Photochemical cycloadditions with carbonyl compounds

N-Substituted pyrroles, furans and dialkylthiophenes undergo photosensitized [2 + 2] cycloadditions with carbonyl compounds to give oxetanes. Furan and benzophenone give the oxetane (192). The photochemical reaction of pyrroles with aliphatic aldehydes and ketones results in the regiospecific formation of 3-(l-hydroxyalkyl)pyrroles (e.g. 193), via an intermediate oxetane which undergoes rearrangement under the reaction conditions (79JOC2949). 

The formation of oxetanes by photochemical (2 + 2)-cycloaddition of carbonyl compounds, such as aldehydes, ketones, and quinones, with carbon-carbon double bonds has been reported for various heterocyclic compounds. Maleic anhydride,142 isocoumarin (and its derivatives),143,144 benzol 61 thiophene 1,1-dioxide,144 l,3-dihydroimidazol-2-ones,131,132... 

R,2S)-Ephedrine has found most application, e.g., as a catalyst in photochemical proton transfer reactions (Section D.2.1.). and as its lithium salt in enantioselective deprotonations (Section D.2.1.). The amino function readily forms chiral amides with carboxylic acids and enamines with carbonyl compounds these reagents perform stereoselective carbanionic reactions, such as Michael additions (Sections D.1.5.2.1. and D. 1.5.2.4.), and alkylations (Section D.1.1.1.3.1.). They have also been used to obtain chiral alkenes for [1 +2] cycloadditions (Section D. 1.6.1.5.). 

Azirine, trans-2-methyl-3-phenyl-racemization, 7, 33, 34 1-Azirine, 2-phenyl-reactions, 7, 69 with carbon disulfide, S, 153 1-Azirine, 3-vinyl-rearrangements, 7, 67 Azirines, 7, 47-93 cycloaddition reactions, 7, 26 fused ring derivatives, 7, 47-93 imidazole synthesis from, 5, 487-488 photochemical addition reactions to carbonyl compounds, 7, 56 photolysis, 5, 780, 7, 28 protonated... 

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. 

As mentioned in Section 7.2, when the electron transfer reaction between electron-rich alkenes and excited carbonyl compounds is energetically favorable, the RI pair becomes an important intermediate in photochemical [2 + 2] cycloaddition reactions (Scheme 7.5). The regioselectivity of these reactions may differ from that observed for the PB reaction involving 1,4-triplet biradical intermediates. Typical examples of PB reactions with very electron-rich alkenes, ketene silyl acetals (Eox = 0.9 V vs SCE), have been reported (Scheme 7.11) [27]. Thus, 2-alkoxyoxetanes were selectively formed as a result of the PB reaction with benzaldehyde or benzophenone derivatives, whereas a selective formation of 3-alkoxyoxetanes was observed in less electron-rich alkenes (see Scheme 7.9). When p-methoxybenzalde-hyde was used in the photochemical reaction, the regioselectivity was less than that observed in the case of benzaldehyde. This dramatic decrease in regioselectivity provided evidence that the selective formation of 2-alkoxyoxetanes occurred via RI pair intermediates. It should be noted that the stereoselectivity is also completely different from that associated with triplet 1,4-biradicals (vide infra). 

There is a striking difference between the photochemical reactivity of oc,(3-unsaturated enones and the corresponding ynones. Whereas many cyclic enones undergo [2+2] cycloaddition to alkenes at the C=C double bond of the enone (probably from the triplet nn state) to yield cyclobutanes, acyclic enones easily deactivate radiationless by rotation about the central C-C single bond. Ynones on the other hand behave much more like alkyl-substituted carbonyl compounds and add to (sterically less encumberd) alkenes to yield oxetanes (Sch. 11) [38,39]. The regioselectivity of the Paterno-Biichi reaction is similar to that of aliphatic or aromatic carbonyl compounds with a preference for primary attack at the less substituted carbon atom (e.g., 41 and 42 from the reaction of but-3-in-2-one 40 with... 

Among these reactions, the photochemical cycloadditions of C=C bom which can create up to four asymmetric carbons during the photochemical sti are particularly interesting, and numerous synthetic applications of this react have been reported. Advances in the understanding of the origin of asymmefa induction, during addition of alkenes with carbonyl derivatives, cyclic enom and aromatic compounds, will be discussed in detail. 

Reaction with thiocarbonyl compounds. The thiocarbonyl compounds obtained by photochemical oxidation of phenacyl sulfides can be trapped efficiently by a 1,3-dipolar cycloaddition with 1 to give 2. This heterocycle can be cleaved to carbonyl compounds by Bu4N F or (CjH5)3N HF. This process is more efficient and more general than photolysis of phenacyl sulfides in the presence of oxygen. 

Alkynes react photochemically with aromatic aldehydes or ketones to give a,p-unsaturated carbonyl compounds (equation 81). This occurs by way of cycloaddition to give an oxete, followed by thermal ring-opening of this intermediate, and the orientation of addition is in accord with a two-step cycloaddition via the more stable biradical intermediate (equation 82). 

If you see a four-membered ring, think [2 + 2] cycloaddition, especially if the ring is a cyclobutanone (ketene) or light is required (photochemically allowed). Ketenes and other cumulenes undergo [2 + 2] cycloadditions with special facility. An oxetane (four-membered ring with one O) is often obtained from the [2 + 2] photocycloaddition of a carbonyl compound and an alkene. 

Under thermal conditions, the TS of the [2 + 2] cycloaddition is made up of if/1 (the LUMO) of one component and i[io (the HOMO) of the other. Positive overlap between the orbitals at both termini of the 1t systems can be obtained only if one of the components reacts antarafacially. This orientation is very difficult to achieve geometrically, and hence [2 + 2] cycloadditions do not normally proceed under thermal conditions. However, under photochemical conditions, one of the components has an electron promoted from fo to //1. Now the HOMO-LUMO interaction is between ) / of the photoexcited component and i// of the unexcited component, and thus both components can be suprafacial in the TS. The [2 + 2] cycloaddition of most alkenes and carbonyl compounds do in fact proceed only upon irradiation with light. 

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