Photocycloadditions of the Carbonyl Group

Another photocycloaddition reaction that has been known for a long time is the Paterno-Buchi reaction, which involves the formation of oxetanes through the addition of an excited carbonyl compound to olefins  

Diastereomeric oxetanes are formed from chiral carbonyl compounds such as menthyl phenylglyoxylate (78) (Buschmann et al., 1989). 

The general kinetic scheme (Fig. 7.34) displays two stages of diastereo-selection (1) a preferred formation of that of the two diastereomeric 1,4- 

An interesting example of diastereoselectivity is provided by the photocycloaddition of aromatic aldehydes to electron-rich cyclic olefins such as 2,3-dihydrofuran (79)  

The stereochemistry of the reaction can be accounted for by the conformational dependence of spin-orbit coupling elements discussed in Section 4.3.4. 

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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). 

The key intermediate in Tobe et al. s synthesis of (+)-marasmic acid (27), 1-oxa-spirohexane (26), was accessed via a photocycloaddition between enone 24 and 1 (Scheme 19.6) [8], The photocydoadduct 25 was obtained in 73% yield with the desired isomer consisting of 91% of the material. The structure of the minor product obtained from this cycloaddition was not confirmed. Reduction of the carbonyl group of 25 and epoxidation of the exocyclic double bond gave 26. An acid-catalyzed rearrangement of 26 afforded the core structure of marasmic acid and was subsequently taken on to complete the synthesis of this natural product. 

By far the most widespread type of photocycloaddition in synthetic applications employs the afkene unit of an c. p u nsaturated carbonyl compound as one of the addends. Simpleexamplesof such reactions are the dimerization of cyclopent-2-ennne (2.71), and the photo-addiiion of 2-methylptopene to cyclohex-2-enone (2.72). The function of the carbonyl group is to bring the absorption of the alkene into... 

As an illustration of the phenomena involved, consider the photocycloaddition of fumaronitrile to 5-X adamantanone, 6 (Scheme 2 X = F, Cl, Br, OH, Ph, or r-Bu) [94], In isotropic solvents, different quantities of adducts to the two carbonyl faces are formed. When 6 is complexed by /J-CD, the intrinsically more reactive face of the carbonyl group becomes more hindered toward attack by fumaronitrile than the less reactive one. As a result of this attractive interaction (NB, hydrogen bonding between the carbonyl oxygen and a hydroxyl on the fl-CD torus), the distribution of photoadducts is reversed. In this example, fl-CD serves the function of a reaction cavity with active walls (i.e., a template). 

The Patemo-Buchi reaction is one of the more predictable photocycloaddition reactions. Regiocontrol of the photoproduced oxetane is a function of the stepwise addition of the carbonyl chromophore to the alkene [30]. In the case of electron-rich alkenes, excitation of the carbonyl group produces a triplet species that adds to the alkene. The product regioselectivity is a result of addition that generates the most stable biradical, and the triplet lifetime of the intermediate biradical allows for substantial stereoselectivity prior to closing (see Scheme 2). Electron poor alkenes are more likely to undergo cycloaddition with carbonyl groups directly from an exciplex [31]. 

The [2+2]-photocycloaddition of carbonyl groups with olefins (Paterno-Buchi reaction) is one of the oldest known photochemical reactions and has become increasingly important for the synthesis of complex molecules. Existing reviews have summarized the mechanistic considerations and defined the scope and limitations of this photocycloaddition73. Although this reaction likely proceeds via initial excitation of the carbonyl compound and not the excited state of the diene, the many examples of this reaction in natural product synthesis justify inclusion in this chapter. 

Vargas and Rivas reported the photocycloaddition of acetylseleno-phene (10) to tetrasubstituted alkenes resulting in two [2+2]-photoadducts, one of them (11) involves the C=C bond of the monoalkene and the fl,y-double bond of the selenophene. The second product 12 is a Paterno-Buchi photoadduct involving the carbonyl group of the selenophene and the C=C... 

The efficiency of these chiral host compounds has been shown in highly enantioselective photocyclization and photocycloaddition reactions of prochiral lactams. These substrates, for example 2-quinolone derivatives, are expected to coordinate to lactam 44 with its NH-group as the hydrogen donor and the carbonyl group as the hydrogen acceptor, as depicted in Scheme 15. In this complex, any... 

