Catalytic (2 + 2)-cycloaddition reactions of silyl enol ethers. A convenient and stereoselective method for cyclobutane ring formation

An efficient catalytic (2 + 2)-cycloaddition reaction leading to the formation of cyclobutane rings has been devised. The process transforms silyl enol ethers and alpha,beta-unsaturated esters into polysubstituted cyclobutanes with a high degree of trans-stereoselectivity. Both the rate and stereoselectivity of the process can be controlled by the choice of the ester group and silyl substituents. The results of stereochemical studies show that the cycloaddition step in this reaction proceeds in a nonstereospecific manner and, thus, by a pathway involving sequential nucleophilic additions via a short-lived zwitterionic intermediate.     

Oxidative cleavage of a cyclobutane pyrimidine dimer by photochemically generated nitrate radicals (no(3)*)

[reaction: see text] Photochemically generated nitrate radicals (NO(3)(*)) cleave the stereoisomeric N,N-dimethyl-substituted uracil cyclobutane dimers 1a-d into the monomeric uracil derivative 2 as the major reaction pathway. A preferred splitting of the syn dimers 1a,b was observed. The reaction is expected to proceed through initial one-electron oxidation with formation of an intermediate cyclobutane radical cation 11. In addition to cycloreversion, competing reaction steps of 11, which lead to the observed byproducts, are suggested.     

FORMATION OF CYCLOBUTANE THYMINE DIMERS PHOTOSENSITIZED BY PYRIDOPSORALENS: A TRIPLET-TRIPLET ENERGY TRANSFER MECHANISM

The 365 nm irradiation of thymine thin films in the presence of pyridopsoralens is shown to induce the formation of cyclobutane thymine dimers, in contrast to other compounds such as 8- and 5-methoxypsoralen. In order to elucidate the mechanism of such a photosensitized reaction, we have determined the energy of the lowest triplet state (T1) of these compounds, using phosphorescence spectroscopy and CNDO/S quantum chemistry calculations. The T1 energy values were found to be significantly higher for pyridopsoralens--up to 0.3 eV--than for 8- and 5-methoxypsoralen (approximately 2.8 eV), which are not able to photoinduce cyclobutane thymine dimers. The determination of the relative efficiency of cyclobutane thymine dimer formation was performed using chromatographic analysis. A good correlation was found between the energy of the T1 state of the psoralen derivatives and the related cyclobutane thymine dimer formation. Moreover, the photosensitized cyclobutane thymine dimer formation appeared to be temperature-dependent. Our results are consistent with a mechanism involving a triplet energy transfer from the pyridopsoralen to thymine.     

Unusual reaction of allylic systems: homo- and cross-cyclizations leading to four-carbon rings

The reaction of stabilized allylic-type carbocations with electron rich olefins was investigated. In most cases a facile cyclobutane ring formation was observed by [2+2] cycloaddition reaction promoted by Brønsted or Lewis acids. Some attempts were made to investigate the mechanistic pathway. After de-racemization the chiral cyclobutane containing diols were obtained as a potential chiral platform for new ligands.     

Photochemistry of nitroso derivatives in solution—XXX: Temperature effects on radical additions to terpenes and reactions of 2-ammonium nitrosoalkanes

Temperature effects on aminium radical initiated photoaddition to three monoterpenes were investigated. Photoaddition of N-nitrosopiperidine to camphene and pinenes gave the α-piperidinium tertiary-nitrosoalkanes as the primary adducts derived from 1,2-addition; the additions to pinenes required a low temperature (?40°) to suppress the cyclobutane ring opening pathway of the C-radical intermediate. Since the functional groups of these α-piperidinium nitrosoalkanes could assume cis-coplanar configuration, they underwent a facile cleavage reaction to give the corresponding oximes and immonium salts. As the photolysis temperature was raised, in the addition to pinenes, the cyclobutane ring opening pathway progressively dominated the reaction giving increasing amounts of 8-nitroso-p-menthene derivatives which underwent solvolysis and elimination reactions. A mechanistic interpretation in favor of the homolytic ring opening process from the C-radical intermediate is presented. The results established a diagnostic rule for stepwise addition to olefins. An efficient preparation of tricyclene from a commercial camphene sample was appended.     

