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

Scheme 2.19
NaBr, acetone
The best yields for the estenfication reaction were obtained using the cesiurn salt
of Boc-L-serine 2.40 or Boc-L-threonine 2.41 with the oxetane bromide 2.39 (85-90%)
(Scheme 2.20). However, the prefemd method is esterification with the oxetane tosylate
2.38 in DMF in the presence of sodium iodide (10 mol%) as distillation and storage of
the sensitive oxetane bromide 2.39 is avoided. In these latter conditions the Boc serine
derivative 2e42 wwas obtained in 6696 yield and the Boc threonine derivative 2-43 in 73%
yield as oils which crystallized upon standing. The formation of the ortho ester 2.44 and
2.45 from the oxetane esters 2.42 and 2e43 was performed in CH2Clz with a catalytic
arnount of BF3*Et20 (2-5 mol%). The more acid sensitive Boc derivative 2.44, in
cornparison to the Fmoc and Cbz denvatives, is obtained in 66% yield after
chrornatography with similar yields obtained for the threonine derivative 2.45. Oxidation
under Swem conditions gave the aldehyde 2-46 and ketone 2e47 in 90-95s yields.
Reduction with NaBb, deprotection and HPLC analysis of the derivatized amino acid
(vide infa) indicated no loss of optical activity during the conversion to the aldehyde
2.46 or ketone 2.47.