6-4 Photoadduct

Cyclobutane derivatives are formed after exposing a mixture of alkenes and maleic anhydride to light. Photoadducts are formed by reaction of maleic anhydride with ethylene [74-85-1] and benzene (50). 

The precedent is strong for the involvement of oxetanes as Intermediates in carbonyl additions to pyrroles. " NMR evidence has been obtained far an oxetane adduct of acetone and N-methylpyrrole. The initial photoadduct was shown to rearrange readily on workup to the 3-(hydroxyalkyl)pyrrole derivative. 

Nonyl aldehyde (32.66 g, 0.23 mol) and furan (200 mL, 187.2 g, 2.75 mol) were mixed in a 250-mL photolysis flask equipped with a quartz immersion well containing a Vycor filter and a 450-W Hanovia Lamp. The system was kept at -20° C with an isopropyl alcohol bath cooled by a Cryocool Immersion Cooler (CClOO). Nitrogen was bubbled throughout the duration of the reaction, and the solution was stirred vigorously. Additional furan (150 mL, 140.4 g, 2.06 mol) was added during the course of the reaction. TLC analysis indicated completion of the reaction after 20 h. After evaporation of excess furan and NMR analysis of the resultant oil (48.70 g, ca. 100%) indicated the desired photoadduct had been formed, without contamination from unreacted nonyl aldehyde. 

Sqheme 3. Stereoselective functionalizations of furan-aldehyde photoadducts. 

The enol ether double bond contained within the ds-fused dioxa-bicyclo[3.2.0]heptene photoadducts can also be oxidized, in a completely diastereoselective fashion, with mCPBA. Treatment of intermediate XXII, derived in one step from a Patemo-Buchi reaction between 3,4-dimethylfuran and benzaldehyde, with mCPBA results in the formation of intermediate XXIII. Once again, consecutive photocycloaddition and oxidation reactions furnish a highly oxygenated system that possesses five contiguous stereocenters, one of which is quaternary. Intermediate XXIII is particularly interesting because its constitution and its relative stereochemical relationships bear close homology to a portion of a natural product known as asteltoxin. 

Our journey begins with the photo-induced union of 3,4-dimethylfuran (19) and / -(benzyloxy)-propanal (18) (see Scheme 5). Irradiation of a solution of these two simple, achiral compounds in benzene with a 450 W Hanovia lamp equipped with a vycor filter results in the exclusive formation of head-to-head, exo photoadduct 17 in 63% yield. As a cw-fused dioxabicyclo[3.2.0]heptene system, intermediate 17 possesses a folded molecular framework to which access is obstructed on the concave face. In the presence of mCPBA, the less hindered convex face of the enol ether double bond is oxidized in a completely diastereoselective fashion, affording intermediate 16 in 80% yield after regioselective opening of... 

Ried and Bopp76 have shown that the photolysis of 3,5-diphenyl-4H-thiopyran-4-one 1,1-dioxide (58) in chloroform very rapidly leads to a trimer, or to photoadducts with... 

Methyl-2(17/)-quinoxalinone (109) and 2-methylacrylonitrile (110) gave the photoadduct, l,2a-dimethyl-3-oxo-2,2a,3,4-tetrahydro-l//-azeto[ 1,2-u]quinoxa-line-l-carbonitrile (111) (CH2CI2, MeOH, hv, N2, <15 h >95%) also analogs using significantly electron-deficient olefines. 

The benzyl ether is a good protecting group as it can be removed under reducing conditions. It turns out that the carbonyl group has another role to play as a mixture of cis and tvans photoadducts is formed,... 

In the crystal of 1,4-dicinnamoylbenzene (1,4-DCB) (see Fig. 12), the distances between the intermolecular photoadductive carbons are 3.973 and 4.086 A for one cyclobutane ring, and 3.903 and 3.955 A for the other. The two topochemical pathways may occur competitively in a single crystal of 1,4-DCB at the initial stage of reaction. Then, both intramolecular photodimerization and intermolecular photopolymerization of the diolefinic mono-cyclobutane intermediate occur competitively to give tricyclic dimer 21,22,23,24-tetraphenyl-l,4,ll,14-tetraoxo-2(13),12(13-diethanol, [4.4] para-cyclophane or oligomers (Hasegawa et al., (1985). On photoirridation at room temperature the 1,4-DCB crystal gives >90% of the tricylic... 

Methyl-l-phenyl-2(lfl)-quinoxalinone (226) and methyl methacrylate (227) gave the photoadduct, methyl l,2a-dimethyl-3-oxo-4-phenyl-2,2a,3,4-tetra-hydro-l//-azeto 1,2-a quinoxaline-l -carboxylate (228) as a separable mixture of two stereoisomers (CH2C12, MeOH, hv, N2, <15 h 40% each) analogs likewise.134... 

