Cycloaddition of enones

The [4 + 2] cycloaddition of enones and electron-rich olefins is a well-known method for the synthesis of pyrane derivatives [45]. Methylenecyclo-alkanediones [46] have also been used extensively for this purpose. 

In cycloadditions of enones to alkenes novel strategies have been adopted for ring expansion of the cycloadducts, either by the choice of appropriate alkenes, e.g. 2-(trimethylsiloxy)buta-1,3-diene,70 vmv-2-trimethylsiloxybuten-2-oales71 or 3,3-dimethylcyclopropene,72 or by using 3-oxo-l-cyeloalkene-l-carboxylates as enones.73 Asymmetric [2 + 2] photocycloaddition of cyclopent-2-enone to a (+ )-dihydrofuran acetonide constitutes the cornerstone of the synthetic strategy in the first total synthesis of the novel antitumor metabolite ( )-echinosporin.74 The cycloaddition product 25 from treatment of 2-(2-carbomethoxyethyl)-2-cyclopentenone (24) with ethene has been used as a precursor for the preparation of tricyclo[4.2.0.01,4]octane.75... 

Cycloadditions of Enones and Pyridinones. When the carbonyl group is conjugated to a C=C double bond, cycloaddition takes place at that double bond and a new ketone is formed. These reactions are fairly general with enones and their derivatives, as illustrated in Figure 4.54. The cyclobutane products are often useful synthetic intermediates. 

As early as 1964, Corey had suggested the intermediacy of an oriented pi complex in the cycloaddition of enones (43) and soon thereafter Hammond and coworkers, on the basis of arene fluorescence quenching by dienes, suggested the possible involvement of a polar excited state complex with substantial charge transfer character (44). Since then the possibility of cycloadditions occurring through the intervention of exciplex or excimer intermediates per se or as precursors for radical ions pairs, eq. 12,... 

Berenjian, N., de Mayo, P., Sturgeon, M.-E., Sydnes, L.K., and Weedon, A.C. (1982) Biphasic photochemistry micelle solutions as media for photochemical cycloadditions of enones. Canadian Journal of Chemistry, 60, 425-436. 

The cycloaddition of enones to olefins is a reaction of considerable synthetic interest 14°). Oxetane formation and cyclobutane formation are sometimes competitive 141>, but the latter reaction is the more common. The photodimerization of enones 142> is a special case of such cycloaddition. It has been shown that triplets are involved in these cycloadditions, since intersystem crossing quantum yields are unity 143> and cycloaddition is totally quenchable by triplet quenchers. Careful kinetic analysis indicates an intermediate which can partially revert to ground state reactants, since quantum yields are lower than unity even when extrapolated to infinite substrate olefin concentration. That a diradical is... 

The synthesis and relative stability of 3,5-diacyl-4,5-dihydro-l//-pyrazoles prepared by dipolar cycloaddition of enones and a-diazoketones has been published <2004JOC9085>. 3-Acyl-4-aryl-2-pyrazolines have been synthesized by the reaction of a,/3-unsaturated ketones with diazomethane <1996IJB1091>. Ethyl diazoacetate added to 1,3-diarylpropenones in a regioselective fashion to give the intermediate 4,5-dihydto-3//-pyrazole derivative 1,3-hydride shift in the latter led to the formation of the isomeric ethyl 4-aryl-5-aroyl-4,5-dihydro-l//-pyrazole-3-carboxylate and ethyl 4-aryl-3-aroyl-4,5-dihydro-l/7-pyrazole-5-carboxylate in a ratio of 5 1 <2001RJ01517>. 1,3-Dipolar cycloaddition of 2-diazopropane with diarylideneacetones afforded diastereomeric bis-A -pyrazolines <1999T449>. 

DeMayo cycloaddition Photochemical [2+2] cycloaddition of enones and alkenes to give substituted cyclobutanes. 132... 

Several review articles have dealt with various aspects of cycloaddition reactions. A short review has presented examples to illustrate the use to which tethered alkenes can be put in the synthesis of cyclobutenes. The photochemical (2 + 2)-cycloaddition of enones to ethene has been studied from a theoretical standpoint. A review has highlighted the use of linear templates to control photochemical reactions such as (2 + 2)-photocycloadditions. The stereochemical control of photochemical reactions in clay-intercalated compounds has been discussed. A review has highlighted the interdisciplinary nature of photochemistry. ... 

The scope of photochemical [2 + 2] cycloadditions of enones to alkenes in solution is limited by the failure of most acyclic oc,/ -unsaturated carbonyl compounds to undergo bimolecular reactions in competition with rapid unimolecular cisjtrans photoisomerization. 

