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

quenched by aqueous work-up. After acid hydrolysis in 6N HCl and ion exchange
purification, the rotation of the resulting glutamic acid 4.60 was comparable to that of the
starting material, indicating no racemization had occurred during esterification, amine
protection, rearrangement to give Cbz-L-Glu(0Me)OBO ester 4.69 or after prolonged
exposure to base. Cbz-D-Glu(0Me)OBO 4.70 was also methylated to give 2R,4R-Cbz-
Glu(y-Me)(OMe)OBO ester 4.75 which haci an identical 'H-NMR spectra to the 2S,4S
product 4.73 as expected, including the minor doublet at 1.05 ppm.
To eliminate the possibility of the methyl ester regioisomer 4.85 king formed in
the initial esterification and king carried through, Cbz-L-Glu(OB0)-OMe was
synthesized via the ~xazolidinone~ and subsequently y-esterified to the oxetane ester 4.86
followed by rearrangement to the OB0 ester 4.87 (Scheme 4.21). Exposure of 4.87 to
conditions identical to those used for the methylation of 4.69 failed to produce any
product after 6 hours as expected.
Scheme 4.21
1, C 5 2 C 0 3 1
CR=""" 4.m
2, =, OMF# R = oxetane ester 4.86
48 h
Kawahata et al. were able to dimethylate PhFbAsp(0Me)OtBu 5.11 by sequential
treamient with KHMDS and MeLn In order to dismiss ydimethylglutarnate as a possible
contaminant, (whose two methyl singlets might be mistaken as the rninor doublet) we
tried to ydmethylate Ch-L-Glu(0Me)-OB0 4.69 and y-monomethylate 2S,4S-Cbz-
162