Seven membered cyclic ethers cyclization

Having developed effective synthetic methodology for the construction of seven-membered cyclic ethers, we were confident that the problem of the frans-fused bis(oxepane) system could now be addressed on a solid foundation. It was our hope that the breve-toxin-type bis(oxepane) system could be assembled by a stepwise strategy utilizing both photochemical dithioester and reductive hydroxy ketone cyclization methods. 

Sulfenoetherification. The reagent in combination with trifluoromethane-sulfonic acid converts suitably unsaturated alcohols into five- to seven-membered cyclic ethers. The cyclization is considered to involve an intermediate episulfonium ion. 

D. Berger, L. E. Overman, and P. A. Renhowe, Total synthesis of (+)-isolaurepinnacin. Use of acetal-alkene cyclizations to prepare highly functionalized seven-membered cyclic ethers, J. Am. Chem. Soc., 119 (1997) 2446-2452. 

Berger D, Overman LE, Renhowe PA (1997) Total Synthesis of (+)-Isolaurepinnacin. Use of Acetal-Alkene Cyclizations to Prepare Highly Functionalized Seven-Membered Cyclic Ethers. J Am Chem Soc 119 2446... 

Asymmetric carbonyl-ene cyclization of alkenyloxy-substituted aldehydes <9ITL6571> afforded six- and seven-membered cyclic ethers of high enantiomeric purity, for example (/ )-(30) possessed a 91% ee (Equation (10)), when chiral 2,2 -dihydroxy-l,r-binaphthyl-based titanium perchlorate was used as a catalyst. 

Preparation of cyclic ethers by intramolecular reactions of the primary (29 and 33) and the secondary alcohols (31 and 35) proceeds more easily using CS2CO3 or K3PO4, and binaphthyl-based monophosphine ligands VI-1, VI-9 [9], The five-, six-, and seven-membered cyclic ethers 30, 32, and 34 were prepared from the aryl chloride 31 and bromides 29 and 33. The benzoxazapine 36 was obtained without racemization of chiral alcohol by the cyclization of the optically active bromo alcohol 35. 

Radical cyclization of allylsiloxy derivatives 148 to l-oxa-2-silacycloheptanes 149 was achieved by treatment of 2-(allyldimethylsiloxy)-l,l-dibromoalkanes with Bun3SnH in the presence of a catalytic amount of triethylborane in benzene (Equation 27). An interesting stereochemical outcome was observed in the cyclization of 1-allyldimethylsi-loxy-2,2-dibromo-l-phenylpropane (R1 = H, Rz = Ph) which gave a stereoisomeric mixture of 2,2,6-trimethyl-7-phenyl-l-oxa-2-silacycloheptane (cisftrans = 87/13). These seven-membered cyclic silyl ethers and acetals were stable and could be isolated by silica-gel column chromatography <1997BCJ2255>. 

This reaction was used for a synthesis of the seven-membered cyclic terpene karahan-aenol (3) from the methyl ether (2) of geranioi by an electrophilic cyclization of an allylsilane. ... 

Several alkenyl hydroperoxides have been successfully cyclized to five-, six- and seven-membered ring peroxides (equation 241).38s 388 Alkaline sodium borohydride reduction of these mercurials is frequently accompanied by epoxide or cyclic ether formation. 

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). 

Palladium-catalyzed cyclizations of bromodialkenyl ethers, in which the key step is vinylic substitution of bromine, result in low to moderate yields of tetrahydrooxepines and methyleneoxepanes <83JOC3894>. y,5-Unsaturated seven-membered lactones are prepared in 50-60% yields from 2-phenylthio-3-butenyldiazomalonates <90CL613> on treatment of the latter with rhodium acetate the reaction involves a [2,3]-sigmatropic rearrangement of the generated cyclic allylsulfonium ylides. 

Reaction with Di- and Polyols. Although intermolecular dehydration between two molecules of alcohols to afford acyclic ethers usually does not occur with the DEAD-TPP system, intramolecular cyclization of diols to produce three to seven-membered ethers is a common and high yielding reaction. Contrary to an early report, 1,3-propanediol does not form oxetane. Oxetanes can be formed, however, using the trimethyl phosphite modification of the Mitsunobu reaction. The reaction of (5)-1,2-propanediol and ( )-l,4-pentanediol with DEAD and TPP affords the corresponding cyclic ethers with 80-87% retention of stereochemistry at the chiral carbon, while (5)-phenyl-1,2-ethanediol affords racemic styrene oxide. In contrast to the reaction of the same 1,2-diols with benzoic acid (eq 4), oxyphos-phonium salts (25a) and (25b) have been postulated as key intermediates in the present reaction (eq 20). ... 

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