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

A tram relationship for H2IH3 in the oxazolidinone was assigned on the basis of
the 'H NMR coupling constant. The lu value of 3.8 Hz was in agreement with those
reported for trans stereochemistry?' In retrospect, formation of the oxazolidinone 3.46
may be explained by the requirement of the j%hydroxyalkylsilane 3.45 to adopt the syn
conformation which is not easily achieved due to steric considerations. Oxazolidinone
formation is a more fasile process as seen in the staggered Newman projection of the p-
hydroxyaikylsilane 3.45 (Figure 3. l). This is in contrast to the synthesis of (S)-2-amino-
(2)-3,s-hexadienoic acid 3.43 which does not suffer from this limitation and is driven by
the formation of extended conjugation.
Figure 3.1: Formation of the Oxazolidinone 3.46.
Since base mediated elimination failed to give Cbz-vinylglycine-OBO, our
attention tumed to the use of acid in order to form vinylglycine 3.7. This has the
advantage that acid hydrolysis in refluxing 6N HCI simultaneously deprotects the ortho
ester and Cbz protecting groups as discussed below.
3.2.3 Removal of Protecting Groups
Refuxing 6N HCI has previously been used to deprotect Cbz protected methyl" or
isopropyl esters" of vinylglycine in good yield. When the same conditions were applied
to both Cbz-vinylglycine-OB0 ester 3.38 and Cbz-Ser(CH2TMS)-OB0 ester 3.45 the
free amino acid 3.7 was achieved in 76% and 74% yield respectively.
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