Photochemical 2+2 cycloadditions

In photochemical reactions, it is important to measure the efficiency of the photolysis, which is done by the parameter known as quantum yield (or quantum efficiency), defined as the number of molecules reacted or formed per light quanta absorbed. Ol The quantum yield for formation of a product ( I form) is 

It can also be expressed in terms of the number of molecules of starting material (SM) which disappear per quantum of light 

For photochemical reactions that give a single product, Oform = dis- If several products are formed, however, I form- If a reaction does not go through a chain mechanism, 0 will have a value 

This type of photocyclization was studied by Hammond and co-worker, who showed that myrcene (358) cyclized to 359 in the presence of a benzophenone sensitizer.507 Direct (unsensitized) photocyclization of 358 gave primarily 360 with a small amount of P-pinene (361).5 8 Photolysis in the presence of the benzophenone sensitizer leads to a triplet diradical intermediate, whereas the direct photolysis generated an excited diene that does not cross to the triplet manifold (see above) prior to cyclization. 

Intramolecular alkene cycloadditions are also important, not only for generation of quaternary centers but also for construction of bigbly bridged molecules. We saw an example of this in tbe photocyclization of 356 

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 the thermal and photochemical modes of reaction lies in orbital-symmetry relationships and was discussed in detail in Part A, Chapter 10. 

Intermolecular addition of alkenes can be carried out by photosensitization with mercury or directly with short-wavelength sources. Relatively little preparative use has been made of simple alkenes, however. Dienes can be photosensitized using such materials as benzophenone, butane-2,3-dione, and acetophenone. Under these conditions, preparatively useful yields of stereoisomeric mixtures of dimers are obtained. Usually, some 4 + 2 adduct accompanies the dominant 2 + 2 adduct. 

The photodimerizations of substituted styrenes were among the earliest photochemical reactions to be studied. These compounds give good yields of dimers 

Cycloaddition of carbon-carbon double bonds can also occur intramolecularly. Direct irradiation of simple dienes leads to cyclobutanes. This is a singlet-state process and is concerted. The stereochemistry of the cyclobutane can be predicted on the basis of orbital-symmetry rules (Part A, Section 10.1). Nonconjugated dienes can also undergo photochemical cyclization employing mercury or carbonyl compounds as sensitizers. Cyclobutane formation is usually unfavorable with 1,4-dienes because it would result in a very strained ring system. When the alkene units are separated by at least two carbon atoms, cyclization becomes more favorable sterically  

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- 

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A more demanding dynamical study aimed to rationalize the product distribution in photochemical cycloaddition, looking at butadiene-butadiene [82]. A large number of products are possible, with two routes on the excited Si state leading back to channels on the ground state. The results are promising, as the MMVB dynamics find the major products found experimentally. They also... 

As final examples, the intramolecular cyclopropane formation from cycloolefins with diazo groups (S.D. Burke, 1979), intramolecular cyclobutane formation by photochemical cycloaddition (p. 78, 297f., section 4.9), and intramolecular Diels-Alder reactions (p. 153f, 335ff.) are mentioned. The application of these three cycloaddition reactions has led to an enormous variety of exotic polycycles (E.J. Corey, 1967A). 

Although photochemical cycloadditions have gained acceptance in synthetic chemistry, most such reactions are limited to a relatively small scale. The use of a 1000-watt street lamp permits the irradiation of up to 1 mol of substrate in less time than 0.2 mol can be irradiated with the conventional 450-watt lamps. Thus, under optimum conditions, the submitters were able to add ethylene to 3-methylcyclohexenone on a 20-g scale in 48 hr (801) with a 450-watt lamp with the apparatus described here 94 g of this enone was condensed with ethylene in 8 hr (91%). 

Scheme 13.1. Some Examples of Photochemical Cycloaddition and Electrocyclic Reactions...

Scheme 13.1 lists some example of photochemical cycloaddition and electrocyclic reactions of the type that are consistent with the predictions of orbital symmetry considerations. We will discuss other examples in Section 13.4. 

