Kinetic Resolutions - The Stoltz Group

Nishiyama, Sekar (our very own!)
n
Kinetic Resolution through S N2 Displacement
OH
R
0.3-0.9 eq BINAP
n = 2; R = Ph, 4-CH 3OPh, 2-CH 3Ph, 3-CH 3Ph, 4-CH 3Ph, 1-Naphthyl, 2-Naphthyl, Cyclohexyl
n = 4; R = Ph
0.9-1.0 eq NCS
THF
48-63% conversion, 69-99% ee, s = 13-118
-10 o C overnight or 10 min at r.t.
BINAP-bisoxide could be reduced back to (S)-BINAP
H
(±) -
OH
OH
H
(±) -
OH
Ph
0.3 eq BINAP
1 eq NCS
THF, 12 h
-74 o C to r.t.
OH
R
+
Cl
R
OH
Ph
+
s = 253
Cl
Ph
(S)-(-)-BINAP
PPh 2
PPh 2
Nishiyama, Sekar, J. Am. Chem. Soc., 2001, 123, 3603
Epoxidation of Allylic Alcohols - Sharpless!!!
Made kinetic resolution a practical technique for synthesis
Most widely used kinetic resolution technique
Bulkier tartrate esters work better
1.2 : 1 tartrate to titanium ratio is best
Can use catalytic amount of tartrate,
though reactions are much slower
(S)-fast
(R)-slow
Ti(Oi-Pr) 4, TBHP
L-(+)-DIPT
CH 2Cl 2, -20 o C
O
H
O
H
H
H
OH
H
OH
H
+
O
H
erythro : threo
98 : 2
+
O
H
R 3
erythro : threo
62 : 38
R 2
H
H
H
OH
H
OH
R 1
OH
D-(-)-(S,S)-Dialkyltartrate
L-(+)-(R,R)-Dialkyltartrate
HO CO 2i-Pr
HO
CO 2i-Pr
(+)-(R,R)-L-Diisopropyltartrate
Sharpless, et. al., J. Am. Chem. Soc., 1981, 103, 6237
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