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-tri-ethoxypent-3-en-1-ols (1) have been converted to perfluoro-alkylated tetrahydrofurans and tetrahydropyrans in a selective fashion by 1-iodoperfluoroalkane addition under radical conditions using sodium dithionite (Na2S2O4) as radical initiator. Direct perfluoroalkylation of I 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-2H-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. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)