A brief introduction to Organocatalysis
A brief introduction to Organocatalysis
Ji Guojing
May. 25th,2013
Contents
1 introduction
2enamine catalysis
i t l i
y
3 iminium catalysis
4 Hydrogen‐bond activation
5 Carbene catalysis
activation modes
6 other
7 summary and outlook
introduction
Organocatalysis is the acceleration of chemical reactions with a substoichiometric g y amount of an organic compound which does not cotain a metal atom.
1970s Hajos L ‐proline
2000 List and MacMillan
In the early 20th century ‐1960s Pracejus alkaloid
j p Bredig Cinchona alkaloid
Used for enantioselective construction of C ‐C, N C O C S bonds
introduction
Inherent benefits C ‐N, ‐O, ‐S, C ‐P , C ‐halogen f
Insensitive to mositure and air Inexpensive
‐Readily avaliable from bio material Operationally easy to handle
Non ‐toxic ,easily removed from waste streams Rich, new avenue for academic thought ,g
Examples: Proline, cinchona alkaloids or other secondary amine derivatives
Organocatalytic Activation modes
introduction
N
N
O
Me
N N S O P O R N
HO 2C
Ph
R
X
H H
Y
O OH R
Me
R
Iminium F F Hydrogen Bonding Hydrogen Bonding
Enamine
O -R 3N
R
S Me
Me
R N R
OH OMe
N N N F
F F Ammonium
Ylide N
Phase Transfer
O Carbene
Enamine catalysis
E i l i
Peter, I. D.; Lionel, M., Angew. Chem. Int. Ed. 2004, 43, 5138.
E i l i
Ald l ti
Enamine catalysis Aldol reaction MacMillan, D. et al. J. Am. Chem. Soc. 2002, 124, 6798.
Jorgensen, K. A . et al. https://www.wendangku.net/doc/051954268.html,mun . 2002, 620.
E i l i
Mannich reaction
Enamine catalysis List, B.; Pojarliev, P . et al. J. Am. Chem. Soc . 2002,124, 827.
Wrdova, A. C.; Barbas III, C. F., Tetrahedron Lett. 2002, 43, 7749.
E i l i
Proposed transition states
Enamine catalysis p List, B. et al. J. Am.Chem. Soc . 2003, 125, 2475.
Dalko, P . I.; Moisan, L., Angew. Chem. Int . Ed . 2004, 43, 5138.
E i l i
Enamine catalysis ‐Ketone Aldehyde Aldol
Aldolization
Additions to Enones
List, B. et al. J. Am. Chem. Soc . 2002, 2395.List, B. et al. Angew. Chem. Int. Ed . 2003, 2758.
Additons to Nitroalkenes
Barbas III, C. et al. Org. Lett . 2004, 2527.List, B. et al. Angew. Chem. Int. Ed . 2004, 3958.
E i l i
α‐Aminooxylation of aldehydes Enamine catalysis y y
MacMillan, D . et al. J. Am. Chem. Soc . 2003, 125, 10808.
S 2 Alkylation N y
List, B. et al. J. Am. Chem. Soc . 2003, 125, 450.
Enamine catalysis
E i l i
Jorgensen, K. A. et al. J. Am. Chem. Soc. 2009, 131, 7153.
E i l i
Asymmetric alkylation of aldehyded Trifluoride of aldehyded Enamine catalysis y y y
y
MacMillan, D . et al. Science , 2008, 322, 77.
MacMillan, D. et al. J. Am. Chem. Soc . 2009, 131, 10875.
E i l i
Michael addition / gold ‐catalyzed reaction
Enamine catalysis Belot, S.; Vogt, K. A.; Besnard, C . et al. Angew. Chem. Int. Ed . 2009, 48, 8923.
Contents
1 introduction
2enamine catalysis
i t l i
y
3 iminium catalysis
4 Hydrogen‐bond activation
5 Carbene catalysis
activation modes
6 other
7 summary and outlook
iminiums catalysis
i i i l i
Mukaiyama‐Micheal
MacMillan, D. et al. J. Am. Chem. Soc. 2003,125, 1192.
i i i l i
Malonate additon
iminiums catalysis Jorgensen, K . A. et al. Angew. Chem. Int. Ed . 2003, 42, 661.
Dicarbonyl additons
Jorgensen, K . A. et al. Angew. Chem. Int. Ed . 2003, 42, 4955.
iminiums catalysis
i i i l i
Diels‐Alder reactions
MacMillan, D. et al. J. Am. Chem. Soc. 2000, 122, 4243. Thiol additions
Deng, L. et al. Angew. Chem. Int. Ed. 2002, 41, 338.
i i i l i
iminiums
catalysis Friedel ‐Crafts Alkylation y
[43]l dditi MacMillan, D. et al. J. Am. Chem. Soc . 2001, 123, 4370.
[4+3]cycloadditions
Harmata, M. et al. J. Am. Chem. Soc . 2003, 125, 2058.
i
i i l i
Domino reaction
iminiums catalysis Jorgensen, K. A . et al. J. Am. Chem. Soc . 2006, 128, 14986.