Cyclic enol ethers, formation

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. 

The addition of sulphinyl chlorides to trimethylsilyl enol ether 138 affording a-ketosulphoxides 139 (equation 76) represents an extension of the reaction of sulphinyl chlorides with ketones. This reaction has attracted attention only recently. Sergeev and coworkers192 reported that treatment of sulphinyl chlorides with acyclic enol ethers afforded a-ketosulphoxides 139 in good to excellent yields. Meanwell and Johnson193 observed that in the case of cyclic enol ethers the corresponding sulphoxides were formed only in very low yields. They found, however, that the introduction of an equivalent amount of a Lewis acid into the reaction mixture markedly promotes the desired reaction, whereas the use of catalytic amounts of a Lewis acid led to a substantial reduction in the yield. This is most probably due to the formation of a complex, between the a-ketosulphoxide and the Lewis acid. 

Preliminary investigations in this area involved treatment of olefinic ester 125 with a large excess (4 equiv) of the Tebbe reagent 93 (Scheme 18) [34a]. After 20 min at 25°C, the mixture was heated at reflux for 5 h. This resulted in the formation of tricyclic enol ether 127 in 71% overall yield. If only 1.3 equiv of Tebbe reagent 93 was employed and the reaction stopped after 20 min at 25°C,the olefinic enol ether 126 could be isolated in 77% yield. The proposed intermediacy of diene 126 in the initial tandem sequence was validated by its subsequent conversion into the cyclic enol ether 127 under the original reaction conditions [34a],... 

An alternative approach involves a two-step procedure, in which carbonyl olefination, using the Tebbe reagent 93, generates an acyclic enol ether-olefin (Scheme 16). In this case, subsequent RCM using molybdenum alkylidene 1 proceeds to give cyclic enol ethers. An efficient, one-pot carbonyl olefination-RCM approach has been developed by Nicolaou et al. for the formation of cyclic enol... 

Formation of cyclic enol ethers by carbonyl methylenation—olefin metathesis. 

In this subsection, two types of cyclodehydrations will be discussed, namely the formation of cyclic Schiff bases, and the formation of cyclic enol ethers and cyclic enamines. 

A. M. Orendt, S. W. Roberts, and J. D. Rainier, The role of asynchronous bond formation in die diastereoselective epoxidation of cyclic enol ethers A density functional theory study, J. Org. Chem., 71 (2006) 5565-5573. 

Intramolecular Addition Formation of Cyclic Enol Ethers and Lactones from Pent-4-yn-1-ols and But-3-yn-1-ols... 

Scheme 10.14 rationalizes the divergent behavior of the two catalytic systems in these selective transformations of pent-l-yn-ols. The presence of phosphine ligands promotes the formation of ruthenium vinylidene species which are key intermediates in both reactions. The more electron-rich (p-MeOC6Fl4)3P phosphine favors the formation of a cyclic oxacarbene complex which leads to the lactone after attack of the N-hydroxysuccinimide anion on the carbenic carbon. In contrast, the more labile electron-poor (p-FC6H4)3P) phosphine is exchanged with the N-hydroxysuccinimide anion and makes possible the formation of an anionic ruthenium intermediate which liberates the cyclic enol ether after protonation. 

Scheme 10.14 Mechanistic proposal for cyclic enol ether and lactone formation based on a common ruthenium vinylidene intermediate.

Formation of the Mo carbene complex 223 from 222 and the Mo carbene complex 19, followed by the alkenation of the ketone in 223 gives seven-membered cycloalkene 224 [71]. The ester in 225 undergoes carbonyl alkenation with the more reactive W complex 20 to afford the cyclic enol ethers 226 [72],... 

Starting from pent-4-yn-l-ols,the previously described catalytic system led to a mixture of lactone and cyclic enol ether [41]. However, in the presence of (Cp)ruthenium complexes bearing an electron-rich ligand such as tris(p-methoxyphenyl)phosphine in the presence of a large excess of the same ligand [system A], the selective formation of lactones was obtained. A simple modification of the catalyst precursor such as the switch to the electron-deficient... 

