Kinetic Resolutions - The Stoltz Group

(±)-
Evans - Oxazolidinone Acylating Agent
R 1
OH
10 eq
R 2
OH
(±)-
Ar Me
O
O
O
N Ph
t-Bu
1.1 eq MeMgBr
CH2Cl2 R 1
R 2
+
OH
+
Vedejs - Chiral DMAP Acylating Agent
Wegler
(±)-
Horner
(±)-
2 eq
OH
1 eq
Cl 3 C
O
NMe 2
N
Chiral Acylating Agent
O
OMe
Cl -
t-Bu
2 eq ZnBr 2, 3 eq Et 3N
OH
Ar Me
Ph
O
R 1
O
R 2
Cl 3C
Ester ee's:
R 1 =Ph, R 2 =Me, ee=95%
R 1 =Ph, R 2 =i-Pr, ee=65%
R 1 =c-C 6H 11, R 2 =Me, ee=5%
Evans, et. al., Tet. Lett. 1993, 34, 5563
+
Carbonate:
Nucleophilic Activators for Acylation
0.25 eq (-)-brucine
0.53 eq Ac 2 O
CCl 4 , 77 o C, 3h
s ~ 3.5
Also used other tertiary amines and acylating agents
OH
OH
0.5 eq amine
OH
0.5 eq AcCl
CH 2 Cl 2 , 12h
-78 o C to r.t.
Screened a variety of temperatures, amines,
solvents, and acylating agents
Vedejs unable to reproduce this result
+
+
O
O
O
Ar Me
Ar = Ph, 25% conv, 93% ee, s = 38
Ar = 1-Naphthyl, 28% conv, 94% ee, s = 44
Ar = 2-Naphthyl, 24% conv, 94% ee, s = 45
Vedejs, et. al, J. Am. Chem. Soc., 1996, 118, 1809
OAc
OAc
68% ee
??% conv.
MeO
MeO
N
N
H
H
O
(-)-brucine
Wegler, Liebigs. Ann. Chem. 1932, 498, 62
Liebigs. Ann. Chem., 1933, 506, 77
Liebigs. Ann. Chem., 1934, 510, 72
NMe 2
Horner, et. al. Liebigs Ann. Chem., 1989, 533
H
H
O
3