Cycloaddition /reactions oxetanes

A-Substituted pyrroles, furans and dialkylthiophenes undergo photosensitized [2 + 2] cycloaddition reactions with carbonyl compounds to give oxetanes. This is illustrated by the addition of furan and benzophenone to give the oxetane (138). The photochemical reaction of pyrroles with aliphatic aldehydes and ketones results in the regiospecific formation of 3-(l-hydroxyalkyl)pyrroles (e.g. 139). The intermediate oxetane undergoes rearrangement under the reaction conditions (79JOC2949). 

Some ketones undergo a cycloaddition reaction with alkenes to form oxetanes ... 

Oxetanes are present in several biologically active natural compounds as, for example, the taxol ring skeleton. An interesting method used to obtain this particular ring is the thermal [2 -i- 2] cycloaddition reaction. Longchar and co-workers reported a novel [2-1-2] cycloaddition of /1-formil enamides 5, often used in other cycloaddition and condensation processes, with acetylenic dienophiles 6 under microwave irradiation (in a domestic oven) to afford ox-etenes 7 in 80% yields [29]. This reaction was directed towards the synthesis of D-ring annelated heterosteroids (Scheme 2). 

Ketenes have cnmnlative bonds and can undergo [2+2] cycloaddition reactions across C=C and C=0 bonds. Interestingly, most of the prodncts obtained are cyclobutanones rather than oxetanes. Thermal [2+2] cycloaddition reactions in the pseudoexcitation band occur between electron donors and acceptors. Alkenes are donors while ketenes are acceptors. In contrast to the experimental observations. 

The dimerization of the parent ketene gives the P-lactone. One molecule of ketene reacts across the C=C bond as a donor and the other molecule reacts across the C=0 bond as an acceptor. This is similar to the concerted [2+2] cycloaddition reaction between bis(trifluoromethyl)ketene and ethyl vinyl ether to afford the oxetane (Scheme 26) [127], A lone pair on the carbonyl oxygen in the ketene molecule as a donor activates the C=C bond as the alkoxy group in vinyl ether. 

Eq. 17 is meant to represent the possibility for a concerted formation of oxetane product. A problem that always exist in cycloadditions is the question of whether the reaction takes place by a two-step biradical reaction pathway or through a concerted mechanism. Such questions have not even been resolved for purely thermal reactions. 4> A recent speculation on this point proposes almost universal concertedness for all cycloaddition reactions. 79> In that work, mixed stereochemistry in the products of [2+2] cycloaddition reactions is generally attributed to a mixture of two concerted reactions, suprafacial-suprafacial, and supra-facial-antarafacial. It will be seen later that the PMO calculations generally do not support this idea. A mixture of biradical and concerted reactions is in better agreement with experimental facts. 

A third type of cycloaddition reaction has recently been reported.74 When 5,5,6-trimethyl-3,6-heptadien-2-one 58 was irradiated, two intramolecular cycloaddition products 59 and 60 were obtained, affording the first example of dihydropyran formation from this reaction. Although a reasonable mechanism, analogous to that leading to oxetane formation, has been proposed, it was recognized that 58 is a special type... 

Benzil undergoes a cycloaddition reaction with stilbene and 1,1-diphenyl-ethylene to form adducts containing the 2,3-dihydro-[l,4]-dioxin ring system and with visnagin to form an oxetane. These reactions and the cycloaddition reactions of the analogous o-quinones are reviewed by Schonberg.87... 

The cycloaddition reactions to give oxetanes readily occurs whenTj state is ( , 7T ) in character and an electrophilic centre is created on carbonyl oxygen atom on photoexcitation (Section 8.1). Paterno-Buchi reaction. 

Four-membered heterocycles are easily formed via [2+2] cycloaddition reac tions [63] These cycloaddition reactions normally represent multistep processes with dipolar or biradical intermediates The fact that heterocumulenes, like isocyanates, react with electron-deficient C=X systems is well-known [116] Via this route, p lactones are formed on addition of ketene derivatives to hexafluoroacetone [117, 118 The presence of a trifluoromethyl group adjacent to the C=N bond in quinoxalines, l,4-benzoxazm-2-ones, l,2,4-tnazin-5-ones, and l,2,4-tnazm-3,5-diones accelerates [2+2] photocycloaddition processes with ketenes and allenes [106] to yield the corresponding azetidme derivatives Starting from olefins, fluonnated oxetanes are formed thermally and photochemically [119, 120] The reaction of 5//-1,2-azaphospholes with fluonnated ketones leads to [2+2] cycloadducts [121] (equation 27)... 

