A Radical Version of the Bromo‐ and the Iodocyclization of Bis(homoallylic) Alcohols — The Synthesis of Halogenated Tetrahydrofurans by Stereoselective Alkoxyl Radical Ring Closures

Abstract

AbstractA new synthesis of bromo‐ and iodomethyl‐substituted tetrahydrofurans has been devised. The sequence starts with the conversion of aryl‐functionalized bis(homoallylic) alcohols1intoN‐alkenoxythiazole‐2(3H)‐thiones6or pyridine‐2(1H)‐thiones7. When photolyzed in the presence of appropriate trapping reagents, thiones6and7efficiently liberated substituted 4‐penten‐1‐oxyl radicals2, which underwent synthetically useful 5‐exo‐trig cyclizations. Cyclized radicals3were trapped with BrCCl3or an adequate iodine atom donor (eithern‐C4F9I or diethyl 2‐iodo‐2‐methyl malonate) to provide halocyclization products4or5. This strategy has been applied for the synthesis of 3‐, 4‐, or 5‐phenyl‐substituted 2‐(1‐bromo‐1‐methylethyl)tetrahydrofurans4a−c(75−90%, 36−96%de), which were not attainable as major products from polar, for example NBS‐mediated, bromocyclizations. Aryl‐substituted 2‐iodomethyl tetrahydrofurans5(46−80%) were prepared in a similar way starting fromN‐alkenoxypyridine‐2(1H)‐thiones7and a suitable iodine atom donor. Diastereomerically pure iodidescis‐5andtrans‐5served as starting materials for a stereochemical analysis of disubstituted tetrahydrofurans by NMR spectroscopy and X‐ray diffraction analysis. The results of this investigation clarified that all new alkoxyl radical cyclizations followed in terms of regio‐ and diastereoselectivity the general guidelines which had been established for this type of ring‐closure reaction. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)