Studies on the Synthesis of Kijanolide: Synthesis of the 2-Acyl Spiro Tetronate and Investigations Concerning the Coupling of the Top and the Bottom Half Fragments

Article abstract of DOI:10.1021/jo00060a036

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 via olefination (e.g., 35 + 23 -> 38) and cross-coupling reactions (e.g., 38 -> 19).This solves the problems encountered due to the introduction of the C(7)-hydroxyl group in our previous synthesis of the kijanolide bottom half 2.Third, a highly efficient procedure was developed for the coupling of kijanolide top half 8 and dioxinone 38 via an acyl ketene intermediate.This is the most efficient of several methods examined for acylating the hindered tertiary hydroxyl group of 8.Attempts to perform the IMDA reaction of 46, 47 or 9 (R = SiEt3) generated in situ from coupling of 8 and the acyl ketene (20) derived from 42 were thwarted by the unexpected tendency of β-keto esters like 47 to fragment and decarboxylate via the acyl ketene intermediate at temperatures above 115 deg C. 2-Acyl tetronates 53 and 54 were prepared, but these systems decomposed upon attempted IMDA cyclization at temperatures approaching 190 deg C.