Download - Lecture6: 123.702
gareth j rowlands©Meredith_Farmer@flickr
LECTURE SIX
organocatalysis
chemistryclean
©Meredith_Farmer@flickr
©triplej*@flickr
wasteavoid
©j / f / photos@flickr
chemistry
must improve
©dullhunk@flickr
many enzymesmetal-freecatalysts
N
OH
OPO
OO
H
lysine
O
OH
PO
OO
©www.biochemsoctrans.orgBiochem. Soc. Trans. (2004) 32, 259
aldolases can use enamine chemistry
samethe
©David Reeves from Flickr
organic
chemistry
reactionin the aldol
H
O
H
O
cat (10%)H
O OH
88%anti / syn 3 / 1
97% ee
NH
O
OHL-proline
organocatalysis
aldolproline-catalysed
mechanism of
NH
O
OH
NO
OH
NO
OH
NO
O
H
H
O
H
H
OHH
O
H
O
©bogenfreund@Flickr
organocatalystgold
rush
enamine catalysis
PrH
O
NSO2PhPhO2S
F
cat. (1%) FH
O
Pr
NaBH4
FOH
Pr95%
96% eeNH OTMS
F3C
CF3
CF3
CF3
enamine-catalysis
N
Pr
O
ArAr
Si
NSO2Ph
PhO2S F N
Pr
O
ArAr
SiF
intermediates
catalysts
N
NH
O
Ph
R1
MacMillan’s imidazolidinone
catalystsMacMillan’ssynthesis of
N
NH
O
Ph
NH
NH2
O
Ph
O
NH2HCl
O
Ph
NH2
O
H
enaminegeneral
mechanism
N
N
R2
R1
O
R2N
NH
O
Ph
R1
O
Ph
N
N
R2R1
O
Ph
N
N
R2R1
O
Ph
E
N
N
R2R1
O
Bn
E
R1
O
R2
E
O
H
MOMO
OCl
ClCl
Cl
ClCl
N
NH•TFA
O
Ph
(5mol%)94%93%ee
O
H
MOMO
Cl
enaminecatalysis
©aussiegall@flickr
(–)-brasosideJ. Am. Chem. Soc., 2005, 127, 3696
OH
H
Me O O OHOH
OHHO
OO
total synthesisenamine catalysis in
O
OMes
NH
CO2H
D-proline(0.4eq)PhN=O
O
OMes
OPhHN
OMes
HO
CO2MeWittig
reaction
56% (2 steps)
O2CO
NH
N
RPh
OH
H
O O OHOH
OHHO
OO
OH
H
O O OHOH
OHHO
OO
total synthesisenamine catalysis in
H
O
OBn
H
O
OBn
NH
CO2H
78%98%ee
H
O
OBn
OHOBn
O OBnOBnTMSO
ROOBn
NH
NHN
HCl
Sch50971Tetrahedron: Asymmetry., 2000, 11, 3867
H
O
NO2
NTrN (20mol%)78%20:1dr99%ee
OHC NO2
NTrNN
H NHSO2CF3
total synthesisenamine catalysis in
NH
NHN
N
H
Ar
NO
OOH
H
NS H
O
OF3C
total synthesisenamine catalysis in
R1
O
R2nuc
R1
O
R2nuc
LALA
LUMO-lowering catalysis
fastslow
R1
N
R2nuc
R1
O
R2nuc
NH
LUMO-lowering catalysis
fastslow
catalysisiminium
Ph
O
BnO OBn
O O
N
NH
CO2HBn
cat. (10%), neat, rt, 165h Ph
CO2BnBnO2C
O86%
99% ee
catalysisiminium ion
catalysisiminium ion
N
N CO2H
H
CO2Bn
BnOO
N
N CO2H
H
CO2Bn
CO2Bn
H
O
OH
O
Ph O
(R)-warfarinAngew. Chem. Int. Ed., 2003, 42, 4955©Rosebud 23@flickr
O
OH
O
Ph O
(R)-warfarinAngew. Chem. Int. Ed., 2003, 42, 4955
in total synthesis
O
OH
O
Ph O
O
OH
O
Ph
O
NH
HN
Ph
Ph
CO2H
96%82%ee
catalysisiminium
96% eeendo / exo
>200 : 1
cat. (20%)HClO4
OMe
Et
O
COEt
OMe
NH
N
Ph
O
O
catalysisiminium
in the Diels-Alder
catalysisiminium
in the Diels-Alder
OMeN
NO
OEt
NN
Et
ArO
©The University of Chicago Medical Center
hydrogenbonding
O
HR1
O
HR1
LAO
HR1
HNN
H
XR2 R3
δ+
unactivated Lewis acid H-bonding
hydrogenbonding catalysis
N
S
O (5mol%)TMSCN
87%97%ee N
S
OTMSNC
HN
NH
NH
NHPr
t-Bu S
O
catalysisH-bond
NH
N
H
H
H
MeO2C OH
(+)-yohimbineOrg. Lett., 2008, 10, 745
NH
NH2
OHCOTBS
NH
N
OTBSAcCl
cat. (10mol%)81%
94%ee
NH
N Ac
OTBScatalysisH-bond
in total synthesis
(iBu)2N NH
NH
N
t-Bu S
O Ph
pictet-spenglerreaction
©1984 Columbia Pictures Industries
(iBu)2N N NN
t-Bu S
OPh
H HCl
NH
N Ac
OTBScatalysis
H-bondin total synthesis
©djwudi@flickr
catalyst ?what is smallest
H
the proton
©limowreck666@flickr
how do you
make a
spherechiral?
OO
PO
O H
phosphoricacids
chiral
Ph
NBz
HN
Ph
OMe
O
Ph
NH
Ph
NCO2MeBz(10mol%)
89%95%ee
proton in aza-enechiral
OOPO
O H
proton in Friedel-Craftschiral
Ar
NBz
NBn
(10mol%)
89-99%90-97%ee N
Bn
ArNHBz
Ph3Si
Ph3Si
OOP
O
OH
proton in hetero Diels-Alder reactionchiral
N
Cl
HO
OTMS
MeO
OMe
(3mol%)
90%97%ee
N
O
OMe
OH
Cl
OOPO
O NH
©CiCCiO.it@flickr
photoredoxchemistry
N
NH
O
t-Bu
N
N
O
t-Bu
C6H13
N
N
O
t-Bu
C6H13
PhC(O)
N
N
O
t-Bu
C6H13
C(O)Ph
H
O
C6H13
H
O
C6H13
Ph
O
cat (0.2eq), Ru(bipy)3Cl2 (0.005eq),
fluorescent light
85%96% ee
Ph
OBr
Ru(bipy)3+
Ru(bipy)32+
*Ru(bipy)32+
light
SET
Ph
O
SET
Ph
OBr
photoredoxchemistry
