Photocycloaddition of cyclic enones

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. 

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... 

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). 

Mechanistic Issues in [2+21-Photocycloadditions of Cyclic Enones to Alkenes... 

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 photocycloaddition of (cyclic) a,(B-unsaturated ketones to alkenes affording cyclobutanes as products comprises the four reaction types shown in Sch. 1, i.e., (a) intermolecular enone + alkene cycloaddition (b) cycloisomerization of alkenylsubstituted enones (c) photocyclodimerization of enones, one ground state enone molecule acting as alkene and (d) cycloisomerization of fe-enones. 

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). 

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... 

Suishu, X., Obata, X, Shimo, X. and Somekawa, K., Species specificity and regio-selectivities in the photocycloadditions of cyclic conjugated enones and heterocycHc conjugated dienones and then-frontier MO analysis, Nippon Kagaku Kaishi, 167, 2000 Chem. Abstr., 132, 293339m, 2000. 

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. 

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. 

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

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). 

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