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

s~ccess.~ The same principle has been used in the synthesis of a number of ysubstituted
glutamic acids but will be discussed in Mer detail in chapter four.
1.3.1.3 Asymmetnc Protonation of Enolates
The protonation of enolates generated from Schiff's bases occurs with moderate
optical purity and is dependent on the structures of the Schiff base, the lithium base and
temperature. For example, the imine 1.21 was deprotonated with lithium
diisopropylamide &DA) and quenched with (Ra)-dipivaloyl-tartaric acid 1.22 to give
predominantly the L-configuration of amino acid esters 1.23 (Scheme 1 .9)29
R = Me, bPr, Ph
Scheme 1.9
1 -22
31 HCI
1 .AS Enantioselective Introduction of the a-Amino Function
R = Me (65% ee)
R = CPr (54% ee)
Numerous groups have addressed the difficulties of the chiral synthesis of a-
amino acids through the concept of enantioselectively introducing the a-amino
fùnctionality. Two approaches rnay be taken; nucleophilic amination based on SN2
displacement or direct electrophilic amination of enolates both of which rely on
previously existing chirality to give the desired selectivity.