Kinetic Resolutions - The Stoltz Group

CO2R PPh3 N N
RO2C
RO2C
CO2R HN NH
Mitsunobu-type KR of ROH
Ph3P CO2R R
N N
RO2C
2 CO2H Step 1 Step 2
Ph3PO R 2 CO 2R 3
Chiral recognition can be introduced at steps 3 and 4
Step 4
Ph 3 PO-R
R 2 -
CO2 Ph 3 P
RO 2C
RO2C
CO2R N NH
R 3 OH
Step 3
CO2R HN NH
Chiral Phosphine, azodicarboxylate, or acid are possible means to induce chiral influence
Kellogg
Tang
(±)-
(±)-
Ar
Ar
OH
OH
1-2 eq Catalyst 9
O
R +
NH
Catalyst 9
1-2 eq ArCO 2H
DIAD, PhH
1 eq 1 eq
Chiral Phosphines for Mitsunobu KR
O
O
O P NMe 2
Ar
OH
+
1) 1 eq Catalyst 9
DEAD, THF
Reflux
2) NH 2 NH 2
DIAD, PhH
Ar
Ar
OCOAr
OH
40-50%
R
13-30% ee
R 2 -
CO2 Chandrasekhar, Tet. Asym. 2002, 13, 615
Ar = Ph, 2-Naphthyl
14-73% conv.
11-39% ee
+
Ar
NH 2
55-62%
R
26-45% ee
Me2N O
P
O
O
N N
CO 2i-Pr
Oi-Pr
Kellogg, et. al., J. Chem. Soc., Perkin Trans. 1, 1995, 2961
Tang, et. al., Tet. Asym., 2002, 13, 145
11