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

Presumably, addition of dlyl bromide and benzyl bromide to 538 occurs with the
same stereochemistry as 5-41, the stereochemistry of the addition products thereby
tentatively assigned as 2S,3S.
5.2.3 Addition of Heteroatom to Cbz-Asp(0Me)OBO 5.38.
In an effort to expand the methodology to incorporate a variety of heteroatoms in
the p-position of 5.38, the enolate of 5.38 was reacted with various heteroatornic
electrophilic reagents.
Davis' 2-sulfonyloxaziridine 4.92 has been used previously to hydroxylate
aspartic acid derivatives giving P-hydroxyaspartate derivative 5.12 (P=Ts, R'=R'=~Bu,
ESH) in 45: 1 anti:syn (2S,3R:2S93S). Using conditions previously optimized for the
hydroxylation of Cbz-Glu(0Me)OBO ester 4.69 (Section 4.2.4), LDA (3 eq.) was added
to a mixture of Cbz-Asp(0Me)OBO ester 5.38 and Davis' oxaziridine 4.92 (5 eq.) in
THF at -78°C to give Cbz-Asp(f%OH)(OMe)OBO ester 5.51 in 5 1 % yield and 3: 1 ratio
of inseparable diastereomers after 18 h at -78°C (Scheme 5.18). The predominant
stereoisomer was tentatively assigned as 2S,3S-Cbz-Asp(B-OH)(OMe)OBO 5.51 based
on the stereochernical assignment of 5.41. Contaminants in the optimized synthesis of
5.51 included remaining starting material 5.38 (15%) and the sulfonarnide 5.52 (26%),
probably in significant quantities due to the prolonged reaction time as compared to 4.96
(Section 4.2.4). Deprotection of 5.51 with refluxing ZN HCl gave fil-hydroxyaspartate 5.5
in 62% yield after purification by cation exchange as a mixture of diastereomers.