Diene cyclic enol ether

Recently, Nicolaou and coworkers have devised a novel, one-pot strategy for the direct transformation of acyclic olefinic esters to cyclic enol ethers [34]. Unlike the molybdenum alkylidene 1 (see Sect. 3.2), initial reaction between the Tebbe reagent 93 and an olefinic ester results in rapid carbonyl olefination to afford a diene intermediate. Subsequent heating initiates RCM to afford the desired cyclic product (Scheme 17). 

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],... 

Analogous boion-ene addition to enol ethers (36) requires 110-140 C. Under these harsh conditions die initially formed 2-alkoxyboranes (37).undergo a spontaneous -eliInination to furnish 1,4-dienes (38) in good yields (Scheme 9 Table 5) Application of this cu-metallo-allylation/syR-elimination sequence to cyclic enol ethers provides a stereocontrolled access to 1,4-dienols containing a trisubstituted alkenic bond, as illustrated by the transformation (39) + (40) - (42) (Scheme 9). 

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 reactions of p-nitrostyrene (81a) with both acyclic and cyclic enol-ethers have been studied. In general, when electron-rich alkenes interact at 1.5 GPa with p-nitrostyrene (81a), mixtures of bicyclic or tricyclic regioisomers are obtained. For example, the reaction of 81a with enol ether 86 (Scheme 7.21) led to a 7 3 mixture of compounds 87 and 88. p-Nitrostyrene (81a) first reacts as an electron-poor diene in an inverse electron demand Diels-Alder reaction with the enol ether, and then as an electron-poor dipolarophile with the formed monoadduct in a 1,3-dipolar cycloaddition. 

Among the pinene-derived mono-alcohols, only (-)-isopinocampheol [(— )-33] has been used as an auxiliary. Its enantiomer ( + )-33 is commercially available or is readily prepared by a hydroboration/oxidation sequence from (+)-a-pinene (for a detailed procedure, see ref 34). The phenyl ether of (—)-33 has been used as a starting material for cyclic enol ethers 35. obtained by Birch reduction of the phenyl group3s, which are used as chiral dienes in Diels-Alder reactions (Section D.1.6.1.1.1.), although no description of the synthesis of the ether has been given. The alcohol has also been used for the synthesis of di(isopinocampheyloxy)-2-propenylborane 3433 (Section D.2.3.5.). 

Studies relating to the stereoselective hydroboration of polyfunctional alkenes continue to appear. Various vinyl substituted pyridines, thiophenes and furans have been reacted with representative hydroborating agents,11" and further aspects of the hydroboration of cyclic dienes have been disclosed.11 The asymmetric hydroboration of cyclic enol ethers and enamines (heterocyclic alkenes) provides access... 

The complex cw-[(OC)4Mo CNMeCH2CH2NMe 2] has been shown to be catalytically active in methylmethacrylate polymerization, and weakly active in the metathesis of octa-1,7-diene. Reactions of pentacarbonyltungstendi-phenylcarbene with cyclic enol ethers have been studied in a series of papers. ... 

The direct method using ene-ene RCM to construct aromatic rings has also been used for the synthesis of benzofurans and indoles. In a paper on the synthesis of cyclic enol ethers by RCM, Fujimura et al. reported that benzofurans 27 could be prepared from dienes 26 by RCM using Schrock s catalyst 4 (Scheme 26.7) [14]. This group applied the method to obtain the naturally occurring antifungal phytoalexine, known as Sophora compound I (30). On the other hand, Arisawa et al. synthesized indoles... 

Cycloalkenones and/or their derivatives can also behave as dienic partners in the Diels-Alder cycloaddition. It is well documented [41] that cyclic acetals, for example, can interconvert with ring-opened enol ether forms, in a reversible manner the latter compounds can then be trapped by various dienophiles. Thus dienes 119 and 120 reacted with [60]-fullerene (Ceo) at high pressure, affording highly thermally stable products [42] (Scheme 5.16). Ketones 123 and 124 could be directly obtained by cycloaddition of enol forms 121 and 122 of 2-cyclopen-ten-and 2-cyclohexen-l-one, respectively. 

Ruthenium complexes B also undergo fast reaction with terminal alkenes, but only slow or no reaction with internal alkenes. Sterically demanding olefins such as, e.g., 3,3-dimethyl-l-butene, or conjugated or cumulated dienes cannot be metathesized with complexes B. These catalysts generally have a higher tendency to form cyclic oligomers from dienes than do molybdenum-based catalysts. With enol ethers and enamines irreversible formation of catalytically inactive complexes occurs [582] (see Section 2.1.9). Isomerization of allyl ethers to enol ethers has been observed with complexes B [582]. 

A wide range of olefins can be cyclopropanated with acceptor-substituted carbene complexes. These include acyclic or cyclic alkenes, styrenes [1015], 1,3-dienes [1002], vinyl iodides [1347,1348], arenes [1349], fullerenes [1350], heteroare-nes, enol ethers or esters [1351-1354], ketene acetals, and A-alkoxycarbonyl-[1355,1356] or A-silyl enamines [1357], Electron-rich alkenes are usually cyclopropanated faster than electron-poor alkenes [626,1015],... 

Enantiomerically pure Diels-Alder adducts of Ceo were prepared by Tsuji and co-workers by use of a chiral auxiliary in the diene component and separation of the diastereoisomeric intermediates.385 The starting material for the diene component was a cyclic cyclopentenone acetal (224, Scheme 1.21) derived from L-threitol, reacting via its cyclopentadiene-containing enol ether isomer.385,386 The diastereoisomeric products 225 and 226, formed without significant diastereoselectivity, were isolated as the acetals, separated and subsequently hydrolyzed to afford the enantiomeric ketones (+)-227 and (—)-227. NOE measurements allowed the determination of the absolute configuration of the diastereoisomeric intermediates 225 and 226 and, therefore, also of the enantiomeric ketones (+)-(R,R)-227 and (—)-(S,S)-227 (Scheme 1.21).385... 

Cyclobutenes possessing an angular O-functionality, obtained from a Lewis acid-mediated [2+2] cycloaddition of cyclic silyl enol ethers to ethyl propynoate and subsequent reduction and butenylation, undergo a ring-opening metathesis that produces a substituted dihydropyran that forms part of a c -diene. After desilylation, an oxy-Cope rearrangement leads to the fused tetrahydropyran 4 <03JA14901>. 

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