yield [%]b
syn/antic
ee [%] synd
1
THF
23
90
99/1
94
2
CH2Cl2
29
87
99/1
96
3
toluene
31
85
97/3
97
4
MeOH
11
98
92/8
91
5
Et2O
23
92
93/7
97
6
H2O
2
99
>99/1
97
7e
H2O
4
92
>99/1
97
8f,g
H2O
14
98
>99/1
98
a
Unless stated otherwise, the reaction was performed with cyclohexanone (3a) (5.0
equiv) and β-nitrostyrene (4a) (0.2 mmol) in solvent (0.2 mL) at 27 oC. b Yield of
analytically pure isolated product. c Determined by 1H NMR analysis of the crude
product. d Determined by HPLC using a Chiralpak AS-H column. e 10 mol% 2b was
loaded. f The reaction was performed at 10 oC. g In the presence of 15 mol% 1b,
inferior results on water were obtained (4 h; 97% yield; 88% ee; 87:13 dr) at room
temperature and (14 h; 92% yield; 93% ee; 90:10 dr) at 10 oC, respectively.
The reaction scope can be further demonstrated with different aryl-substituted
nitro-olefins (Figure 1). A variety of adducts can be afforded in high yields (85-99%)
with good stereoselectivities (up to >99:1 dr; 90-98% ee).
NO2
O
Ph
O
O
NO 2
NO2
5a : 98% yield
(98% ee; >99:1 dr)
5b: 85% yield
(94% ee; >99:1 dr)
Cl
Br
O
5f: 95% yield
(94% ee; >99:1 dr)
5c : 95% yield
(92% ee; 97:3 dr)
5g: 95% yield
(96% ee; 98:2 dr)
O
F
NO 2
5d: 95% yield
(92% ee; >99:1 dr)
5e: 96% yield
(95% ee; >99:1 dr)
OCH3
O
NO2
NO2
NO2
CH3
O
NO 2
O
NO2
O
O
O
NO2
NO2
NO 2
5h : 96% yield
(98% ee; >99:1 dr)
5i: 89% yield
(95% ee; >99:1 dr)
5j: 99% yield
(90% ee; >99:1 dr)
Figure 1.
In conclusion, new types of organocatalysts bearing sulfide or sulfone functions (1 or
2) were designed and studied for the direct asymmetric Michael addition of
cyclohexanone (3a) toward nitroolefins 4. The organocatalyst 2b, bearing a
pyrrolidine and a sulfone moiety, showed very high catalytic activity toward the direct
asymmetric Michael reaction of ketones and aromatic nitroolefins to furnish the
corresponding adducts in excellent yields and with high stereoselectivities on water in
the presence of low loading of this catalyst (15 mol%) without any acidic additive. In
addition, this orgaocatalyst can be easily prepared in a few steps from (S)-proline in
good yields.
References:
[1] For selected recent literature, see: (a) Knudsen, R. K.; Mitchell, C. E. T.; Ley, S.
V. Chem. Commun. 2006, 66. (b) Cao, C.-L.; Ye, M.-C.; Sun, X.-L.; Tang, Y. Org.
Lett. 2006, 8, 2901. (c) Zu, L.; Wang, J.; Li, H.; Wang, W. Org. Lett. 2006, 8, 3077.
(d) Martin, H. J.; List, B. Synlett 2003, 1901. (e) Xu, D.-Q.; Wang, L.-P.; Luo, S.-P.;
Wang, Y.-F.; Zhang, S.; Xu, Z.-Y. Euro. J. Org. Chem. 2008, 1049. (f) Enders, D.;
Chow, S. Eur. J. Org. Chem. 2006, 4578. (g) Pansare, S. V.; Pandya, K. J. Am. Chem.
Soc. 2006, 128, 9624.
[2] For selected recent literature, see: (a) Hayashi, Y.; Gotoh, H.; Hayashi, T.; Shoji,
M. Angew. Chem., Int. Ed. 2005, 44, 4212. (b) Chi, Y.; Gellman, S. H. Org. Lett.
2005, 7, 4253. (c) Mossé, S.; Laars, M.; Kriis, K.; Kanger, T.; Alexakis, A. Org. Lett.
2006, 8, 2559. (d) Mandal, T.; Zhao, C.-G. Tetrahedron Letts. 2007, 48, 5803.
[3] For selected recent literature, see: (a) Mase, N.; Watanabe, K.; Yoda, H.; Takabe,
K.; Tanaka, F.; Barbas III, C. F. J. Am. Chem. Soc. 2006, 128, 4966. (b) Vishnumaya;
Singh, V. K. Org. Lett. 2007, 9, 1117. (c) Luo, S.; Mi, X.; Zhang, L.; Liu, S.; Xu, H.;
Cheng, J. Angew. Chem., Int. Ed. 2006, 45, 3093.
[4] Tan, B.; Zeng, X.; Lu, Y.; Chua, P. J.; Zhong, G. Org. Lett. 2009, 11, 1927.
[5] Syu, S.; Kao, T.-T.; Lin W. Tetrahedron 2010, 66, 891-897.