A Repetitive Approach to the Synthesis of Medium and Large Ring Compounds with a Ring-Opening/Ring-Closure Cascade Reaction of Siloxycyclopropane Derivatives as Crucial Step

Abstract

Starting from siloxycyclopropyl-substituted dimethyl malonates 1 and 2 a chain elongation was performed to give new malonates 8, 9, 10, and 18 in reasonable overall yield. Further elongation by five carbon atoms transforms 10 into 15. Precursor 21 was prepared by alkylation of cyclopropanecarboxylate 20 with dibromide 17 and subsequent treatment with sodium dimethyl malonate. Compounds 8, 9, 10, 15, 18, and 21 were subjected to cesium fluoride under high dilution which induced a ring-opening/ring-closure cascade reaction giving cyclopentadecanone derivatives 11, 12, 13, cycloeicosanone derivative 16, cyclotetradecanone derivative 19 and cyclononane derivative 22 (together with 23). The efficiency of this reaction including an intramolecular Michael addition is discussed. The sequence allows efficient synthesis of medium and large carbocycles by a highly flexible building block system involving in principle unlimited repetition of construction steps. An X-ray analysis of 19 reveals its crown-like conformation which is slightly distorted to a more planar skeleton compared with a ten-membered ring analog 24.