The photochemical cycloadditions of alkenes and alkynes with aromatic compounds have received by far the most attention. Yields of [2+2] cydoadducts can be good, but reaction times are often long and secondary rearrangement products are common [139, 140, 141,142, 143,144, 145,146] (equations 63-65). The pioneering mechanistic and synthetic work on aromatic photocycloadditions has been reviewed [147],... 

The photochemical cycloaddition of a carbonyl compound 1 to an alkene 2 to yield an oxetane 3, is called the Patemo-Buchi reaction - This reaction belongs to the more general class of photochemical [2 + 2]-cycloadditions, and is just as these, according to the Woodward-Hofmann rules, photochemically a symmetry-allowed process, and thermally a symmetry-forbidden process. 

Thermal and photochemical cycloaddition reactions always take place with opposite stereochemistry. As with electrocyclic reactions, we can categorize cycloadditions according to the total number of electron pairs (double bonds) involved in the rearrangement. Thus, a thermal Diels-Alder [4 + 2] reaction between a diene and a dienophile involves an odd number (three) of electron pairs and takes place by a suprafacial pathway. A thermal [2 + 2] reaction between two alkenes involves an even number (two) of electron pairs and must take place by an antarafacial pathway. For photochemical cyclizations, these selectivities are reversed. The general rules are given in Table 30.2. 

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... 

Benzene rings can undergo photochemical cycloaddition with alkenes. The major product is usually the 1,3 addition product, 116 (in which a three-membered ring has also been formed), though some of the 1,2 product (117)... 

Hoomaert has studied Diels-Alder reactions of pyridine oquinodimethane analogs generated from functionalized o-bis(chloromethyl)pyridines <96T(52)11889>. The photochemical cycloaddition of 2-alkoxy-3-cyano-4,6-dimethylpyridine with methacrylonitrile gives a bicyclic azetine, 6-alkoxy-3,5-dicyano-2,5,8-trimethyl-7-azabicyclo[4.2.0]octa-2,7-diene, in moderate yield <96CC1349>. Regiospecific hydroxylation of 3-(methylaminomethyl)pyridine to 5-(methylaminomethyl)-2-(17/)-pyridone by Arthrobacter ureafaciens has been reported <96MI173>. 

Now let us return to our discussion of the conical intersection structure for the [2+2] photochemical cycloaddition of two ethylenes and photochemical di-Jt-methane rearrangement. They are both similar to the 4 orbital 4 electron model just discussed, except that we have p and p overlaps rather than Is orbital overlaps. In Figure 9.5 it is clear that the conical intersection geometry is associated with T = 0 in Eq. 9.2b. Thus (inspecting Figure 9.5) we can deduce that... 

Let us summarize briefly at this stage. We have seen that the point of degeneracy forms an extended hyperline which we have illnstrated in detail for a four electrons in four Is orbitals model. The geometries that lie on the hyperline are predictable for the 4 orbital 4 electron case using the VB bond energy (Eq. 9.1) and the London formula (Eq. 9.2). This concept can be nsed to provide nseful qualitative information in other problems. Thns we were able to rationalize the conical intersection geometry for a [2+2] photochemical cycloaddition and the di-Jt-methane rearrangement. 

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. 

The most widely exploited photochemical cycloadditions involve irradiation of dienes in which the two double bonds are fairly close and result in formation of polycyclic cage compounds. Some examples of alkene photocyclizations are given in Scheme 6.9. Entry 1 is a transannular cyclization. The preference for the observed product over tricyclo[4.2.0.02,5]octane does not seem to have been analyzed in detail. Entries 2, 3, and 4 involve photolysis in the presence of Cu03SCF3. Entries 5 and 6 are cases in which the double bonds are in close proximity and can cyclize to caged structures. 

Photocycloaddition Reactions ofEnones. Cyclic a,(3-unsaturated ketones are another class of molecules that undergo photochemical cycloadditions.188 The reactive... 

Scheme 5.9. Photochemical cycloaddition/iminium ion cyclization affording quinolizidines and higher analogues.

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