In a related example, the [D, A] complex of hexamethylbenzene and maleic anhydride reaches a photostationary state with no productive reaction (Scheme 17). However, if the photoirradiation is carried out in the presence of an acid, the anion radical in the resulting contact ion pair14 is readily protonated, and the redox equilibrium is driven toward the coupling (in competition with the back electron transfer) to yield the photoadduct.81... 

Benzotriazole and its 2-alkyl derivatives 300 undergo [2+2] cycloaddition to maleinimide when irradiated with UV light at A>290nm to give photoadducts 301 (Equation 10). In all cases, only exo diastereomers are formed. Since 1-alkylbenzotriazoles are completely unreactive under such conditions, unsubstituted benzotriazole must react as its... 

The cyclononadiene in (4.72) is obtained by thermal rearrangement of the photoadduct of a cyclobutene carboxylic acid ester and cyclopentene 484). 

These cycloadducts, at their most elementary level, are excellent intermediates for the synthesis of 3-substituted furan derivatives. For example, Kawanisi and coworkers reported a synthesis of perillaketone 174 in which the critical step was a Paterno-BUchi photocycloaddition between furan and 4-methylpentanal in the presence of methanesul-fonic acid (Scheme 39)82. This reaction furnished two initial photoadducts, 172 and 173. The unexpected product 173 presumably arises from a Norrish Type II cleavage of 4-methylpentanal to give acetaldehyde, and subsequent cycloaddition with furan. The desired cycloadduct 172 was then converted uneventfully to 174 via acid-catalyzed aromatization and oxidation. 

Schreiber and his coworkers have published extensively over the past decade on the use of this photocycloaddition for the synthesis of complex molecules730 81. Schreiber was the first to recognize that the bicyclic adducts formed in these reactions could be unmasked under acidic conditions to afford threo aldol products of 1,4-dicarbonyl compounds (175 to 176) (Scheme 40). The c -bicyclic system also offers excellent stereocontrol in the addition of various electrophilic reagents (E—X) to the enol ether of these photoadducts on its convex face (175 to 177). This strategy has been exploited in the synthesis of a variety of architecturally novel natural products. 

An application of this strategy to the synthesis of the antifungal metabolite ( )-avenaciolide 182 is shown in Scheme 4183. The photoadduct in this case, 178, was hydrogenated and hydrolyzed to give 179. Reaction of 179 with vinylmagnesium bromide and subsequent manipulation afforded aldehyde 180, which could be transformed via ozonol-ysis, epimerization of the dialdehyde and acidification of the dialdehyde acetonide to protected bis(lactol) 181. Oxidation and methylenation then afforded the desired target 182. 

Coal tar contains numerous hydrocarbon compounds formed from distillation of bituminous coal. Ultraviolet B (UVB) light-activated coal tar photoadducts with epidermal DNA and inhibits DNA synthesis. This normalized epidermal replication rate reduces plaque elevation. 

A recent paper 26) also reported that the photo [2 + 2] reaction between the olefin (63) and the ester (56) would yield the desired photoadduct (64), which was then reduced by LiAlH4 to afford the diol (65). The diol (65), upon oxidation, gave the a-methylene-S-lactone (67) via the intermediate lactol (66) (Table 3)26). 

The chemistry of cyclobutanes was remarkably exploited by Oppolzer42, who reported that the aldol condensation of the acetal (122) with l,2-Ws(trimethylsiloxy)-cyclobutene was catalyzed by BF3 Et20 to afford the eyclobutanone (123), which was refluxed with pTsOH in benzene to give 1,3-cyclopentanedione (124). On treatment with acetylchloride in pyridine at 0 °C, the compound (124) was transformed to the enol acetate (125) Irradiation of (125) gave the intramolecular photoadduct (126). Then on successive treatments with MeMgl, KOH and MsCl in... 

A new formal synthesis of ( )-zizaene (136) via the fragmentation reaction is a typical example 45,46). When the enol acetate (132) was irradiated, the isolable photoadduct (133) was formed together with other isomers. Reduction and mesylation of which afforded the mesylate (134). Then, fragmentation reaction would yield an epimeric mixture of the alkenone (755) in the presence of NaOH in aqueous dioxane at 60 °C, thus formulated a total synthesis of (+)-zizaene (136) 45-46). 

A cyclobutane ring-opening of the photoadduct (426) by the reaction of BF3 Etfi in refluxing benzene gave isopropenylcyclohexenone (427). The reaction could be applied to more complex compounds. Thus, (428), (430), (432) and (434) were converted accordingly to (429), (431), (433) as well as (435) 145). 

There are ample evidences which suggest that a cyclic periodate ester is the intermediate 148). Cyclobutane-1,2-diols can also be cleaved oxidatively and this aspect has been used in organic synthesis. Thus, photocycloaddition of l,2-bis(tri-methylsiloxy)cyclobutene to (—)piperitone (381) gave the photoadduct (438). Desilyla-... 

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