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

Scheme 123
Rapoport has also studied the use of the N-(9-phenylfluoren-9-yl) (PhH)
protecting group for preventing racemization in the serine aldehyde equivalents 1.51 and
1S2.65 The buky protecting group is proposed to prevent enolization by obstructing
removal of the a-proton.
Probably the most versatile serine aldehyde synthon is Garner's aldehyde 1.53.
Fiat reported in 1984," with an Orgunic Syntheses preparation appearing in 199 1 ," this
synthon has been used extensively for the synthesis of various chiral arnino alcohols such
as sphingosine 156 and a-arnino acids, particularly p,y-unsaturated amino acids such as
1.57 (Scheme 1.24).' The numerous exarnples of successful reactions include Wittig
olefinations with unstabilized ylides," a-phosphonocarbo~ylates,~~ Takai olefinations."
Reformatsky reactions," cuprate additionsn and Grignard reactions." Most of the
described reactions occur in both good yield and with minimal racernization at the a-
carbon even under relatively basic conditions. Stereoselectivity at the p-carbon after
various addition reactions to 1.53 varied between 3:l for vinylmagnesium bromide
(antixyn) to 98:2 (syn:anti) for the 1,4-addition of ~uprates.".'~ Perfect stereocontrol has
been obtained with chiral reagents such as allyl-Ti complexes chelated with a di01 ligand
derived from tartrate."