Oxocene unsaturated

Cyclization of mixed acetals (13,300).4 This reaction is a particularly useful route to eight-membered cyclic ethers (oxocanes) and provides the first practical route to a natural oxocene, (- )-laurenyne (3), from an optically active mixed acetal 1. Thus cyclization of 1 followed by O-desilylation affords 2 as the only cyclic product. Remaining steps to 3 involved C-desilylation, for which only HF/pyridine is useful, introduction of unsaturation into the C2-side chain, and extension of the C8-side chain. Exploratory studies showed that unsaturation at the p- or y-positions to the cite of cyclization of 1 prevent or retard cyclization with a wide variety of Lewis acids. The cyclization is apparently more tolerant of substitution in the terminator position, C3-Q, of the oxocene. 

Oxocenes.1 A general route to these unsaturated eight-membered cyclic ethers involves an intramolecular cyclization of a hydroxyl group with a sulfonium ion, generated from a dithioketal by NCS-AgN03 (4,216) and a base (2,6-lutidine). Example ... 

An impressive application is the highly stereocontrolled and enandoselective synthesis of (-)-laure-nyne (113 Scheme 54). The key step is the cyclization of the mixed acetal (110) to give the oxocene (112), with the required endocyclic unsaturation at the correct position. The formation of this eight-mem-bered cyclic ether, instead of the corresponding seven-membered ring with an exocyclic double bond, may be rationalized by an intramolecular ene-type reaction of the intermediate oxocarbenium ion (111). 

The vinylsilane-terminated cyclization strategy has been extended to the preparation of eight-membered cyclic ethers. Oxocenes (Scheme 17) with A -unsaturation (3,6,7,8-tetrahydro-2//-oxocins) were prepared efficiently by the SnCU-catalyzed cyclization of the mixed acetals (39) with complete re-giochemical control. Electrophilic addition on the 2-(trimethylsilyl)-l-alkene occurs predominantly at the terminal position of the alkene to form a tertiary a-silyl, rather than a primary P-silyl, carbocation. The... 

Eight- and nine-membered cyclic ethers are also generated via type-III reactions by treating the 5-hexen-l-ol acetals with Lewis acids. 8-endo Cyclization of 5-hexenyl methoxyethoxymethyl ether in the presence of two equivalents of tin(IV) chloride forms a 2 1 mixture of chlorinated and unsaturated 1 -oxycyclooctanes 11 and 1232. Vinylsilane undergoes an 8-endo Prins cyclization. After O-desilylation, oxocene 13, which is used as a precursor in a laurenyne synthesis, is obtained in 37% yield33. 

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