Carbonyl compounds photocycloaddition reactions

As was mentioned in Section 13.2, the [27t + 27i] photocycloaddition of alkenes is an allowed reaction according to orbital symmetry considerations. Among the most useful reactions in this categoty, from a synthetic point of view, are intramolecular [27t + 2ti] cycloadditions of dienes and intermolecular [2ti + 2ti] cycloadditions of alkenes with cyclic a, -unsaturated carbonyl compounds. These reactions will be discussed in more detail in Section 6.4 of Part B. 

Synthetic application of Paterno-Bilchi reaction of simple dienes with carbonyl compounds is rare. While seemingly an extension of the photocycloaddition of olefins and carbonyl compounds, the reaction between dienes and carbonyls is often complicated by the fact that triplet excited states of carbonyl compounds are quenched by dienes, although the formation of oxetanes can be observed during these reactions. Recall also that the photosensitized dimerization of diene triplet excited states is also a well known reaction vide infra), these two observations would seem to naturally limit the synthetic potential of this process. Kubota and coworkers found that irradiation of propanal in the presence of 1,3-cyclohexadiene produced oxetanes 164a and 164b in a 4 1 ratio (Scheme 37). ... 

Photocycloaddition Reactions of Carbonyl Compounds and Alkenes. Photocycloaddition of ketones and aldehydes with alkenes can result in formation of four-membered cyclic ethers (oxetanes), a process often referred to as the Paterno-Buchi reaction.196... 

Scheme 6.11. Photocycloaddition Reactions of Carbonyl Compounds and Alkenes...

This article will only discuss two particular kinds of photocycloaddition reactions, the photodimerization or cross-cycloaddition of two olefins to yield a cyclobutane derivative, and the photoreaction of an olefin with a carbonyl compound to give an oxetane, Eq. 1 and Eq. 2. The inportance of substituent effects in reactions of these types is pointed... 

The photocycloaddition of an aldehyde or ketone with an olefin to yield an oxetane was reported by Paterno and Chieffi in 1909. 58> Contemporary studies on the synthetic utility and mechanistic features were initiated nearly 50 years later by Biichi et al. 59) Two review articles summarizing synthetic aspects of Paterno-Biichi reactions have been published 6.12)) and mechanistic studies have been reviewed several times. 6,38,60-62) The reaction involves the addition to olefin of a photo-excited carbonyl moiety. This circumstance makes it advantageous to review this reaction before a discussion of olefin-olefin additions, because the solution photochemistry of carbonyl compounds is probably better understood than any other aspect of organic photochemistry. Many of the reactions of carbonyl compounds have been elucidated during studies of the important phenomena of energy transfer and photosensitization. 63-65)... 

The [2+2]-photocycloaddition of carbonyl groups with olefins (Paterno-Buchi reaction) is one of the oldest known photochemical reactions and has become increasingly important for the synthesis of complex molecules. Existing reviews have summarized the mechanistic considerations and defined the scope and limitations of this photocycloaddition73. Although this reaction likely proceeds via initial excitation of the carbonyl compound and not the excited state of the diene, the many examples of this reaction in natural product synthesis justify inclusion in this chapter. 

The Paterno-Buchi photocycloaddition between carbonyl compounds and furans was first described in 1965 (equation 6)80. This report noted that only the head-to-head product 171 was formed, and that high exo face selectivity was exhibited. Subsequent to this and other early reports, this reaction has been systematically explored by several groups, owing largely to the various ways in which the 2,7-dioxabicyclo[3.2.0]hept-3-ene ring system can be exploited730,81. 

On irradiation with alkenes, carbonyl compounds undergo photocycloaddition to give oxetanes in the Paterno-Biichi reaction ... 

The photocycloaddition of a carbonyl compound to an alkene was discovered as early as 1909 by Paterno and Chiefifi [78] who employed sunlight as the irradiation source. In the 1950s the reaction was more intensively investigated by Biichi et al. [79] using artificial light sources. The Paterno-Biichi reaction has been studied mechanistically [80] and some important aspects are summarized in Scheme 37. Upon n r -excitation (1=280-350 nm), aldehydes... 

VII. Tabular Survey of Photocycloaddition Reactions of Carbonyl Compounds to Unsaturated Systems which Yield Oxetanes. 349... 

The photocycloaddition of a carbonyl compound to an olefin with the formation of an oxetane 3 was first observed by Paterno and Chieffi in 1909.1 They reported obtaining a compound in good yield from the irradiation of benzophenone in a petroleum mixture rich in 2-methyl-2-butene, for which they proposed the oxetane structure. Although Paterno and Chieffi had suggested the correct structure, it was not until 1954 that Buchi and his collaborators reinvestigated this reaction and... 

