Paterno-Buchi products

Similar effects were obtained for methylenecycloalkanes 108 with preferential formation of the photo-Conia products 111. Increasing ring size in 110 as well as H/D exchange favored the formation of the Paterno-Buchi products 112. 

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. 

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 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...

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. 

The Paterno-Buchi photocycloaddition between carbonyl compounds and furans was first described in 1965 (equation 6)80. This report noted that only the head-to-head product 171 was formed, and that high exo face selectivity was exhibited. Subsequent to this and other early reports, this reaction has been systematically explored by several groups, owing largely to the various ways in which the 2,7-dioxabicyclo[3.2.0]hept-3-ene ring system can be exploited730,81. 

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. 

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

The intramolecular Paterno-Buchi reaction is capable of installing new oxetane units with significant regio- and stereoselectivity, as is evident in the construction of a tetracycle related to merrilactone (Equation (26) see also Section 2.06.12.2) <2005OL3969>. The chirality of an atropoisomer recrystallized from an interconverting (4/z = 468 s at — 20 °C) mixture of enantiomers was preserved by photocycloaddition (Equation 27) the atropoiso-meric oxetane products do not interconvert unless heated <2003JOC942>. 

Attempts to obtain stereoselective Paterno-Buchi reactions were performed carrying out the reaction between 3,4-dimethylfuran and R-isopropylidene dia-stereoisomer. The coupling products were obtained with an overall yield of 35% as a 1.2 1 mixture of diastereoisomers. Furthermore, the compound 37 was obtained with 54% ee (Scheme 3.39) [76, 77]. This behavior suggests the operation of a mechanism that is insensitive to the substitution pattern of chiral aldehydes. Reaction between an excited aldehyde (singlet or triplet state) and furan... 

Vargas and Rivas reported the photocycloaddition of acetylseleno-phene (10) to tetrasubstituted alkenes resulting in two [2+2]-photoadducts, one of them (11) involves the C=C bond of the monoalkene and the fl,y-double bond of the selenophene. The second product 12 is a Paterno-Buchi photoadduct involving the carbonyl group of the selenophene and the C=C... 

Time-resolved (fs/ps) spectroscopy revealed that the (singlet) ion-radical pair is the primary reaction intermediate and established the electron-transfer pathway for this Paterno-Buchi transformation. The alternative pathway via direct electronic activation of the carbonyl component led to the same oxetane regioisomers in identical ratios. Thus, a common electron-transfer mechanism applies involving quenching of the excited quinone acceptor by the stilbene donor to afford a triplet ion-radical intermediate which appear on the ns/ps time scale. The spin multiplicities of the critical ion-pair intermediates in the two photoactivation paths determine the time scale of the reaction sequences and also the efficiency of the relatively slow ion-pair collapse ( c=108/s) to the 1,4-biradical that ultimately leads to the oxetane product 54. 

The irradiation of methyl phenylglyoxylate, benzil, benzophenone as well as 1,4-benzoquinone in the presence of homobenzvalene 103 gave, as products of the Paterno-Buchi reaction, oxetane derivatives which contain the tricyclo[4.1.0.02,7] heptane subunit as well as ring-opened products (Sch. 31) [100]. 

The photochemistry of ketones in the presence of exocyclic olefins has not yet been systematically studied. Chung and Ho reported the photochemistry of acetone in the presence of several exocyclic olefins. Surprisingly, homoalkylation occurred resulting in a series of 4-cycloalkylbutan-2-ones (with quantum yields of 0.14 0.01) rather than the expected Paterno-Buchi reaction (Sch. 33). With perdeuterated acetone, the photocycloaddition path increased due to the primary kinetic isotope effect (as shown for products 108 and 109, respectively, from 2-methyleneadamantane 107) [105]. 

