Solution and Solid Phase Synthesis of Unusual a-Amino Acids From

R
Scheme 6.13
1) 1 :1 TFA:CH2CI2
2) Cs2C03, MeOH
3) cation exchange -
H2
R1koH
C02H
Overall yields of the B-hydroxy-a-amino acids after purification ranged from 19-
418 on Wang or TentaGe1 PHBa resin. Derivatization and HPLC analysis (as described
in section 2.4.15a) indicated a slight reduction in the diastereoselectivity of addition when
compared to Grignard addition in the solution phase to Boc, Cbz and Fmoc protected
Ser(aid)-OB0 ester 2.46, 3.42 and 2.37 respective1 y (Table 6.1 ).6 The optimized solvent
conditions for the addition of Grignard reagents described in chapter two is a 1 : 1 mixture
of Et20:CH2CI2. However. as previously described, the swelling problems associated
with the use of Et20 meant it was oniy added to the reaction mixture during addition of
the Grignard reagent. Of note. is the observation in chapter two that the use CH2C12 as
the reaction solvent results in an erosion of diastereoselectivity.
HPLC analysis also indicated a significant amount of racemization (15- 188) was
occumng. Two likely sources are during Swern oxidation or after addition of the
Grignard reagent. Racemization has been show to occur during the Swem oxidation,"