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

Figure 4=1. (a) Anti versus Syn carbamate isomers (b) Hydrogen bonding in the Syn
conformational wmer of Z,4S and 2S,m Cbz-L-Glu(yMe)(OMe)OBO ester 4.73
and 4.74.
Once the high diastereoseIectivity of addition had been established, Our attention
tumed to optimizing alkylation (Table 4.1). Other counterions were investigated for the
generation of the enolate. NaHMDS gave the same results as LiHMDS, however, the
potassium enolate resulted in a 1:l mixture of 4-methylated product. This is in
agreement with results reporteci by Gu and Hessonn (Scheme 4.13.4A6 P-PNB. R'=R~=
=Me) where a chelated dianion mechanism was proposed and subsequently described
by Hanessian and Schuarn (Section 4.2.10). An excess of base was also required since 2
equivalents of LiHMDS, titrated according to the method of Love and Jonesp gave a
lower yield of product (entry 8). Inverse addition (i.e. addition of the substrate dropwise
to a mixture of base) was also necessary, implying that the reaction is under kinetic
control? In order to identify whether an E or Z enolate was formed we attempted to trap
the enolate with TMSCl as described by Humphrey et al.= and compare the chernical
shift of the silyl ketene acetal to literature values described by Ireland and Daub?
However, al1 trapping experiments failed and the addition of HMPA had no effect on
either yield or diastereoselectivity.