Stereospecificity photochemical 2-1-2 cycloaddition reaction

In contrast with the photochemical cycloaddition reaction of two alkenes, the [2+2] cycloaddition of a ketene and an alkene occurs under thermal conditions. The ketene is formed typically from an acid chloride and a mild base such as EtsN, or from an a-halo-acid chloride and zinc. Cycloaddition with an alkene occurs stereospecifically, such that the geometry of the alkene is maintained in the cyclobutanone product. The regioselectivity is governed by the polarization of the alkene, with the more electron-rich end of the alkene forming a bond to the electron-deficient central carbon atom of the ketene. Thus, the product from cycloaddition of dimethylketene with the enol ether Z-171 is the cyclobutanone m-172, whereas with -171, the isomer trans-lll is formed (3.116). ... 

Diradicals. Orbital symmetry arguments suggest the [2+2] cycloaddition should not be concerted, and experiments of various types suggest that these reactions do, indeed, involve diradicals (9a,53-55). The arguments are primarily based on the lack of stereospecificity in cycloaddition reactions. However, recently, several reports have been published in which 1,4-diradi-cals have been trapped by added reagents. Table III presents these data. Most of the diradicals are produced photochemically. 

Direct photochemical excitation of unconjugated alkenes requires light with A < 230 nm. There have been relatively few studies of direct photolysis of alkenes in solution because of the experimental difficulties imposed by this wavelength restriction. A study of Z- and -2-butene diluted with neopentane demonstrated that Z E isomerization was competitive with the photochemically allowed [2tc + 2n] cycloaddition that occurs in pure liquid alkene. The cycloaddition reaction is completely stereospecific for each isomer, which requires that the excited intermediates involved in cycloaddition must retain a geometry which is characteristic of the reactant isomer. As the ratio of neopentane to butene is increased, the amount of cycloaddition decreases relative to that of Z E isomerization. This effect presumably is the result of the veiy short lifetime of the intermediate responsible for cycloaddition. When the alkene is diluted by inert hydrocarbon, the rate of encounter with a second alkene molecule is reduced, and the unimolecular isomerization becomes the dominant reaction. 

In a photochemical cycloaddition, one component is electronically excited as a consequence of the promotion of one electron from the HOMO to the LUMO. The HOMO -LUMO of the component in the excited state interact with the HOMO-LUMO orbitals of the other component in the ground state. These interactions are bonding in [2+2] cycloadditions, giving an intermediate called exciplex, but are antibonding at one end in the [,i4j + 2j] Diels-Alder reaction (Scheme 1.17) therefore this type of cycloaddition cannot be concerted and any stereospecificity can be lost. According to the Woodward-Hoffmann rules [65], a concerted Diels-Alder reaction is thermally allowed but photochemically forbidden. 

It must be emphasized once again that the rules apply only to cycloaddition reactions that take place by cyclic mechanisms, that is, where two s bonds are formed (or broken) at about the same time. The rule does not apply to cases where one bond is clearly formed (or broken) before the other. It must further be emphasized that the fact that the thermal Diels-Alder reaction (mechanism a) is allowed by the principle of conservation of orbital symmetry does not constitute proof that any given Diels-Alder reaction proceeds by this mechanism. The principle merely says the mechanism is allowed, not that it must go by this pathway. However, the principle does say that thermal 2 + 2 cycloadditions in which the molecules assume a face-to-face geometry cannot take place by a cyclic mechanism because their activation energies would be too high (however, see below). As we shall see (15-49), such reactions largely occur by two-step mechanisms. Similarly. 2 + 4 photochemical cycloadditions are also known, but the fact that they are not stereospecific indicates that they also take place by the two-step diradical mechanism (mechanism... 

It is possible that some of these photochemical cycloadditions take place by a lA + A] mechanism, which is of course allowed by orbital symmetry when and if they do, one of the molecules must be in the excited singlet state (5i) and the other in the ground state.The nonphotosensitized dimerizations of cis- and trans-2-butene are stereospecific,making it likely that the [n2s + n2s] mechanism is operating in these reactions. However, in most cases it is a triplet excited state that reacts with the ground-state molecule in these cases the diradical (or in certain... 

Photocycloaddition of Alkenes and Dienes. Photochemical cycloadditions provide a method that is often complementary to thermal cycloadditions with regard to the types of compounds that can be prepared. The theoretical basis for this complementary relationship between thermal and photochemical modes of reaction lies in orbital symmetry relationships, as discussed in Chapter 10 of Part A. The reaction types permitted by photochemical excitation that are particularly useful for synthesis are [2 + 2] additions between two carbon-carbon double bonds and [2+2] additions of alkenes and carbonyl groups to form oxetanes. Photochemical cycloadditions are often not concerted processes because in many cases the reactive excited state is a triplet. The initial adduct is a triplet 1,4-diradical that must undergo spin inversion before product formation is complete. Stereospecificity is lost if the intermediate 1,4-diradical undergoes bond rotation faster than ring closure. 

