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

5.2 Results and Discussion
5.2.1 Methylation of Cbz-Asp(0Me)OBO ester 5.38: Optirnizution and Detemination
of Diastereoselectivity
While examining the 1,3-asymmetric induction of the addition of various
electrophiles to glutamic acid (chapter four) we concurrently investigated the 1,2-
induction in aspartic acid 5.31- Regioselective esterification of 5.31 was achieved under
similar conditions to those described in chapter four.@ TMSCl was added in two separate
aliquots to aspartic acid 5.31 stimng in fieshly distilled methanol and after 18 hours the
solvent was evaporated to give a white solid of the monomethyl ester (Scheme 5.16). N-
Protection of the crude product as the Cbz denvative was accomplished with CbzOSu to
give 5.32. Purification was difficult and so the a-carboxylate was esterified with oxetane
tosylate 2.38 to give the hilly protected aspartic acid derivative 5.35 in 66% overall yield
for three steps. Commercially available y-t-butyl ester 5.33 and y-benzyl ester 5.34 were
esterified under identical conditions to give 5.36 and 537 in 998 and 97% yields
respectively, after cotumn chromatography. Al1 three oxetane esters 5.35-5.37 could be
stored for prolongeci periods at rwm temperatun without loss of optical activity. Boron
trifluoride etherate mediated remangement of the oxetane esters 5.35-5.37 gave the onho
esters 5.38-5.40 which were recrystallized from Et0AC:hexanes in 91%, 68% and 78%
yields respective1 y.
At first, both LLHMDS and LDA were used as bases in the generation of enolates.
although the use of LDA was later abandoned due to inconsistent results. Baldwin et
al!& and Seebach et al? also observed increased substrate decomposition and
racemization with LDA. Three equivalents of base were used, titrated according to the
method of Love and Jones,"' since the use of two equivalents resulted in a significant
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