Oxidative rearrangement of spiro cyclobutane cyclic aminals: efficient construction of bicyclic amidines

A new rearrangement reaction of spirocyclic cyclobutane N-halo aminals is described. This process, promoted by treatment of the aminals with N-halosuccinimides (NXS, X = Br or Cl), efficiently produces bicyclic amidines by a pathway involving initial N-halogenation of one of the aminal nitrogens followed by cyclobutane ring expansion through 1,2-C-to-N migration with simultaneous N-X bond cleavage.     

Electron-transfer-induced intermolecular [2+2] cycloaddition reactions based on the aromatic "redox tag" strategy

Novel electron-transfer-induced intermolecular [2+2] cycloaddition reactions between an aliphatic cyclic enol ether and several unactivated olefins have been demonstrated on the basis of the aromatic "redox tag" strategy. The aromatic "redox tag" was oxidized during the formation of the cyclobutane ring, affording the relatively long-lived aromatic radical cation, which was then reduced to complete the overall reaction that constructed the corresponding [2+2] cycloadducts. The aromatic "redox tag" was also found to facilitate electron-transfer-induced cycloreversion reactions of cyclobutane rings.     

Triplet-Induced Lesion Formation at CpT and TpC Sites in DNA

UV irradiation induces DNA lesions particularly at dipyrimidine sites. Using time-resolved UV pump (250 nm) and mid-IR probe spectroscopy the triplet pathway of cyclobutane pyrimidine dimer (CPD) formation within TpC and CpT sequences was studied. The triplet state is initially localized at the thymine base but decays with 30 ns under formation of a biradical state extending over both bases of the dipyrimidine. Subsequently this state either decays back to the electronic ground state on the 100 ns time scale or forms a cyclobutane pyrimidine dimer lesion (CPD). Stationary IR spectroscopy and triplet sensitization via 2′-methoxyacetophenone (2-M) in the UVA range shows that the lesions are formed with an efficiency of approximately 1.5 %. Deamination converts the cytosine moiety of the CPD lesions on the time scale of 10 hours into uracil which gives CPD(UpT) and CPD(TpU) lesions in which the coding potential of the initial cytosine base is vanished.     

Stereospecific solid-state [2+2] autophotocycloaddition of a styryl dye containing a 18-crown-6 fragment

A procedure was developed for the synthesis of a 18-crown-6-containing styryl dye of the pyridine series. Phototransformation products of the dye that formed upon irradiation with visible light in solution, films, and crystals were studied by ¹H and ¹³C NMR spectroscopy and spectrophotometry. Irradiation of solutions of this dye in acetonitrile leads only to reversible E-Z photoisomerization of the C=C bond. Irradiation of a film of the dye induces stereospecific [2+2] photocycloaddition to form exclusively the rctt isomer of tetrasubstituted cyclobutane. The latter was found to undergo base-catalyzed isomerization giving rise to the rcct isomer. X-ray diffraction study showed that photocycloaddition occurs in single crystals without their destruction. The structures of the E isomer of the dye and the resulting rctt isomer of the cyclobutane derivative were established. The characteristic features of the molecular packing of the dye favorable for topochemical photocycloaddition in the crystal and the structural changes that accompany the cyclobutane formation are discussed. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1896–1908, August, 2005.     

Photochemical studies on a phenolic phenylcoumarone lignin model molecule in relation to the photodegradation of lignocellulosic materials. Part 2. Photophysical and photochemical studies

The structure of the photoproducts obtained by irradiation of a phenylcoumarone molecule PCO, model of the photodegradation of lignin, being established, the mechanism of their formation was approached by fluorescence and flash photolysis techniques, low temperature absorption spectroscopy in rigid matrix, and continuous irradiation in solution and in the solid state. Some evidence was given for the formation of a phenoxy radical leading either by oxidoreductive processes to the formation of a catechol IR3, or by coupling with the starting phenol to the generation of a cyclobutane radical dimer, prone to be transformed into stilbene phenoxy radical by retro “2π+2π” reaction. It was proposed that the oxidation of the latter could give the very coloured quinone methide IR1 or the α-carbonylstilbenol IR2. The singlet manifold appears to be the main pathway of the production of IR1, IR2 and IR3 which are formed in the presence of ground state oxygen.     

