Eight-membered cyclic ethers

I11 Nicolaou s total synthesis of brevetoxin B, for example, out of the eleven transfused six- to eight-membered cyclic ethers, THP rings B, F, G, and I are constructed by application of this methodology through cydization of the appropriate... 

Intramolecular allylation of a-chloroacetoxy ether 185 followed by RCM (Scheme 35) was used by Yamamoto and coworkers to construct the eight-membered cyclic ether in the F-K ring segment 186 of the marine neurotoxin brevetoxin B (184) [91]. 

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. 

In a different study, a d-allenyl alcohol 81 containing a chiral substituent was oxidized by DMDO and then cyclized to afford the substituted tetrahydropyran 82 with good diastereoselectivity [19] (Scheme 17.24). Interestingly, when oxone was used instead of DMDO, the eight-membered cyclic ether 83 was formed via the allene oxide intermediate. 

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 ... 

The ring-closure (cyclodehydration) of dihydroxy compounds affords five-, six-, seven-, and eight-membered cyclic ethers. The reaction can efficiently and conveniently be carried out with Nafion-H.687,688 Even diphenols (2,2 -dihydroxybiphenyls) undergo dehydration to afford oxolane derivatives276 [Eq. (5.244)]. The low yields of the fc/T-butyI-substituted compounds result from trans-terf-butylation (see Section 5.2.6). Cyclodehydration of stereoisomeric... 

Seven-membered cyclic ethers 736 have been prepared by palladium(0)-catalyzed ring expansion of the adducts resulting from the addition of the intermediate 719 to 4,4-dialkylisochromanones 7351061. However, when isochromanones 737 were used as electrophiles, the resulting adducts afforded the corresponding eight-membered cyclic ethers... 

The vinylsilane-terminated cyclization strategy has been extended to the preparation of eight-membered cyclic ethers. Oxocenes (Scheme 17) with AAunsaturation (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 predominanfiy at the terminal position of the alkene to form a tertiary a-silyl, rather than a primary 3-silyl, carbocation. The... 

Through the efforts of the Overman research group, the acetal-vinylsilane cyclization reaction has been shown to be a useful strategy for the stereoselective preparation of a variety of medium-sized oxygen heterocycles. This cyclization strategy has been used successfully in the asymmetric synthesis of the marine natural product (-)-laurenyne (40a), an eight-membered cyclic ether. These molecules are members of an unusual class of C-15 nonisoprenoid metabolites. 

CycliTjotion Chelation effect directs the formation of an eight-membered cyclic ether. 

Bratz M, Bullock WH, Overman LE, Takemoto T. Total synthesis of (4-)-laurencin. Use of acetal-vinyl sulfide cyclizations for forming highly functionalized eight-membered cyclic ethers. 7 Am. Chem. Soc. 1995 117(22) 5958-5966. 

Overman, L.E. and Thompson, A.S. (1988) Total synthesis of (—)-laurenyne. Use of acetyl-initiated cyclizations to prepare functionalized eight-membered cyclic ethers./. Am. Chem. Soc., 110, 2248-2256. 

Ortega, N., Martin, T, and Martin, V.S. (2006) Stereoselective synthesis of eight-membered cyclic ethers by tandem Nicholas reaction/ring-closing metathesis a short synthesis of (-l-)-cts-lauthisan. Org. Lett., 8, 871-873. 

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