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

OTBDMS
3 TolSCH&i&.
Scheme 2.9
&CHO 2 eq. BUG NO2 3) TBDMSOTf
R = Me. Pr. Ph 2.27 2.28
2.1.3.4 Synthesis fiom Glycine Enolates
Most of the methods of synthesizing a-amino acids via glycine enolates as
discussed in chapter one (section 1.3.3) can be used to synthesize f3-hydroxy-a-amino
acids. The majority of glycine enolate equivalents tend to produce the syn or threo
stereochernistry upon addition to aldehydes with no oppominity of producing the other
diastereomer. The stereochernistry at the a-center is usually well defined in these
electrophilic additions of aldehydes to glycine anion equivalents, whereas variable
selectivity occurs at the p-carbon, in this instance the p-hydroxy functionality.
In general, Schollkopf s bis-lactim ether 1.33 (Scheme 1.15). the Ni(@ glycine
Schiff base 1.39 of Belekon et al. (Scheme 1.18) and Seebach's oxazolidinone 1.42
(Scheme 1-19) al1 add to aldehydes and ketones to give the threo diastereomer. Williams'
glycine boron enolate equivalent derived from oxazinone 1.34 (Scheme 1.16) gives
predorninantly the eryrhro isorner.
Williams' oxazinone 1.34 h a been used as a boron enolate to add to acetaldehyde
to give the protected L-alfo-threonine derivative 2.30 in 85: 15 diastereoselectivity and
57% yield (Scheme 2. IO)."