Meta Photocycloaddition Research Articles

Arene Activation through Iminium Ions: Product Diversity from Intramolecular Photocycloaddition Reactions

AbstractWhile 2‐alk‐ω‐enyloxy‐sustituted benzaldehydes do not display any photochemical reactivity at the arene core, the respective iminium perchlorates were found to undergo efficient reactions either upon direct irradiation (λ=366 nm) or under sensitizing conditions (λ=420 nm, 2.5 mol% thioxanthen‐9‐one). Three pathways were found: (a) Most commonly, the reaction led to benzoxacyclic products in which the olefin in the tether underwent a formal, yet unprecedented carboformylation (13 examples, 44–99 % yield). The cascade process occurred with high diastereoselectivity and was found to be stereoconvergent. (b) If a substituent resides in the 3‐position of the benzene ring, a meta photocycloaddition was observed which produced tetracyclic skeletons with five stereogenic centers in excellent regio‐ and diastereoselectivity (2 examples, 58–79 % yield). (c) If the tether was internally substituted at the alkene, an arene photocycloaddition was avoided and an azetidine was formed in an aza Paternò–Büchi reaction (2 examples, 95–98 % yield).

Arene Activation through Iminium Ions: Product Diversity from Intramolecular Photocycloaddition Reactions.

While 2-alk-ω-enyloxy-sustituted benzaldehydes do not display any photochemical reactivity at the arene core, the respective iminium perchlorates were found to undergo efficient reactions either upon direct irradiation (λ=366 nm) or under sensitizing conditions (λ=420 nm, 2.5 mol% thioxanthen-9-one). Three pathways were found: (a) Most commonly, the reaction led to benzoxacyclic products in which the olefin in the tether underwent a formal, yet unprecedented carboformylation (13 examples, 44-99 % yield). The cascade process occurred with high diastereoselectivity and was found to be stereoconvergent. (b) If a substituent resides in the 3-position of the benzene ring, a meta photocycloaddition was observed which produced tetracyclic skeletons with five stereogenic centers in excellent regio- and diastereoselectivity (2 examples, 58-79 % yield). (c) If the tether was internally substituted at the alkene, an arene photocycloaddition was avoided and an azetidine was formed in an aza Paternò-Büchi reaction (2 examples, 95-98 % yield).

Photochemical Approaches to the Bilobalide Core

Bilobalide is a tetracyclic sesquiterpene containing three contiguous γ‐lactone rings and an unusual tert‐butyl group, which is found in the leaves of the ginkgo tree (Ginkgo biloba). Three different photochemical approaches towards bilobalide's unique skeleton are presented. A meta photocycloaddition, a [2 + 2] photocycloaddition, and a Paternò–Büchi‐reaction were chosen as the respective key steps.

Investigating the Arenyl-Diene Double [3 + 2] Photocycloaddition Reaction

The double [3 + 2] photocycloaddition reaction involving arenyl-dienes has been used to assemble seven separate [5.5.5.5] fenestrane structures that include ether and aza variants. The primary photolysis step was a meta photocycloaddition reaction, while a secondary photocycloaddition step formed the fenestrane structure. Investigations involving the insertion of an additional methylene group into the basic arenyl-diene skeleton failed to afford the desired [5.5.5.6] fenestrane structure. The presence of an oxime moiety in the aromatic photosubstrate allowed the primary photolysis step to take place; however, an attempted secondary photocycloaddition reaction involving the oxime did not provide the intended polyheterocyclic fenestrane. An alternative strategy to form various "criss-cross" double meta photocycloadducts was investigated and led to the discovery of a Paterno-Büchi cycloaddition reaction between acetone and an angular meta photocycloadduct. Other novel thermally and photochemically mediated skeletal rearrangement reactions were also recorded.

ChemInform Abstract: Stereochemical Control in meta Photocycloaddition of Alkenes to the Benzene Ring: The Anomalous Behaviour of Cyclohexene.

