Cyclic enones 2+2 photocycloaddition

This chapter summarizes and discusses the recent advances in the organic photochemistry of C=C double bonds. Special attention is focused on the photocycloaddition of alkenes to cyclic enones, including the mechanism, regio- and stereoselectivity and synthetic applications of the reaction. 

Prediction of the regioselectivity in the intermolecular photocycloaddition of enones to alkenes following this method provides similar results to those rationalized by the oriented -complex. However, it is in contrast with Weedon s previously discussed trapping results which indicate no selectivity in the first bond formation at the a- or /J-carbon positions in cyclic enones. 

The intermolecular photocycloaddition of alkenes to cyclic enones was found to afford cis- and trans-fused bicyclic systems. This stereoselectivity and the diastereofacial selectivity of chiral alkenes and/or enones is discussed below. 

Demonstration of the unique synthetic utility of the [2 + 2] photocycloaddition reaction of enones to alkenes and the success in controlling the stereoselectivity, to some extent, in the intermolecular additions (discussed above) prompted further studies and development of new synthetic applications in the intramolecular photoadditions during the last decade. In most cases that have been studied, the alkene was tethered to the cyclic enone by three carbon units or two carbons and one heteroatom. 

Schuster, D.I., Kaprinidis, N Wink, D.J., and Dewan, J.C. (1991) Stereochemistry of [2 + 2] photocycloaddition of cyclic enones to alkenes structural and mechanistic considerations in formation of trans-fused cycloadducts. Journal of Organic Chemistry, 56, 561-567. 

Bahaji, M. and Margaretha, P. (2007) Photocycloaddition of six-membered cyclic enones to propen-2-yl isocyanate. Helvetica Chimica Acta, 90, 1455-1460. 

In the preparative application of [2 + 2]-photocycloadditions of cyclic enones to (substituted) alkenes, two factors concerning product formation are of decisive relevance, namely the regioselectivity and the (overall) rate of conversion. Regarding the regioselectivity in the addition to mono- and 1,1-disubstituted alkenes, Corey had shown that the preferred addition mode of cyclohex-2-enone to isobutene or 1,1-dimethoxyethylene was the one leading to—both cis- and trans-fused—bicyclo[4.2.0]octan-2-ones with the substituents on C(7) [8]. In contrast, in the reaction with acrylonitrile, the alternate orientation was observed to occur preferentially. Similar results were also reported by Cantrell for the photocycloaddition of 3-methyl-cyclohex-2-enone to differently substituted alkenes [14]. No significant differences in the overall rates of product formation for the different alkenes were observed in these studies. In order to explain these observed... 

The mechanism of the [2 + 2] photocycloaddition of alkenes with cyclenones is a multistep process that involves the addition of alkenes to the 3 7t,tt triplet state of a cyclic enone and the formation of 1,4-biradical intermediates [35]. Except for the reaction of 1-alkenes, up to four new stereogenic centers are formed during the cycloaddition (Scheme 10). 

Introduction of chiral auxiliaries in the starting materials is very attract for applications to organic synthesis. However, to be of synthetic interest, chiral auxiliaries have to be inexpensive, readily introduced on the starting ma rial, inert in the conditions of irradiation, and readily removed from the photo ducts. Even if the first requirements can be easily satisfied with chiral ket esters, and amides, it is often difficult to avoid side reactions involving auxiliary [63]. In order to control all the asymmetric centers created in the in molecular photocycloadditions of cyclic enones with alkenes, esters of c alcohols were first considered. Although menthyl and bomyl derivatives ga only low de, 8-phenylmenthyl esters produced a far better asymmetric inducti [64]. The facial selectivity was found to depend on the syn/anti nature of t cycloadducts and the structure and location of the chiral auxiliary on either tl enone or the alkenyl moiety. More surprisingly the selectivity also depe strongly on the nature of the solvent (Scheme 21). 

All these results indicate that enantioselective photocycloadditions of s thetic interest should be possible with the help of a removable chiral auxilii as soon as the right chiral auxiliaries could be defined. In order to test the limit of this strategy, functionalized cyclohexenones and cyclopentenones were si lected to look for new chiral inductors. When co-alkenyl substituents were attach to the cyclic enone through an enamide, a carboxamide, or an ester group (Schei... 

