Studies on the synthesis of kijanolide: synthesis of the 2-acyl spirotetronate and investigations concerning the coupling of the top and bottom half fragments

Abstract

Several studies directed toward the synthesis of kijanolide are described. First, a method for synthesis of the 2-acyl spiro tetronate substructure (15, 52) via a Dieckmann cyclization protocol was developed. Second, a 10-step synthesis of 7,7-dibromo-2,4-dimethyl-5-[(tert-butyldiphenylsilyl)oxy]heptenal 35 was developed, making possible the synthesis of a range of kijanolide bottom half precursors olefination (e.g., 35+23≡038) and cross-coupling reactions (e.g., 38≡019). This solves the problems encountered due to the introduction of the C(7)-hydroxyl group in our previous synthesis of thekijanolide bottom half 2. 2a Third, a highly efficient procedure was developed for the coupling of kijanolide top half 8 and dioxinone 38 via an acyl ketene intermediate. 2-Acyl tetronate 53 and 54 were prepared, but these systems decomposed upon attempted iMDA cyclization at temperatures approaching 190°C