Oxetanes, carbonylation

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). 

The precedent is strong for the involvement of oxetanes as Intermediates in carbonyl additions to pyrroles. " NMR evidence has been obtained far an oxetane adduct of acetone and N-methylpyrrole. The initial photoadduct was shown to rearrange readily on workup to the 3-(hydroxyalkyl)pyrrole derivative. 

The Patemo-Buchi reaction " is the photo-eatalyzed eJeetrocyeJization of a carbonyl 1 with an alkene 2 to form polysubstituted oxetane ring systems 3. 

The mechanism of the Patemo-Biichi reaction is not well understood, and while a general pathway has been proposed and widely aceepted, it is apparent that it does not represent the full scope of reactions. Biichi originally proposed that the reaction occurred by light catalyzed stimulation of the carbonyl moiety 1 into an excited singlet state 4. Inter-system crossing then led to a triplet state diradical 5 which could be quenched by olefinic radical acceptors. Intermediate diradical 6 has been quenched or trapped by other radical acceptors and is generally felt to be on the reaction path of the large majority of Patemo-Biichi reactions. Diradical 6 then recombines to form product oxetane 3. 

Two different alkenes can be brought to reaction to give a [2 -I- 2] cycloaddition product. If one of the reactants is an o, /3-unsaturated ketone 11, this will be easier to bring to an excited state than an ordinary alkene or an enol ether e.g. 12. Consequently the excited carbonyl compound reacts with the ground state enol ether. By a competing reaction pathway, the Patemo-Buchi reaction of the 0, /3-unsaturated ketone may lead to formation of an oxetane, which however shall not be taken into account here ... 

The photochemical cycloaddition of a carbonyl compound 1 to an alkene 2 to yield an oxetane 3, is called the Patemo-Buchi reaction - This reaction belongs to the more general class of photochemical [2 + 2]-cycloadditions, and is just as these, according to the Woodward-Hofmann rules, photochemically a symmetry-allowed process, and thermally a symmetry-forbidden process. 

By reaction with the appropropriate aryl halides can be prepared a variety of aryltin compounds that are not accessible from the reactions involving arylmagnesium halides and organotin halides (88,89) there is evidence that an aryne intermediate may be involved (90). However, for some purposes, such as the addition to carbonyl compounds, ox-iranes, and oxetanes, to give hydroxyalkyltin compounds, the Sn-Mg reagents may have advantages (see Section II,E) (91-93). 

Grignard reagents having bulky alkyl groups react with trialkyltin hydrides to give compounds having a Sn-Mg bond, and are synthetically useful as a source of nucleophilic RsSn in particular, they react with carbonyl compounds, oxiranes, and oxetanes to give the -, jS-, or... 

Ordinary aldehydes and ketones can add to alkenes, under the influence of UV light, to give oxetanes. Quinones also react to give spirocyclic oxetanes. This reaction, called the Patemo-BUchi reaction,is similar to the photochemical dimerization of alkenes discussed at 15-61.In general, the mechanism consists of the addition of an excited state of the carbonyl compound to the ground state of the alkene. Both singlet (5i) and n,n triplet states have been shown to add to... 

Photochemical reactions of carbonyl compounds with alkenes give the oxetanes (Scheme 30). The stereochanical course depends on the substituents of the alkenes [16]. The reactions proceed with the retention of the configuration of the alkenes for the electron accepting substituent, e.g., CN. The stereochemical integrity is lost for the donating group, e.g., OCH. ... 

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. 

Photocycloaddition of Alkenes and Dienes. Photochemical cycloadditions provide a method that is often complementary to thermal cycloadditions with regard to the types of compounds that can be prepared. The theoretical basis for this complementary relationship between thermal and photochemical modes of reaction lies in orbital symmetry relationships, as discussed in Chapter 10 of Part A. The reaction types permitted by photochemical excitation that are particularly useful for synthesis are [2 + 2] additions between two carbon-carbon double bonds and [2+2] additions of alkenes and carbonyl groups to form oxetanes. Photochemical cycloadditions are often not concerted processes because in many cases the reactive excited state is a triplet. The initial adduct is a triplet 1,4-diradical that must undergo spin inversion before product formation is complete. Stereospecificity is lost if the intermediate 1,4-diradical undergoes bond rotation faster than ring closure. 

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... 

With aromatic carbonyls, oxetane formation appears to arise from the carbonyl triplet state, as evidenced by quenching studies. For example, benzaldehyde irradiated in the presence of cyclohexene yields products indicative of hydrogen abstraction reactions and an oxetane ... 

The reaction of carbonyl compounds to olefins often yields products difficult to obtain synthetically by other routes. The excellent yields obtainable under proper conditions make this reaction of definite preparative interest. Examples of some synthetic applications of oxetane formation follow ... 