In case of Paterno-Buchi reaction of cycloalkenes with prostereogenic aromatic carbonyl compounds (which show rapid ISC to the triplet excited carbonyl) less clear results were obtained. The reaction of cyclohexene with benzaldehyde was reported in the literature [51] and the spectral data of the main product 56 (35%) described as consistent with the assignment of exo-stereochemistry (Sch. 35) [110]. 

PET reaction of carbonyl compounds with olefins form either oxetanes (Paterno-Buchi reaction, Eq. 31) by direct coupling or a radical pair reaction leading to coupling product or reduction. The carbonyl-olefin radical pairs are formed by proton transfer within their radical ion pairs (Eq.32). Both these aspects of ketone-olefin photoreaction have been recently rationalized by Mattay et al. [167] from the photoreactions of 2,3-butanedione (208) with different olefins such as 209 and 210 as shown in Scheme 39. Photoprocesses of... 

When salt crystals of the aryl 1-phenylcyclopenty 1 ketone carboxylic acid 40 with chiral amines such as (+ )-bomylamine or (—)-1-phenylethylamine were irradiated, the optically active exo- and endo-oxetanes 41 or 42 were formed in low to moderate enantiomeric excesses (Scheme 10) [57]. The formation of the oxetanes is believed to occur through Norrish type 1 cleavage and hydrogen abstraction, producing an alkene and an aldehyde, followed by a Paterno-Buchi reaction within the crystal lattice cage. In contrast, solution photolysis of 40 in acetonitrile afforded product 43 as the only isolable product via a typical Norrish type I a-cleavage followed by radical coupling. 

There have only been a few new reports of reactivity of this type. The Paterno-Buchi reaction of 92 with substituted pyruvates gives the endo- and < ti-products shown (Equation 2) <1996TL1195>. In a later study, the corresponding cycloadditions of l,3-dioxol-2-one with a variety of aldehydes and ketones were also examined <2007ARK(viii)58>. 

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. 

Friedel-Crafts acylation of furan gives 2-acylfurans. A complementary photochemical procedure has been published for the preparation of 3-acylfurans which involves irradiation of a furan in the presence of a thioamide. The reaction is proposed to occur by regioselective Paterno-BUchi addition of the thioamide to the furan the thietane produced then eliminates and hydrolyses to the observed product. 

Transformations of arene substituents can also be achieved by transfer of an electron from a ground state donor to the excited state of the arene ring, or from an excited state donor to the ground state arene. Thus the retro Paterno-BUchi reaction of the benzo-phenone-tetramethylethylene oxetane (373) can be induced by irradiation in the presence of triethylamine as the electron donor. This yields 1,l-diphenyl-2-methylpropene the regiochemistry of this fragmentation is the opposite to that obtained by irradiation of electron acceptor arenes in the presence of (373), in which case benzophenone is the product. 

The regio- and stereochemistry of the Paterno-Buchi reaction depend on the structures of the reactants, on the electronic energy of the excited state carbonyl compound, and on the multiplicity of the excited state. With unsymmetrical alkenes, the products suggest preferential formation of the more substituted radical center in the biradical intermediate, but steric and electronic factors are also important. Stereoselectivities depend on the multiplicity of the excited state. For example, the reaction of excited singlet and triplet states of propanal (84) with 2,3-dihydrofuran (85) gave the diastereomers of 7-ethyl-2,6-dioxabicyclo[3.2.0]heptane (86) in different ratios (equation 12.63). ... 

Irradiation of a solution of longicamphenilone (9) in cyclohexane furnishes a complex mixture of products, in which a crystalline oxetane (196) predominates to the extent of 30%. The reaction proceeds by way of an initial Norrish type-I cleavage to (195) which is followed by a secondary Paterno-Buchi photocycloaddition (130) to give the tetracyclic oxetane (131). 

The intramolecular Paterno-Buchi reaction is a way for generating highly strained compounds. As an example, the Diels-Alder adducts between 2-cyclohexenone and 2-cycloheptenone were found to give strained polycyclic oxetanes upon irradiation (see Scheme 7). The products suffered smooth... 

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