Photocycloaddition with olefins

The photochemical reactivity of P-ketoesters is different form that of P-diketones. Irradiation of a P-ketoester in the presence of an alkene produces oxetane via the ketone carbonyl instead of the desired cyclobutane ring system. Therefore, it is necessary to covalently lock the ketoesters as the enol tautomers. To this end, silyl enol ethers, 129 and 132a, and enol acetates, 130 and 132b, were prepared, but these substrates still fail to undergo the desired intramolecular [2 + 2] photocycloaddition with olefins. The only new products observed in these reactions result from the photo-Fries rearrangement of the cyclic enol acetate (130 to 131) and cis-trans isomerization of both acyclic substrates 132a/b. However, tetronates are appropriate substrates for both intermolecular and intramolecular photocycloadditions with olefins. In addition, enol acetates and silyl enol ethers of p-keto esters are known to undergo [2 + 2] photoaddition with cyclic enones (vide infra). 

Benzene undergoes photocycloaddition with simple olefins to produce 1,3, 1,2 and 1,4 adducts as shown below for tetramethylethylene ... 

The final type of reaction that will be discussed is the highly interesting cross photocycloaddition of cyclic a, (3- unsaturated ketones with olefins. Examples were given in Eqs. 28—31. A general mechanism 94), to which there may be exceptions to be discussed later, would involve a triplet state of the enone and the reactions steps given in Eqs. 32, 33, and 35, complex formation, biradical formation, and product formation. An earlier idea that two different excited triplet states were reacting has been discounted. 100,141,142) The inefficiency of the reaction is attributed to an alternate decay of complex 77,78,ioo,i42)( an(j the excited state has a n-n configuration. 100,142)... 

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. 

In Bettolo and co-workers approach to (+)-methyl trachyloban-18-oate (16), enone 13 was subjected to a photocycloaddition with 1,2-propadiene (1) to afford the [2 + 2]-cycloadduct 14 as a single product in 67% yield (Scheme 19.3) [5]. The addition proceeded exclusively from the /3-face. The resulting exocyclic olefin was eventually converted to a ketone using osmium tetroxide and NaI04 and taken on to 15, constituting a formal total synthesis of 16. 

Kaiser and Wulfers reported the first example of a thietane formation reaction involving photolysis of thiobenzophenone with olefins [27]. Since then a large number of systems have been reported. Thiobenzophenone and related compounds, xanthione and related compounds, the a,p-unsaturated thiones such as thiocoumarin, and adamantanethione have been most thoroughly examined. The wavelength dependence of these reactions has been systematically investigated in order to ascertain differences, if any, in the photochemistry of the thione S2 and T states. Scheme 1 shows one example of photocycloaddition of... 

Photocycloaddition with electron-deficient olefins, where it is proposed that the reaction pathway involves attack by the electron in the it orbital, can be stereospecific.32-63 The irradiation of acetone 42 with cis- 43 or /ranj-dicyanoethylene 44 leads to the stereoisomeric oxetanes. 

When acetone is irradiated in the presence of cyclobutene, the same competition between photocycloaddition and olefin dimerization is observed, with transfer being about ten times more efficient than oxetane formation. In this case, both reactions involve the triplet, since no reaction occurs upon addition of biacetyl.83... 

For photocycloaddition, to benzene the following conclusions were drawn from this empirical correlation [124], Olefins with poor electron-donor or poor electron-acceptor abilities yield mainly meta adducts with benzene (i.e., if AG > 1.4-1.6 eV, all other olefins yield mainly ortho adducts). Even ethene, which had seemed to behave exceptionally, fits into this correlation provided that it acts as the acceptor. The transition area from ortho to meta cycloaddition (i.e., the AG region where ortho meta = 1 1) is relatively large ( 0.2 eV). This is considered not to be surprising because the AG correlation is based on many different types of olefins. When only AG values for derivatives of 1,3-dioxole and for 1,4-dioxene were used, the transition area was narrowed to 0.03 eV. Not only ethene but also vinylene carbonate now fit into the correlation. According to the ionization potential rule, this compound should give only ortho photocycloaddition with benzene. Mattay s empirical rule predicts mainly meta addition, which is indeed found experimentally. 

