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

stereosele~tivities.~ Numerous examples exist of the synthesis of a-amino acids using
this methodology including the recent synthesis of a novel phosphotyrosyl mimetic?' and
p,y-dehydrovaline?'" Evans' chiral N-acyloxazolidinones methodology thus provides
access to both R- and S-a-amino acid enantiomers.
1.3.3 Stereoselective Introduction of the Side Chain
An obvious disconnection in the synthesis of a-amino acids is the stereoselective
incorporation of the sidechain to a glycine equivalent. A cyclic chiral template usuall y
induces stereochemical orientation and a revie w of the literature indicat es the majorit y of
methods describing the asymmetnc synthesis of a-amino acids employ this approach.
Both nucleophilic and electrophilic additions are used in order to introduce a wide range
of side chains ont0 the template. Numerous examples of these chiral synthons exist.
however, only the most important and frequentiy used systems will be discussed.
2.3.3.1 Glycine a-Anion Equivalents
The first cyclic template developed, the most versatile and widely used was the
bis-lactim ether 1.32 developed by Schollkopf et al. of which several reviews have
appeared." The dimethoxy lactirn ether 1.32 was formed from the diketopiperazine 1.31
in 70-8096 yields and was subsequently used to generate a-methyl amino acids by
reaction of its enolate with alkyl halides or carbonyls (Scheme 1.14).