Rearrangement photocycloaddition

In this section we will discuss photochemical synthesis of macrocycle, photoini-tiated oxidation of alkenes, photo-Fries rearrangement, photocycloaddition and chiral photochemical synthesis within a number of microreactors. 

Whereas the cycloaddition of arylazirines with simple alkenes produces A -pyrrolines, a rearranged isomer can be formed when the alkene and the azirine moieties are suitably arranged in the same molecule. This type of intramolecular photocycloaddition was first detected using 2-vinyl-substituted azirines (75JA4682). Irradiation of azirine (54) in benzene afforded a 2,3-disubstituted pyrrole (55), while thermolysis gave a 2,5-disubstituted pyrrole (56). Photolysis of azirine (57) proceeded similarly and gave 1,2-diphenylimidazole (58) as the exclusive photoproduct. This stands in marked contrast to the thermal reaction of (57) which afforded 1,3-diphenylpyrazole (59) as the only product. 

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],... 

In this synthesis, we have witnessed the dramatic productivity of the intramolecular enone-olefin [2+2] photocycloaddition reaction. This single reaction creates three contiguous and fully substituted stereocenters and a strained four-membered ring that eventually provides the driving force for a skeletal rearrangement to give isocomene. 

Cyclobuta[fc]chroman-4-ols, derived from chromones by a [2+2] photocycloaddition to ethylene, are prone to acid-catalysed rearrangements. Elaboration of the parent system prior to rearrangement has enabled the marine sesquiterpene filiformin <96JOC4391>, the henzo-1,3-dioxan nucleus of averufin <96JOC9164> and cyclobuta[h][l]benzoxepin-8,9-diones <96CC1965> to be synthesised. 

The second reaction mode is rearrangement of the ketocarbene to a ketene. In the presence of a C—C double bond this species reacts further via an intramolecular photocycloaddition (cf. chapter 4.3.3), as shown in (2.23) 238). 

It is apparent from the quantity of material included in this chapter that there is an extensive body of work concerning the utilization of diene and polyene photochemistry in a synthetic setting. The unique behavior of the excited chromophores permits the application of powerful new methods for the construction of complex molecules. Unusual photochemical rearrangements and photocycloaddition pathways often lead to substantial increases in molecular complexity, allowing such processes to serve as key strategic steps in target oriented syntheses. 

Ring enlargement.1 A new route to seven-membered ring systems from a cyclohexenone (1) involves a photocycloaddition of ethylene to provide the bicy-clooctanone 2. Addition of lithio-1,3-dithiane to 2 provides the adduct 3, which on reaction with HgO and HBF4 forms an unstable rearranged hydroxy aldehyde... 

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. 

Only a trace of the corresponding cubane 167 is formed on irradiation of the tricy-clooctadiene 168 in pentane at ambient temperatures using a 125-watt mercury arc lamp. The principal product 169 is the result of rearrangement within a biradical intermediate79. A review of the synthetic approaches to cubane and to its reactions has been published77. The diene 170 photochemically converts on irradiation in pentane solution at 254 nm to yield a photostationary mixture of the cubane 171, the starting material 170 and the isomeric diene 17280. Other additions of this type have been used for synthesis of the propellaprismane 173, essentially a heavily substituted cubane, by the intramolecular (2 + 2)-photocycloaddition of the diene 17481. 

In contrast to the [2-1-2]-photocycloaddition which is a widely used method to generate four-membered rings, Koreeda and Zhang used a thermal rearrangement key step to construct the tricyclic framework of kelsoene [23]. In earlier work, it was shown that upon treatment with base, y-keto-p-toluene-sulfonate rac-32 is converted to a 44/56 mixture of bicyclo[3.1.1 ]heptanone rac-33 and bicyclo[3.2.0]heptanone rac-34 (Scheme 10) [24-26]. 

Both target compounds discussed in this review, kelsoene (1) and preussin (2), provide a fascinating playground for synthetic organic chemists. The construction of the cyclobutane in kelsoene limits the number of methods and invites the application of photochemical reactions as key steps. Indeed, three out of five completed syntheses are based on an intermolecular enone [2+2]-photocycloaddition and one—our own—is based on an intramolecular Cu-catalyzed [2+2]-photocycloaddition. A unique approach is based on a homo-Favorskii rearrangement as the key step. Contrary to that, the pyrrolidine core of preussin offers a plentitude of synthetic alternatives which is reflected by the large number of syntheses completed to date. The photochemical pathway to preussin has remained unique as it is the only route which does not retrosynthetically disconnect the five-membered heterocycle. The photochemical key step is employed for a stereo- and regioselective carbo-hydroxylation of a dihydropyrrole precursor. 

The Dauben-Walker approach has yielded the smallest and most strained fenestrane known to date Following the intramolecular Wadsworth-Enunons cyclization of 443 which also epimerizes the butenyl sidechain to the more stable exo configuration, intramolecular photocycloaddition was smoothly accomplished to provide 444. Wolff-ELishner reduction of this ketone afforded the Cj-symmetric hydrocarbon 445. Application of the photochemical Wolff rearrangement to a-diazo ketone 446 p,ve 447. 

The Pirrung synthesis is notable for its brevity and clever amalgamation of [2 + 2] photocycloaddition and Wagner-Meerwein rearrangement chemistry Enol ether 757 was reacted with the Grignard rea nt from 5-bromo-2-methyl-l-pentene, subjected to acid hydrolysis, and irradiated to generate the tricycle 738. Wittig olefination of this ketone and treatment with p-toluenesulfonic acid provided racemic isocomene. 

Some carbonyl compounds are unreactive in the photocycloaddition reaction because their excited states undergo molecular rearrangement. Illustrative of this point is the isomerization process involved upon irradiation of 2-methylbenzophenone. This ketone is known to be stable to irradiation in isopropanol,45 and irradiation in the presence of isobutylene yields a complex mixture which contains little, if any,... 

Photocycloaddition of an alkene to the thione group of 13 gave the thietane 14 which was stable at room temperature, but on refluxing 14 in toluene an iminothietane 15 and/or a 2-substituted benzoxazole were obtained by rearrangement processes <99JCS(P1)1151>. 

Intermolecular [2 + 2] photocycloadditions of either 2-pyrones126 or cyclohexa-2,5-dienones127 proceed in low yields due to either competing [4 + 2] cycloadditions or due to monomolecular rearrangements. 

The benzo[ ]-fused systems participate in a number of [2 + 2] cycloaddition reactions (81JOC3939, 81TL521). The photocycloaddition products of benzo[b]thiophenes and DMAD are dependent on the irradiation wavelength at 330 nm (196) is formed, while at 360 nm the rearranged product (197) is produced. 

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