Cyclic ethers stereochemistry

Robinson, P.L., Barry, C.N., Kelly, J.W., and Evans, S.A., Diethoxytriphe-nylphosphorane a mild, regioselective cyclodehydrating reagent for conversion of diols to cyclic ethers. Stereochemistry, synthetic utility, and scope, /. Am. Chem. Soc., 107, 5210, 1985. 

Alko xy ally 1)stannane aldehydes (57) can cyclize either thermally or with Lewis or protic acid catalysis to give cyclic ethers (58).85 The interrelationship of the reactant and product stereochemistries has been investigated, as have the methods used to promote the reaction. For both thermal and proton-promoted reactions, [(Z)-57 gave (cis-58), and [(E)-57] gave trans-58), whereas trans-58) was the predominant or exclusive product of Lewis acid mediation, regardless of the double bond geometry of... 

Oxypalladation of vinyl ether, followed by alkene insertion, is an interesting synthetic route to functionalized cyclic ethers. In prostaglandin synthesis, the oxypalladation of ethyl vinyl ether (40) with the protected cyclopentenediol 39 generates 41 and its intramolecular alkene insertion generates 42. The intermolecular insertion of the alkene 43, and /1-elimination of 44 occurred as one-pot reaction at room temperature, giving the final product 45 in 72% yield [46], The stereochemistry of the product shows that the alkene insertion (carbopalladation of 41) is syn. It should be noted that the elimination of /1-hydrogen from the intermediate 42 is not possible, because there is no /1-hydrogen syn coplanar to the Pd and, instead, the insertion of alkene 43 occurs. 

We have excluded pathways which might involve concerted decomposition of dioxyphosphoranes to cyclic ethers with retention of stereochemistry at least for symmetrical 1,2-diols by examining the reaction of d, l-2,3-butanediol with DTPP. The C NMR spectrum of the reaction mixture is consistent only with the cis epoxide exhibiting resonances at 6 12.9 and 52.4 ppm. 

The third compound was made by a Pauson-Khand reaction using the same starting material = the first. The only difference between these two target molecules is the position of the double bor. In the Nazarov reaction, it goes into the thermodynamically most favourable position but in 1-Pauson-Khand reaction it goes where the alkyne was. So we simply react the cyclic ether wci acetylene cobalt carbonyl complex. The cis stereochemistry is inevitable. 

A further correlation with a compound of known stereochemistry was achieved by Hofmann degradation of dregamine methiodide, which gave the methine (151) via its less stable A -isomer reduction of the ketone and ester groups, and formation of the cyclic ether (152) then afforded a compound identical with dihydro-taberpsychine methine (Scheme 17). In independent experiments it was established that C-16 had not suffered epimerization. ... 

Returning to a reaction we met right at the start of this chapter will illustrate that the regio-and stereochemistry of many different electrophilic reactions with alkenes can be controlled by intramolecular nucleophiles. The mercuration of the cis alkene Z-184 leads to a 6 1 ratio of diastereoisomers of a cyclic ether 185 by a related trapping of the intermediate by the internal OH group. 

We shall illustrate this with Prestwich s synthesis11 of the natural anti-cancer compound (—)-aplysistatin 69. This interesting compound with a seven-membered cyclic ether and a bromine atom proclaiming its marine origin is probably made in nature by a polyolefin cyclisation and that strategy was used in the synthesis. The alkene must be removed 70 before the cyclisation can be reversed. The stereochemistry of the extra centre in 70 is unimportant until the realisation that it can be made by alkylation of a hydroxylactone 71 whose stereochemistry must be anti. 

The study of the Diels-Alder adducts of levopimaric acid has continued with an examination of the structure and stereochemistry of the adducts with cyclopentenone and cyclopent-l-ene-3,5-dione. The major product with cyclo-pentenone is the endo,cis adduct (83). The enedione gives a mixture of enolic endo,cis adducts whose stereochemistry was determined by photocyclisation to give compounds such as (84). A correlation was also achieved with the benzo-quinone adduct through a Favorskii-type ring-contraction of the epoxide (85) to (86). The 13(14) double bond of these adducts is hindered to oxidation, excepting the adduct with acetylenedicarboxylic acid. Condensation of 12-hydroxymethylabiet-7(8)-en-18-oic acid with formaldehyde gives the cyclic ether (87). 

We will first consider some relevant additional chemical evidence bearing on the stereochemistry shown in CCCLXX. It has been shown that exhaustive methylation of dihydroisocodeine leads to a very small yield of the cychc ether 6-codiran (CCCLXXI), whereas no cyclic ether can be obtained from dihydrocodeine under these circumstances (416). 

A number of closely related naturally occurring pyrrolizidine cyclic ethers have been identified.74 Four of these, loline (=festucine75) (119), norloline (120), lolinine (121), and decorticasine (122), have had their structures and relative configurations established by chemical methods. In addition, the relative stereochemistry of loline has been defined by an X-ray crystal structure determination of its dihydrochloride.76 The absolute configurations for all these alkaloid bases have now been established by the X-ray technique of anomalous dispersion using the same dihydrochloride of loline (119).7 7... 

Treatment of 12 with (Me3Si)3SiH and Et3B predominantly alforded cyclic ethers with cis stereochemistry [17], Construction of oxepines (n = 2) proceeded at low concentration. Additionally, the reaction at low temperature was effective to suppress decarbonylation of the intermediary acyl radical derived from acyl selenide (Scheme 10). 

An extensive use of /hh couplings has been made by Mondol et al to establish the structure of cyclic ether-containing 24-membered isomeric macrolactones isolated from a marine Bacillus sp. The absolute stereochemistry of two ieodoglucomides A and B, unique glycolipopeptides consisting of an amino acid, a new fatty acid, and a sugar isolated from a marine-derived bacterium Bacillus licheniformis has been established by Tareq et al by the use of /hh couplings, and Marfey s and Mosher s methods. 

The multifunctional nature of Cinchona alkaloids makes them especially prone for a complex reactivity that occurs with a degradation or rearrangement of the carbon moiety, often controlled by the stereochemistry of the particular alkaloid. These characteristic for Cinchona alkaloid transformations include an acid-catalyzed formation of cinchotoxines 59 described as early as in 1853 by Pasteur [108] or synthesis of diverse cyclic ethers, for example, )S-isoquinidine 60 or jS-isocupreidine 61, bearing oxazatwistane moiety [180, 201, 202] (Scheme 21.5). This can be used as an efficient catalyst of a stereoselective Baylis-HiUman reaction [8-10, 203, 204]. Hoffmann studied in detail the two distinct cage rearrangements... 

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