Efficient visible light photocatalysis of [2+2] enone cycloadditions

We report that Ru(bipy)3Cl2 can serve as a visible light photocatalyst for [2+2] enone cycloadditions. A variety of aryl enones participate readily in the reaction, and the diastereoselectivity in the formation of the cyclobutane products is excellent. We propose a mechanism in which a photogenerated Ru(bipy)3+ complex promotes one-electron reduction of the enone substrate, which undergoes subsequent radical anion cycloaddition. The efficiency of this process is extremely high, which allows rapid, high-yielding [2+2] cyclizations to be conducted using incident sunlight as the only source of irradiation.     

REPAIR OF CYCLOBUTANE DIMERS AND (6–4) PHOTOPRODUCTS IN ICR 2A FROG CELLS

Abstract— The removal of cyclobutane dimers and Pyr(6–4)Pyo photoproducts from the DNA of UV-irradiated ICR 2A frog cells was determined by radioimmunoassay. In the absence of photoreactivat-ing light, 15% of the cyclobutane dimers and 60% of the (6–4) photoproducts were removed 24 h post-irradiation with 10 J m⁻², Exposure to 30 kJ m⁻² photoreactivating light resulted in removal of 80% of the cyclobutane dimers and an enhanced rate of repair of (6–4) photoproducts, resulting in a loss of 50% of these lesions in 3 h. The preferential removal of (6–4) photoproducts by excision repair resembles previously published data for mammalian cells.     

Synthesis of Highly Substituted Cyclobutane Fused‐Ring Systems from N‐Vinyl β‐Lactams through a One‐Pot Domino Process

In this contribution, aminocyclobutanes, as well as eight‐membered enamide rings, have been made from N‐vinyl β‐lactams. The eight‐membered products have been formed by a [3,3]‐sigmatropic rearrangement, whereas the aminocyclobutanes have been derived from a domino [3,3]‐rearrangement/6π‐electrocyclisation process. The aminocyclobutanes have been obtained in a highly diastereoselective fashion. The cyclobutane ring system tolerates fusion even if adjacent quaternary centres are present. Systems containing up to four fused rings are readily accessible. The reaction profile has been investigated by using Gaussian 03. This study suggests that two reaction pathways for aminocyclobutane formation are possible. In one pathway the [3,3]‐sigmatropic rearrangement is the rate‐limiting step and in the second pathway the electrocyclisation is rate limiting. Taken together, these reactions should facilitate the construction of fused heterocycles.     

Visible-Light-Mediated Heterocycle Functionalization via Geometrically Interrupted [2+2] Cycloaddition

The [2+2] photocycloaddition is the most valuable and intensively investigated photochemical process. Here we demonstrate that irradiation of N-acryloyl heterocycles with blue LED light (440 nm) in the presence of an Ir^III complex leads to efficient and high yielding fused γ-lactam formation across a range of substituted heterocycles. Quantum calculations show that the reaction proceeds via cyclization in the triplet excited state to yield a 1,4-diradical; intersystem crossing leads preferentially to the closed shell singlet zwitterion. This is geometrically restricted from undergoing recombination to yield a cyclobutane by the planarity of the amide substituent. A prototropic shift leads to the observed bicyclic products in what can be viewed as an interrupted [2+2] cycloaddition.     

Electrocatalytic formal [2+2] cycloaddition reactions between anodically activated enyloxy benzene and alkenes

Electrocatalytic formal [2+2] cycloadditions between anodically activated enyloxy benzene and alkenes have been accomplished in a lithium perchlorate/nitromethane electrolyte solution. The enyloxy benzene moiety of these electrolytic substrates played an important role in the formation of a radical cation that could accept nucleophilic alkenes, followed by intramolecular electron transfer between the cyclobutane and phenyl ether moieties of the intermediates.     