The photochemical addition of 2H-azirines to the carbonyl group of aldehydes, ketones and esters is completely regiospecific (77H143). Besides the formation of the isomeric oxazolines 18 from 3 and ethyl cyanoformate, there is also formed the imidazole 19 from addition to the C = N in the expected regioselective manner. Thioesters lead to thiazolines 20, while isocyanates and ketenes produce heterocycles 21 (Scheme 4). The photocycloaddition of arylazirines with a variety of multiple bonds proceeds in high yield and provides a convenient route for the synthesis of five-membered heterocyclic rings. Some of the dipolarophiles include azodicarboxylates, acid chlorides, vinylphospho-nium salts and p-quinones. 

Photocycloadditions also proceed to give predominantly endo products. For example, the light-induced dimerization of thymidine occurs with endo selectivity. The carbonyl group of one ring positions itself over the other ring, and the more sterically crowded stereoisomer is obtained. 

Scheme 14. [2 + 2] Photocycloaddition of cyclenones with alkenes Asymmetric induction by chiral centers vicinal to the carbonyl group.

The product distribution in flie photoreactions of organosilicon compounds with electron-deficient compounds often depends on the reaction media. " In nonpolar solvents, the photocycloaddition of allylsilanes to electron-deficient aromatic compounds occurs to give cyclobutanes via exciplex intermediates. In contrast, photoallylation of the aromatic compounds or the carbonyl group takes place via free radical ions in polar solvents. Some examples are shown in Schemes 5 and 6. 

In contrast, Nishimura et al. obtained stable monoadducts 62a-g possessing a hydroxy group suitable for further derivatization from the [2 -1- 4]-photocycloaddition of the corresponding carbonyl compounds 60a-g and [60]fullerene (Scheme 26). The adducts 62 were found to adopt one or both of two conformers A and E, which possess pseudoaxial and pseudoequatorial hydroxy groups, respectively (see Table 28.4). Two conformers existed for 62a, c, d, and f, while 62b, e, and g exclusively adopted E, A, and E, respectively. The comformer ratios remarkably depend on the bulkiness of the substituents attached to the aromatic nucleus and the cyclohexene ring. 

Alcohol (34) is needed and we shall want to use a photocycloaddition to make some derivative of it (ether or ester). One partner in the cycloadd ition will be nucleophilic (CH2=CH0R) so we need a carbonyl group conjugated with the cyclohexene. FGA is required. 

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. 

Wender and Dreyer have demonstrate that meta-areiw photocycloaddition chemistry can lead expediently to modhephene A( tate 7S>5, a photoproduct derived from indane and vinyl acetate was converted to tetracyclic ketone 797 (Scheme XCVI). Because the enolate of 797 partakes of the dynamic behavior of semibuUvalenes, it proved possible to trimethylate the substance to produce 798. A fourth methyl group was introduced by conjugate addition and the carbonyl was simultaneously converted to an olefinic center. Selective hydrogenation of799 provided modhephene in seven steps. 

Little has been reported concerning the mechanism of the photocycloaddition reaction however, much is known about the photoreduction of carbonyl compounds.15,16 It has been shown that both hydrogen abstraction, leading to photoreduction, and most photocycloaddition reactions of carbonyl groups are characteristic of the same type of excited state reagent, that is, the carbonyl n,n state.17 Furthermore, much is known about the emission (phosphorescence and fluorescence) of carbonyl compounds, and all of this knowledge can be brought to bear upon the photocycloaddition reaction. 

Oxetanes can be formed by intramolecular reaction between a carbonyl group and an alkene, and this has been used (4.74) in making analogues of thromboxane A, (one of the compounds responsible for the control of blood clotting), albeit usually as the minor product. A special case of intramolecular reaction is seen for a,p-unsaturated carboxylic acids 14.75), where the product is an oxete that is tautomeric with a p-lactone. Oxetes may also be formed by photocycloaddition of ketones or aldehydes with alkynes the oxete normally ring-opens at room temperature to give an a,p-unsaturated carbonyl compound (4.76), but at lower temperatures its spectral... 

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