7-alkene-1,5-diol tetrahydropyran

Starting with geraniol (126), Sharpless asymmetric epoxidation [68] proceeded in 95% yield and with 93% ee (see Scheme 29) [69]. Hydrobromination of the alkene was achieved under standard conditions using NBS in THF and water (5 1) to afford a 64% yield of diastereomeric bromo alcohols (127). Cyclization to the tetrahydropyran diol was accomplished by treating 127 with camphorsulphonic acid in diethyl ether, followed by diol cleavage with sodium periodate to give a mixture of aldehydes 128 and 129. Upon... 

Aliphatic alkenes also undergo the Prins reaction and a well-conducted example is with propene, formaldehyde and HC1. The product is 4-chloro-tetrahydropyran in good yield.32 This compound presumably arises from the cyclisation of another diol 194 and that clearly comes from one molecule of propene and two of formaldehyde. What is different from the last example is that the two molecules of formaldehyde must have been added to opposite ends of the original propene. 

Formaldehyde can be coupled to an alkene in the presence of an acid to give a diol (152) or a 1,3-dioxane derivative (154) in what is known as the Prins reaction. l Allylic alcohols such as 153 can also be produced in this reaction. Camphene (155) reacted with formaldehyde and acid to give a 1 1 mixture of allylic alcohol 156 and the acetate 157, in 94% yield. Scandium tiiflate has been used to prepare tetrahydropyran-4-ol derivatives from aldehydes and homoallylic alcohols via a Prins-type cyclization. 3... 

Marine macrolides have numerous asymmetric centers, oxygenated function-ahties including alcohols, carbonyl groups, the tetrahydropyran moiety, di-and trisubstituted alkenes, and macrocycUc lactones. For completion of their total synthesis, efficient and stereoselective introduction of these characteristic units should be crucial. Recently, an excellent review on asymmetric synthesis of 1,3-diol, macrolactonization, and glycosidation in the syntheses of macrolides has been pubUshed by Nakata [5]. The multisubstituted tetrahydropyran moieties are often found in the marine macrohdes, and the efficient preparation of these moieties is recognized as the key reaction in their total synthesis. In this decade, efficient methods for their stereoselective construction have been developed and used in the total synthesis of marine macrolides, wherein the relative configuration of 2- and 6-substituents is pivotal. In this section, recent progress in the preparation of tetrahydropyrans is described (for a previous review on the preparation of tetrahydropyrans, see [9]). 

Leighton et al. described an effective and nuld palladium-catalyzed tandem alkene addition/carbonylation procedure in the synthesis of leucascandrolide A [50]. Intramolecular alkoxycarbonylation of diol 65 under Semmelhack conditions proceeded efficiently to provide the desired 2,6-cis-tetrahydropyran 66 in 75 % yield with a dr of >10 1 (Scheme 22). Reaction optimization showed that use of benzonitrile as a cosolvent leads to cleaner and more efficient reactions. The functional group tolerance and chemoselectivity of the reaction simplified the protecting group strategy. 

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