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

The direct electrophilic azidization of enolates has previously been described,
pnmarily in a landmark study by Evans et al. showing that treatnient of the potassium
enolate of chiral oxazolidinones with trisyl azide producecl the corresponding 2-azido
derivatives in good yield and excellent selectivity (Section 1.3.2.2)." Hanessian et al.
have investigated the azidation of 3-substinited-butyrolactones although no
diastereoslectivities were reported." Encourageâ by the excellent selectivity we
encountered in the y-hydroxylation of Cbz-Glu(0Me)OBO ester 4.69, we attempted the
azidation of Cbz-Glu(0Me)OBO ester 4-49 under conditions previously reported by
Evans et aP3
Initially visyl azides 4-105 was added to the potassium enolate of Cbz-
Glu(0Me)OBO ester 4.69 as described by Evans et al." with littie success. However,
reaction of the lithium dianion gave the desired azide 4.106 although prolonged reaction
times resulted in a decrease of product as shown in Figure 4.9. This was monitored by
both quenching the reaction and isolating the product and by following the progress of
the reaction by ESI-MS. A variety of conditions were investigated including counter-ion,
temperature and lengh of reaction, however, after op timization 2S,4S-Cbz-Glu(y-
N3)(OMe)OB0 ester 4.106 was synthesized in 54% yield with 32% recovery of starting
rnaterial (Scherne 4.27). Only one stcreoisomer was detected by TLC. 'H-NMR and 13c-
NMR, presumably the S,4S isomer based on earlier results. nie reasons for apparent
decomposition of y-azide 4-106 during prolonged reaction times are unclear. Evans et
aLg3 have reported the use of acetic acid to quench the reaction and decompose the
diazonium sait fonned, however, the sensitivity of the OB0 ester to acidic conditions