The intermolecular meta photocycloaddition of cycloalkenes to benzenes occurs with marked endo stereoselectivity, although the exo process would be favoured on purely steric grounds. Additions normally occur 2,6 to monoalkylbenzenes, but increasing the size of the alkyl group in the order Me, Pri, But leads to an increasing tendency for 3,5-addition without significant loss of the endo stereoselectivity. These effects are attributed to a weak but orienting interaction between the α-CH in the alkene and the S1 state of the aromatic species: this is termed ‘intermolecular hyperconjugation’. In the bichromophoric system 14b, models show that only an endo orientation is feasible, but that this is subject to steric hindrance resulting from unfavourable orientations of the α-methylene groups in the cyclohexenyl ring: hence the low quantum efficiency of the meta addition process, in contrast with the relatively efficient endo process in the cyclopentene 14a where there is no analogous steric effect. In compounds 15a and 15b, only an exo orientation between the cycloalkene moiety and the aromatic ring is sterically feasible. Accordingly, the meta cycloadditions are stereospecif ically exo, and occur with comparable quantum yields for the cyclohexene and cyclopentene derivatives. The anomalously low reactivity of cyclohexene in meta photocycloaddition to benzene applies only to the normally favoured endo process, and is attributable to sterically unfavoured ‘chair’ conformations of the cycloalkene.

New Molecular Entities via Intermolecular meta Photocycloaddition.

AbstractFor Abstract see ChemInform Abstract in Full Text.

New molecular entities via intermolecularmetaphotocycloaddition

The intermolecular meta photocycloaddition of 1,3-dihydroisobenzofuran and 1,3-dihydroisoindole-2-carboxylic acid methyl ester with cyclopentene and 2,5-dihydrofuran affords two new classes of photoadducts. The photoadducts were identified by the SORT&gen algorithm as New Molecular Entities in two-dimensional scaffold space. The structures of the adducts were established by NMR spectroscopy and the stereo-, regio- and chemoselectivity of the reactions is discussed.

The use of temporary tethers in the meta photocycloaddition reaction

The use of temporary tethers in facilitating meta photocycloaddition reactions between phenol and allyl alcohol derivatives has been investigated. The merits of silicon, carbonate and methylene acetal tethers were assessed, whilst considering strategies for the preparation of the natural products gymnomitrol and gelsemine. The photoadducts were epoxidised, and then subjected to acid catalysed fragmentation with concomitant cleavage of the tether. Depending on whether water or methanol was used during the fragmentation stage of the methylene tethers, the methylene group was either removed altogether or transformed into a MOM group.

Asymmetric induction in intramolecular meta photocycloaddition: cyclodextrin-mediated solid-phase photochemistry of various phenoxyalkenes.

[reaction: see text]. An approach to the asymmetric intramolecular meta photocycloaddition of phenoxyalkenes is described. The beta-cyclodextrin complexes of several phenoxyalkenes have been synthesized and irradiated in the solid phase. The effect of the CD-hosting on the regio- and enantioselectivity is discussed. Values of ee up to 17% were obtained.

Intramolecular ortho and meta photocycloadditions of 4-phenoxybut-1-enes substituted in the arene residue with carbomethoxy, carbomethoxymethyl, and 2-carbomethoxyethyl groups

On irradiation of 4-phenoxybut-1-enes substituted with a carbomethoxy group in the arene, only the ortho compound 1 led to notable ortho photocycloaddition, while the meta regioisomer 2 furnished meta and ortho photocycloadducts albeit in low yield, and the para-substituted compound 3 resulted only in intractable polymers. On irradiation of the carboxymethyl- and 2-carboxyethyl homologues 4– 9, the photoreactivity altered dramatically. The highest yields of meta photocycloadducts were observed on irradiation of the ortho-substituted compounds 4 and 7. Due to steric hindrance, only one of the two possible regioisomers 18 and 19, respectively, was formed. The meta-substituted compounds 5 and 8 gave significant amounts of meta photocycloadducts as mixtures of regioisomers 13+ 16 and 14+ 17, respectively. The intramolecular meta photocycloaddition was directed exclusively to the 2′,6′-positions of the arene and only 1,5-bridged dihydrosemibullvalenes were formed. On irradiation of the ortho- and para-substituted compounds 4 and 7, and 6 and 9, respectively, considerable amounts of reaction products derived from initial ortho photocycloaddition were detected.

