Stereocontrolled construction of 1, 7-dimethyl A.B.C.[6.6.6] tricycles. Part I. transannular Diels-Alder reactions of 14-membered macrocycles containing frans-dienophiles

Article abstract of DOI:10.1139/v93-152

Transannular Diels-Alder reactions of 14-membered macrocyclic trienes possessing a methyl substituent on both the diene and dienophile moiety have been investigated. Macrocyclic structures la, lb, and lc having cis-trans-trans (CTT), trans-cis-trans (TCT), and trans-trans-trans (TTT) geometries could be stereoselectively constructed by coupling appropriately functionalized dienes 5 and dienophile 4 following an intramolecular displacement of an allylic halide by the anion of an appropriately located dimethyl malonate unit. The transannular Diels-Alder reaction performed on la led to a mixture of four major tricyclic products, including 34 possessing the unexpected trans-anti-cis (TAC) stereochemistry. When heated at 300°C, macrocycle lb underwent an unique conversion via an ene-retroene, Diels-Alder process, producing the unexpected tricycle 41 (racemic form) containing five contiguous chiral centers. A rationale for the above experimental facts is presented. In contrast to the previous results, the transannular Diels-Alder reaction of macrocycle lc was straightforward, producing a 95% isolated yield of trans-anti-cis (TAC) tricycle 34. This investigation demonstrates a general methodology for the stereocontrolled synthesis of 1, 2-dimethyl A.B.C[6.6.6] tricyclic compounds, which are potential precursors to polycyclic natural products such as steroids and terpenes.