Another important class of cycloaddition reactions is the formation of oxetane rings between a photoexcited carbonyl compound and an unsaturated molecule. These reactions also occur probably through an exciplex although these exciplexes are non-fluorescent as they are formed from the triplet state of the ketone or aldehyde. The formation of the four-membered oxetane ring is an interesting example of a typical photochemical reaction... 

Orbital Symmetry Conservation in Bimolecular Cycloadditions. The cycloaddition reactions of carbonyl compounds to form oxetanes with ethylenes, as well as those of enones and their derivatives to form cyclobutanes, are examples of reactions which originate from triplet excited states and lead in the first step to biradical intermediates. Such reactions are of course not concerted, and they show little or no stereo-specificity. 

Scheme 7.3 Formation of oxetanes in the thermal [2 + 2] cycloaddition reaction.

The synthesis of fused oxetane derivatives via the Paterno-Bchi cycloaddition of carbonyls and alkenes is discussed in detail in a representative example is shown in Scheme 7 <2001CEJ4512>. See also Sections 3.3.1.8.3 and 3.4.1.10.5 for the preparation of fused oxetanes and azetdines by [2 + 2] cycloaddition reactions. Benzox-etan-2-one 10 has been prepared in an argon matrix by C02 loss from phthaloyl peroxide <1973JA4061>. 

The pyrimidine nucleobases have the highest quantum yields for photoreactivity, with thymine uracil > cytosine. The purine nucleobases have much lower quantum yields for photochemistry, but can be quite reactive in the presence of oxygen. As can be seen from Figure 9-3, thymine forms primarily cyclobutyl photodimers (ToT) via a [2ir + 2tt cycloaddition, with the cis-syn photodimer most prevalent in DNA. This is the lesion which is found most often in DNA and has been directly-linked to the suntan response in humans [65]. A [2Tr + 2Tr] cycloaddition reaction between the double bond in thymine and the carbonyl or the imino of an adjacent pyrimidine nucleobase can eventually yield the pyrimidine pyrimidinone [6 1]-photoproduct via spontaneous rearrangement of the initially formed oxetane or azetidine. This photoproduct has a much lower quantum yield than the photodimer in both dinucleoside monophosphates and in DNA. Finally, thymine can also form the photohydrate via photocatalytic addition of water across the C5 = C6 bond. 

Ab initio MO calculations for the uncatalyzed [2 + 2]cycloaddition reaction between ketenes e.g. chloroketene) and carbonyl compounds e.g. formaldehyde) to yield oxetan-2-ones (y9-lactones) predict a relatively synchronous, concerted process, with a [ 2s + 2s +, i2s)] arrangement of the reactants in the activated complex and a negligible solvent effect [813],... 

Fluorine-containing aldehydes, ketones and acid fluorides undergo photoinitiated cycloaddition reactions with fluorinated alkenes to give oxetanes.The addition of hexafluoroacetone... 

Table 8. Fluorinated Oxetanes by [2 -(- 2]-Cycloaddition Reactions of Carbonyl Compounds with Fluorinated Alkenes...

Phenanthrene undergoes a cycloaddition reaction (23) with dimethyl fumarate to give a cyclobutane [50] and an oxetane (Creed and Caldwell,... 

Fluorine-containing aldehydes, ketones and acid fluorides undergo photoinitiated cycloaddition reactions with fluorinated alkenes to give oxetanes.90 91 The addition of hexafluoroacetone (11) to fluoroalkenes can also be performed in the presence of the Lewis acid, aluminum chloride fluoride.92-1 22-1 23 Unlike the photochemical cycloaddition of hexafluoroacetone with trifluoroethene, the Lewis acid catalyzed addition is regioselective.92 Fluorooxetanes (c. g., 14) have also been synthesized by the addition of formaldehyde to fluoroalkenes in hydrogen fluoride.94 Examples of the formation of fluorooxetanes by [2 + 2]-cycloaddition reactions arc-given in Table 8. 