The other photochemical reactions of simple carbonyls mentioned earlier in this chapter—type I cleavage (a-cleavage) and oxetane formation—will be discussed in Chapter 4. 

The Photochemistry of Simple Carbonyl Compounds Type I Cleavage and Oxetane Formation... 

In Chapter 3 we discussed two photochemical reactions characteristic of simple carbonyl compounds, namely type II cleavage and photoreduction. We saw that photoreduction appears to arise only from carbonyl triplet states, whereas type II cleavage often arises from both the excited singlet and triplet states. Each process was found to occur from discrete biradical intermediates. In this chapter we will discuss two other reactions observed in the photochemistry of carbonyls, type I cleavage and oxetane formation. 

Table 4.10. Reactivity of Various Aromatic Carbonyls toward Oxetane Formation and Photoreduction Compared to the Nature of the Lowest TripletiB3,9 Bm...

Aldehydes and ketones also add to allenes to form oxetanes.ai0,111) Further reaction of the oxetanes produced with excited carbonyls results in dioxaspiro[3.3]heptane derivatives(111) ... 

Aryl ketones are often used to effect cis and tram isomerization of olefins.(118-ia0) Although this, in some cases, can be viewed as an energy transfer process where the ketone triplet transfers its energy to the olefin, which then isomerizes, the failure of noncarbonyl sensitizers of comparable triplet energy to isomerize the olefins suggests that a process other than energy transfer may be involved. Schenck and Steinmetz<118) suggested that isomerization results from decomposition of a biradical carbonyl-olefin adduct similar to that involved in oxetane formation ... 

As is the case with aryl carbonyls previously studied, aliphatic carbonyls add to olefins to form oxetanes. The picture in this case is far more complicated, however, primarily due to the increased importance of singlet state carbonyl addition to the olefin. In Chapter 1 we saw that in an n->v ... 

Further examples of oxetane formation from aliphatic carbonyls are as follows 1106,184-129 ... 

The synthesis of nitrogen containing heterocyclic systems by photocylo-addition processes is virtually limited to examples involving [ 2 + 2] cycloaddition of imines, nitriles, and azo compounds. Successful additions are few in number and the requirements for success uncertain. The reactions do not proceed with the facility with which carbonyl containing compounds undergo photocycloaddition to alkenes to give oxetans, and various explanations have been advanced to account for this observed lack of reactivity.226... 

The photoinduced [2 + 2] cycloaddition of carbonyl acceptors with electron-rich olefins leads to oxetanes (Paterno-Biichi reaction) with high regio- and stereoselectivities (equation 25). 

The scope of the Patemo-Buchi cycloaddition has been widely expanded for the oxetane synthesis from enone and quinone acceptors with a variety of olefins, stilbenes, acetylenes, etc. For example, an intense dark-red solution is obtained from an equimolar solution of tetrachlorobenzoquinone (CA) and stilbene owing to the spontaneous formation of 1 1 electron donor/acceptor complexes.55 A selective photoirradiation of either the charge-transfer absorption band of the [D, A] complex or the specific irradiation of the carbonyl acceptor (i.e., CA) leads to the formation of the same oxetane regioisomers in identical molar ratios56 (equation 27). 

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)... 

A clear division of Paterno-Biichi reactions into several distinct categories is possible on the basis of the type of reacting carbonyl compound (alkyl or aromatic), the excited state responsible for reaction (n—71 or Ti—n, singlet or triplet), and the type of olefin (electron deficient or electron-rich). Some examples of these reactions are given in Eqs. 7—11, where only the oxetane products are shown. 

Mechanistic evidence indicates 450,451> that the triplet enone first approaches the olefinic partner to form an exciplex. The next step consists in the formation of one of the new C—C bonds to give a 1,4-diradical, which is now the immediate precursor of the cyclobutane. Both exciplex and 1,4-diradical can decay resp. disproportionate to afford ground state enone and alkene. Eventually oxetane formation, i.e. addition of the carbonyl group of the enone to an olefin is also observed452. Although at first view the photocycloaddition of an enone to an alkene would be expected to afford a variety of structurally related products, the knowledge of the influence of substituents on the stereochemical outcome of the reaction allows the selective synthesis of the desired annelation product in inter-molecular reactions 453,454a b). As for intramolecular reactions, the substituent effects are made up by structural limitations 449). 

Oxetanes are the cycloadducts from a carbonyl compound and an olefin. This one step photochemical formation of a four membered ring heterocycle has been named the Paterno-Buchi reaction 489a> b). Oxetanes are important synthetic intermediates as they can fragment into the carbonyl-olefin pair by which they were not formed (a so termed carbonyl-olefin metathesis). Two examples of such oxetan cracking reactions are shown below in (4.76)490) and in (4.77)491) in this last example the oxetane was used as a precursor for the pheromone E-6-nonenol,... 

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