Photoaddition/fragmentation

A photoaddition-fragmentation sequence similar to that described in Scheme 17 was subsequently reported by Schell and Cook, who described the isolation of ketoimine 77 on irradiation of secondary vinylogous amide photosubstrate 75 in f-butanol (Scheme 18). The observed product was presumed to form via the intermediacy of cyclobutane 7639. Exposure of 77 to Schotten-Bauman conditions produced the diketo-amide 78. 

Antoulinakis, E. G., Schultz, A. G. The intramolecular Patemo-Buchi photoaddition-fragmentation route to polyquinane natural products. Chemtracts Org. Chem. 1996, 9, 224-227. 

There are few examples of formation of simple azetidines from [2 + 2] fragments, although this type of approach is important for certain azetidine derivatives, e.g. azetidin-2-ones (see Section 5.09.3). Nitrogen analogues of the Paterno-Buchi route to oxetanes are rare an example involves the photoaddition of 3-ethoxyisoindolone (37) to the enol ether (38) (75JA7288, 72CC1144). 

The photoadditions proceed through 1,4-diradical intermediates. Trapping experiments with hydrogen atom donors indicate that the initial bond formation can take place at either the a- or (3-carbon of the enone. The excited enone has its highest nucleophilic character at the (3-carbon. The initial bond formation occurs at the (3-carbon for electron-poor alkenes but at the a-carbon for electron-rich alkenes.191 Selectivity is low for alkenes without strong donor or acceptor substituents.192 The final product ratio also reflects the rate and efficiency of ring closure relative to fragmentation of the biradical.193... 

Photoaddition of l,2-bis(trimethylsiIoxy)cyclobutene 214 to various cyclohexenones followed by subsequent fragmentation of the produced four-membered ring was elegantly applied for the synthesis of various sesquiterpenes and diterpenes101. The photoaddition of 214 was applied102 in the total synthesis of the sesquiterpene (+)-daucene 217, which was obtained in a three-step sequence from the naturally occurring (—)-piperitone 213 (Scheme 46). 

Oppolzer, W. (1982) Intramolecular [2 + 2] photoaddition/cydobutane-fragmentation sequence in organic synthesis. Accounts of Chemical Research, 15, 135-141. 

Scheme 27)48. Irradiation of 111 led to the formation of 112, which was formed by a sequence involving photoaddition and retro-Mannich fragmentation to the intermediate ketoimine, followed by tautomerization of the imine to enamine, transannular closure and dehydration. 

The photochemistry of vinylogous amides is not limited to [2 + 2] photoadditions. This section will describe some of the migration and fragmentation reactions observed on irradiation of vinylogous amides. Schell and coworkers have reported that irradiation of 125 leads to the formation of 126, the formal product of an aza-Claisen reaction, in 57% yield (equation 16)40. 

A second piece of experimental evidence to be considered at this point is the photoaddition of I to a substrate that is sensitive to the appearance of a free radical in its vicinity, that is, the cyclopropyl ethylene derivative X. This sensitivity is expressed by its fast fragmentation to a pentenyl derivative XIII that would give rise to coupling compound XIV. 

Some studies directed at the synthesis of the b + c + d rings of gibberellic acid, and in particular the fragment (134), have been reported.The Diels-Alder addition of butadiene to the cyclopentenone (135) afforded (136), which was converted via its iodo-lactone (137) into the tricyclic compound (138). However, the synthesis broke down at the removal of the ring D substituents. l-Hydroxy-7-methylenebicyclo[3,2,l]octane (139) provides a model for the gibbane-steviol c/d ring system. A synthetic route involves the photoaddition of allene to 1-cyclopentene-l-aldehyde to give l-formyl-7-methylenebicyclo-... 

Figure 7.39. Photoaddition of formaldehyde and ethylene. Schematic representation of the carbon-oxygen attack as a function of the C,C distance Rcc and the dihedral angle q> between the formaldehyde and ethylene fragments (by permission from Palmer et al., 1994).

A fragmentation of a similar tricyclus has been used by Oppolzer for the synthesis of the hydroazulene ketone (74 Scheme 25), precursor of the bulnesenes (75). The tricyclic ketone (71), obtained by intramolecular photoaddition, is converted to the diol (72). Fragmentation is accomplished in one... 

Intramolecular [ 2 + 2] photoadditions often proceed very efficiently with good stereochemical and regiochemical control. The vinylogous amide (96) is converted in this way into the adduct (97) with a high level of asymmetric induction retro-Mannich fragmentation of this adduct affords the imine (98), a useful intermediate in a synthesis of vindorosine. Intramolecular [ 2 + 2] photoadditions have also been observed in the N -( -alkenyl)-pyrimidines (99) and afford the diazatricyclodiones (100) as the sole photoproducts. 

Reviews relevant to this section which have been published within the year describe general photo-substitution reactions,72 and the mechanism of photoaddition-substitution reactions of six-membered aza-aromatic compounds,73 but both of these are in Russian. The reactions of aromatic nitro-compounds via their triplet states have received a very comprehensive review treatment hydrogen abstraction, reduction, incorporation of solvent fragments, and addition and substitution processes have been described for a wide variety of systems.74 In view ... 

Photoaddition of enol acetate 20 produces the straight adduct 21 in high yield. This regiochemistry is consistent with the general preference for the formation of five-membered rings when possible. Adduct 21 is fragmented under basic conditions to generate diketone 22. 

The regioselectivity of photoaddition of the enol acetate of 40 depends on reaction temperature, and the ratios of 41 to 42 are 11 89, 2 3, and 51 49 at -70 °C, 25 °C, and 65 °C, respectivelyOf note is that the acetylation of 1,3-diketone 40 is not regiospecific, but the two enol acetates interconvert via a photo-Fries process. However, only the enol acetate leading to 41 and 42 participates in the cycloaddition. Fragmentation of adducts 41 and 42 gives diketone 44 and the aldol product 45 via diketone 43. 

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