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

The Peterson olefination has been widely utilized for olefin synthesis as a
silicon analog of the Wittig or Homer-Emrnons reactions. One of the features of this
reaction is that both E and Z olefins cm be obtained stereospecifically from a single
diastereomer of B-bydroxyalkylsilane by altenng the reaction conditions (acid or
base).53vH
The p-hydroxyalkylsilane 3.45 was generated by reaction of Cbz-Ser(a1d)-OB0
ester 3.37 with trimethylsilylmethylenemagnesium chloride and proceeded in quantative
yield with threo stereochernistry as previously observed (Section 2.2.5). in an effort to
maintain the integrity of the OB0 ester and thereby allow fuxther functionalization, base
mediated elirnination was attempted. However, those reaction conditions consistently
failed to gïve the desired olefin regardless of base used, temperature or length of reaction,
instead forrning the oxazolidinone 3.46 as a asult of attack of the oxyanion on the
carbarnate of the Cbz group. Various bases investigated include KH.52 NaH," KO~BU,~
LDA, LHMDS, nBuLi and KHDMS. Methods pioneered by Chans6 to convert the
alcohol into a better leaving group were also explored including BF3 EbO,Y
MSCVE~~N,~" AcC~,'~ AcD/pyridine, nB~Li/Mscl,~ ACCVF;~ Acfikat. T.MSClS9 and
AczO/cat. TMSOTf," al1 of which either resulted in no reaction or total decomposition of
the starting material, generally as a resuit of hydrolysis of the OB0 ester.
Scheme 3.22
TMSCH2MgCI ,
THF, A -1 0°C