Synthesis of stereopentad analogues of the C14-C22 segment of callystatin A through additions of chiral allenylzinc reagents to stereotriads

The addition of (P)- and (M)-allenylzinc reagents, prepared in situ through Pd-catalyzed metalation of (R)- and (S)-8-butyn-2-ol mesylates, to diastereomeric stereotriad aldehydes 8, 13, 18, and 23 of syn,syn, syn,anti, anti,anti, and anti,syn stereochemistry was examined. Additions to the former two aldehydes afforded the four anti adducts with high diastereoselectivity and negligible mismatching. Significant mismatching was observed with the latter two aldehydes and the (All)-allenylzinc reagent. An evaluation of possible transition states is presented in consideration of steric and dipolar control elements.