Meta photocycloaddition reaction

Chappell, D. and Russell, A.T. (2006) From a-cedrene to crinipellin B and onward 25 years of the alkene-arene meta-photocycloaddition reaction in natural product synthesis. Organic tg Biomolecular Chemistry, 4 (24), 4409-4430. 

A series of 5-(2-methoxyphenyl)pent-l-enes (65), substituted at the a-, P-, or y- positions with either an OH or OSiMe3 group, undergo an intramolecular meta photocycloaddition reaction to give a product (66) having endo stereochemistry at the substituted carbon atom. The diastereoselectivity is a consequence of minimisation of steric interactions between the side chain substituent and the ortho-MQO group of the arene unit. A molecular mechanics study of the regio- and stereoselectivity of cation-dependent [2 + 2]-photo-... 

Some years ago Cornelisse reported that deuteration of alkyl benzenes results in a deuterium isotope effect upon the quantum yield of the meta photocycloaddition reaction with alkenes. In a new report the same group has published an analysis describing how the observed isotope effect upon the reaction quantvun yield can be ascribed to a kinetic deuterium isotope effect on the excited state reaction and distinguished from an effect upon the unimolecular photophysical modes of decay of the excited state. In addition, it is reported that when the quantum yield of meta photocycloaddition of cyclopentene to alkyl benzenes is measured using a mixture of deuterated and non-deuterated benzenes, the quantum yield is arene concentration dependent.The authors argue that this arises from competition between cycloaddition and the formation of mixed excimers between deuterated and non-deuterated alkyl benzenes which dissociate to yield excited deuterated alkyl benzene and ground state non-deuterated alkyl benzene preferentially. 

The Wender group has extensively studied the Q+T)-meta photocycloaddition reaction of double bonds and benzenoids, which furnishes highly condensed polycyclic compounds not accessible by other means. An intramolecular version, with the correct spacer, can produce such a situation as shown in Scheme 60, whereupon uiuaveling leads to the pseudoguaiane rudmollin [98]. 

Wender, P. A. and Dore, T. M., A formal synthesis of crinipellin B based on the arene-alkene meta-photocycloaddition reaction. Tetrahedron Lett., 39, 8589, 1998. 

The intramolecular [5 + 2] cycloaddition mode has been studied extensively. The chemistry bears a remarkable similarity to the arene-olefin meta-photocycloaddition [53] reaction (e.g. 114... 

Cycloaddition of alkenes to the benzene ring does not occur when both molecules are in their ground electronic states. The reaction can only be brought about by photoexcitation of either of the two addends. Three types of photochemical cycloaddition of alkenes to benzene and its derivatives are presently known. Ortho photocycloaddition, also referred to as 1,2-photocycloaddition or [2 + 2] photocycloaddition, leads to bicyclo[4.2.0]octa-2,4-dienes. Meta photocycloaddition, also referred to as 1,3-photocycloaddition or [2 + 3] photocycloaddition, gives triyclo[3.3.0.02 8]oct-3-enes, also named l,2,2a,2b,4a,4b-hexahydrocyclo-propa[crf]pcn(alcnes. Para photocycloaddition, also referred to as 1,4-photocy-cloaddition or [2 + 4] photocycloaddition, results in bicyclo[2.2.2]octa-2,5-... 

To prevent the meta photocycloaddition, the use of rigid face-to-face skeletons is also an effective strategy. Acetone-sensitized excitation of 208 gave only 209 reversibly [262-264] reactions of 210 and 211 gave similar results [265,266] (Scheme 61). X-ray analysis of 210 showed the distance of the aromatic carbons which react is 3.04 A [263],... 

The last two chapters by Hoffmann and Ramamurthy deal with a collection of photochemical reactions with arenes, the ortho-, meta- and para photocycloadditions and with a conceptually exciting concept in organic photochemistry, the use of contrained media. Retigeranic acid (16, by formal asymmetric synthesis) was synthesized via a fabulous reaction sequence involving an intramolecular meta photocycloaddition as key step [16]. 

While the meta photocycloaddition occurs at the n,n singlet state of the arene [4], different cases must be distinguished for the ortho cycloaddition depending on the structure of the substrates [5] (a) excitation of a ground state charge-transfer complex (b) excitation of the alkene (or alkyne) reaction partner (c) excitation of the arene partner and reaction at the singlet state and (d) excitation of the arene followed by intersystem crossing and reaction with the alkene at the triplet state. 

