Stereochemistry cyclic ether reactions

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. 

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. 

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). 

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... 

The carbon patterns of the products (Chart 3.1) of the drastic degradation of strychnine can all be discerned in the parent molecule but cannot by themselves be used to deduce a unique formula. That the A and B rings were six and five membered respectively was reconfirmed over the years often at the cost of considerable labour. One such case concerned dinitrostrychol-carboxylic acid, one of the nitric acid oxidation products of strychnine. It was first obtained about the turn of the century and after considerable work in the late twenties was found in the early thirties to be 5,7-dinitroindole-2-carboxylic acid. Actually the structure of strychnine would probably have been realized much earlier than it was if any one of a number of degradations had been persevered with in a systematic way. The constitution arrived at by the chemical methods rests on the properties of the functionalities in their special environments and their interlocking reactions. The advent of commercial recording infrared and ultraviolet machines played an important part in the latter phase of this work. A synthesis of the alcohol, isostrychnine I (strychnine with its cyclic ether opened at dotted line and A double bond) has confirmed these conclusions as has the determination of the structure and absolute stereochemistry by the X-ray crystallographic method. 

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. 

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). ... 

Quinoline364 and isoquinoline behave much like pyridine toward DMAD, and only the more interesting reactions will be noted. Isoquinoline in ether at -60° with DMAD and carbon dioxide gives, via the postulated intermediate 295, zwitterion 296 (m.p. 83°-84°), which is far more stable than its pyridine analogs (cf. 2).365 Its stereochemistry has not been established but its IR spectrum shows absorption due to the carboxylate anion and excludes the cyclic formulation 297. Replacing the carbon dioxide by ethyl carbonate gives 298.366 In wet ether the... 

An aluminium-promoted, cobalt-mediated O C rearrangement reaction of cyclic enol ethers has been reported to give functionalized cyclohexanones with good diastereocontrol (Scheme 81).123 The product stereochemistry has been shown to be ( ) dependent on the 7Z-stereochemistry of the starting enol ether. 

The Claisen rearrangement has been instrumental in the synthesis of a number of natural products.279-289 Many useful derivatives have been prepared using the Claisen-type rearrangement including enol ethers,290 amides,291-293 esters and orthoesters,294-296 acids,297-298 oxazolines,299 ketene acetals,300-301 and thioesters.302 Many of these variants use a cyclic primer to control relative and absolute stereochemistry. The Claisen and oxy Cope provide the best candidates for scale up as a result of the irreversible nature of these reactions. 

Substrates containing an electron-rich double bond, such as enol ethers and enol acetates, are easily oxidized by means of PET to electron-deficient aromatic compounds, such as dicyanoanthracene (DCA) or dicyanonaphthalene (DCN), which act as photosensitizers. Cyclization reactions of the initially formed silyloxy radical cation in cyclic silyl enol ethers tethered to an olefinic or an electron-rich aromatic ring, can produce bicyclic and tricyclic ketones with definite stereochemistry (Scheme 9.14) [20, 21]. 

On the other hand, the [4 +- 2] cycloaddition of diethyl diazenedicarboxylate and cyclic enol ethers is performed efficiently under UV irradiation. Without irradiation and by increasing concentration, the ene reaction product can be obtained from the substrates. The oxadiazine structure, as well as the stereochemistry of the cycloadduct 13 obtained from a cyclopropane-fused dihydrofuran and diethyl diazenedicarboxylate, was established by X-ray29. 

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