Seven membered cyclic ethers

Alkyl aryl ethers and enol ethers are also accessible by the Mitsunobu method. Cyclic ethers can be obtained by an intramolecular variant, which is especially suitable for the synthesis of three- to seven-membered rings ... 

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. 

Clark s group also reported on ring-closing enyne metathesis for the preparation of six- and seven-membered cyclic enol ethers 428 n= 1,2) as potential building blocks for the synthesis of marine polyether natural compounds such as brevetoxins and ciguatoxins. Metathesis products 428 were obtained from ene-ynes 427 in 72-98% yield when the NHC-bearing catalyst C was used (Scheme 84) [179]. 

In order to construct the thiepin conjugation, the seven-membered cyclic ketones containing sulfur could be converted to either their enol ethers or enol acetates. The resulting thiepins should have a number of substituents. The first stable 3,5-diacetoxy-4-phenylbenzo[6]thiepin (15) has been obtained by Hofmann et al. from the diketone (14) by acetylation with acetic anhydride in pyridine in good yield 13). By this methodo-... 

The six or seven-membered cyclic ethers that comprise the Brevetoxin subunits could be prepared by Mo-catalyzed RCM (Eq. 42) [13]. It is noteworthy that the most successful substrates were those in which R, =H and R2=Me. The first metal-containing intermediate in that circumstance therefore is likely to be that in which there is an oxygen bound to the alkylidene carbon atom yet that alkyli-dene behaves in a ring-closing reaction in the expected manner. 

As depicted in Eqs. 6.5—6.7, kinetic resolution of a variety of cyclic allylic ethers is effected by asymmetric Zr-catalyzed carbomagnesation. Importantly, besides six-membered ethers, seven- and eight-membered ring systems can readily be resolved by the Zr-catalyzed protocol. 

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. 

Oxygenated allenylstannanes have also been employed in intramolecular additions to aldehydes [82]. Both six- and seven-membered cyclic ethers have been synthesized with high diastereoselectivity by this route (Eq. 9.103). 

Allenyl ethers 202, which are easily accessible by the methods described in Chapter 1, consequently lead to cyclic ethers 203. The alkoxyallenes were much more reactive than the alkylallenes from the previous example. Thus the amount of catalyst could be reduced to 0.1mol% and 820 turnovers were reached. Five- to seven-membered rings were isolated (Scheme 15.65) [131],... 

The five- and six-membered isopropylidene 2-azacycloalkylidenemalo-nates (468, n = 0 and 1, R2 = R4 = H) were prepared in 94% and 76% yields, respectively, in the reactions of Meldrum s acid (421) and the appropriate cyclic lactim ether (465, n = 0 and 1, R2 = H, R5 = OMe) in the presence of triethylamine in boiling benzene overnight (79JOC3089). Under these conditions, caprolactim methyl ether did not react, but if the latter reaction was carried out in the presence of acetic acid and piperidine in boiling benzene overnight, a seven-membered cyclic compound (468, n = 2, R2 = R4 = H) was obtained in 58% yield (79JOC3089). 

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. 

In contrast, homo-chrysanthemol (129) reacts exclusively by capture at the quaternary cyclopropane carbon, generating the five-membered cyclic ether (130 ). Apparently, the five-membered transition state leading to 130 is significantly favored over the seven-membered one required for capture at the terminal carbon of the double bond of 129 +. 

Polyethers are prepared by the ring opening polymerization of three, four, five, seven, and higher member cyclic ethers. Polyalkylene oxides from ethylene or propylene oxide and from epichlorohydrin are the most common commercial materials. They seem to be the most reactive alkylene oxides and can be polymerized by cationic, anionic, and coordinated nucleophilic mechanisms. For example, ethylene oxide is polymerized by an alkaline catalyst to generate a living polymer in Figure 1.1. Upon addition of a second alkylene oxide monomer, it is possible to produce a block copolymer (Fig. 1.2). 

Tetrahydrofuran, a five-member cyclic ether, polymerizes cationically to yield an elastomeric polymer [28]. Oxepane, a seven-member analog, polymerizes to a crystalline polymer. 

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. 

Relatively few examples of photoreactions of seven-membered and larger heterocycles have been reported. The major products of irradiation of liquid oxepin are hex-5-en-l-ol and hexanal234 photodecomposition of cyclic ethers has, in general been shown to be largely dependent on ring size. Irradiation of the valence bond isomer (287) of hexakis(trifluoromethyl) oxepin gave the unexpectedly stable oxet (288) via a mixture of (Z)- and... 

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... 

In the preparation of cyclic ethers by diene-ene RCM, there is a competition between the formation of cyclic allyl ether with a smaller ring size and of cyclic pentadienyl ether with a larger ring size (Scheme 24). In particular, in the competition between five- and seven-membered ring formation, both dihydrofuran and dihydrooxepine derivatives are formed in comparable amounts, whereas in the competition between seven- and nine-membered rings, a dihydrooxepine forms exclusively <2006JOC3977>. 

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... 

Formation of the Mo carbene complex 223 from 222 and the Mo carbene complex 19, followed by the alkenation of the ketone in 223 gives seven-membered cycloalkene 224 [71]. The ester in 225 undergoes carbonyl alkenation with the more reactive W complex 20 to afford the cyclic enol ethers 226 [72],... 

The seven-membered cyclic ether 161 containing the Co-stablized triple bond was prepared by the Nicholas reaction of 160. The decomplexation and reduction of the triple bond to the double bond to produce 162 were achieved by Rh-catalysed hydrogenation. The method was used for the preparation of the A/B fragment of ciguatoxin [41]. 

The formation of five-, six-, and seven- membered ring cyclic alkenyl ethers from the intramolecular O-vinylation (.S n2) reactions of vinyl bromides containing a y- or 5-011 or -keto group, has been reported.17 The reactions, which require a Cul catalyst, a diamine, and K2CO3, are complete in a few hours in refluxing THF. 

By using a,co-dihalides, three- to seven-membered cyclic ethers have been prepared, simply by treatment with excess sodium hydroxide in the presence of sodium formate212. The synthesis of epoxides by this simple method in 70% yield is rather surprising, considering that the competing side reactions like elimination are usually fairly facile. 

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