Photochemical cycloaddition regioselectivity

Fluorine-containing aldehydes, ketones and acid fluorides undergo photoinitiated cycloaddition reactions with fluorinated alkenes to give oxetanes.90 91 The addition of hexafluoroacetone (11) to fluoroalkenes can also be performed in the presence of the Lewis acid, aluminum chloride fluoride.92-1 22-1 23 Unlike the photochemical cycloaddition of hexafluoroacetone with trifluoroethene, the Lewis acid catalyzed addition is regioselective.92 Fluorooxetanes (c. g., 14) have also been synthesized by the addition of formaldehyde to fluoroalkenes in hydrogen fluoride.94 Examples of the formation of fluorooxetanes by [2 + 2]-cycloaddition reactions arc-given in Table 8. 

Copper-catalysed Michael addition followed by an aldol reaction with formaldehyde, gives a 1 1 mixture of diastereoisomers of the aldol 86 that can be eliminated to the enone 83. The resulting efficient photochemical cycloaddition gives ketone 82 with total regioselectivity probably because it is intramolecular. 

Hastings, D. J., Weedon, A. C., Origin of the Regioselectivity in the Photochemical Cycloaddition Reactions of Cyclic Enones with Alkenes Chemical Trapping Evidence for the Structures, Mechanism of Formation, and Fates of 1,4 Biradical Intermediates, J. Am. Chem. Soc. 1991, 113, 8525 8527. 

A contrast can be seen between photochemical cycloaddition of ketenes, which show reverse regioselectivity and that of allenes (cf. Table 5, entries 12 and 13128,129). 

A novel photochemical cycloaddition between 2-cyanofuran and 2-alkoxy-3-cyanopyridines gave the 4+4] product as the major isomer. The regioselectivity and stereoselectivity of this singlet photoaddition process was explained by frontier molecular orbital theory <04TL4437>. 

Hastings DJ, Weedon AC (1991) The origin of the regioselectivity in the 2+2 photochemical cycloaddition reactions of N-benzoylindole with alkenes trapping of 1,4-biradical intermediates with hydrogen selenide. Tetrahedron Lett 32 4107-4110... 

In contrast with the photochemical cycloaddition reaction of two alkenes, the [2+2] cycloaddition of a ketene and an alkene occurs under thermal conditions. The ketene is formed typically from an acid chloride and a mild base such as EtsN, or from an a-halo-acid chloride and zinc. Cycloaddition with an alkene occurs stereospecifically, such that the geometry of the alkene is maintained in the cyclobutanone product. The regioselectivity is governed by the polarization of the alkene, with the more electron-rich end of the alkene forming a bond to the electron-deficient central carbon atom of the ketene. Thus, the product from cycloaddition of dimethylketene with the enol ether Z-171 is the cyclobutanone m-172, whereas with -171, the isomer trans-lll is formed (3.116). ... 

Photochemical Cycloadditions. Isobutene has been widely used in intermolecular [2 + 2] photocycloaddition reactions with enones. The weakly polarized isobutene is often used to study the regioselectivity of the photocycloaddition. Cyclohexenones (eq 9), cyclopentenones (eq 10), and functionalized enones (eq 11 ) undergo cycloaddition with isobutene. Patemo-Biichi... 

Photochemical [2 + 2] cycloaddition is a powerful way to produce cyclobutanes, which, in turn, are reactive synthesis intermediates. N-Methylpyrrole adds aldehydes via [2 -I- 2] photocycloaddition to give transient oxetanes with high regioselectivity Ring-opening produces 3-(oi-hydroxyalkyl)pyrroles which are oxidized easily to 3-arylpyrroles, such as 3-BUTYROYL-l-METHYL-PYRROLE. With a special apparatus, ethylene is conveniently added to 3-methyl-... 

The regioselectivity observed in these reactions can be correlated with the resonance structure shown in Fig. 2. The reaction with electron-rich or electron-poor alkynes leads to intermediates which are the expected on the basis of polarity matching. In Fig. 2 is represented the reaction with an ynone leading to a metalacycle intermediate (formal [4C+2S] cycloadduct) which produces the final products after a reductive elimination and subsequent isomerisation. Also, these reactions can proceed under photochemical conditions. Thus, Campos, Rodriguez et al. reported the cycloaddition reactions of iminocarbene complexes and alkynes [57,58], alkenes [57] and heteroatom-containing double bonds to give 2Ff-pyrrole, 1-pyrroline and triazoline derivatives, respectively [59]. 

Theoretically, the regioselectivity observed in photochemical [2 + 2] cycloaddition of 56 with 1,1-dimethoxyethene is in good agreement with experimental results and has been explained on the basis of pertubational molecular orbital theory." Hartke and co-workers" described an interesting contrast in the reactivity of tropolones in an intramolecular Diels-Alder reaction (Scheme 6.18). Thus, alkylation of 64a and 64b with 65 gave 66a and 66b, respectively, that were subjected to cyclization in refluxing toluene. Whereas 66a decomposed under the reaction conditions, 66b afforded 67b in high yield. 

The cycloaddition of an enone with electron-rich alkenes also proceeds with remarkable regioselectivity. The rationalization is that in the excited state, polarization of the enone double bond is opposite in direction as compared with the ground state [190], In other words, photochemical excitation induces contrapolarization. With this consideration the head-to-head dimerization generally observed is reasonable as it involves one molecule each in the ground and excited states. 

Unlike thermal [2 + 2] cycloadditions which normally do not proceed readily unless certain structural features are present (see Section 1.3.1.1.), metal-catalyzed [2 + 2] cycloadditions should be allowed according to orbital symmetry conservation rules. There is now evidence that most metal-catalyzed [2 + 2] cycloadditions proceed stepwise via metallacycloalkanes as intermediates and both their formation and transformation are believed to occur by concerted processes. In many instances such reactions occur with high regioselectivity. Another mode for [2 + 2] cyclodimerization and cycloadditions involves radical cation intermediates (hole-catalyzed) obtained from oxidation of alkcnes by strong electron acceptors such as triarylammini-um radical cation salts.1 These reactions are similar to photochemical electron transfer (PET) initiated [2 + 2] cyclodimerization and cycloadditions in which an electron acceptor is used in the irradiation process.2 Because of the reversibility of these processes there is very little stereoselectivity observed in the cyclobutanes formed. 

Cydohexenones.2 This enone undergoes photochemical [2 + 2]cycloaddition to alkenes. The products, obtained in high yield, can be converted into cydohexenones in two steps. An example is formulated in equation (1). The regioselectivity of the cycloaddition depends on both sleric and electronic factors.1... 

FMO calculations using PM3-C1 were used to investigate the regioselectivities obtained by the photochemical reactions between 2-pyridone and pcnta-2,4-dienoate.46 The hard and soft acid-base principle has been successfully used to predict product formation in Patemo-Buchi reactions.47 The 2 + 2-photo-cycloaddition of homobenz-valene with methyl phenylglyoxylate, benzyl, benzophenone, and 1,4-benzoquinone produced the corresponding Patemo-Buchi products.48 The photo-cycloaddition of acrylonitrile to 5-substituted adamantan-2-ones produces anti- and svn-oxetanes in similar ratios irrespective of the nature of the 5-substituent49... 

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