Cyclohexenones, photocycloaddition alkenes

Weedon s data clearly demonstrate that not only is it not necessary to invoke exciplexes or oriented Jt-complexes in order to explain the regioselectivity in [2+2]-photocycloaddition of cyclopentenones and cyclohexenones to alkenes, but also that expectations based on the exciplex mechanism are contrary to experimental observations. It is clear that regioselectivity is entirely due to differences in behavior of the intermediate triplet 1,4-biradicals, not to their rates of formation, as was originally hypothesized. ... 

Further studies, on the same principle, were carried out by Lange and coworkers on the intermolecular photocycloadditions of cyclohexenones 167 to alkene 168, possessing different chiral auxiliaries at the enone91 or alkene92. Diastereomeric mixtures of cis,anti,cis 169 and cis,syn,cis isomers were obtained in low to moderate diastereomeric excess (Scheme 37). 

The effect of substituents on the stereoselectivity of the intramolecular photocycloadditions of alkenes to cyclohexenones was systematically examined by Becker and coworkers84 who obtained high stereofacial selectivity in compounds 283a-c. However, small changes in the position, geometry or steric effect of the substituents have dramatically affected the selectivity, indicating the complexity in predicting the stereoselectivity in such system (Scheme 61). 

Cyclohexenones require essentially identical irradiation conditions as cyclopente-nones (vide supra). The outcome of the intermolecular [2 + 2]-photocycloaddition to alkenes is somewhat more complex as compared to cyclopentenones, because the... 

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 photocycloaddition chemistry of oc,P-unsaturated 8-lactones is similar to the chemistry of y-lactones. Complications arise as with cyclohexenones because anti-addition to the a,P-unsaturated double bond can occur, particularly in the intermolecular addition mode. Even if one product prevails, intermolecular [2 + 2]-photocycloaddition reactions are often sluggish. Despite the fact that alkene 92, for example, was employed in a twofold excess relative to dihydropyranone 91, the reaction delivered only 32% of the desired product 93 (43% based on recovered starting material Scheme 6.33). The relative product configuration, which was established by X-ray crystallography, came as a surprise because the lactone apparently... 

Properly alkylated bicyclo[4.2.0]-octan-2-ones formed by 2+2 photocycloaddition of alkenes to cyclohexenones cleave to 5, -unsaturated ketones, one example leading to a sesquiterpene synthesis [73]. 

The first such reaction published in 1908 by Ciamician and Silber was the light induced carvone —> carvonecamphor isomerization, corresponding to type b [1]. Between 1930 and 1960 some examples of photodimerizations (type c) of steroidal cyclohexenones and 3-alkylcyclohexenones were reported [2-5]. In 1964, Eaton and Cole accomplished the synthesis of cubane, wherein the key step is again a type b) photocycloisomerization [6]. The first examples of type a) reactions were the cyclopent-2-enone + cyclopentene photocycloaddition (Eaton, 1962) and then the photoaddition of cyclohex-2-enone to a variety of alkenes (Corey, 1964) [7,8]. Very soon thereafter the first reviews on photocycloaddition of a,(3-unsaturated ketones to alkenes appeared [9,10]. Finally, one early example of a type d) isomerization was communicated in 1981 [11]. This chapter will focus mainly on intermolecular enone + alkene cycloadditions, i.e., type a), reactions and also comprise some recent developments in the intramolecular, i.e., type b) cycloisomerizations. 

Electron-rich alkenes are often used as addends for this type of cycloaddition. As described by R. Neier a cyclic P-amido cyclohexenone (compare with the open-chain substrate before) undergoes clean [2+2] cycloaddition to tetramethylethylene. Additionally a useful method for the enhancement of diastereomeric purity is described. Many starting materials, which are used for [2+2] photocycloaddition reactions, are protected enols of... 

