Synthesis of Enantiomerically Pure Unsaturated α-Amino Acids Using Serine-Derived Zinc/Copper Reagents

Article abstract of DOI:10.1021/jo00112a048

Treatment of the serine-derived organozinc reagent 2, in benzene/dimethylacetamide, with a THF solution of CuCN*2LiCl gives rise to a zinc/copper reagent 6 which reacts directly with allylic halides and tosylates to give the corresponding enantiomerically pure substitution products 9 in 32-65percent yield (11 examples).The reaction proceeds by formal S_N2' displacement of the leaving group.Reaction with propargyl halides gives the corresponding terminal allene 12a.The zinc reagent 2 may also be prepared directly from protected iodoalanine 1 in THF by the Knochel method.Reaction with propargylic tosylates as electrophiles gives rise to the corresponding protected terminal allenic amino acids in 51-81percent yield (four examples); use of enantiomerically enriched propargylic tosylates results in the formation of diastereoisomerically enriched 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.Finally, the possibility of using the serine-derived iodide 20, in which the carboxylic acid is protected as a methyl ester, is established.This reagent offers advantages over the corresponding benzyl ester protected reagent 6 for the synthesis of unsaturated amino acids.