A Photochemical Approach to the Gelsemine Skeleton

A silicon-tethered intramolecular meta photocycloaddition reaction was utilized to prepare a photoadduct, which was subsequently fragmented using m-CPBA to give a model for the skeleton of the alkaloid gelsemine.

Use of arene 1,3-substituents to control cyclopropane ring formation during meta photocycloaddition of ethenes to the benzene ring

The 3-trifluoromethyl derivatives of benzyl alcohol, benzyltrimethylsilane and phenoxytrimethylsilane undergo 2,6-photocycloaddition to cyclopentene to give the 1,11-disubstituted-tetracyclo[6.3.0.02,11.03,7]undec-9-enes 7, 10, 11 and 12. This specificity in isomer formation is considered to originate from an intramolecular attractive interaction between the 1,3-substituents on the arenes during the addition of the ethene and this causes an asymmetric distortion of the C6 ring which then controls the cyclopropane ring formation in the adduct. Similar reaction of 3-trifluoromethyl-phenol, -benzyl alcohol and -benzyltrimethylsilane, with vinyl acetate yields the 2-trifluoromethyl-endo-6-acetoxytricyclo[3.3.0.02,8]oct-3-enes 16, 17 and 18 respectively, showing that the directing influence of substituents on the arene dominates any effect of the acetoxy group on the photocycloaddition process. The control by Si· · ·F interaction is not, however, significant during the intramolecular photocycloaddition of the bichromophores 19 and 20 and only the 1,6-bridged dihydrosemibullvalene 24 and products derived from ortho cycloaddition are respectively formed.

Intramolecular meta photocycloaddition of 3-benzyl(dimethylsila)prop-1-enes

The regiochemistry of intramolecular meta photocycloaddition of 3-benzyl(dimethylsila)prop-1-enes is controlled by the silicon in the tether and the presence of an electron donor substituent on the phenyl ring. For 1′,3′-addition, the preferred formation of the angular rather than the linear triquinane isomer is interpreted in terms of an asymmetric orientation of the S 0 ethene and S 1 benzene inducing a non-synchronous addition which then promotes specific 2′,4′-cyclisation to give the cyclopropane ring of the dihydrosemibullvalene skeleton.

Structural assignment of the intramolecular meta photocycloadduct isomers from 4‐phenoxybut‐1‐enes and 3‐benzyloxyprop‐1‐enes by proton NMR spectroscopy

Abstract1H NMR data (400 and 500 MHz) are reported for the intramolecular meta photocycloaddition products from 4‐phenoxybut‐1‐enes and 3‐benzyloxyprop‐1‐enes. The structures of these photoproducts, and in particular the discrimination between the 1,6‐ and 7,8‐bridged isomers, are deduced from COSY 45 and 60 experiments and spin‐decoupling techniques.

Intramolecular meta photocycloaddition of conformationally restrained 5-phenylpent-1-enes. Part II: Steric and electronic effects caused by 4-mono- and 4-disubstitution

The meta photocycloaddition of 4-substituted 5-phenylpent-1-enes, 10–18, has been studied. The monosubstituted derivatives always prefer 2,6 addition, independent of the size of the substituent. For 2,6 addition two basic conformations are possible. Disubstituted compounds yield predominantly 1,3 addition with the sterically more demanding group exo. Except for the methoxymethyl and THF derivative the oxygen is found exo as a result of repulsion, while the monohydroxy derivative gives also endo which might be explained by hydrogen bonding. The products from compound 11 change from mainly endo-OH in cyclohexane to chiefly exo-OH in methanol. Much similarity is found with Diels-Alder cycloaddition.

