STEREOSPECIFIC SYNTHESIS OF NATURALLY-OCCURRING 4-ALKYLIDENEGLUTAMIC ACIDS, 4-ALKYLGLUTAMATES AND 4-ALKYLPROLINES

The enaminone 4, prepared from (2S)-pyroglutamic acid, has been found to react in an apparent 1,4-manner with DIBAL and Grignard reagents to afford a variety of alkylidene derivatives 8 which, except for the vi nyl derivatives 8e, are formed only as the (E)-isomers. Three of these have been converted to the 4-alkylideneglutamic acids, 1, 2 and 3, wh ich are identical to known natural products, the synthesis confirming 2 and 3 as the E-isomers. Catalytic reduction of the 4-alkylidenepyrog lutamate derivatives 8 is stereospecific and affords an effective rout e to (2S,4S)-4-alkylglutamic acids and (2S,4S)-4-alkylprolines. Cuprat e addition to the enone 5 affords access to the (2S,4R)-epimer 15 and carbene addition allows cyclopropylglutamic acids 32 and 33 to be prep ared.