Little has been reported concerning the mechanism of the photocycloaddition reaction however, much is known about the photoreduction of carbonyl compounds.15,16 It has been shown that both hydrogen abstraction, leading to photoreduction, and most photocycloaddition reactions of carbonyl groups are characteristic of the same type of excited state reagent, that is, the carbonyl n,n state.17 Furthermore, much is known about the emission (phosphorescence and fluorescence) of carbonyl compounds, and all of this knowledge can be brought to bear upon the photocycloaddition reaction. 

There has been very little study of the photocycloaddition reaction, where the carbonyl compound was excited with light of varying wavelengths. For the simple carbonyl compounds, irradiation absorbed only by the n - it transition has been used with success. Irradiation of the more complex carbonyl compounds, for example, benzophenone, can be such that both the w and the (of the benzene chromo-... 

One of the limitations of the photocycloaddition reaction is that the unsaturated system may itself act as a quencher. Conjugated dienes fall within this category since they quench the n,ir triplet of some carbonyl compounds. For the photoreduction of benzophenone in benzhydrol, the ratio, kqlka, for m-piperylene is 750 (Table II), which indicates that this diene is indeed an efficient quencher for the reaction. 

Irradiation of carbonyl compounds in the presence of dienes usually leads to the isomerization38 and dimerization39 (in concentrated diene solutions) of the dienes, but no photocycloaddition products. These reactions indicate that the dienes have quenched the carbonyl triplet. It is also known from spectroscopic studies that the triplet... 

Thus, the observations that (a) dienes quench the photoreduction reaction (b) the isomerization and dimerization of dienes is sensitized by the it,n carbonyl triplet and (c) there is a lack of photocycloaddition products with dienes, taken in conjunction with the relative energy levels of carbonyl compounds and dienes, form a consistent picture. 

Some carbonyl compounds are unreactive in the photocycloaddition reaction because their excited states undergo molecular rearrangement. Illustrative of this point is the isomerization process involved upon irradiation of 2-methylbenzophenone. This ketone is known to be stable to irradiation in isopropanol,45 and irradiation in the presence of isobutylene yields a complex mixture which contains little, if any,... 

One of the most important and difficult questions to answer for any photochemical reaction is which excited state is involved. Since these are the reagents, it is obviously important, if generalizations are to be made, to know which state is responsible for a given reaction. The question is difficult to answer because several different types of excited states, both singlet and triplet, are attainable even with the simplest of carbonyl compounds, and their reactivity may, in some cases, be similar. All of the discussion thus far has implied that the photocycloaddition reaction is characteristic of the n,n state. What is the evidence that this state can be involved and what is the character of this state which makes it reactive ... 

In general, carbonyl compounds that are reactive in the photocycloaddition reaction are also reduced upon irradiation in isopropyl alcohol.17 Subject to the limitation of triplet-triplet transfer to the olefin mentioned previously, the converse is also true. That is, carbonyl compounds that are photoreduced in isopropyl alcohol can form oxetanes unless their triplet energies are high enough for the olefins to act as quenchers. Thus, the two reactions are characteristic of the same type of excited state. (This is not an exclusive generalization.) The quenching experiments mentioned on pp. 308-311 provide evidence that the reactive state can be the triplet and, in some cases, only the triplet. Evidence for this state being n,ir comes from the fact that carbonyl compounds which are reactive usually emit from the n,n triplet, while those which are unreactive emit from some other excited state. 

One important reaction which competes with photocycloaddition is hydrogen abstraction. The n,ir state can both abstract hydrogen from, and add to olefins. If the starting olefin or carbonyl compound has easily abstractable hydrogens, this competing reaction can become so important that oxetane formation is excluded. 

An example where this abstraction from the carbonyl compound competes with photocycloaddition was discussed in the previous section (p. 312). In that case, 2-methylbenzophenone underwent intramolecular hydrogen abstraction, yielding the tautomeric enol,46 a process which completely inhibited the photocycloaddition reaction.37... 

The importance of the carbonyl n,tr state as a reagent for the photocycloaddition reaction has been mentioned (p. 305). This represents a major limitation, for many carbonyl compounds attain states other than the n,it which are either unreactive, react inefficiently, or undergo other photochemical reactions. It is impossible, at this time, to provide rigorous rules for predicting when a carbonyl compound will attain, and maintain long enough to react, an n,n state. It is perhaps best to mention additional examples of carbonyl compounds that do not yield oxetanes upon irradiation in the presence of simple olefins, presumably because the n,n state is not attained and/or maintained, and to point out how, in some cases, it has been possible to exert some control over this limitation. 

The irradiation of , 3-unsaturated carbonyl compounds in the presence of olefins does not usually lead to oxetanes. In some cases, however, a photocycloaddition reaction takes place, yielding a cyclobutane ring. This has proved to be a useful reaction which has warranted recent review.71 These carbonyl compounds typically are not reduced upon irradiation in isopropanol, nor do they show any phosphorescence emission. The mechanism of this reaction has been discussed 72,73 however, the nature of the excited state involved (n,n or 7r,7r singlet or triplet) is still in question. 

