SYNTHESIS OF ENANTIOMERICALLY PURE UNSATURATED ALPHA-AMINO-ACIDS USING SERINE-DERIVED ZINZ COPPER REAGENTS/

Treatment of the serine-derived organozinc reagent 2, in benzene/dimet hylacetamide, with a THF solution of CuCN . 2LiCl gives rise to a zinc /copper reagent 6 which reacts directly with allylic halides and tosyl ates to give the corresponding enantiomerically pure substitution prod ucts 9 in 32-65% yield (11 examples). The reaction proceeds by formal S(N)2' displacement of the leaving group. Reaction with propargyl hali des gives the corresponding terminal allene 12a. The zinc reagent 2 ma y also be prepared directly from protected iodoalanine 1 in THP by the Knochel method. Reaction with propargylic tosylates as electrophiles gives rise to the corresponding protected terminal allenic amino acids in 51-81% yield (four examples); use of enantiomerically enriched pro pargylic tosylates results in the formation of diastereoisomerically e nriched allenic products. Reactions of the zinc/copper reagent 6 with a range of representative electrophiles is explored; use of relatively reactive electrophiles is necessary to obtain satisfactory yields. Fi nally, the possibility of using the serine-derived iodide 20, in which the carboxylic acid is protected as a methyl ester, is established: T his reagent offers advantages over the corresponding benzyl ester prot ected reagent 6 for the synthesis of unsaturated amino acids.