Electron-rich unsaturated ketones

The electron-rich unsaturated ketones 85—87 can be subjected to [4 + 2] cycloaddition with ketenes to give 3,4-dihydro-2-pyranones 88—90 which are readily transformed into the 2-pyranones 91 and 92 in the presence of zinc in moist acetic acid (Scheme 29) (1983JOC5337, 1969AGE312). 

The electron-rich unsaturated ketones 428 react with diphenylketene to give the [4-1-2] cycloadducts 429 in a stepwise process... 

This heteroannular dienone system causes rings A and B to assume a half-chair conformation. Carbon atoms 1, 3, 4, 5, 6, 8, 9, 10, 11 are all in one plane while carbon atom 2 projects above and carbon atom 7 below the plane. The rest of the molecule is below the plane. Addition of the second unsaturation to the A -3-ketone enone system provides an additional electron-rich unsaturated residue, i.e., it enhances the electron delocalization. The result will be an enlarged contribution of ionic resonance structures such as... 

Historically, the asymmetric synthesis of epoxides derived from electron-poor alkenes, for example a, (3-unsaturated ketones, has not received as much attention as the equivalent reaction for electron-rich alkenes (vide supra). However, a recent flurry of research activity in this area has uncovered several... 

The utility of the electrode to promote bond formation between functional groups of the same polarity provides researchers with an opportunity to explore the chemistry of interesting intermediates, and synthetic strategies that are based on their intermediacy [1,2], Reduction at a cathode, or oxidation at an anode, renders electron-poor sites rich, and electron-rich sites, poor. For example, the reduction of an a, 8-unsaturated ketone leads to a radical anion in which the -carbon possesses nucleophilic, rather than electrophilic character. Similarly, oxidation of an enol ether affords a radical cation wherein the -carbon displays electrophilic, rather than its usual nucleophilic behavior [3]. 

The CM of olefins bearing electron-withdrawing functionalities, such as a,/ -unsaturated aldehydes, ketones, amides, and esters, allows for the direct installment of olefin functionality, which can either be retained or utilized as a synthetic handle for further elaboration. The poor nucleophilicity of electron-deficient olefins makes them challenging substrates for olefin CM. As a result, these substrates must generally be paired with more electron-rich crosspartners to proceed. In one of the initial reports in this area, Crowe and Goldberg found that acrylonitrile could participate in CM reactions with various terminal olefins using catalyst 1 (Equation (2))." Acrylonitrile was found not to be active in secondary metathesis isomerization, and no homodimer formation was observed, making it a type III olefin. In addition, as mentioned in Section 11.06.3.2, this reaction represents one of the few examples of Z-selectivity in CM. Subsequent to this report, ruthenium complexes 6 and 7a were also observed to function as competent catalysts for acrylonitrile... 

Photocycloadditions are common and usually involve diradical intermediates photo-excited ketones react with a variety of unsaturated systems (Scheme 1). Both the singlet and the triplet (n, it ) excited states of the ketones will form oxetanes with electron-rich alkenes. With electron-deficient alkenes only the singlet states give oxetanes. Diradicals are the immediate precursors to the oxetanes in all cases, but the diradicals are formed by different mechanisms, depending on the availability of electrons in the two components. 

A novel formal inverse-electron-demand hetero-Diels-Alder reaction between 2-aryl-a,/3-unsaturated aldehydes and ketones produces dihydropyran derivatives stereo-specifically.161 The inverse-electron-demand Diels-Alder reaction of 3,4-r-butylthio-phene 1-oxide with electron-rich dienophiles shows vyn-jr-face and endo selectivity.162 (g) The inverse-electron-demand Diels-Alder reaction of dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate with a variety of dienophiles produces phthalazine-type dihydrodiol and diol epoxides which were synthesized as possible carcinogens.163... 

Diels-Alder reactions with electron-rich alkenes.1 Simple a,(i-unsaturated im-ines (1-aza-1,3-butadienes) do not undergo Diels-Alder reactions with dienophiles. In contrast, the N-phenylsulfonyl imines derived from an aldehyde or ketone undergo Diels-Alder reactions under forcing conditions with electron-rich dienophiles to... 

Of particular interest is the observation that in certain cases products such as 24 resulting from domino processes are obtained After the formation of the furan, evidently a double Michael-type addition of these intermediates to the remaining starting material 23 can take place at the unsubstituted 5-position. Preliminary experiments to investigate scope and limitations of such addition reactions in the presence of gold salts also confirm the applicability to the functionalization of other electron-rich arenes (Scheme 6) Besides furans, azulene 28 and di- and trialkoxybenzene are suitable as nucleophiles for the reaction with unsaturated carbonyl compounds [14]. For instance, 2-methylfuran (25) reacts at the reactive 5-position with methyl vinyl ketone 26 to give the addition product 27, and with azulene 28 a twofold... 

