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

Cbz-Glu(0Me)OBO ester 4.69 was added to N-bromosuccinimide (NBS) under
conditions simüar to that reporteci by Evans et al? After generation of a deep purple
colour, the reaction was quenched to give the protected ybromoglutamate 4.112 O(rBr)
in 64% yield (Scheme 4.29). A number of side-reactions occurred since only 8% of Cbz-
Glu(0Me)OBO ester 4.66 was recovered, although none of these contaminants were
isolated. 'H-NMR integration gave a 90:10 ratio of diastereomers, the major product
presumabiy the 2S,4S stereoisomer based on previous electrophilic additions. The
reduced diastereoselectivity is perhaps due to displacement at the a-bromoester with a
brornine anion to give the 2S,4R stereoisomer by an SN2 reaction. Higher
diastereoselectivities (955) were achieved after shorter reaction times although yields
were drastically lower (&O%), quenching the reaction after six hours was a compromise
between diastereoselectivity and yield.
Scheme 4.29
4.69 X+=NBS, DAST, NFSI, 4.112 X=Br
Selectfiuor
Al1 attempts at synthesizing the yfluoro derivative 4.112 (X=F) failed although
lithium, sodium and potassium enolates were feacted with a number of fluorinating
reagents including diethylaminosulfur trifluoride (DAST), Selec$luorTU and N-
fluorobenzene sulfonamide (NFSI) using methods previously reported for the successful
electrophilic fluorination of enolates?' Complex mixtures of products generali y resulted
178