PREPARATION OF ALPHA-BRANCHED PHENYLALANI NES AND OF 1,1-DISUBSTITUTED ETHYLENEDIAMINES VIA CHIRAL IMIDAZOLIDINONES AND OXAZOLIDINONES OF GLYCINE - PREPARATIVE AND MECHANISTIC ASPECTS

To test the structural prerequisites for a new carbanionoid rearrangem ent of valoyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid to buto xycarbonyl)-1-amino-2-methylindan-2-carboxylic acid (A --> B), various alpha-branched phenylalanines (C) were required. Geminal dialkylation of the chiral glycine building block Boc-BMI (1) occurs in excellent yields and selectivities and can be carried out in a one-pot procedure (products 2-10). However, phenylalanines with methoxy groups on the b enzene ring and alpha-branching by substituents larger than methyl can not be set free by hydrolysis of the corresponding imidazolidinones, w hich, on the other hand can be reduced through N-methyl amino acid ami des (13-15) to geminally disubstituted N-methyl-ethylenediamines (16-1 8). A series of 2-t-butyl-5-oxo-1,3-oxazolidin-3-carboxylates (19-27) was prepared and could be resolved on ChiraSphere, Chiralcel OD, and P irkle columns (Table 1). Alkylation (Me, Et, Bu), allylation, and benz ylation of the rac-oxazolidinones lead to trans-disubstituted products (29-43) which were alkylated a second time (products 44-51); yields a nd selectivities are satisfactory (Table 2). Hydrolysis of 4,4-dibenzy l-substituted oxazolidinones to the amino acid derivatives is possible (examples 52-54). - Comparison of the methylation selectivities of se ven 2-t-butyl-1,3-oxazolidin-5-one Li-enolates bearing different N-acy l groups (Figure 1) and an X-ray crystal structure analysis of a pheno l carbamate (26, Figure 2 and Table 3) show that our previous mechanis tic model obtains: t-butyl in the COR group gives the poorest selectiv ity (3:1), O-phenyl the highest (>50:1). This is compatible with the v iew that the acyl groups (on pyramidalized nitrogens!) in these hetero cyclic -acetals occupy one face of the average plane of the rings, and the substituents on the acetal center (here t-Bu) the other one (Figu re 1).