Whether the role of the second olefinic partner is catalytic or a triplex intermediate is involved is not yet clear. The role of triplexes in photoreactions of aromatic compounds with olefins may be even more complex. For example, excited biphenyl forms both a fluorescent dual and triple exciplex with 2,3-dimethyl-2-butene [120]. The possibility of these two pathways of deactivation can explain the inefficient photocycloaddition in the particular case of 1biphenyl /cyclopentene [121]. 

We examined initially the photochemical reactivity of 2-ethoxypyrrolin-5-one (12) with olefins because of its obvious similarity to 2-cyclopentenone. Irradiation of 12 in the presence of 1,1-dimethoxyethene or cyclohexene in ferr-butyl alcohol solvent did not give a (2 + 2)-cycloadduct but the rearrangement product ferr-butyl N-(ethoxycyclopropyl)carbamate (I3)l4 The novelty and synthetic potential of the rearrangement of 12 to 13 lured us temporarily away from our original pursuit. However, as will become evident later, our studies of the rearrangement reaction were important in our eventual discovery of the (2 + 2)-photocycloaddition reaction. 

The formation of trans-products is observed to a lesser extent in the reaction of 3-alkoxycarbonyl-substituted cyclohexenones, in the reaction with electron-deficient alkenes and in the reaction with olefinic reaction partners, such as alkynes and allenes, in which the four-membered ring is highly strained (Scheme 6.11). The ester 26 reacted with cyclopentene upon irradiation in toluene to only two diastereomeric products 27 [36]. The exo-product 27a (cis-anti-cis) prevailed over the endo-product 27b (cis-syn-cis) the formation of trans-products was not observed. The well-known [2 + 2]-photocycloaddition of cyclohexenone (24) to acrylonitrile was recently reinvestigated in connection with a comprehensive study [37]. The product distribution, with the two major products 28a and 28b being isolated in 90% purity, nicely illustrates the preferential formation of HH (head-to-head) cyclobutanes with electron-acceptor substituted olefins. The low simple diastereoselectivity can be interpreted by the fact that the cyano group is relatively small and does not exhibit a significant preference for being positioned in an exo-fashion. 

The regioselectivity of the Paterno-Biichi reaction with acyclic enol ethers is substantially higher than with the corresponding unsymmetrically alkyl-substituted olefins. This effect was used for the synthesis of a variety of 3-alkoxyoxetanes and a series of derivatives [55]. The diastereoisomeric cis-and tnms-l-methoxy-l-butenes were used as substrates for the investigation of the spin state influence on reactivity, regio- and stereoselectivity [56]. The use of trimethylsilyloxyethene 62 as electron rich alkene is advantageous and several 1,3-anhydroapiitol derivatives such as 63 could be synthesized via photocycloaddition with l,3-diacetoxy-2-propanone 61 (Sch. 17) [57]. 

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). ... 

One well-known class of photocycloadditions is that of aldehydes and ketones with olefins to give oxetanes375 (e.g. the reaction of 462 with 463 to give 464 and 465).376 This kind of reaction is known as the Patemo-Biichi reaction. The excited state of the ketone is the n-rc one, and it is the orbitals of this state which interact with the ground-state orbitals of the olefin. Often it is the triplet state which is involved, but occasionally the singlet state is important. The orientation usually observed is shown in the following examples, where C- and X-substituted olefins are involved.377,376... 

Clarke and Shanks have examined the influence of sample thickness on the benzoin photoinitiated polymerization of butyl acrylate. They found that as the photoinitiator concentration increases so the extent of polymerization become less susceptible to changes in sample thickness. Grauchak et al. have successfully photopolymerized acrylic monomers in polyamide matrices with aromatic carbonyl compounds. In the photocycloaddition of olefins to poly(4,-vinylbenzo-phenone) and its copolymers with styrene, the rate of addition was found to be independent of the glass transition temperature suggesting that large-scale molecular motion is unimportant in this photoreaction. 

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