Intramolecular ortho and meta photocycloadditions of 3-alkyl-4-phenoxybut-1-enes

Upon irradiation of 3-alkyl-4-phenoxybut-1-enes 1a-d at 254 nm in cyclohexane, ortho and meta photocycloadditions occur. The ortho photocycloadducts rearrange readily, while the meta photocycloaddition involves the 2′,6′-positions of the arene as directed by the alkoxy group. In each case only a single meta photocycloadduct with an endo alkyl group is formed resulting in six contiguous stereocentres. A 3-alkyl group does not influence significantly the mode selectivity.

Heteroatom control of isomer formation in the intramolecular meta photocycloaddition of arene - ethene bichromophores

The presence of a dimethylsilylene unit at the 4-position of 5-phenylpent-1-ene bichromophores induces high selectivity into their intramolecular meta photocycloadditions: the regiochemistry of addition is dependent on the substituent at the 2′-position of the benzene ring.

Funnels and barriers in the photocycloaddition of arenes to alkenes and dienes

In the photocycloaddition of benzene to alkenes, products are formed in the ortho and meta addition modes; in the photoaddition of benzene to the terminal atoms of a diene system, products are formed in the meta and para modes. On the basis of orbital symmetry correlations, meta photocycloaddition has been described as an allowed process. The situation regarding the ortho and para modes is less clear. It is shown that orbital symmetry correlations can also be used to predict the occurrence of reactive minima or funnels in the potential energy surface of the first excited state of the reactants. The presence of these funnels can be used to rationalize the abundance of ortho and meta adducts in the photoaddition of arenes to alkenes, and the occurrence of meta and para adducts in the photoaddition of arenes to dienes. The role of charge transfer in the selection of the addition mode and in the regioselectivity in the ortho mode for arenes to alkenes is discussed.

Factors influencing the reaction‐mode selectivity and regiochemistry of intermolecular photocycloaddition reactions of ethenes to polysubstituted benzenes

AbstractThe photoreactions of the methylbenzonitriles; 2,3‐, 2,4‐, 2,6‐, 3,4‐, and 3,5‐ benzonitriles; and 2′‐ and 4′‐ methoxyacetophenones with cyclopentene and ethyl vinyl ether have been investigated. Meta photocycloaddition is the major process for the benzonitriles with cyclopentene, and regiochemical features reflect the influence of polar factors along the reaction pathway. The enol ether yields ortho cycloadducts exclusively from all the benzenoid derivatives. The thermal ring opening of the primary photoadduct and the photolability of the cycloocta‐1,3,5‐triene isomer depend markedly on the position of the substituents.

Stereochemical features of meta photocycloadducts derived from 3‐alkyl‐4‐phenoxybut‐1‐enes

Abstract3‐Alkyl‐4‐phenoxybut‐1‐enes (alkyl: methyl, isopropyl, tert‐butyl) on excitation at 254 nm in cyclohexane give rise to 4‐alkyl‐2‐oxatetracyclo[5.4.0.01,8.05,11]undec‐ 9‐enes via intramolecular meta photocycloaddition. Prevailing stereochemical features are the configuration of the alkyl group at C‐4 and the conformation of the tetrahydropyran ring contained in the tetracyclic system. These are revealed by detailed 1H‐NMR analysis and interpretation of the coupling constants. Whereas the alkyl group at C‐4 invariably occurs in the exo configuration, the conformation of the tetrahydropyran ring depends on the bulkiness of the alkyl substituent. Thus, the C‐4 methyl group occupies an equatorial position in a chair conformation, while a flattened chair conformation accomodates appropriately the C‐4 isopropyl group in the pertaining structure. The required equatorial position of the tert‐butyl group at C‐4, on the other hand, forces the tetrahydropyran ring into a boat conformation, thereby alleviating steric constraints.