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)-3-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 (M)-allenylzinc reagent. An evaluation of possible transition states is presented in consideration of steric and dipolar control elements.
Marshall
J A
JA
Department of Chemistry, University of Virginia, Charlottesville, VA 22904, USA. jam5x@virginia.edu
Schaaf
G M
GM
D000447:Aldehydes / Q000737:chemistry*; D000466:Alkadienes / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis / Q000737:chemistry*; D011161:Porifera / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry*
D000447:Aldehydes; D000466:Alkadienes; D000970:Antineoplastic Agents; D005231:Fatty Acids, Unsaturated; C421091:callystatin A; C025947:propadiene; D015032:Zinc