Product studies cyclic ether reactions

Cyclization of mixed acetals (13,300).4 This reaction is a particularly useful route to eight-membered cyclic ethers (oxocanes) and provides the first practical route to a natural oxocene, (- )-laurenyne (3), from an optically active mixed acetal 1. Thus cyclization of 1 followed by O-desilylation affords 2 as the only cyclic product. Remaining steps to 3 involved C-desilylation, for which only HF/pyridine is useful, introduction of unsaturation into the C2-side chain, and extension of the C8-side chain. Exploratory studies showed that unsaturation at the p- or y-positions to the cite of cyclization of 1 prevent or retard cyclization with a wide variety of Lewis acids. The cyclization is apparently more tolerant of substitution in the terminator position, C3-Q, of the oxocene. 

In 1985, Dbtz et al. reported during a study on the reaction of Fischer-type carbene complexes with alkynes [10] that 2-oxacyclopentylidene chromium complex 24 was obtained as a side product. Thus, treatment ofmethyl(methoxy)carbene complex with 3-butynol at 70 °C in dibutyl ether gave the cyclic carbene complex 24 in 23% yield along with the desired metathesis product 23. The authors briefly commented that the cyclic carbene complex 24 might be obtained through the vinylidene complex 25, generated by the reaction of the alkyne with the liberated pentacarbonylchromium species (Scheme 5.7). 

The principal side reaction is telomerization, which is mainly formation of a cyclic tetramer, a 16-membered cyclic ether. A great deal of study has been given to suppression of this undesired by-product by variations in catalysts, promoters and other conditions. 

The reactions of various triphenylalkylidenephosphoranes with acetylenic esters have been studied.275-271 In general, it has been found that the products formed in these reactions are to a large extent influenced by the nature of the solvent employed. Thus, the reaction of triphenylphosphorylideneacetophenone (472) with DM AD in an aprotic solvent such as dry ether gives the phosphorane 474, through the cyclic phosphorane 473. In contrast, the reaction of472 in a protic solvent like methanol gives the Michael adduct (475) (Scheme 75).277... 

Elimination reactions are facile processes as far as they have been studied in the gas phase. It is, however, often difficult to distinguish them from SN2 substitution reactions since both reactions mostly lead to the same product ions, but not to the same neutral products which in most experiments are not known (Smith et al., 1980 Jones et al., 1985). In that respect the reactions of cyclic compounds, such as cyclic ethers, are good probes for the study of elimination reactions because the leaving group remains with the anion. For example, the reaction of NH2 with tetrahydrofuran leads to (M — H) ions. Deuterium labelling has shown that the proton is abstracted exclusively from the P-position (DePuy and Bierbaum, 1981b DePuy et al., 1982b). 

The ability of fluoro-2 -phosphanes to transform silyl ethers into fluorides was first observed during a study of the reactions of phosphorus pentafluoride and its derivatives R PF5 (n = 1, 2, 3 R = hydrocarbon group) with trimethylsilyl ethers. Subsequently, this reaction was proposed as a new method for the preparation of C-F compounds from silyl ethers or silicic acid esters with fluoro-A -phosphanes. Pentafluorophenyl-substituted fluoro-A -phos-phanes were found to react similarily, Other workers found that tctrafluoro(phenyl)-A -phos-phane. which was chosen as the most convenient reagent with regard to reactivity and stability, gave considerable amounts of elimination products, especially with primary and cyclic alcohols. Good yields of fluorinated products are obtained when stable carbocations can be formed at the site of substitution, such as in tertiary alcohols, but 2-phcnylethanol. benzyl alcohol and diphcnylmethanol, on the other hand, give only poor yields of fluorinated products ethers and polymers are the main products. ... 

In an earlier report Mazzocchi and his coworkers reported that the photo-reaction of A) methylnaphthalimide (325) with phenyIcyclopropane involved the production of a radical cation/radical anion pair. The product from the reaction was the cyclic ether (326). - A study of the mechanism of this reaction using suitably deuteriated compounds has demonstrated that the reaction is not concerted and takes place via the biradical (327). - Other systems related to these have been studied. In the present paper the photoreactivity of the naphthalimide (328) with alkenes in methanol was examined. Thus, with 1-methylstyrene cycloaddition occurs to the naphthalene moiety to afford the adducts (329) and (330). The mechanism proposed for the addition involves an electron transfer process whereby the radical cation of the styrene is trapped by methanol as the radical (331). This adds to the radical anion (332) ultimately to afford the observed products. Several examples of the reaction were descr ibed. 

Over the past twenty years, the intramolecular allylation of aldehydes has been used in the synthesis of natural products containing a-methylene-y-lactones [95-101] (e.g. confertin [99] and cembranolide [100, 101]), polyene-containing macro-lides [102, 103] (e.g. asperdiol [102]) and, more recently, cyclic ether containing natural products (e.g. (-i-Vlaurencin [104] and hemibrevetoxin B [105]). However, the principles that govern the stereoselectivity in these cyclization reactions have only recently been studied in a systematic manner (see below). 

