Paterno cycloadduct

Oxetanes are the cycloadducts from a carbonyl compound and an olefin. This one step photochemical formation of a four membered ring heterocycle has been named the Paterno-Buchi reaction 489a> b). Oxetanes are important synthetic intermediates as they can fragment into the carbonyl-olefin pair by which they were not formed (a so termed carbonyl-olefin metathesis). Two examples of such oxetan cracking reactions are shown below in (4.76)490) and in (4.77)491) in this last example the oxetane was used as a precursor for the pheromone E-6-nonenol,... 

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. 

Trimethyloxazole 257 undergoes photochemically induced [2 + 2] cycloaddition with aromatic and aliphatic aldehydes to provide bicyclic oxazolines 258 with excellent regiochemical and stereochemical control. Diastereoselec-tivities from 75-99% can be achieved, which is the first reported example of a Paterno-Biichi reaction involving an oxazole. The oxetane cycloadducts can be hydrolyzed to a-amino-(3-hydroxy ketones. Other oxazoles have not been evaluated to determine if they undergo the photochemical cycloaddition (Scheme 8.71). 

Glycals can also undergo cycloaddition reactions and their derivatives are of interest for synthetic purposes. Diels-Alder [4+2], Paterno-Biichi [2+2], and 1,3-dipolar additions can be applied to the construction of fused cycloadducts (O Scheme 21) [26,27,28]. 

The photo-Diels-Alder reaction of a-acetonaphthone 145 with the chiral a-enaminonitrile 146 yielded the cycloadduct 147 with almost complete diastere-oselectivity (Scheme 37) [91,92]. The intermediately formed biradical R is particularly stable owing to delocalization of the radical on the aromatic moiety and to a captodative effect on the enamine moiety. In analogy to the Paterno-Btichi reaction (see Scheme 7), the chiral induction occurred in two steps. In the first step, a chiral center is created at the a-position of the acyl group. In the second step of the diastereoselection, one of the two diasteromeric intermediates undergoes preferential cyclization to yield the final product 147, while the other one is decomposed to form the starting material [92]. 

This reaction can be done in the presence of a rather Wide range of functionality. It has been used with aromatic compounds such as 2-furylmethanol derivatives, as in the reaction of 382 with benzophenone to give a 65% yield of 383 along with a 20% yield of 384.322 -ghg photocycloaddition product of the Paterno-Biichi reaction with these substrates is an acetal or a ketal, and it can be hydrolyzed to produce acyl derivatives or other functionality. This synthetic route is attractive since achiral fragments generate cycloadducts with several contiguous chiral centers whose relative stereochemistry can usually be predicted with great accuracy. 

An extensive review of 2 + 2-photocycloadditions of dienones and quinones has been published. The photocycloaddition of heterocyclic 2,3-diones (18) with electron-rich alkenes in the presence of the photosensitizer benzophenone yields 2-1-2-cycloadducts (19) and (20) with high regio- and stereo-selectivity (Scheme 1) Time-resolved spectroscopy has shown that in the photochemical cycloaddition between stilbenes and quinones, the (singlet) ion-radical pair [S ", Q+ ] is the primary reaction intermediate and therefore establishes the electron-transfer pathway for this typical Paterno-Biichi transformation. A kinetic study of the Paterno-Biichi cycloaddition of stilbene to chloranil shows that solvent polarity and donicity control the formation as well as the reaction path of the ion-radical. The photoirradiation of chloranil with... 

Coyle has summarized the photochemistry of carboxylic acid derivatives. For arene carboxylic acid esters it has been shown that [2-1-2]-cycloaddition competes with hydrogen abstraction by the excited ester from an allylic position of the alkene. The addition of methyl benzoate 17 to 2-methyl-2-butene gave a 1 1 mixture of the Paterno-Bilchi adduct 18 and the coupling product 19. Less electron-rich alkenes (e.g., cyclopentene) did add preferentially toward the benzene ring of 17 in an ortho- and metacycloaddition manner. Furans could also be added photochemically to methyl benzoate and other aren-ecarboxylic acid esters. The resulting bicyclic oxetanes could be transformed into a series of synthetically valuable products. [2-1-2]-Cycloadducts and/or their cleavage or rearrangement products have also been described for photoreactions of alkenes with diethyl oxalate,benzoic acid, " and carbamates. ... 

Another clever example involving the hydroboration of cyclic systems was reported by Schreiber in a study of Paterno-Biichi cycloadducts produced from substituted furans and aromatic aldehydes (Scheme 7.15, see also... 

Important studies by Sakurai have highlighted the use of Paterno-Buchi cycloaddition reactions of carbonyl compounds and furans to give fused ox-etanes with high regio- and diastereocontrol [143]. An elegant synthetic application was reported by Schreiber, who used the conversion of furan into cycloadduct 228 as the only observed isomer (>99%, Scheme 18.37) [144, 145]. This cycloaddition could readily be conducted on a 50 g scale and formed the cornerstone in the total synthesis of the antifungal metabolite avenaciolide (229) [145]. 

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