Five photochemical rearrangement

A. Padwa, in P. de Mayo (ed.). Rearrangements m Ground and Excited States, vol. 3, Academic Press (1980). This review looks at the photochemical rearrangements of heterocyclic compounds with a five-membered ring. 

Padwa, A. (1980) Photochemical rearrangements of five membered ring heterocycles, in Rearrangements in Ground and Excited States, Vol. 3 (ed. P. de Mayo), Academic Press, New York, pp. 501—547. 

This has been synthesized starting from the 2+2 cycloadduct between cyclopentenone and cyclobutene by introducing the diazo function and applying the Wolff rearrangement for building a tricyclic alkene. A further photochemical cycloaddition with a cyclopentenone derivative, followed by a new introduction of the diazo function, photo-Wolff rearrangement, and reduction of the acidic function for enabling insertion of the chain lead to the acid, after this succession of (five ) photochemical reactions (Scheme 6.19). 

Carbene lv is photolabile, and 400 nm irradiation produces a mixture of products.108 By comparison with calculated IR spectra the major product was identified as cyclopropene 3v. The formation of 3v is irreversible, and it cannot be thermally (by annealing the matrix) nor photochemically converted back to carbene lv. The lv -> 3v rearrangement is calculated (B3LYP/6-31G(d) + ZPE) to be endothermic by only 5.4 kcal/mol with an activation barrier of 18.2 kcal/mol. Due to the two Si-C bonds in the five-membered ring of 3v this cyclopropene is less strained than 3s, which is reflected by the smaller destabilization relative to carbene lv. The thermal energy available at temperatures below 40 K is much too low to overcome the calculated barrier of 12.8 kcal/mol for the rearrangement of 3v back to lv, and consequently 3v is stable under the conditions of matrix isolation. 

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. 

Photochemical or thermal extrusion of molecular nitrogen from a-diazocarbonyl compounds generates a-carbonylcarbenes. These transient species possess a resonance contribution from a 1,3-dipolar (303, Scheme 8.74) or 1,3-diradical form, depending on their spin state. The three-atom moiety has been trapped in a [3 + 2] cycloaddition fashion, but this reaction is rare because of the predominance of a fast rearrangement of the ketocarbene into a ketene intermediate. There are a steadily increasing number of transition metal catalyzed reactions of diazocarbonyl compounds with carbon-carbon and carbon-heteroatom double bonds, that, instead of affording three-membered rings, furnish five-membered heterocycles which... 

Though the rearrangement step transforms a stable tertiary cation into a less stable secondary cation, relief of strain in expansion from a four- to a five-membered ring makes the alkyl migration favourable. In 1964, E.J. Corey published a synthesis of the natural product a-caryophyllene alcohol that made use of a similar ring expansion. Notice the photochemical [2+2] cycloaddition (Chapter 35) in the synthesis of the starting material. 

The scope of this methodology was established by forming imidazoles fused to five-, six- and seven-membered rings, 165, as outlined in Scheme 3856c,d. It was also found that while N-monosubstituted enaminonitriles such as 166 underwent photochemically mediated rearrangement to give imidazole 167, the reported conversion of 2-(dimethyl-amino)-1 -cyclohexene-1 -carbonitrile to 1,2-dimethyl-4,5,6,7-tetrahydrobenzimidazole could not be reproduced, i.e. no reaction was observed with A, 7V-disubstituted enaminonitriles5 6cd 58. 

The Nazarov cyclization is an example of a 47r-electrocyclic closure of a pentadienylic cation. The evidence in support of this idea is primarily stereochemical. The basic tenets of the theory of electrocyclic reactions make very clear predictions about the relative configuration of the substituents on the newly formed bond of the five-membered ring. Because the formation of a cyclopentenone often destroys one of the newly created centers, special substrates must be constructed to aUow this relationship to be preserved. Prior to the enunciation of the theory of conservation of orbital symmetry, Deno and Sorensen had observed the facile thermal cyclization of pentadienylic cations and subsequent rearrangements of the resulting cyclopentenyl cations. Unfortunately, these secondary rearrangements thwarted early attempts to verify the stereochemical predictions of orbital symmetry control. Subsequent studies with Ae pentamethyl derivative were successful. - The most convincing evidence for a pericyclic mechanism came from Woodward, Lehr and Kurland, who documented the complementary rotatory pathways for the thermal (conrotatory) and photochemical (disrotatoiy) cyclizations, precisely as predicted by the conservation of orbital symmetry (Scheme 5). 

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