Preparation of 2‐Ethoxy‐3‐hydroxy‐4‐(perfluoroalkyl)tetrahydropyran Derivatives from Substituted 4‐Ethoxybut‐3‐en‐1‐ols

A number of 1‐substituted and 1,1‐disubstituted ( E )‐4,5,5‐triethoxypent‐3‐en‐1‐ols ( 1 ) have been converted to perfluoroalkylated tetrahydrofurans and tetrahydropyrans in a selective fashion by 1‐iodoperfluoroalkane addition under radical conditions using sodium dithionite (Na 2 S 2 O 4 ) as radical initiator. Direct perfluoroalkylation of 1 gave the former products only, and the yields were moderate (50–75 %), but when 1 was converted to corresponding 6‐substituted and 6,6‐disubstituted 2,3‐diethoxy‐5,6‐dihydro‐2 H ‐pyrans before perfluoroalkylation was carried out, the transformation turned out to be significantly more successful and afforded, as the only product, 6‐substituted and 6,6‐disubstituted 2‐ethoxy‐4‐(perfluoroalkyl)tetrahydropyran‐3‐ones in 77–100 % yield as stereoisomeric mixtures. Subsequent reduction of the keto group with sodium borohydride in ethanol was uneventful and completed the syntheses of a range of 4‐perfluorobutylated tetrahydropyran derivatives; the yields in this step were in the 81–94 % range. The best result was obtained with ( E )‐2‐methyl‐5,6,6‐triethoxyhex‐4‐en‐2‐ol which was converted to a diastereoisomeric mixture of 2‐ethoxy‐6,6‐dimethyl‐4‐(perfluorobutyl)tetrahydropyran‐3‐ol in 85 % yield in three steps. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)