Reactions Paterno-Buchi

The first total synthesis of the cytotoxic agent (+)-euplotin A was completed by the research team of R.L. Funk. The key step of the synthetic effort was the intramolecular hetero DIels-Alder cycloadditlon of a 3-acyl oxadiene (generated from 5-acyl-4H-1,3-dioxins via thermal retrocycloaddition) with a substituted dihydrofuran to afford the tricyclic skeleton of the natural product. The correct relative stereochemistry of the required dihydrofuran substrate was established using the Paterno-Buchi reaction between ethyl glyoxylate and furan. Subsequently, the oxetane ring was opened stereoselectively under Lewis acid catalysis. 

The Patemo-Buchl reaction of furan and various aldehydes was shown to be a highly stereoselective photochemical version of the aldol reaction by S.L. Schreiber and co-workers in which the furan serves as an enolate equivalent. This strategy was applied to the total synthesis of the antifungal metabolite (+)-avenaciolide. The photocycloaddition of nonanal with excess furan proceeded in nearly quantitative yield, and the two out of the three required stereocenters were created in a single step. The photocycloadduct was first hydrogenated then hydrolyzed under acidic conditions. 

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In general however the various possible reaction pathways give rise to formation of a mixture of products. The type I-cleavage reaction is only of limited synthetic importance, but rather an interfering side-reaction—e.g. with an attempted Paterno-Buchi reaction, or when an aldehyde or ketone is used as sensitizer in a [2 -I- l -cy do addition reaction. 

In addition to the intermolecular Paterno-Buchi reaction, the intramolecular variant has also been studied the latter allows for the construction of bicyclic structures in one step. For example the diketone 8 reacts quantitatively to the bicyclic ketone 9 ... 

Although the Paterno-Buchi reaction is of high synthetic potential, its use in organic synthesis is still not far developed. In recent years some promising applications in the synthesis of natural products have been reported. The scarce application in synthesis may be due to the non-selective formation of isomeric products that can be difficult to separate—e.g. 6 and 7—as well as to the formation of products by competitive side-reactions such as Norrish type-I- and type-II fragmentations. 

Scheme 2. The Paterno-Buchi reaction as a photochemical aldol equivalent.

Typical chemical reactions of photoexcited aldehydes and ketones are cleavage reactions, usually designated as Norrish Type I [equation (54)], II [equation (55)] and III [equation (56)], hydrogen abstraction [equation (57)] and cycloadditions, such as the Paterno-Buchi reaction [equation (58)]. Of these, Norrish Type II cleavage and the related... 

Photocycloaddition Reactions of Carbonyl Compounds and Alkenes. Photocycloaddition of ketones and aldehydes with alkenes can result in formation of four-membered cyclic ethers (oxetanes), a process often referred to as the Paterno-Buchi reaction.196... 

Some other examples of Paterno-Buchi reactions are given in Scheme 6.11. 

Scheme 1 UV-light induced formation of the two major photo lesions in DNA. T=T cyclobutane pyrimidine dimer. (6-4)-photo product (6-4)-lesion, formed after ring opening of an oxetane intermediate, which is the product of a Paterno-Buchi reaction...

In 1954 this reaction was more extensively investigated by Buchi,. Inman, and Lipinsky,(81) who confirmed the oxetane structure of the photoproduct. To credit their initial work on this interesting reaction, it commonly is referred to as the Paterno-Buchi reaction. 

In the general context of donor/acceptor formulation, the carbonyl derivatives (especially ketones) are utilized as electron acceptors in a wide variety of reactions such as additions with Grignard reagents, alkyl metals, enolates (aldol condensation), hydroxide (Cannizzaro reaction), alkoxides (Meerwein-Pondorff-Verley reduction), thiolates, phenolates, etc. reduction to alcohols with lithium aluminum hydride, sodium borohydride, trialkyltin hydrides, etc. and cyloadditions with electron-rich olefins (Paterno-Buchi reaction), acetylenes, and dienes.46... 

A very complex group of observations and speculations has been presented in Section IV. It might almost seem illogical to apply a single theoretical approach to so diverse a set of reactions, but the utility of PMO theory for correlating the several aspects of Paterno-Buchi reactions has already been demonstrated. 38-39> The newer results to be presented below will help to confirm the idea that PMO theory gives a unified useful theoretical picture for the majority of [2+2] photocycloaddition reactions. First, however, the many approximations and postulates inherent in this work should be made clear. 

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,... 

B. Paterno-Buchi Reactions Employing Conjugated Dienes. 297... 

The [2+2]-photocycloaddition of carbonyl groups with olefins (Paterno-Buchi reaction) is one of the oldest known photochemical reactions and has become increasingly important for the synthesis of complex molecules. Existing reviews have summarized the mechanistic considerations and defined the scope and limitations of this photocycloaddition73. Although this reaction likely proceeds via initial excitation of the carbonyl compound and not the excited state of the diene, the many examples of this reaction in natural product synthesis justify inclusion in this chapter. 

Predict the products of the reactions of excited-state carbonyl compounds with alkenes (Paterno-Buchi reaction). 

The cycloaddition reactions to give oxetanes readily occurs whenTj state is ( , 7T ) in character and an electrophilic centre is created on carbonyl oxygen atom on photoexcitation (Section 8.1). Paterno-Buchi reaction. 

PATERNO-BUCHI REACTION. Formation of oxetanes by photochemical cycloaddition of carbonyl compounds to olefins. 

The photochemical addition of a carbonyl compound to an olefin to form an oxetane is called the Paterno-Buchi reaction (Equation 13.52) and is one of... 

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