At the singlet excited state, ortho and meta photocycloadditions are often competitive processes and physicochemical investigations were carried out to rationalize the modes of cycloaddition of arenes with alkenes. In the context of the study of photochemical electron transfer reactions, it has been proposed that the difference of the redox potentials of the reaction partners might play an important role in this competition [10]. Such a discussion involves the intervention of an exciplex as intermediate. The Rehm-Weller equation [11] was used to quantify the relationship. When an electron transfer process is strongly endergonic (AG>1.5eV), the meta cycloaddition should be favored. When such a process is less endergonic (1 < AG< 1.5 eY), the ortho addition dominate [12]. This means that the... 

Recent results revealed that the ortho photocycloaddition frequently occurs concomitantly with the meta photocycloaddition even in cases where only meta derivatives are obtained. Especially in the case or electron-donor substituted benzene derivatives, the competitive ortho cycloaddition is less stereo- or regioselective and the resulting products are less stable. Aside the meta adducts as main products, complex mixtures of ortho products or products resulting from rearrangements of these primary photoproducts have been obtained [15,16], Improved separation techniques recently enabled a better characterization of these products. Furthermore, using particular conditions like an acidic reaction medium, the intermediates resulting from ortho photocycloaddition could be transformed selectively in more stable final products [17]. 

The meta photocycloaddition is frequently observed in cases of alkyl or electron-donor substituted benzene derivatives. Two exo/endo isomeres 2a,b are obtained in high yields in the reaction of anisole 1 with cyclopentene (Sch. 2) [18]. The reaction was also efficiently carried out in an intramolecular way. Two efficient reactions of this type are depicted in Sch. 2. The azatriquinane 3 [19] and the silane derivative 4 [20] were obtained in high yields. The formation of different regioisomers can be controlled by the heteroatoms in the side chain. The longer C-Si bonds particularly favor the formation of compound 4. 

The competition of ortho and meta photocycloaddition is much more expressed when the mesomeric effects of the substituents are weak [30,31]. A more precise analysis of the products revealed that ortho and even para side products are formed in minor amounts in cases were normally the meta cycloaddition should be observed as dominant reaction [32]. Bichro-mophroric substrates carrying electron donor substituents on the benzene ring and any electron active groups on the alkene moiety range in this category [15,31,33]. 

Among the variety of terpenes which were synthesized with an intramolecular meta photocycloaddition as key step, triquinane derivatives were particularly well studied. Two isomers of these compounds are readily accessible via intramolecular meta cycloaddition in position 1,3 (Sch. 9). The following cyclopropanation reaction of intermediate O controls which of the angular or linear isomers is formed (Sch. 17) [67]. As this step is almost always unselective, both isomers are concomitantly formed. However, one of the isomers can be obtained predominantly via an additional photochemical equilibration step (compare Sch. 11). The triquinane frame is obtained by rupture of the distant C-C bond of the cyclopropane in connection to the 10-membered ring moiety. 

The photochemical transformations of vinylcyclopropanes are of mechanistic interest, but because of the high energy of the reaction intermediates, especially in the triplet manifold, practical applications are scarce. The regio- and stereo-selective aspects are, however, similar to those of the thermal processes. Additional methods that provide for the cyclopentene rearrangement involve the degenerate photochemical rearrangements observed by Wender during meta-photocycloaddition of arenes and alkenes and utilized extensively in the synthesis of triquinane sesquiterpenes. -" -" (See Section 8.1.9 or ref. 41 for a recent summary.)... 

Full details of the effects of acid and solvent polarity on various photocycloaddition reactions of ethylenes and acetylenes to benzene have been published and a mechanistic rationale of the observations has been presented. Thus the largely homopolar concerted meta cycloaddition of ethylenes to benzene, which yields the tricyclo[3.3.0.0 "]oct-3-ene system (36), has little sensitivity to either solvent polarity change or the presence of a proton donor, but the onho process leading to bicyclo[4.2.0]octa-2,4-diene derivatives (37)... 