If the motion had been disrotatory, this would still have been evidence for a cyclic mechanism. If the mechanism were a diradical or some other kind of noncyclic process, it is likely that no stereospecificity of either kind would have been observed. The reverse reaction is also conrotatory. In contrast, the photochemical cyclobutene—1,3-diene interconversion is disrotatory in either direction.368 On the other hand, the cyclohexadiene—1,3,5-triene interconversion shows precisely the opposite behavior. The thermal process is disrotatory, while the photochemical process is conrotatory (in either direction). These startling results are a consequence of the symmetry rules mentioned in Chapter 15 (p. 846).Vl,As in the case of cycloaddition reactions, we will use the frontier-orbital and Mdbius-HQckel approaches.37"... 

The stereochemical results of eiectrocyclic and cycloaddition reactions carried out photochemically often are opposite to what is observed for corresponding thermal reactions. However, exceptions are known and the degree of stereospecificity is not always as high as in the thermal reactions. Further examples of photochemical pericyclic reactions are given in Section 28-2D. 

This chapter follows on from chapter 12 where we introduced some basic ideas on stereocontrol. Since then we have met many stereospecific reactions such as pericyclic reactions including Diels-Alder (chapter 17), 2 + 2 photochemical cycloadditions (chapter 32), thermal (chapter 33) cycloadditions, and electrocyclic reactions (chapter 35). Then we have seen rearrangements where migration occurs with retention at the migrating group such as the Baeyer-Villiger (chapters 27 and 33), the Amdt-Eistert (chapter 31) and the pinacol (chapter 31). 

Finally, it should be mentioned that the photochemically allowed [2 + 2] cycloaddition reaction of alkenes can be considered to be a radical-mediated process. Photoexcitation of an alkene gives a 1,2-diradical. The radical at Cl adds to one terminus of the other alkene to give a 1,4-diradical, which then cy-clizes to give the observed product. Spectroscopic measurements at the femtosecond time scale have recently proven that the 1,4-diradical is a true intermediate along the reaction pathway of [2 + 2] cycloadditions. However, the lifetime of the 1,4-diradical is shorter than the rate of rotation about C-C a bonds, as [2 + 2] cycloadditions are stereospecific. 

Another class of molecules that are quite prone to undergo photochemical cycloadditions are a,/3-unsaturated carbonyl compounds. The reactive state in photochemical cycloadditions of or,-unsaturated ketones is believed to be the n-Tt triplet." Conservation of spin then implies that the initial intermediate is a triplet diradical, and the reaction need not be stereospecific with respect to the alkene component." The reaction has been most thoroughly studied in the case of cyclopen-... 

Non-stereospecific photochemical [2+2]-cycloadditions occur in the dimerization of phenyl cyclohexene 23 in the presence of a sensitizer to produce 24 and 25 [17], and in reactions of Z/E-2 butene with cyclohexenone 26 to give 27 and 28 [18] through the formation of intermediate diradicals. The photoaddition of cyclohexene to an enolised form of 1,3 diketone 29 gives 30 in a concerted process via the formation of an unstable cycloadduct [18]. 

The reaction mechanism of photochemical cycloadditions is not always well known. A concerted pericyclic process is likely when the reaction is highly stereospecific, while a two-step mechanism involving a diradical or diion intermediate is more probable when a mixture of stereoisomers is obtained. This is not a rule and a recent example is the [2 - - 2] photodimerization reaction of diethyl l,2-benzoxaphosphorine-6-bromo-3-carboxylate(an analog to coumarin) performed in solvents of different polarities (H2O, MeOH, PhH, CH3C02H). In water, the reaction is highly stereoselective in favor of a centrosymmetric anti-head-to-tail stereoisomer. Theoretical data, however, indicate that the process is not pericyclic, but that the reaction proceeds through a diradical or dipolar intermediate. 

You may think that there s not much to say about the no-mechanism pericyclic reactions, but there is. First, how they proceed stereochemically and even whether they proceed at all depends on whether the reaction is conducted thermally or pho-tochemically. For example, many [2 + 2] cycloadditions proceed only photochem-ically, whereas all [4 + 2] cycloadditions proceed thermally. Second, all pericyclic reactions proceed stereospecifically, but the stereochemistry of the products sometimes depends on the reaction conditions. For example, 2,4,6-octatriene gives cis-5,6-dimethylcyclohexadiene upon heating and /ran,v-5,6-dimethylcyclohexadienc upon photolysis. These phenomena can be explained by examining the MOs of the reactants. The rules governing whether pericyclic reactions proceed and the stereochemical courses when they do proceed are known as the Woodward-Hoffmann rules. 

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