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

5.2.2 Addition of Other AIkylation Agents to Cbz-Asp(0Me)OBO 5.38.
Having optimized the methylation of 5.41, out attention turned to investigating
the addition of other akylating reagents. AUyl bromide was added to the enolate of 5-38
under the optimized conditions determined for 5.41. Allylation to give 5-45 occurred
with a 4: 1 diastereoselectivity, determined by 'H-NMR cornparison of the B-protons, and
in a yield of 68% after 12 hours (Scheme 5.16). The diastereomers were readily
separated by flash chromatography and the starting material could be recovered. The
main diastereorner had a lower Rf than the rninor isomer, which corresponds with the
observation for 5.41. As with 5.41 the reaction failed to go to completion even after
prolonged reaction times and the addition of HMPA. The yield based on recovered
starting material was 88%. Deprotection of the separated diastereomers in refluxing 6N
HCI gave both 2s-diastereomers of 5-48 in approximately 35% yield after purification by
cation exchange.
Benzyl bromide was used to benzylate 5.38 to give 5.46 in 3: 1 diastereoselectivity
and 6 1% yield. Diastereomenc ratios were detennined by 'H-NMR integration of the p-
protons. The main contaminant was starting material although the reaction was
maintained at -78°C for 16 hours. The yield, based on recovered starting material, was
88% and the reaction could be driven to completion with warming although
diastereoselectivity decreased to 1.5: 1. Both diastereomers were easily separated by flash
chromatography and subsequently deprotected in refluxing 6N HCl to give both 2S-
diastereomers of 5.49 in approximately 55% yield.