The meta photocycloaddition of cis-cyclooctene to benzene was one of the first examples of this reaction reported, and the addition of this cycloalkene to low molecular weight polystyrene and mono- and di-aromatic model-compounds has now been described. The results were analysed by mass spectroscopy, and it was reptorted that for polymers having up to six styrene units, more than one phenyl group in each chain had reacted. In the 2 1... 

Yamamura has extensively explored the intramolecular [5 - - 2]-cycloaddition mode. This chemistry bears a remarkable similarity to the so-called arene olefin meta-photocycloaddition [64] reaction (e.g., 267 to 268) that has frequently been used in the synthesis of complex bioactive natural products. While different intermediates are involved, the photo-and electrochemical reactions provide access to many of the same basic ring systems. This is nicely demonstrated by comparing key steps and the outcome of an electrochemical approach to the total synthesis of pentalene (53) [65] and a photochemical pathway that ultimately led to cedrene (compare equations 48 and 49). 

Arene-alkene photocycloaddition reactions have been reviewed in detail. This review includes a tabular survey, synthetic applications and exhaustive bibliography. Many of the reactions considered in this review were however performed to determine answers to mechanistic questions, therefore they are not necessarily optimized and chemical yields are not indicated. Tables 2 and 3 bring together, from the references cited in the review , those intermolecular photochemical meta cycloadditions which are principally synthetic methods. More concise general treatments of this reaction have since been published, as have other papers mainly concerned with its mechanistic aspects. """ ... 

Wender and co-workers continue to make elegant synthetic use of the intramolecular meta photocycloaddition of phenyl-ethenyl non-conjugated bichromophoric systems and this year describe three such applications of the reaction. The synthesis of ( )-silphinene (40), the first member of a new family of tri-quinane natural products, has been achieved in three steps and... 

Intramolecular Cyclization Reactions This Section is concerned with photo-induced cyclization reactions of aromatic compounds in which the final product is also an arene. Examples of intramolecular cyclization in which the product is a stable aliphatic system (e.g. intramolecular meta photocycloaddition of ethylenes to benzenes) are considered in Section 3 of this Chapter. The present type of process occurs for a wide variety of systems and may involve arene-arene and arene-ethylene photo-oxidative cyclization or reactions proceeding by loss of halogen acid. For several years now one of the major interests in these processes has been in their use as synthetic procedures and again within the review period there have appeared a number of accounts which illustrate this feature. Stilbene-... 

The simultaneous formation of two or more a-bonds has always attracted synthetic chemists since complex molecules can be built up in one single step. Therefore it is not surprising that highly developed syntheses of natural and artificial products often made use of cycloaddition procedures. The meta photocycloaddition of aromatic compounds to alkenes certainly belongs to this category and has reached its summit of application in the admirable work of Wender s group. Hence this chapter describes photocycloadditions of various types covering mainly meta [3+2], ortho [2+2] and para [4+2] ones. Even an unusual example of an [6+6] cycloaddition is presented. The fact that only one substitution reaction is described may indicate that synthetic studies of electron transfer activation only started recently. 

Potentially useful synthetic reactions may not always proceed in high yields. The intramolecular meta photocycloadditions of (15 X = CH2, SiMe2 R R, R = H, Me), for example, gave the corresponding 1,6-bridged di-hydrosemibullvalene adducts (16) in yields of only 7-19%, but starting with relatively simple precursors provide an approach to complex molecular systems not readily accessible by conventional means (Penkett et al.. Chapter 4). 

Among the photochemical reactions of aromatic compounds, the photocycloadditions are most frequently applied to the synthesis of complex polycyclic compounds [6, 9]. The [2+3] or meta photocycloaddition of aromatic compounds and alkenes is the most prominent example [10]. This transformation also demonstrates complementarities between photochemical and ground state reactions since such reactions are almost impossible using conventional activation. A [2+2] ot ortho photocycloaddition between carbocyclic aromatic compounds and alkenes is observed as well. It is often competitive with other cycloaddition modes, in particular the [2+3] mode [11]. Many of these reactions are reversible, and photostationary equilibria are involved. This reaction was much less applied to organic synthesis. Recently, it was found that an acidic reaction medium may have an influence on the outeome of the reaction. The intramolecular photocycloaddition of resorcinol derivatives such as 1 is difficult due to its reversibility (Scheme 29.1). However, in an acidic reaction medium, the cycloadducts 2a,b are protonated at the oxygen atom of the tetrahydrofuran moiety... 

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