Page 12 - Demo-1

Chemical Dynamic Kinetic Resolution: !-allyl Pd Catalysis
! Chiral catalyst effectively opens diene monoepoxides - Trost 2.5% Pd0Ln*
99 % yield 98% ee
O
O
Me
phthalamide 5% Na2CO3 RT, CH2Cl2
2.5% Pd0Ln*
phthalamide 5% Na2CO3 RT, CH2Cl2
OH Nphth
OH
OO NH HN
PPh2 Ph2P
72 % yield 87% ee
Nphth Me
! Epoxide opening facilitates synthesis of anti-epileptic drug Vigabatrin MeO
Ln*
Nphth CO2CH3
Trost, JACS, 2000, 122, 5968.
Trost and Toste, JACS, 1999, 121, 3543.
OH Nphth
i. 6N HCl
Tf2O
97% yield
OTf
O
O NH3
(R) - Vigabratin
O O
THF, 0 °C
64% yield
Trapping of phenol nucleophiles with butenolides:
CO2CH3
Nphth
Na
MeO
ii. Ion exchange resin
96% yield
Chemical Dynamic Kinetic Resolution: Silylated "-Amino Acid Synthesis ! Racemic zirconaaziridines are readily available
1. 2 eq. BuLi
O
Ph
Cp2ZrCl2
N
N Ph
Cp2Zr
2. TMS
THF, —78 °C to RT, 6h, 60%
! DKR of zirconaaziridines affords unnantural "-amino acids O
TMS
MeO
Ar
OO
Ph N
Ar O
Cp2Zr
N OPh
O
O
Cp2Zr
Ar
Ph Ph Ph
2-3 hour syringe pump addition
NaOH/MeOH
NHPh
Ph 83% de
Syringe pump addition required to achieve high selectivity due to slow racemization of SM relative to insertion
Norton, JOC, ASAP Norton, JACS, 1999, 121, 4520.