Enol/allyl ethers and olefins

Dehydrodimerization of Cyclic Enol/Allyl Ethers and Olefins... 

B. Dehydrodimerization of cyclic enol/allyl ethers and olefins... 

Figure 22. Synthesis of allyl hydrazines through addition of cyclic allyl/enol ethers and olefins to 1,2-diazenes photocatalyzed by ZnS or CdS.

Generally, isolated olefinic bonds will not escape attack by these reagents. However, in certain cases where the rate of hydroxyl oxidation is relatively fast, as with allylic alcohols, an isolated double bond will survive. Thepresence of other nucleophilic centers in the molecule, such as primary and secondary amines, sulfides, enol ethers and activated aromatic systems, will generate undesirable side reactions, but aldehydes, esters, ethers, ketals and acetals are generally stable under neutral or basic conditions. Halogenation of the product ketone can become but is not always a problem when base is not included in the reaction mixture. The generated acid can promote formation of an enol which in turn may compete favorably with the alcohol for the oxidant. 

Recently, Grubbs138 demonstrated that olefin isomerization of allyl-lic ethers and alcohols is catalyzed by Ru(II)(H20)6(tos)2 (tos = p-toluenesulfonate) in aqueous medium. The olefin migration products, enols, and enol ethers thus generated are unstable and are hydrolyzed instantly to yield the corresponding carbonyl compounds (Eq. 3.34). 

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]. 

Olefin isomerization catalyzed by ruthenium alkylidene complexes can be applied to the deprotection of allyl ethers, allyl amines, and synthesis of cyclic enol ethers by the sequential reaction of RCM and olefin isomerization. Treatment of 70 with allyl ether affords corresponding vinyl ether, which is subsequently converted into alcohol with an aqueous HCl solution (Eq. 12.37) [44]. In contrast, the allylic chain was substituted at the Cl position, and allyl ether 94 was converted to the corresponding homoallylic 95 (Eq. 12.38). The corresponding enamines were formed by the reaction of 70 with allylamines [44, 45]. Selective deprotection of the allylamines in the presence of allyl ethers by 69 has been observed (Eq. 12.39), which is comparable with the Jt-allyl palladium deallylation methodology. This selectivity was attributed to the ability of the lone pair of the nitrogen atom to conjugate with a new double bond of the enamine intermediate. 

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. 

Protic-acid-catalyzed Michael additions (59) are subject to most of the limitations of base-catalyzed Michael additions (regioselectivity and stereoselectivity of enol generation, polyaddition, etc.), and hence, the stereochemistry has been little studied (60). At low temperatures silyl and stannyl enol ethers,+ ketene acetals, and allyl species are unreactive to all but the most reactive activated olefins. However, it was discovered by Mukaiyama and co-workers that enol ethers and ketene acetals react with a,/f-unsaturated carbonyl compounds in the presence of certain Lewis acids (4,61,62). Sakurai, Hosomi, and co-workers found that allylsilanes behave similarly (5,63,64). 

Addition of a Lewis acid has been noted to improve the stereoselectivity (Table 12, entries 1-3). High stereocontrol is observed for products which can equilibrate via enolization (Table 12, entries 6-10) and for the sterically demanding sulfone derivative (Table 12, entry 4). Application of this methodology to EPC synthesis is illustrated by the use of lactones prepared in 8 to 9 steps from mannose (Table 12, entries 11-18)1 4. The stereochemical information within the reactive allyl ether moiety is faithfully transmitted and, remarkably, the Z geometry of the olefins is retained during formation of the vinylcyclopentanes. These more sterically hindered substrates may give mixtures of 5- and 7-membered rings (Table 12, entries 11,12, and 14-16). 

Early extensive accounts of the 4v participation of a,/)-unsaturated carbonyl compounds in [4 + 2] cycloadditions detailed their reactions with electron-deficient dienophiles including a,/3-unsaturated nitriles, aldehydes, and ketones simple unactivated olefins including allylic alcohols and electron-rich dienophiles including enol ethers, enamines, vinyl carbamates, and vinyl ureas.23-25 31-33 Subsequent efforts have recognized the preferential participation of simple a,/3-unsaturated carbonyl compounds (a,/3-unsaturated aldehydes > ketones > esters) in inverse electron demand [4 + 2] cycloadditions and have further explored their [4 + 2]-cycloaddition reactions with enol ethers,34-48 acetylenic ethers,48 49 ke-tene acetals,36-50 enamines,4151-60-66 ynamines,61-63 ketene aminals,66 and selected simple olefins64-65 (Scheme 7-1). Additional examples may be found in Table 7-1. 

The addition of 1,4-benzoquinone was also found to prevent olefin isomerization in a number of ruthenium-catalyzed olefin metathesis reactions of allylic ethers (Scheme 12.32) [57]. When the siloxy ether 107, which bears a ds-olefin, was treated with Ru catalyst 3 (5 mol%) in CD2CI2 at 40 C for 24 h, a mixture of 107 and the corresponding tram isomer of 107 was observed in 19% yield, while 81% of the reaction mixture was the isomerized silyl enol ether product 108. The addition of 1,4-benzoquinone or acetic acid completely suppressed olefin migration, and mixtures of cis- and tram-105 were the major products (> 95%). Phenol, another common additive in olefin metathesis reactions, failed to inhibit olefin migration, and enol ether 108 was formed as the major product. 

Applications Based on a-Lithio-selenoxides. Full details have appeared on the uses of cf-lithio-selenoxides, generated by low-temperature deprotonation of selenoxides with LDA. They are probably less nucleophilic than the corresponding cf-lithio-selenides. Their reactions leading to olefins, allylic alcohols, and (less well explored) enones are summarized in Scheme 15, and they have also been applied in the synthesis of silyl enol ethers (Scheme 16). 

With respect to the olefinic substrate, various functional groups are tolerated, e.g. ester, ether, carboxy or cyano groups. Primary and secondary allylic alcohols, e.g. 14, react with concomitant migration of the double bond, to give an enol derivative, which then tautomerizes to the corresponding aldehyde (e.g. 15) or ketone ... 

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