Enone-alkene photocycloadditions

Cubane-type compounds have been synthesized by a variety of routes. Most take advantage of the tethered 2+2 photocycloaddition. The first synthesis was reported by Eaton [33], although his synthetic route employed an enone+alkene photocycloaddition. An alkene+alkene cycloaddition was used to synthesize the propellacubane shown in Sch. 21 [34]. A more recent report decribed the synthesis of permethylated cubane using the alkene+ alkene photochemical approach [35]. That photocycloaddition is shown in Sch. 22. Although this particular reaction is inefficient, the product was made in sufficient quantity to allow for its complete characterization. 

An early synthetic application of such intermolecular enone + alkene photocycloadditions was presented by de Mayo in 1964. 5,5-Dimethyl-3-hydroxycyclohex-2-enone (1), i.e., the enol of dimedone, adds to e.g., cyclohexene, and the primarily formed cyclobutane 2 undergoes a... 

In contrast to these intermolecular enone + alkene photocycloadditions, the regioselectivity in the corresponding intramolecular cycloisomerizations of alkenylcycloalkenones is controlled primarily by... 

Enantioselectivity in intermolecular enone+ alkene photocycloadditions is quite difficult to accomplish, due to the fact that stereochemical information inherent in the starting materials can easily be lost on the stage of the triplet 1,4-biradical intermediate. Nevertheless highly enantioselective photocycloadditions of quinolones to alkenes mediated by a chiral lactam... 

Three typical procedures will be presented (Sch. 19). The first represents one of the (only) two enone + alkene photocycloaddition reactions which have published as a procedure in Organic Synthesis [75], the second one is of... 

A complete overview of syntheses of nonnatural cyclobutanes via enone + alkene photocycloadditions would be far beyond the scope of this chapter, recent reviews on this topic having been published recently [33,83]. 

The ready availability of four-membered rings of defined stereochemistry from enone-alkene photocycloadditions has been the origin of several syntheses which employ Wagner-Meerwein rearrangements in subsequent steps. This is exemplified by a neat and very short synthesis of a-caryophyllene alcohol (40) from cyclopentene and 3-methylcyclohexenone which was described some years ago (see Scheme 15). The rearrangement in 40% sulfuric acid proceeded remarkably smoothly. A short synthesis of iso-comene (41 Scheme 16) also Illustrates this strategy... 

The course of intramolecular enone alkene photocycloaddition is dependent on the number of atoms between the two reactive C=C bonds. For example, E- and Z-isomers of 1-acylhepta-1,6-diene (147) form a 1 1 mixture of stereoisomeric cycloadducts 148 and 149 upon irradiation, while no E Z isomerization occurs (Scheme 6.67a).764 The initial bonding takes place between the C2 (Cp) and C6 atoms, in agreement with the empirical rule of five,165 the regioselective, kinetically preferred formation of five-membered ring biradical intermediates over larger rings due to the entropies of cyclization. As a result, the biradical 150 is not observed. For comparison, the acylhexadiene 151 photolysis also proceeds via a 1,4-biradical (152) formed by an initial 1,5-cyclization (Scheme 6.67b).766... 

Lifetimes and Energies of 1,4-Biradical Intermediates in Enone-Alkene Photocycloadditions... 

Alkyl tethered alcohols such as D-mannitol and L-erythritol [20], have been used to bring cinnamyl units together for photocycloadditions. However, this probably involves cycloaddition between an excited enone moiety and the tethered alkene. Other examples of carbon linked alkenes include perhaps the earliest example of alkene+alkene photocycloaddition. Liu and Hammond [21] reported the formation of cyclobutane from the triplet irradiation of myrcene (see Sch. 11). 

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. 

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. 

Although the intramolecular variant of the enone-alkene [2 + 2] photocycloaddition was first discovered by Ciamician in 19081, less attention was paid to this type of reaction until the 1970s. Since then it has been successfully applied to the construction of complex organic molecules9 12 14 91. 

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. ... 

Stereochemistry of Ring Fusion of Cycloadducts Stereochemistry of the Alkene Component in Enone Photocycloadditions Regiochemistry in Enone-Alkene [2+2]-Photocycloadditions Reactivity of Alkenes Toward Photoexcited Enones... 

The lack of a relationship between product quantum yields and the rate constants of a single reaction step in a multistep reaction pathway was demonstrated dramatically many years ago by Wagner for Norrish type II reactions of aromatic ketones. In this reaction, quantum efficiencies are determined by the competition between reversion of 1,4-biradical intermediates to starting material and product formation and do not correlate at all with the rate constants for formation of the biradicals from ketone triplet states. Because 1,4-biradicals clearly play a crucial role in enone photocycloaddition to alkenes, it would be surprising if relative yields of enone-alkene photoadducts directly reflect the rates of the initial interaction of alkenes with enone triplet excited states.In fact, such a correlation does not exist. 

Scheme 6.10. Photocycloadditions of Enones with Alkenes and Alkynes... 

Mechanistic evidence indicates 450,451> that the triplet enone first approaches the olefinic partner to form an exciplex. The next step consists in the formation of one of the new C—C bonds to give a 1,4-diradical, which is now the immediate precursor of the cyclobutane. Both exciplex and 1,4-diradical can decay resp. disproportionate to afford ground state enone and alkene. Eventually oxetane formation, i.e. addition of the carbonyl group of the enone to an olefin is also observed452. Although at first view the photocycloaddition of an enone to an alkene would be expected to afford a variety of structurally related products, the knowledge of the influence of substituents on the stereochemical outcome of the reaction allows the selective synthesis of the desired annelation product in inter-molecular reactions 453,454a b). As for intramolecular reactions, the substituent effects are made up by structural limitations 449). 

A very remote secondary H/D isotope effect has been measured for the 2 + 2-cycloaddition of TCNE to 2,7-dimethylocta-2,fran -4,6-triene. The reaction of nitric oxide with iV-benzylidene-4-methoxyaniline to produce 4-methoxybenzenediazonium nitrate and benzaldehyde is thought to proceed via a 2 + 2-cycloaddition between nitric oxide and the imine double bond. A novel mechanism for the stepwise dimerization of the parent silaethylene to 1,3-disilacyclobutane involves a low-barrier [1,2]-sigmatropic shift. Density functional, correlated ab initio calculations, and frontier MO analysis support a concerted 2 + 2-pathway for the addition of SO3 to alkenes. " The enone cycloaddition reactions of dienones and quinones have been reviewed. The 2 + 2-photocycloadditions of homochiral 2(5H)-furanones to vinylene carbonate are highly diastereoisomeric. ... 

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. 

In cycloadditions of enones to alkenes novel strategies have been adopted for ring expansion of the cycloadducts, either by the choice of appropriate alkenes, e.g. 2-(trimethylsiloxy)buta-1,3-diene,70 vmv-2-trimethylsiloxybuten-2-oales71 or 3,3-dimethylcyclopropene,72 or by using 3-oxo-l-cyeloalkene-l-carboxylates as enones.73 Asymmetric [2 + 2] photocycloaddition of cyclopent-2-enone to a (+ )-dihydrofuran acetonide constitutes the cornerstone of the synthetic strategy in the first total synthesis of the novel antitumor metabolite ( )-echinosporin.74 The cycloaddition product 25 from treatment of 2-(2-carbomethoxyethyl)-2-cyclopentenone (24) with ethene has been used as a precursor for the preparation of tricyclo[4.2.0.01,4]octane.75... 

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