Electron deficient enol acetates

The hetero Diels-Alder [4+2] cycloaddition (HDA reaction) is a very efficient methodology to perform pyrimidine-to-pyridine transformations. Normal (NHDA) and Inverse (IHDA) cycloaddition reactions, intramolecular as well as intermolecular, are reported, although the IHDA cycloadditions are more frequently observed. The NHDA reactions require an electron-rich heterocycle, which reacts with an electron-poor dienophile, while in the IHDA cycloadditions a n-electron-deficient heterocycle reacts with electron-rich dienophiles, such as 0,0- and 0,S-ketene acetals, S,S-ketene thioacetals, N,N-ketene acetals, enamines, enol ethers, ynamines, etc. 

Silyl enol ethers are inherently less reactive than silyl ketene acetals but are competent partners in this reaction with increased reaction times. Electron- deficient aldehydes provide the highest yields while 4-methoxybenzaldehyde proceeds in only 10% yield after 65 h (Eq. 36). 

Condensation products of 4(5//)-oxazolonium salts with aldehydes and orthoesters are the subject of a series of papers by Kosulina and co-workers Reaction of 2-methyl-4(5//)-oxazolonium perchlorates 44 with an ortho ester gives rise to an enol ether, which reacts with furanamides to afford the frani-eneamides 45 (Scheme 6.14). " Using electron deficient anilines in a three component condensation affords either 46 or 47 in 64-80% and 78-84% yields, respectively, depending on whether the reaction is performed in acetic acid or acetic anhydride. Electron-rich anilines are unreactive since they are merely protonated by the perchloric acid present in the reaction medium. ... 

Substrates containing an electron-rich double bond, such as enol ethers and enol acetates, are easily oxidized by means of PET to electron-deficient aromatic compounds, such as dicyanoanthracene (DCA) or dicyanonaphthalene (DCN), which act as photosensitizers. Cyclization reactions of the initially formed silyloxy radical cation in cyclic silyl enol ethers tethered to an olefinic or an electron-rich aromatic ring, can produce bicyclic and tricyclic ketones with definite stereochemistry (Scheme 9.14) [20, 21]. 

Lead tetra-acetate oxidation of the allylic alcohols (170)—(172) and (182) leads to the formation of the epoxides (183)—(186), products of a novel internal addition reaction of the electron-deficient alcohol oxygen to the allylic double bond. In some cases, (171) and (172), the formation of a new type of acetoxylated enol ether (173) and (174) is observed. Oxidation of the allylic dienols (175) and (176) gives the epoxyacetates (187) and (188). A variety of cyclization products was also isolated. Their formation requires an isomerization of the allylic trans double bond to cis.69 Lead tetra-acetate oxidation of dihydro-y-ionol (189) gives the new bicyclic ether... 

While enol acetates from saturated ketones were useful a-oxygenation substrates, the corresponding dienol acetates are not. The relatively electron-deficient alkene bearing the acetoxy group is less attractive h> elecm hilic oxygenating agents than the unsubstituted double bond. Thus, for example, peracid treatment leads to epoxidation the unfiinctionalized alkene.However, it would seem likely that re-... 

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. 

Among the reactions of the 1,2,4-triazines, the hetero-DlELS-ALDER reactions with electron-rich alkenes and alkynes are of special importance in preparative chemistry [168]. The heterocyclic ring reacts with enamines, enol ethers and ketene acetals as an electron-deficient 2,3-diazadiene across the ring positions C-3 and C-6 ... 

Photoinduced reactions of cyclic a-diketones with different alkenes takes place via [2 + 2], [4 + 2] or [4 + 4] photocycloaddition pathways. Photoaddition of electron deficient silyl ketene acetals to 2-, 3- and 4-acetylpyridine generates oxetanes as major products. The reaction is favoured in non polar solvents. The photoreaction between silyl enol ethers and henzil affords [2 + 2] cycloaddition products, while in the case of 9,10-phenanthrenequinone [4 + 2] cycloacidition predominates. Photocycloaddition of p-henzoquinones to hicyclopropylidene affords spirooxetanes (21) as the primacy products further irradiation leads to rearranged spiro[4.5]deca-6,9-diene-2,8-diones. With 9,10-anthraqui-none, in addition to the spirooxetane, a spiro[indan-l,l -phthalan]-3 -one is also obtained. ... 

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