Serendipitous acid-catalyzed rearrangement of 13-Methoxy-1,6,8-trioxidaspiro(4.1.5.3)pentadecane to 3-Choroman-5-ylpropan-1-ol

2 pages, 1 scheme, 1 chart.-- PMID: 11671542 [PubMed].The molecular arrangement of trioxadispiroacetals appears in nature in a small number of polyether ionophores. The formation of this three-ring system linked in a spiro fashion at two ketal carbons represents a synthetic challenge. Thus, only a few natural products and simpler models possessing this structure have been synthesized so far. Not surprisingly, the field of the trioxadispiroacetal reactions has not been fully explored. For the less complex dioxaspiro compounds, only a few reactions have been studied, the most noteworthy being the acid-catalyzed spiroisomerization, the opening of spiroacetals to thermodynamically less favored ketones by treatment with mineral acids, and the reductive ring opening to monocyclic compounds or to a 1,6-dioxadecalin system.We report here on the unexpected rearrangement undergone by the trioxadispiroacetals of type 1-4 in the presence of acid to produce a chroman derivative 5 (Chart 1). The removal of the methoxyl group and the aldol condensation reaction play a decisive role in the displacement of the equilibria from the tricyclic structures to the new bicyclic aromatic arrangement.This work was supported by the Investigation Programme no. PB93-0171 of the Dirección General de Investigación Científica y Técnica and Programmes nos. 93/030 and 93/014 of the Dirección General de Universidades e Investigación del Gobierno de Canarias. A.M. thanks the Ministerio de Educación y Ciencia, Spain, for a fellowship