Translation of these results into compound I leads to structure X. Unraveling of the strained zwitterion XI derived from this would yield keto aldehyde XII, a structure that plays a central role in the various possible reaction mechanisms that branch off from the starting material I. Furthermore, under photo-lytic conditions, some alkenes react with carbonyl compounds to form four-membered cyclic ethers, namely, oxetanes, by way of a [2-1-2] cycloaddition reaction known as the Patemo-Buchi process. Such a reaction would be all that is necessary to convert XII into the bicyclic cyclopropanone XIII required for the Favorskii-type rearrangement (see Scheme 42.3). Splitting by methanol attack would directly yield compound II. 

The cage compound (301) is formed efficiently on irradiation of the adduct (302).Irradiation of the ene dione (303) affords the cage compound (304) by a (6 + 2)-cycloaddition. The Diels-Alder adducts (305) are photochemically reactive. Irradiation of (305) affords either the cage compounds (306) by a (2+2)-cycloaddition reaction, a process favoured by the adducts (305 a,b), or the oxetanes (307). The structures (306, 307) were verified by 2L ray diffraction studies The quinone adduct (308) also undergoes photochemical cyclization to afford the cage diketone (309). This material was subjected to flash vacuum pyrolysis to yield the diketone (310) important in the synthesis of perhydroindacenes. ... 

Bach d has reviewed photochemical (2 + 2)-cycloaddition reactions including oxetane-forming processes and the stereochemical aspects of the reactions are highlighted. Earlier studies by the same author reported the results of irradiation of the alkene (88) in benzene with benzaldehyde to give the oxetane (89). These 3-oxetanols have been subjected to further study and have been... 

Cycloaddition reactions of triplet excited 1,4-quinones to ground-state alkenes occur either via a triplet exciplex intermediate, which collapses to a triplet biradical,1000 or via separated radical ion intermediacy.990 The existence of biradical intermediates has been proven by measurements of chemically induced dynamic nuclear polarization (CIDNP) (Special Topic 5.3), for example in the reaction of 1,4-benzoquinone (313) with norbomadiene (314) yielding two products, the spiro-oxetane 315 and the spiro-oxolane 316 (Scheme 6.139).1001 Interestingly, quadricyclane (317) provides the same reaction as norbomadiene. 

The hetero [2+2] cycloaddition reaction is a synthetically important reaction for the construction of 4-membered heterocyclic compounds. As far as the catalytic asymmetric reaction is concerned, however, only the cycloaddition between ketenes and aldehydes has been reported. The thus synthesized chiral oxetan-2-ones are employed as monomer precursors for the biologically degradable co-polyesters and also as chiral building blocks for natural product synthesis. Two types of catalysts. Cinchona alkaloids and a chiral Lewis acid, are known to promote this reaction. 

A C2-symmetric N,W-di-3,5-bis(trifluoromethyl)benzenesulfonyl-(ll ,21 )-l,2-diphenylethylenediamine 20-Et3Al complex promotes the [2-1-2] cycloaddition reaction between ketene and aldehydes to afford optically active 4-substituted oxetan-2-ones 21 (Scheme 20) [50]. The catalyst is prepared by mixing the bis-sulfonamide 20 and EtjAl, and the reaction proceeds by the coordination of the aldehyde to the chiral Lewis acid. 

A preliminary examination of asymmetric induction in photochemical [2 + 2] cycloaddition reaction of an enone to an alkene employed a chiral auxiliary attached to the alkene component74. The photocycloaddition of 2-cyclopentenone to the optically active ketene acetal 1 led both to oxetanes and cyclobutanes in the ratio 6.5 3.5 with a total yield of 60%. The m-[2C + 2C] addition of the chiral alkene I to 2-cyclopentenone was completely regioselective and gave four diastereomeric head-to-tail cycloadducts 2-4 in the ratio 6 29 33 32. 

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