Ethers, cyclic hydrogenolysis

Addition of a hydroxy group to alkynes to form enol ethers is possible with Pd(II). Enol ether formation and its hydrolysis mean the hydration of alkynes to ketones. The 5-hydroxyalkyne 249 was converted into the cyclic enol ether 250[124], Stereoselective enol ether formation was applied to the synthesis of prostacyclin[131]. Treatment of the 4-alkynol 251 with a stoichiometric amount of PdCl2, followed by hydrogenolysis with formic acid, gives the cyclic enol ether 253. Alkoxypalladation to give 252 is trans addition, because the Z E ratio of the alkene 253 was 33 1. 

Cyclic Acetals Benzyl ethers are obtained from benzylidene acetals on Ni but the product ethers are cleaved about as readily as the acetals.166 The hydrogenolysis of a p-bromobenzylidene derivative was achieved on 10% Pd/C in AcOEt and NaHC03.154... 

Open-chain aliphatic ethers are completely resistant to hydrogenolysis. Cyclic ethers (for epoxides, see p. 83) may undergo reductive cleavage under strenuous conditions. The tetrahydrofuran ring was cleaved in vigorous hydrogenations over Raney nickel [420] and copper chromite [420] to give, ultimately, alcohols. 

The reagent of choice for the reduction of ketals to ethers is alone prepared in situ from lithium aluminum hydride and aluminum chloride in ether. At room temperature ethers are obtained in 61-92% yields [792, 934]. Cyclic ketals prepared from ketones and 1,2- or 1,3-diols afford on hydrogenolysis by alanes alkyl P- or y-hydroxyalkyl ethers in 83-92% yields [792]. 

The alkaloid chaenorhine (C31H40O5N4 mp 263-268° dec. [a]D + 46.7°) proved to be maerocyclic containing a spermine moiety. The entire gamut of spectral studies was involved to determine its structure (60). Of special interest is the observation that the hydrogenolysis of the alkaloid with sodium in liquid ammonia occurred at the ether linkage and generated 61 with concomitant reduction of the cyclic double bond. Hydrolysis, some chemical degradation, and further spectral studies served to elucidate the entire structure (31). 

Cyclic nitrones generated by [4+ 2]-cycloaddition of nitroalkenes undergo various, synthetically very valuable reactions. Thus, Denmark et al. have developed an elegant access to different enantiopure, 3- and 3,4-substituted pyrrolidine derivatives by reductive ring contraction of the cyclic nitrone resulting from a hetero Diels-Alder reaction [389,390]. Upon reaction of -2-nitrostyrene 4-51 with the chiral enol ether 4-52 in the presence of the bulky Lewis acid MAPh (4-53), three diastereomeric cycloadducts 4-54, 4-55 and 4-56 were formed. Hydrogenolysis of the main product 4-54 yielded the desired pyrrolidine 4-57 in excellent optical purity and allowed nearly quantitative recovery of the chiral auxiliary (Fig. 4-12) [391]. It is noteworthy that the nature of the Lewis acid catalyst, especially its steric demand, decisively influences the stereochemical course of such cycloadditions [392]. 

Scheme 13.1 Formation and hydrogenolysis of bicyclic acetals in the hydrogenation of a cyclic enol ether 1.

Elaboration of isoxazolines has been used in the synthesis of other heterocycles. Electrophilic cyclization reactions of 5-alkenyl-substituted isoxazolines (150) have been used in the synthesis of cyclic ethers (Scheme 68) (87JA7577 90JOC283). Hydrogenolysis and decarboxylation of the... 

Splitting by hydrogenolysis is not a property unique to benzyl ethers among the groups often employed in carbohydrate chemistry. The tri-phenylmethyP ethers and the cyclic acetals derived from benzalde-hyde are also cleaved by this means. This property of these... 

Enol ethers and esters can be hydrogenated over 5% Pd-on-BaSO or SrC03 in ethanol at RT and atm P, but hydrogenolysis is often a concomitant reaction, sensitive to substrate, solvent and catalyst, e.g., triflate of cyclic or steroidal ketones are readily hydrogenated over PtOj ... 

Several 6-lactones hydrogenolize to the cyclic ether under mild conditions (RT, 1(X) kPa) over large quantities of platinum oxide in acetic acid with a catalytic amount of HCIO4 [equation (i)] . The reaction is applicable to 4-oxa-3-oxo-5a-cholestane (giving 92% of 4-oxa-5a-cholestane) but not to y- or e-lactones. However, butyrolactone yields tetrahydrofuran through hydrogenolysis over a Co—Re catalyst in dioxane. ... 

Hydrogenolysis of open-chain ethers is also difficult whereas cyclic ethers are much more reactive. Cyclic ethers can be classified into two groups-strained three- and four-membered rings (oxiranes and oxetanes) are sufficiently reactive to be transformed even at room temperature whereas the five- and six-membered rings (oxolanes and oxanes) undergo transformation at higher temperatures only. 

The Chemistry of Ringc.—The modification of ring c has centred on making available relays that are suitable for elaboration into more complex diterpenoids, the diterpenoid alkaloids, and triterpenoids. The unsaturated ketone (53) has proved to be a valuable relay for synthesis. It had been prepared previously from neoabietic acid, which is difficult to obtain pure. It has now been obtained from the levopimaric acid-formaldehyde adduct (50). Oxidation of the adduct with potassium permanganate not only formed the glycol but in an unusual step converted the cyclic ether into the (5-lactone (51). Dehydration, ozonolysis of the newly formed double bond, and then treatment of the keto-acetate (52) with chromous chloride afforded the a -unsaturated ketone (53). The last step involved hydrogenolysis, / -elimination. and decarboxylation. 

In the presence of a platinum oxide catalyst tomatidine absorbs one mole of hydrogen in this reaction a cyclic ether is split. The same hydrogenolysis can be achieved with lithium aluminum hydride whereby... 

Keywords Alkane Biomass ConformatitMi Cyclic ether Diol Hydride Hydrogenolysis Ir Mo Polyol Re Rh 8 2... 

Chen K, Mori K, Watanabe H, Nakagawa Y, Tomishige K (2012) C-O bond hydrogenolysis of cyclic ethers with OH groups over rhenium-modified supported iridium catalysts. J Catal 243 171-183... 

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