Chloro-l-hydroxynaphthalene is converted into the sulphonate 246 on eosin-sensitized irradiation in the presence of sodium sulphite. A study of the chain substitution of the chloro group in 4-chloro-l-hydroxynaphthalene by aqueous sodium sulphite has shown that two mechanisms for the photoinitiation have been identified and two intermediates have been detected a radical anion of 4-chloro-l-naphthoxide and the sulphite radical anion. Thus, an SjjajI mechanism is suggested and is one that involves reaction with the radical anion of sulphite. An example of the S n 1 process between a phenol and the (2-cyanoaryl)azo-f-butylsulphides has been reported. The 1 reactivity of several compounds (Scheme 27) have demonstrated that 247 is a product however, this is also photochemically reactive and is converted into the cyclic ether 248 . 

As with polystyrene sulfonic resins, Nafion-based acid catalysts are highly efficient for hydration and dehydration processes and, in general, for condensation reactions that occur with the formation of water or similar secondary products. Formation of ethers has been studied for various alcohols [109-111]. Dehydration of 1,4- and 1,5-diols at 135 °C affords the corresponding cyclic ethers such as 20 in excellent yields (Scheme 10.7), while 1,3-diols experience different transformations depending on their structure [112]. The dehydration of 1,2-diols mainly proceeds via the pinacol rearrangement. Further condensation of the initially formed carbonyl compound and unreacted diol affords 1,3-dioxolanes [113]. The catalyst could be efficiently reused following a reactivation protocol. Formation of aryl ethers is also possible, and the synthesis of dibenzofurans 21 (X = O) from 2,2 -dihydroxybiphenyls has been reported (Scheme 10.7) [114]. The related reaction... 

Miscellaneous Reactions. - p-Toluenesulfonaraide undergoes Mitsunobu-type reactions in the presence of alcohols and cyanomethylenetriphenyl-phos-phorane (56) to give predominantly mono-N-alkylation products. This reaction has also been applied to the synthesis of cyclic ethers from diols and cyclic amines from amino alcohols and to carbon-carbon bond formation. Examples of cyclic amine synthesis include that of (+)-a-skytanthine (57). A comparative study of the reactions of active methine compounds (58) as nucleophiles using... 

Rare examples of normal Michaelis-Becker reactions which involve co-chloroalkanal diethyl acetals are to be found, and although the formation of dialkyl acylphosphonates from sodium dialkyl phosphites and, for example, benzoyl chloride, is to be observed at -85 °C, the system is further complicated, even at -10 °C, by further addition steps followed by rearrangements which would seem to render the process of little value for the synthesis of oxoalkyl phosphonic esters On the other hand, in a more detailed and systematic study of reactions between sodium dialkyl phosphites, (RO)2PONa(R = Et or Bu), and the ketones R CO(CH2) Cl, Sturtz and others have observed the formation of epoxides when n = 1 and (1-hydroxy alk-2-enyl)phosphonic diesters when n = 2(R = Me or Pr ), according to the displacement in 532, and of derivatives of tetrahydrofuran or tetrahy-dropyran, according to 533 n = 3 or 4) when R = Et, the formation of the cyclic ethers was accompanied by low yields of the expected (oxoalkyl)phosphonic diester, but otherwise the latter were isolated as a single product only for R = Me, n = 5, and R = Et or Pr when n = 2. 

Olah et al. reported the triflic acid-catalyzed isobutene-iso-butylene alkylation, modified with trifluoroacetic acid (TFA) or water. They found that the best alkylation conditions were at an acid strength of about//q = —10.7, giving a calculated research octane number (RON) of 89.1 (TfOH/TFA) and91.3 (TfOH/HaO). Triflic acid-modified zeohtes can be used for the gas phase synthesis of methyl tert-butyl ether (MTBE), and the mechanism of activity enhancement by triflic acid modification appears to be related to the formation of extra-lattice Al rather than the direct presence of triflic acid. A thermally stable solid catalyst prepared from amorphous silica gel and triflic acid has also been reported. The obtained material was found to be an active catalyst in the alkylation of isobutylene with n-butenes to yield high-octane gasoline components. A similar study has been carried out with triflic acid-functionalized mesoporous Zr-TMS catalysts. Triflic acid-catalyzed carbonylation, direct coupling reactions, and formylation of toluene have also been reported. Tritlic acid also promotes transalkylation and adaman-tylation of arenes in ionic liquids. Triflic acid-mediated reactions of methylenecyclopropanes with nitriles have also been investigated to provide [3 + 2] cycloaddition products as well as Ritter products. Tritlic acid also catalyzes cyclization of unsaturated alcohols to cyclic ethers. ... 

It is noteworthy that azobisisobutyronitrile (AIBN) catalyzed homopolymerization of MA was fastest in 1,4-dioxane among a number of cyclic ethers studied.Thus, polymerization may be an important side reaction which can explain the poor addition of 1,4-dioxane. Efforts such as high MA dilution or slow additions of initiator and MA appear worth undertaking for higher yields of these interesting products. 

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