Benzophenone (Amax = 340 nm, log e = 2.5, n-ir electronic transition) can be used as a photochemical reagent and eq. 4.25 shows a radical Michael-addition reaction with benzophenone. The formed benzophenone biradical (triplet state, Tx) abstracts an electron-rich a-hydrogen atom from methyl 3-hydroxypropanoate (62) to generate an electron-rich a-hydroxy carbon-centered radical [III], then its radical adds to the electron-deficient (3-carbon of a, (3-unsaturated cyclic ketone (63) through the radical Michael addition. The electrophilic oxygen-centered radical in the benzophenone biradical abstracts an electron-rich hydrogen atom from methyl 3-hydroxypropanoate (62) [70]. So, an a-hydroxy carbon-centered radical [III] is formed, and an electron-deficient a-methoxycarbonyl carbon-centered radical [III7] is not formed. 

Diels-Alder reactions carbohydrates.2 This 3,y-unsaturated a-keto ester undergoes Diels-Alder reactions with electron-rich dienophiles to provide protected sugars. The thermal and pressure-promoted reaction of 1 with ethyl vinyl ketone provides the endo-adduct 2, which can be converted in two steps into the ethyl (3-mannopyranoside 3. The same reaction of 1 with (Z)-l-acetoxy-2-benzy-loxyethylene is even more endo-selective, and gives the endo-adduct 4, which can be converted into a derivative of benzyl DL-mannopyranoside. 

The reaction of a, /3-unsaturated ketones with electron-rich arenes is catalysed by AUCI3, which was shown to be efficient under very moderate reaction conditions 45 but in the case of sterically demanding products, HBF4 was a better catalyst. 

The oxidative reanangement most widely used in synthesis b the oxidative 1,2-shift of an alkene or enol, which b shown in the fonnal sense in equation (33). The alkoie may be elecnon deficient such as an unsaturated ketone, or electron rich such as an enol, enol ether or enamine. 

Simple a,3-unsaturated aldehydes, ketones, and esters (R = C02Me H > alkyl, aryl OR equation l)i, 60 preferentially participate in LUMOdiene-controlled Diels-Alder reactions with electron-rich, strained, and selected simple alkene and alkyne dienophiles, - although the thermal reaction conditions required are relatively harsh (150-250 C) and the reactions are characterized by the competitive dimerization and polymerization of the 1-oxa-1,3-butadiene. Typical dienophiles have included enol ethers, thioenol ethers, alkynyl ethers, ketene acetals, enamines, ynamines, ketene aminals, and selected simple alkenes representative examples are detailed in Table 2. - The most extensively studied reaction in the series is the [4 + 2] cycloaddition reaction of a,3-unsaturated ketones with enol ethers and E)esimoni,... 

One of the most effective approaches to implementing the Diels-Alder participation of 1-oxa-1,3-butadienes is through the use of an intramolecular [4 + 2] cycloaddition reaction.A select set of thermal and Lewis acid-catalyzed intramolecular cycloaddition reactions of unactivated and electron-rich alkenes with a,P-unsaturated aldehydes and ketones has been detailed. Two examples of the poorly matched intramolecular Diels-Alder reaction of an a,P-unsaturated aldehyde (4 ir component) with an a, 3-unsaturated amide (2ir component) have proven successful (190-160 °C) and may be attributed to the entropic assistance provided by the intramolecular reaction. These observations have been applied in... 

MO calculations have been carried out on the isomerization of cyclopropane to propene, and the MNDO method has been used to study the reaction pathway and to optimize the structure of reactant, transition structure, and product of the ring opening reaction of bicyclo[1.1.0]butane. Various methods have been employed to estimate the rate constants for ring opening of the 2-cyclopropyl-2-propyl radical. 1-Acceptor-1-sulfenyl-substituted 2-vinylcyclopropanes of the type (430) have been found to afford 6-sulfenyl-a,jS y, -unsaturated carboxylic esters and nitriles (431) upon treatment with acid, by a process which involves C(l)—C(2) bond fission and a novel 1,5-sulfenyl rearrangement (see Scheme 110). It has been shown that the benzophenone-sensitized photolysis of vinyl norcaradiene derivatives, such as 5-(2-methylprop-l-enyl)-3-oxatricyclo[4.4.0.0 ]deca-7,9-dien-4-ones (432), results in the regioselective cleavage of only one of the cyclopropyl c-bonds to afford isochroman-3-one derivatives (433). It has been reported that the major product obtained from the reaction of structurally diverse a-diazo ketones with an electron-rich alkene in the... 

In addition to the normal photochemical reactions of saturated ketones, p,y-unsaturated carbonyl compounds undergo carbonyl migration via a [1,3] shift. Compound 139 in Scheme 45 represents a typical example. Compounds with an alkyl substituent in the P position such as 140 may also undergo a Norrish type II reaction (Kiefer and Carlson, I%7), while for ketones with electron-rich double bonds such as 141, oxetane formation is also observed (Schexnayder and Engel, 1975). 

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