Lipkowitz et al. observed that the hydrogenation of cyclic enol ether 1 to 2 over a 10% Pd-C in ethanol was accompanied by the formation of bicyclic acetals of the formula 3, of which the endo isomer was hydrogenolyzed to give 2 much more rapidly... 

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

As vinyl ethers were known to be poor substrates in Ru-catalyzed olefin metath-eses, it has been difficult to obtain cydic enol ethers by RCM of the vinyl ethers. Recently, a novel method to obtain cyclic enol ethers has been reported, which afforded cydic enol ethers directly from easily prepared dienes containing an allyl ether moiety [46]. Treatment of 70 with diene 99 in CH2CI2 in the presence of small amount of H2 resulted in a formation of dihydropyran 101 (Eq. 12.40). Treatment of 70 with H2 has been thought to produce an active catalyst for the olefin isomerization, and only metathesis products are formed until a small amount of H2 is introduced in the reaction. These results implied that this reaction most likely proceeded by way of a formation of the cyclic olefin 100, which was subsequently converted to dihydropyran 101 by the newly formed isomerization catalyst. In addition to the tandem reaction shown in Eq. 12.40, another method for obtaining cydic enol ethers from allyl ethers has also been demonstrated [46b]. This method induded addition of the hydride donor, such as NaBH4, to the reaction solution after the metathesis reaction had been completed. Although attempts to observe an active species for olefin isomerization in the presence H2 failed, these results suggested participation of hydride species in the olefin isomerization. 

The protic reaction on occasion is a useful method of alkene formation, but is far from general because the cation intermediate tends to undergo rearrangements.Further, even for cases in which elimination to an alkene is the predominant pathway, the regioselectivity of the process is often mediocre. A key step in the synthesis of (+)-a-eudesmol and (-)-a-selinene exemplifies this point (Scheme 60). There are, however, isolated examples of excellent selectivity, such as the reaction of a 3-ketotetrahydrofuran tosyl-hydrazone salt to give the corresponding cyclic enol ether as the major product (Scheme 61), the intro-... 

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. 

This reaction constitutes a method for the transformation of saturated cyclic or acyclic carbonyl compounds in three steps (silyl enol ether formation, halocarbene addition, rearrangement) to a,) -unsaturated carbonyl compounds with one-carbon ring enlargement or chain elongation, respectively. The rearrangement can be induced under acidic, basic, or thermolytic conditions, or with silver(I) salts. 

Formation and trapping of the lithium enolate gave only the E silyl enol ether 202 (that is with a cis alkene in the ring). As this is a cyclic enol ether, a boat-like transition state is expected and the formation of a single diastereoisomer of 203 confirms that this is true. Diagrams 204 and 205 should clarify the conformation of the molecule as it reacts, the mechanism, and the stereochemistry of the product. The product was converted into kainic acid 206 in a few steps. 

Several cyclic enol ethers are intramolccularly cyclopropanated using rhodium(II) acetate as a highly effective catalyst 1 7. When the connecting chain becomes too long (n = 2, 3, 4), carbon-hydrogen insertion of the carbenoid competes with the intramolecular [2 + 1] cycloaddition. However, when R is methyl and n is 2 or 3, cyclopropane formation is again the dominant... 

Oxidations. Benzyl ethers are removed by oxidation with (Bu4N)2S20 and alcoholysis. Primary amines are oxidized to nitriles with Ni-Cu formates as catalyst. Oxidative cycloaddition. The oxidation of 1,3-dicarbonyl compounds in the presence of cyclic enol ethers leads to fused acetals. 

Although numerous examples of successful RCM reactions have been demonstrated, a few limitations and/or side-reactions have been uncovered. Some cases where the RCM reaction proceeds with complications are depicted in Scheme 18. Sometimes RCM reactions are competitive with alkene isomerization. For example, the unexpected formation of 162 from precursor 160 was attributed to alkene isomerization (affording 161), followed by RCM to afford the ring-contracted compound 162. Later investigators went on to exploit this observation for the synthesis of cyclic enol ethers. Treatment of the allyl ether 164 with a ruthenium carbene complex catalyst affords the RCM... 

Harvey, S., Wiesler, D. Novotny, M. 1989. Formation of cyclic enol ethers from a labile biological precursor an example of analytical artifacts. J. Chromatogr., 491, 27—36. 

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