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

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A new synthesis of bromo- and iodomethyl-substituted tetrahydrofurans has been devised. The sequence starts with the conversion of aryl-functionalized bis(homoallylic) alcohols 1 into N-alkenoxythiazole-2(3H)-thiones 6 or pyridine-2(1H)-thiones 7. When photolyzed in the presence of appropriate trapping reagents, thiones 6 and 7 efficiently liberated substituted 4-penten-1-oxyl radicals 2, which underwent synthetically useful 5-exo-trig cyclizations. Cyclized radicals 3 were trapped with BrCCl3 or an adequate iodine atom donor (either n-C4F9I or diethyl 2-iodo-2-methyl malonate) to provide halocyclization products 4 or 5. This strategy has been applied for the synthesis of 3-, 4-, or 5-phenyl-substituted 2-(1-bromo-1-methylethyl)tetrahydrofurans 4a−c (75−90%, 36−96% de), which were not attainable as major products from polar, for example NBS-mediated, bromocyclizations. Aryl-substituted 2-iodomethyl tetrahydrofurans 5 (46−80%) were prepared in a similar way starting from N-alkenoxypyridine-2(1H)-thiones 7 and a suitable iodine atom donor. Diastereomerically pure iodides cis-5 and trans-5 served 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)