Page 11 - Demo-1

Chemical Dynamic Kinetic Resolution: !-allyl Pd Catalysis ! Equilibration between diastereomers is not a trivial problem
OH krac
R R
1 2 —krac
enantiomers
OH
R1 R2
OH
R R2 1
Me
kinv
—kinv
diastereomers
OH
R1
R2
krac = —krac
! Enhanced diastereomeric ratio after internal trapping suggests rapid equilibration of Pd complexes
Me
OOPd0O O
Ph N O Ligand Ph N PdLn Ph N PdLn
Ph NO
Bn —CO2 Bn Bn Bn
Low DR
Higher DR
Can the epimerizing intermediates be irreversibly trapped with nitrogen nucleophiles in a DKR?
Cook, ACIEE, 1999, 38, 110.
Chemical Dynamic Kinetic Resolution: !-allyl Pd Catalysis ! Phthalamide is able to trap intermediates in a dynamic kinetic resolution
OOOO 1 mol% Pd0 - dppe
NHCOPh
Nphth
Ph N O
Me
phthalamide 20 h, RT, THF
Ph N PdLn
Me
Ph N PdLn
Me
Me
! Chiral ligands on Pd afford matched/mismatched cases
O O
P N O h
Me
1 mol% Pd0
(S) - BINAP
NHCOPh
Nphth
O O Ph N O
Me
Pd0
NHCOPh
Me
Nphth
Me
(R) - BINAP
kinv = —kinv
The rates of epimerization of two diastereomers are not necessarily equal
Product oxazolines are also ionized by the catalyst, giving rise to thermodynamic product mixtures
97% yield 97 : 3 dr
As size of substituent increases, so does diastereoselectivity
96 : 4 dr
88 : 12 dr
Cook, ACIEE, 1999, 38, 110.