Intramolecular.—A full account of the synthetic approaches using intramolecular cycloaddition of enones (1) eventually to yield the hirsutane skeleton (2, Scheme 1) has supplemented the material originally published in note form. ... 

Table 1 Examples of [2 + 2] Intermolecular Cycloaddition of Enones to Alkenes with Different Substituents...

The mechanism of [3 + 2] reductive cycloadditions clearly is more complex than other aldehyde/alkyne couplings since additional bonds are formed in the process. The catalytic reductive [3 -i- 2] cycloaddition process likely proceeds via the intermediacy of metaUacycle 29, followed by enolate protonation to afford vinyl nickel species 30, alkenyl addition to the aldehyde to afford nickel alkoxide 31, and reduction of the Ni(ll) alkoxide 31 back to the catalytically active Ni(0) species by EtsB (Scheme 23). In an intramolecular case, metaUacycle 29 was isolated, fuUy characterized, and iUustrated to undergo [3 + 2] reductive cycloaddition upon exposure to methanol [45]. Related pathways have recently been described involving cobalt-catalyzed reductive cycloadditions of enones and allenes [46[, suggesting that this novel mechanism may be general for a variety of metals and substrate combinations. 

Scheme 6.9 records some examples of photochemical cycloaddition of enones and alkenes. 

In 2007, Fu described the first examples of diastereo- and enantioselective Cu-catalyzed [4+1] cycloadditions of enones 180 with diazo compounds 181 using the planar chiral bipyridine ligand 179. This new method furnishes synthetically useful, highly substituted 2,3-dihydrofuran derivatives 183 with good efficiency and stereoselection (Scheme 11.39) [60]. 

The nickel-iminophosphine-catalysed 4- -2-cycloaddition of enones with allenes formed highly substituted dihydropyrans. The enantioselective amine-catalysed 4-I-2-cycloaddition of allenoates with oxo-dienes produced polysubstituted dihydropyrans in high yields and with high enantioselectivities. Novel enam-ine/metal Lewis acid bifunctional catalysis has been used in the asymmetric inverse-electron-demand hetero-Diels—Alder reactions of cyclic ketones with Q ,j9-unsaturated a-ketoesters. The 4- -2-cycloaddition of acylketenes (80) with 2-unsubstituted and 2-monosubstituted 3-aryl-2//-azirines (81) produced 1 1 (82) or 2 1 (83) adducts, being derivatives of 5-oxa-l-azabicyclo[4.1.0]hept-3-ene or 5,7-dioxa-l-azabicyclo[4.4.1]undeca-3,8-diene. The formation of the monoadducts proceeds via a stepwise non-pericyclic mechanism (Scheme 25). A-heterocyclic carbene-catalysed 4- -2-cycloaddition of ketenes with 1-azadienes yielded optically active 3,4-dihydropyrimidin-2-ones (93% ee) ... 

Abstract Photochemical reactions are generally easily carried out, at least in laboratory scale, and require no expensive apparatus. Some general reactions, e.g. the cycloaddition of enones to alkenes and various oxygenations have been extensively investigated and represent an excellent choice for preparative applications. Many other possibilities are known—and a few are presented below. This suggests that photochemical steps should be considered more often in synthetic planning. 

Along with the cycloaddition of enones, photooxidation is probably the most consistently used photochemical reaction for synthetic purposes. This is also one... 

Thiapyrans.—As part of a general study of the synthesis of pheromones, Lip-kowitz and his coIIeagues have studied the [4 + 2]cycloaddition of enones to yield dihydropyrans, which in turn are easily converted into the corresponding thia-analogues (Scheme 65). 

The formal 2 -l- 2-cycloaddition of enones bearing a bulky substituent group at the P-position with alkynes, in the presence of [Ni(cod)2l and tricyclohexylphosphine, yielded substituted cyclobutenes. The mechanism is thought to involve an oxidative cyclization of an enone with the alkyne to give a > -oxyallylnickel intermediate that is converted to the cyclobutene by reductive elimination. ... 

In the intramolecular [3-1-2] cycloadditions of enones and benzyl allenyl ethers in the presence of AuCl, benzyl protected phenols are formed. For example, from 346, generated... 

Tricyclic core of the cytotoxic marine alkaloid madangamine A, was prepared by Weinreb using aza enone as a dienophile partner in the Diels-Alder reaction (Scheme 46) [69]. Although a [4+2] cycloaddition of enone 189 with butadiene could not be effected xmder thermal conditions, the desired c/s-keto azadecalin derivative 190 could be formed at high pressure (12 kbar) in good yield. Attempted cycloaddition of enone 189 with butadiene using Lewis acids gave low yields of a mixture of cis- and frans-azadecalins that could only be separated by HPLC [70]. 

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