Time-resolved study of thymine dimer formation

The formation of thymine dimers in the single-stranded oligonucleotide, (dT)20, is studied at room temperature by laser flash photolysis using 266 nm excitation. It is shown that the (6-4) adduct is formed within 4 ms via a reactive intermediate. The formation of cyclobutane dimers is faster than 200 ns. The overall quantum yield for the (6-4) formation is (3.7 +/- 0.3) x 10-3, and that of the cyclobutane dimers is (2.8 +/- 0.2) x 10-2. No triplet absorption is detected, showing that either the intersystem crossing yield decreases by 1 order of magnitude upon oligomerization (<1.4 x 10-3) or the triplet state reacts with unit efficiency in less than 200 ns to yield cyclobutane dimers.     

Transient states in [2 + 2] photodimerization of cinnamic acid: correlation of solid-state NMR and X-ray analysis

13C-CPMAS and other solid-state NMR methods have been applied to monitor the solid-state reactions of trans-cinnamic acid derivatives, which are the pioneer and model compounds in the field of topochemistry previously studied by X-ray diffraction, AFM, and vibrational spectroscopy. Single-crystal X-ray analyses of photoirradiated alpha-trans-cinnamic acid where the monomers are arranged in a head-to-tail manner have revealed the formation of a centrosymmetric alpha-truxillic acid photodimer. For a centrosymmetric dimer, however, two cyclobutane carbon signals and one carbonyl carbon signal were expected apart from other aromatic carbon signals. Instead, four cyclobutane and two carbonyl carbon signals were observed suggesting the formation of a non-centrosymmetric photodimer. Removing hydrogen bonds from the system by esterfication of alpha-truxillic acid yield a centrosymmetric photodimer. Careful analysis of the obtained products via solid-state NMR clearly showed that the observed peak splittings in the 13C-CPMAS spectra did not originate from packing effects but rather result from asymmetric hydrogen bonds distorting the local symmetry. Further evidence of this rather dynamic hydrogen-bonding stems from high-temperature X-ray data revealing that only the joint approach of both X-ray analysis and solid-state NMR at similar temperatures allows for the successful characterization of dynamic processes occurring in topochemical reactions, thus, providing detailed insight into the reaction mechanism of organic solid-state transformations.     

A simple approach to carbocyclic thromboxane A2 from a cyclubutane

A short route from the cyclobutane derivative (1) to the key intermediate (4) allows easy access to the carbocyclic thromboxane A₂ analogue (5).     

Cascade dimerization of 2-styryl-1,1-cyclopropanedicarboxylate upon treatment with gallium trichloride

2-Styrylcyclopropane-1,1-dicarboxylate treated with anhydrous gallium trichloride undergoes dimerization with the cyclopropane ring opening and the styryl substituent double bond involvement, leading to the formation of polysubstituted cyclic and bicyclic structures with the predominance of the former or the latter depending on the reaction conditions. Most compounds are formed with very high diastereoselectivity. Thirteen major and minor dimeric structures were isolated and reliably characterized, two of which were found to additionally include a chlorine atom. A rare for the reactions of donor-acceptor cyclopropanes example of the formation of a product with the fused cyclobutane ring was effected at–80 °C. Plausible mechanisms of observed processes were discussed.     

Role of anions in the synthesis of cyclobutane derivatives via [2 + 2] cycloaddition reaction in the solid state and their isomerization in solution

trans-3-(4'-Pyridyl)acrylic acid (4-PA) is inert to photodimerization reaction both in solution and solid state. It is made photoreactive by forming salts with various acids. The anions of these salts play a key role in directing the packing of 4-PAH(+) in the solid state. The anions CF(3)CO(2)(-), Cl(-), ClO(4)(-), and BF(4)(-) direct the parallel alignments of 4-PAH(+) in head-to-tail (HT) fashion and lead to the formation of HT-photodimer. On the other hand, bivalent anion SO(4)(2-) directs parallel alignment of 4-PAH(+) in head-to-head (HH) fashion and lead to the formation of HH-photodimer. The details of the anion-controlled stereoselective syntheses of these two cyclobutane derivatives are presented. Interestingly, both cyclobutane compounds undergo isomerization from rctt-form to rctc-form in solution catalyzed by acid.