Formal total syntheses of crocacin A-D

A concise route to the common polyketide fragment 5 of crocacin A -D (1-4) is presented which has previously been converted into all members of this fungicidal and cytotoxic family of dipeptidic natural products by various means. Our synthesis features a syn-selective titanium aldol reaction controlled by a valinol-derived auxiliary, a zinc-mediated, palladium-catalyzed anti-selective addition of propargyl mesylate 10 to the chiral aldehyde 9, as well as a comparison of palladium-catalyzed Stille and Suzuki cross-coupling reactions for the formation of the diene moiety of the target.