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

Abstract

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 (Na2S2O4) 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‐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. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Approaches to the Synthesis of Perfluoroalkyl‐Modified Carbohydrates and Derivatives: Thiosugars, Iminosugars, and Tetrahydro(thio)pyrans

“…The key step was the addition of the organometallic (Li or Mg)-CF 2 P(O)(OEt) 2 reagent to the C-1 of compound 71 (Scheme 23), which occurs with concomitant ring-opening. Further mesylation of the remaining hydroxy group and removal of the sulfinyl group allowed the ring-closure by nucleophilic attack of the resulting amine group Valdersnes and Sydnes [63] reported the synthesis of racemic 6substituted 2-ethoxy-4-(perfluorobutyl)-tetrahydropyran-3-ols from simple non-carbohydrate starting materials. This approach to synthesize fluoroalkyl-substituted carbohydrate surrogates (i.e., the building block approach) can be synthetically demanding, but one interesting advantage is that the fluoroalkyl moiety may be appended at an initial stage of the synthetic protocol.…”

“…Valdersnes and Sydnes [63] reported the synthesis of racemic 6‐substituted 2‐ethoxy‐4‐(perfluorobutyl)‐tetrahydropyran‐3‐ols from simple non‐carbohydrate starting materials. This approach to synthesize fluoroalkyl‐substituted carbohydrate surrogates (i.e., the building block approach) can be synthetically demanding, but one interesting advantage is that the fluoroalkyl moiety may be appended at an initial stage of the synthetic protocol.…”

Formation of an Isomeric Mixture of Dienynes Instead of a Diallene

“…Since the synthesis of 3,3,4,4-tetraethoxybutyne (TEB) was reported some 15 years ago [1][2][3], many of its chemical properties have been uncovered and used to prepare a range of chemical compounds with rich structural diversity [4][5][6][7][8][9][10][11][12][13][14][15]. Among the most densely functionalized molecules made is 1,1,2,2,7,7,8,8-octaethoxyocta-3,5-diyne (1), which has one ketal moiety in propargylic position to each of the triple bonds [16].…”

1,1,2,2,7,7,8,8-Octaethoxyocta-3,5-diyne

“…3,3,4,4-tetraethoxybut-1-yne (TEB) (1) [8], toward a number of reagents under a variety of conditions. This has eventually led to the synthesis of a range of different products including functionalized allylic and homoallylic alcohols [9,10], highly substituted furans [11,12], amino-substituted furfurals [13], functionalized triazoles [14], deoxygenated carbohydrate analogues [9,[15][16][17], various heterocycles [18][19][20], and functionalized 1,3-dithianes [17,21].…”