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

In our system, the diastereoselective alkylations of the Li-enolate of 5.38 gave
predominantly 2S,3S stereochernistry. Ireland et al. have reported that LiHMDS/THF
systems produce (B-lithium ester enoiates? Trapping experiments with the enolate of
Cbz-Asp(0Me)OBO 5.38 failed to provide any insight to the enolate king formed, and
therefore the lithium enolate cannot be assurneci to be the E-enolate, especially with the
observation that the addition of HMPA has no effect on stereoselectivity or yield and
Chamberlin's observations.
Adapting previously proposed models for chelation in which the (E)-lithium
enolate of 5.38 chelates to the Cbz protected nitrogen, the predicted stereochemistry is
2S,3R which is inconsistent with the obsewed results. However, if the (a-lithium
enolate chelates in a 7-member ring with an oxygen in the OB0 ester, the system is
locked in a conformation in which alkylation of the enolate gives 2S,3S stereochemistry
in the product (Figure 5.4a). Additionally. the Li bonded to nitrogen cannot chelate to the
ester enolate since this would also give the incorrect stereochemistry. However, the N-Li
bond may also chelate to an oxygen in the OB0 ester to give a 5-membered ring (Figure
5.4a) This model is an adaptation of that proposed by Seebach and Wasmuth.JS
Fredriksen and Dalen have shown that polyether ligands complex with Li+ and Na', in
some cases in slightly more stable complexes with Li+ which may explain the small
increase in selectivity when LiHMDS is used over NaHMDS and KHMDS.
Conversely, in a non-chelation controlled model, if the (2)-lithium enolate is
considered it becornes apparent that the oM+ group cannot form a cyclic chelate because
of its (2)-geometry and as such adopts a hydrogen-in-plane conformation (Figure 4b) that
is attacked opposite the OB0 group which is buikier than the Cbz group (Le. from the re