Additions to Cyclohexenones and Related Systems - Caldwell and his coworkers have studied the photochemical addition of 1,1-diphenylethene to 4,4-dimethylcyclohex-2-enone. The products from this reaction, carried out in cyclohexane, are shown in Scheme 1. Although other evidence (see reference 9b above and references cited therein) has suggested that an exciplex is not a key interaction in such (2+2)-photocycloaddition reactions Caldwell et al. conclude from their detailed study of this system that a triplet exciplex is involved. Schuster and his coworkers have reported that a variety of cyclic enones (17) -(19) add photochemically to fullerene. The yields of the adducts vary but with some of the less heavily substituted enones the yields can be reasonable as shown by the data under the appropriate structure. Suginome et aO report the synthesis of the cycloadducts (20) by the photochemical addition of various ethenes to the enone (21). The adduct (22) was also synthesized by photochemical addition of methoxycyclohexene to the enone (20). 

An interesting use of removable chiral auxiliaries in photocycloaddition reactions concerns imminium salts. With cyclic enones, the observed asymmetric induction does not result from an approach of the double bonds in parallel planes because of the triplet nature of the reactive excited state. In contrast, the corresponding imminium salts react through their singlet excited state, and an approach of the reactants in parallel planes is now required during the cycloaddition process. For chiral imminium salts 130 derived from a cyclohexenone and a pyrrolidine having a C2 axis of symmetry, the intramolecular [2 -I- 2] photocycloaddition process occurs with a de up to 82%. As expected, the stereochemis-... 

However, the lowest energy triplet state of cyclic enones is a 3jt,jt state, not a 3n,Jt state,761 and it is now believed that the regioselectivity in adduct formation rather reflects differences in the efficiencies of cyclization to products and the efficiencies of regeneration of the starting material via fragmentation of the singlet 1,4-biradicals (Scheme 6.63). For example, [2 + 2] photocycloaddition of cyclopentanone... 

Cyclic enones, such as substituted cyclohex-2-enones or cyclohexa-2,5-diones, also undergo sigmatropic photorearrangement to form bicyclo[3.1.0]hexanones (lumiketones) or bicyclo[3.1.0]hex-3-en-2-ones, respectively, for which both concerted and stepwise (biradical) reaction mechanisms have been proposed.640,641,770 For example, a [l,2]-shift concurrently with the ring contraction (termed the type A reaction) is observed upon irradiation of the methylphenyl derivative 159 in polar solvents, whereas phenyl migration (termed the type B reaction) predominates in nonpolar solvents (Scheme 6.70).771,772 The reactions are believed to proceed via both the n,n and n,Tt triplet ketone states. In the presence of alkenes, cyclic enones may readily undergo a competitive photocycloaddition reaction (Section 6.1.5). 

Stereochemistry of enone photocycloaddition is more complicated than regiochemistry. Considering the stereochemistry at the four carbons of the newly formed cyclobutane ring, eight stereomers can result from each regiomer. However, not all of the possible products are usually obtained. Structure I represents a typical photoadduct from a cyclic enone and an acyclic alkene5. 

The photocycloaddition reaction of a cyclic enone to a cyclic alkene affords a tricyclic ring system (see II). 

For the photoadducts derived from cyclic enones and alkenes, stereochemistry at the ring junction is influenced by the structure and especially by the ring size of the starting reagents. For steric reasons, only cis-fused cycloadducts can be formed on photocycloaddition of cyclopentenones (n = 0). From cyclohexenone derivatives (n = 1), cis- and transfused adducts can be isolated, even if the cis-fused structure is thermodynamically more stable. This indicates that trans-fused cycloadducts result from a kinetic rather than a thermodynamic control. Fortunately, trans-fused cycloadducts can be epimerized easily to the more stable cis stereoisomers (Scheme 11). 

Stereoselective [2+2] photocycloadditions of alkenes are a powerful tool for the synthesis of cyclobutanes.However, in diastereoselective reactions cyclic enones have been intensively examined with moderate success. By double stereodifferentiation an increase in selectivity was achieved. 

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). 

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