Studies directed toward the synthesis of the scabrosins: validation of a tandem enyne metathesis approach

A synthetic approach to the scabrosin family of antibiotics using a ruthenium carbene-catalyzed tandem metathesis and a Pd(II)-catalyzed cyclization is described. The chiral propargyl amino acid is furnished through enantioselective phase-transfer propargylation. The synthesis of the cyclohexadiene ring system is achieved through ring synthesis using tandem enyne metathesis, previously developed in our lab. The complementary methods of methylene-free and 1,5-hexadiene-alkyne metatheses are compared. The indoline heterocycles are formed using a two-step chloroacetoxylation (Bäckvall reaction) with subsequent nucleophilic attack by an amide nucleophile. The indoline subunits were joined and cyclized to furnish the core diketopiperazine ring. The stereochemical assignment of intermediates is also discussed.

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