Asymmetric O- and N- Nitroso Aldol Reaction- - Chemistry

15 Pages·2004·0.62 MB·English

Asymmetric O- and N- Nitroso Aldol Reaction-
an efficient access to α-oxy and α-amino carbonyl compound
1. Momiyama, N.; Yamamoto, H. J. Am. Chem. Soc. 2004, 126, 5360.
2. Zhong, G. Angew. Chem. Int. Ed. 2003, 42, 4247.
3. Bogevig, A.; Sunden, H.; Cordova, A. Angew. Chem. Int. Ed. 2004, 43, 1109.
4. Hayashi, Y.; Yamaguchi, J.; Sumiya, T.; Shoji, M. Angew. Chem. Int. Ed. 2004, 43, 1112.
Group Presentation
Zhenjie Lu
May 27, 2003
Introduction
O O
E+ ∗ E
R1 R1
chiral cata.
R2 R2
A. Enolate with
transition metal catalyst.
B. Enamine with
metal-free catalyst.
Metal Enolates as the Nucleophile
ligand: AgX 2:1 1:1 1:2
X= OTf, OAc, OCOCF
3
Momiyama, N.; Yamamoto, H. J. Am. Chem. Soc. 2004, 126, 5360.
Asymmetric O-Nitroso Aldol Reaction Using Metal Enolate
P
Catalyst B 1:1  AgX
P
OSnMe O O OH
3
R1 R3 + ON (R)-TolBINAP.AgOTf R1 ∗ O N Ph + R1 ∗ N Ph
R2 Ph THF, -78oC, 2h R2 R3 H R2 R3
2 1 3 4
entry enolate cat.(mol%) yield(%) 3 / 4 ee of 3(%)
OSnMe
1 3 10 95 >99:1 97
2 2 78 >99:1 96
OSnMe
3
3 10 92 >99:1 90
OSnMe
3
4 10 93 >99:1 92
OSnMe
5 3 10 92 81/19 94
Momiyama, N.; Yamamoto, H. J. Am. Chem. Soc. 2003, 125, 6038.
Asymmetric N-Nitroso Aldol Reaction Using Metal Enolate
P AgX
Catalyst C 1:2

P AgX
OSnBu (R)-BINAP.2AgOTf O O OH
3
O (4 mol%)
R1 R3 + N R1 ∗ O N Ph + R1 ∗ N Ph
R2 Ph EtOCH2CH2OEt, R2 R3 H R2 R3
-78oC, 2h
3 4
entry enolate yield(%) 4 / 3 ee of 4 (%)
1 n= 1 90 97/3 86
OSnMe
3
2 n= 2 95 96/4 >99
n
3 n= 3 96 >99:1 97
OSnMe
3
4 Ph 94 >99:1 77

OSnMe
3
5 97 >99:1 98

Momiyama, N.; Yamamoto, H. J. Am. Chem. Soc. 2004, 126, 5360.
Metal-free Proline Catalyzed α-Aminoxylation of Carbonyl Compound
 Possible nucleophilic addition of the enamine intermediate on the nitroso double bond.
O
CO H
N 2
H +
H
R proline
4
✶ Only the O-regioselective product 1 was observed after the addition.
Zhong, G. Angew. Chem. Int. Ed. 2003, 42, 4247.
Enantioselective (S)-Proline Catalyzed α-Aminoxylation of
Aldehydes
 Direct catalytic enantioselective α-aminoxylation of aldehydes
Zhong, G. Angew. Chem. Int. Ed. 2003, 42, 4247.
Enantioselective (S)-Proline Catalyzed α-Aminoxylation of
Aldehydes
 α-Aminoxylation - by Macmillan
 α-Aminoxylation - by Hayashi
O L-proline(30mol%) OH
Ph
N CH CN,24h,-20oC ONHPh
+ 3
H
O
then NaBH
R 4 R
(62%-Quant)
(95-99%ee)
R = Me, Et, n-Pr, i-Pr, Ph, CH Ph
2
1. Brown, S. P.; Brochu, M. P.; Sinz, C. J.; MacMillan, D. W.C. J. Am. Chem. Soc. 2003, 125, 10808.
2. Hayashi, Y.; Yamaguchi, J.; Hibino, K.; Shoji, M. Tetra. Lett. 2003, 44, 8293.
Proposed Catalytic Cycle for the (S)-Proline-catalyzed
α-Aminoxylation of Carbonyl Compounds

Merino, P.; Tejero, T. Angew. Chem. Int. Ed. 2004, 43, 2.
Enantioselective α-Aminoxylation of Ketone
 α-Aminoxylation of ketones - using tin-enolate with chiral L.A. (Yamamoto)
OSnMe (R)-TolBINAP.AgOTf O O
3
O CuSO (30mol%)
+ (10 mol%) ∗ ONHPh 4 ∗ OH
Ph THF, -78oC, 2h MeOH
 α-Aminoxylation of ketones - using (s)-proline
91% yield
HPh
70% yield 22% yield
Bogevig, A.; Sunden, H.; Cordova, A. Angew. Chem. Int. Ed. 2004, 43, 1109.