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

amount of unreacted starting material. Methyl iodide was chosen as the initial alkylating
agent since the easily identifiable doublet could be integrated by NMR methods to
determine diastereoselectivity.
Scheme 5.16
1) TMSCI. MeOH. 18 h ,
2) CbzOSu, Na2C03
C02H H&/do- Cb2H CbZH
1 ) BFjEt20,
CHd39 m CbzH
2) Et3N 2) E+, -78°C a*
1) 6N HCI, A
5.38 R=Me
5.39 R=~u
5.40 R=Bn
5.41 R=E=Me (2S,3S)
5.42 R=E=Mû (2S.3R)
5.43 heu. €=Me
5.U R=Bn, €=Me
5.45 R=Me, Edutyl
5.48 R=Me, E=Bn
5.47 €=Me
5.48 E4Iyl
5.49 E=Bn
Addition of LiHMDS to 538 at -30°C and quenching with methyl iodide
disappointingly gave a I : 1 ratio of fbmethylaspartate 5.41 diastereomers, based upon 'H
NMR integration of the new methyl doublet at 6 1.12 ppm (major) and 1 .O8 ppm (minor)
and the a- and B-protons. Al1 attempts to increase the diastereoselectivity failed until the
order of addition was altered. Inverse addition of 538 to base at -30°C followed by the
addition of methyl iodide gave a 3:l ratio of diastereomers (Table 5.1, entries 1-3).
Cooling to -78°C resulted in an increase of diastereoselectivity to 10: 1 in 8 1 k yield after
8 hours (entry 5). However, although a number of other conditions were investigated
including the use of other countenons, additives (HMPA and LiCl) and alternative p-
ester protecting groups (?Bu 543, Bn 5.44), no further increase in diastereoselectivity was
O