4-Methylene-2,6-disubstituted tetrahydropyrans

Methylene-2,6-disubstituted tetrahydropyrans are formed from the In-catalysed reaction of aldehydes with homoallylic alcohols which proceeds by an intramolecular oxonium-ene cyclisation and exhibits excellent diastereoselectivity <02TL7193>. 

Smith utilized Petasis-Ferrier rearrangement [17] in the total syntheses of zampanoUde (Sect. 3.2.1) and phorboxazole [18,19]. The l,3-dioxan-4-ones 11 are transformed into 4-methylene-1,3-dioxanes 12, which are treated with Lewis acids to give oxonium intermediates 13. like the Prins reaction described above, the cfs-2,6-disubstituted tetrahydropyran-3-ones 14 are preferentially synthesized via the C - C bond formation (Scheme 5). 

Hoye described an RCM-based total synthesis of the 20-membered marine macrolide dactylolide 288 and its subsequent conversion to the natural carbinolamide zampanolide 289 (Scheme 56), both feature a common highly unsaturated macrolide core, bridging a m-2,6-disubstituted 4-methylene tetrahydropyran unit. When the polyunsaturated acyclic lactone 286 (1 1 epimeric mixture around the /i r/-butyldimethylsilyl (TBS)-protected carbinol center) was in situ protected with bis-trimethylsilylacetamide (BSA) and then treated with catalyst G in benzene at 60 °C, each diastereomer smoothly cyclized to the corresponding cycloalkene 287 with exclusive ( )-geometry at the newly formed double bond. 

Keck, G. E., Covel, J. A., Schiff, T., Yu, T. Pyran Annulation Asymmetric Synthesis of 2,6-Disubstituted-4-methylene Tetrahydropyrans. 

Hoye achieved the total synthesis of (-)-dactylolide via two distinct macro-cyclization strategies, involving Ti(IV)-mediated macrolactonization of an epoxy-acid (route A) and a RCM macrocyclization (route B) (Scheme 29). The czs-2,6-disubstituted-4-methylene tetrahydropyran was constructed by Prins... 

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