Additions to Cyclopentenones and Related Systems. (2 + 2)-Cycloadditions are reported following the irradiation of mixtures of alkyl and aryl 2-thioxo-3/f-benzoxazole-3-carboxylates with alkenes. Cycloaddition also occurs to the CS double bond. The photochemical additions of arylalkenes to 3-phenylcyclo-pentenone and 3-phenyl cyclohexenone have been studied. The regio- and stereochemistry observed in the additions has been rationalized in terms of the stability of the intermediate biradicals. Photocycloaddition of allene to the cyclopentenone derivative (6) in methylene chloride solution at — 78°C affords... 

Further examples of mixed [2 + 2] photocycloadditions, in which various chiral auxiliaries were attached to the alkene. are shown for the reactions of 3-methyl-2-cyclohexenone with the chiral enoates 6a-c75. Irradiation of a toluene solution gave the cis-anti-cis, head-to-head adducts as inseparable mixtures of diastereomers 7a-c and 8a-c. Reduction and spontaneous lactonization of the adduct mixture with sodium borohydride in refluxing methanol led to the formation of the lactone 9 as an unequal mixture of enantiomers. 

Intermolecular de Mayo reactions are efficient for cyclic 1,3-diketones such as dimedone (5,5-dimethyl-l,3-cyclohexanedione)96,103,104 and acyclic systems such as acetylacetone93-95. Unsymmetrical acyclic /l-diketones, such as 1-phenyl-1,3-butanedione98 can enolize in two directions, however, reaction normally occurs preferentially from a single enol form. Examples of alkene photocycloaddition to trapped ends of /(-dicarbonyl compounds (e.g., 2,2-dimethyl-3(2/f)-furanone and 2,2.6-trimethyl-4/f-l,3-dioxin-4-one) are given in Table 1 (entries 26, 27) and Table 2 (entry 35) 10°. If the enol is stabilized by derivatization (e.g., acetylated dimedone 3-acetoxy-5,5-dimethyl-2-cyclohexenone), the primary cyclobutane photoproducts can be isolated96. 

Investigation of [2 -l- 2] photocycloaddition of enones to monosubstituted alkynes indicates that the reaction proceeds with an opposite regioselectivity compared to that of alkenes [71]. Generally, head-to-head adducts are major products except when the group substituted on the alkyne is -CO2R or -OR (see Scheme 17). Thus, methyl propynoate (60, R = CO2CH3) photoadds to cyclopentenone 59 to give 1 1 HH and HT products. Cycloaddition of cyclohexenone to 1-hexyne has also been studied and the HH HT ratio varies from 2 1 to 7 1 as a function of substituents at the enone 3-position. It... 

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). 

Additions to Cyclohexenones and Related Systems - A re-investigation of the photodimerization of isophorone (37) has been reported. The study examined the influence of solvent and of the concentration of the enone. Some of the results and the yields of dimers obtained are shown in Scheme 4. From this detailed study the authors suggest that supramolecular structures are involved in the dimerization. These apparently take part even at low concentrations of enone. The photocycloaddition of enones such as (39) to buckminsterfullerene (Ceo) has been studied. The outcome of the addition is the formation of low yields of furanylfullerenes. This addition occurs to the exclusion of de Mayo type of addition. Photocycloaddition of the cyanocyclohexenone derivative (40) to alkenes has been reported. ... 

Following Eaton s original discovery of the photocyclodimerization of 2-cyclopentenone (CP) and of photocycloaddition of this enone to cyclopentene (Eq. (72.1)),- Corey and co-workers reported [2+2]-photocycloadditions of 2-cyclohexenone (CH) to a variety of alkenes, and established many of the characteristic features of this reaction. 

Stereochemical scrambling in intramolecular photocycloadditions of cyclohexenones with tethered alkene moieties has also been extensively investigated. Becker and Haddad found that the isomeric 5-ltnked l-acyl-l,6-heptadienes 5 and 6 (R = CH3) give a 1 1 mixture of stereoisomeric cycloadducts 7 and 8,but the dienes do not isomerize during the irradiation process ... 

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