Cyclic ethers formation

Redox-sensitive resin 24 designed for solid-phase peptide synthesis (SPPS) [29] was prepared from commercially available 2,5-dimethylben-zoquinone in seven steps [30] and loaded to a support via a Wittig reaction. Release of the peptide occurs using two sequential mild conditions, reduction with NaBH4 followed by TBAF-catalyzed cyclic ether formation (Scheme 8) which provide orthogonality to acid sensitive reactions. 

Nicolaou hydroxy-ketone reductive cyclic ether formation... 

Finally, it should be pointed out that in some cases epoxides are opened by a remote hydroxy group within the molecule to give the five-membered ethers [41]. We are currently investigating how the conformation of an open chain epoxy polyol might be responsible for cyclic ether formation [43]. 

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. 

A similar cyclic ether formation was observed in systems containing octaeth-yl-a-hydroxyporphyrinato zinc(II) or Ni(II) complexes [244]. 

We have systematically examined the facility with which DTPP promotes the cyclodehydration of simple diols to cyclic ethers 1,3-propanediol (1) - oxetane (2) (2-5%) 1,4-butanediol (3) te-trahydrofuran (4) (85%) 1,5-pentanediol (5) - tetrahydropyran (6) (72%) 1,6-hexanediol (7) - oxepane (8) (55-68%). Increased alkyl substitution at the carbinol carbon s gnificantly diminishes the facility for cyclic ether formation. For example, a mixture of meso- and d, 1 —2, 6-heptanediol gave only 6-10% of the cis- and trans-2,6-dimethyltetrahydropyrans when treated with DTPP. While diol 1 resists cyclodehydration with DTPP to oxetane, some 2,2-di-substituted 1,3-propanediols are readily converted to the appropriate oxetanes [e.g., 2-ethyl-2-phenyl-l,3-propanediol -> 3-ethyl-3-phenyloxetane (78%)]. 

Alkynylbenzaldehydes yield isochromenes in a Pd-catalysed reaction with alcohols. The Pd plays a dual role, behaving as a Lewis acid to effect the formation of a hemiacetal and coordinating to the alkyne moiety to promote cyclic ether formation <02JA764>. 

The appearance either of simple cyclic ethers or of the lactols derived from difunctionalisation is markedly dependent upon the particular steroid sites concerned, and has been elegantly interpreted [34,33,37] in terms of steric and conformational effects. Cyclic ether formation requires rear-side attack of the oxygen substituent on a -CH I group, leading to... 

HF-SbFs is also an efficient cationic polymerization catalyst [2]. HF-SbFs and other acids such as HF-BF3 readily oligomerize ethylene oxide to mixtures of cyclic ethers [108] which can be subsequently separated (Eq. 48). The key to cyclic ether formation is the presence of anhydrous HF in the conjugate acid systems chain polymers would otherwise be obtained. 

In view of the fact that many complex dihydro- and tetrahydro-furans possess valued biological properties, a variety of procedures for the construction of such systems has been reported. f The reactivity pattern of the cyclic ether formation with respect to ring size has been briefly discussed. - ... 

Hong, F.-T., Paquette, L. A. Olefin metathesis in cyclic ether formation. Direct conversion of olefinic esters to cyclic enol ethers with Tebbe-type reagents. Copper(l)-promoted Stille cross-coupling of stannyl enol ethers with enol triflates construction of complex polyether frameworks. Chemtracts t997, 10,14-19. 

Interesting cyclic ether formations by 2-step Ti-catalyzcd epoxidation/ring closure reactions have been reported by Corma cl al. and by Tatsumi cl al. Thus linalool was converted by treatment with t-butyl hydroperoxide over Ti-Beta and Ti-MCM-41 via the mono 6,7-epoxidc to a mixture of five- and sixmembered cyclic ethers [75]. 

Formation of oxacycles via intramolecular radical addition reactions of oxygen-centered radicals under oxidative and reductive conditions is known [116] (see also Chapter 5.2, Volume 2). However, cyclic ether formation via intramolecular displacement reaction of iodohydrins obtained by hydrogen abstraction of oxy radicals has been more widely used, as exemplified in the reports by Suarez [117]. The usefulness of this reaction was amply demonstrated by Paquette in the synthesis of (-t-)-epoxydiclymene (179) [118] (Scheme 61), in which the strained trans-... 

For the transformation of 13, and 27 - 37 into the corresponding cyclic ether derivatives, we considered the procedure of Nolte that converts Iph into 38. This involves hydroxymethylation with formaldehyde under basic conditions, followed by cyclic ether formation under strongly acidic conditions (HCl, pH 1, reflux)." To circumvent the anticipated issues with ester hydrolysis, we developed a one step procedure that proceeds under anhydrous acidic conditions (TFA, (CH20) ) where the esters are stable. In the synthesis of 39 from lco2Et, we isolated and crystallographically characterized by-product 40, which contains an 8-membered dioxygenated ring. Scheme 8 shows the structures of a variety... 

Glycols HO(CH2)/iOH lose water both inter- and intramolecularly when treated with dry HBr at 80-200°, so that bis(bromoalkyl) ethers, Br(CH2) 0(CH2) Br are obtained as byproducts and also cyclic ethers when favored ring systems can be formed.906 A notable case of cyclic ether formation is that of tetrahydrofuran from 1,4-butanediol for the reverse reaction see page 237. 

Yamaguchi A, Hiyoshi N, Sato O, Bando KK, Shirai M (2009) Enhancement of cyclic ether formation from polyalcohol compounds in high temperature liquid water by high pressure carbon dioxide. Green Chem 11 48-52... 

The EF-ring of ciguatoxin 3C has been stereoselectively synthesized by iterative use of a cyclic ether formation process based on chirality-transferring Ireland-Claisen rearrangement and ring-closing alkene metathesis (Scheme 21). ... 

A comparison of the relative rates of cyclic ether formation reveals a surprising fact Three-membered rings form quickly, about as fast as flve-membered rings. Stx-membered ring systems, four-membered rings, and the larger oxacycloalkanes are generated more slowly. 

Ester Formation. A variety of alcohols react at room temperature with carboxylic acids in the presence of DEAD and TPP to produce the corresponding esters. When polyols are used, the reaction generally takes place at the less hindered hydroxyl group, as exemplified in the reaction of 1,3-butanediol (eq 3). When 1,2-propanediol or styrene glycol is used, however, the more sterically encumbered C-2 benzoate is predominantly obtained with complete inversion of the stereochemistry. This result has been explained by the formation of a dioxaphospholane (8) as the key intermediate (eq 4) 3b, i9,20a acyclic 1,4-diols such as isomaltitol, five-membered cyclic ether formation takes place in preference to esterification. 

Scheme 61 Chiral catalyst for enantioselective cyclic ethers formation...

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