For carbonyl compounds that ordinarily would react in the n,n triplet state, an important reaction which can compete with photocycloaddition is energy transfer to the unsaturated system. When the triplet energy of the unsaturated system is below that of the carbonyl compound, triplet-triplet transfer may take place to the exclusion of oxetane formation. Such is the case when irradiation of a carbonyl compound in the presence of a diene results in isomerization and dimerization of the diene, while no direct photocycloaddition takes... 

The same inefficiencies occur in the photocycloaddition reaction of carbonyl compounds with high-energy triplets to acyclic olefins (Table VIII). Here, the olefin triplet presumably deactivates before dimerization can occur. 

Another example of competition between the photocycloaddition reaction and energy transfer is provided by the irradiation of carbonyl compounds in the presence of dimethyl-AL(2-cyanopropyl)ketenimine 71.96 Here, the energy transfer is indicated by decomposition of the ketenimine. The ratio of photocycloaddition to decomposition products is dependent upon the n,n triplet energy of the carbonyl compound. These experiments are summarized in Table IX. Unlike the previously mentioned case with norbomene, the threshold energy for the competition is very broad, although in about the same region. 

It is conceivable that a carbonyl compound with an n,n triplet energy lower than that of benzophenone could yield the photocycloaddition product in some of these cases. A reaction which may illustrate this point is the photocycloaddition of ethyl glyoxylate to styrene and 1,1-diphenylethylene.66 Unfortunately, the triplet energy of ethyl glyoxalate has not been measured however, there is adequate reason to believe it is lower than that of benzophenone (see Table VI). 

The conditions for the photocycloaddition (discussed in detail in a later section of this review) can be relatively mild. There is usually a small probability of the oxetane being destroyed in dark reactions which would probably preclude isolation after preparation by any method. One mode of decomposition of oxetanes is fragmentation, either back to the starting materials or to the other possible carbonyl compound and olefin. For example, the oxetane from 4,4 -dimethoxybenzophenone and isobutylene forms readily and is easily detected and characterized by infrared and NMR spectroscopy. All efforts to purify it, however, have led to its decomposition into formaldehyde and the diarylethy-lene.17 37 In some cases, as with fluorenone and isobutylene37 or 2-methyl-2-butene,25b the oxetane is apparently too unstable for detection, but the presence of the olefin 96 attests to its formation. 

VII. TABULAR SURVEY OF PHOTOCYCLOADDITION REACTIONS OF CARBONYL COMPOUNDS TO UNSATURATED SYSTEMS WHICH YIELD OXETANES... 

Oxetane Formation—The Patemo-Bnchi Reaction. A large number of carbonyl compounds, primarily aldehydes, ketones, and quinones, form oxetanes by photocycloadditions to olefins.61-63 In general, it is observed that (/) carbonyl compounds which have low-lying (77, ) triplet states and which are photoreduced in isopropyl alcohol form oxetanes most readily, and (2) oxetane formation takes place when energy transfer from the carbonyl compound to the olefin is unfavorable because of the relative location of their triplet levels.64,65 Hence, oxetanes are most readily formed from simple olefins and allenes63,66 but are seldom formed from dienes.67 An extensive review by Arnold63 covers the mechanism and scope of this reaction. 

With conjugated dienes, photocycloaddition of carbonyl compounds occurs at one of the double bonds to give vinyloxetanes. An interesting example is the reaction of acetone with 2-methyl-l,3-butadiene, which gave the two oxetanes (60) and (61) in a ratio of 3 1 and a total yield of about 20% (72JA8761). Other alkenes which have been used for photosynthesis of oxetanes include enol ethers, ketene acetals, enamines, allenes and diketene, with the reaction of the last compound with benzaldehyde illustrated in equation (105) (75CPB365). 

Cyclobutane formation via light-induced [2 + 2] cycloaddition is probably one of the best studied photochemical reactions and has been reviewed thoroughly up to 1972 (Houben-Weyl, Vols. 4/5 a and 4/5 b). The most important types of C —C double-bond chromophores undergoing such reactions arc alkenes, 1,3-dienes, styrenes, stilbenes, arenes, hetarenes, cycloalk-2-enones, cyclohexa-2,4(and 2,5)-dienones, 1,4-benzoquinones, and heteroanalogs of these cyclic unsaturated carbonyl compounds. For p notocyciodimerizations see Houben-Weyl, Vol. 4/5 a, p 278 and for mixed [2 + 2] photocycloadditions of these same chromophores to alkenes see Section 1.3.2.3. 

By far the most widespread type of photocycloaddition in synthetic applications employs the afkene unit of an c. p u nsaturated carbonyl compound as one of the addends. Simpleexamplesof such reactions are the dimerization of cyclopent-2-ennne (2.71), and the photo-addiiion of 2-methylptopene to cyclohex-2-enone (2.72). The function of the carbonyl group is to bring the absorption of the alkene into... 

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