Oxetane intermediate

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...

Kinetic data on the influence of the reaction temperature on the enantioselectivity using chiral bases and prochiral alkenes revealed a nonlinearity of the modified Eyring plot [16]. The observed change in the linearity and the existence of an inversion point indicated that two different transition states are involved, inconsistent with a concerted [3+2] mechanism. Sharpless therefore renewed the postulate of a reversibly formed oxetane intermediate followed by irreversible rearrangement to the product. 

It can be concluded that the [3+2] pathway seems to be the only feasible reaction pathway for the dihydroxylation by permanganate. The study on the free activation energies for the oxidation of a. P unsaturated carboxylic acids by permanganate shows that the [3+2] mechanism is in better agreement with experimental data than the [2+2] pathway. Experimentally determined kinetic isotope effects for cinnamic acid are in good agreement with calculated isotope effects for the [3+2] pathway, therefore it can be concluded that a pathway via an oxetane intermediate is not feasible. 

Most of the work reported with these complexes has been concerned with kinetic measurements and suggestions of possible mechanisms. The [Ru(HjO)(EDTA)] / aq. HjOj/ascorbate/dioxane system was used for the oxidation of cyclohexanol to cw-l,3-cyclohexanediol and regarded as a model for peroxidase systems kinetic data and rate laws were derived [773], Kinetic data were recorded for the following systems [Ru(Hj0)(EDTA)]702/aq. ascorbate/dioxane/30°C (an analogue of the Udenfriend system cyclohexanol oxidation) [731] [Ru(H20)(EDTA)]70j/water (alkanes and epoxidation of cyclic alkenes - [Ru (0)(EDTA)] may be involved) [774] [Ru(HjO)(EDTA)]702/water-dioxane (epoxidation of styrenes - a metallo-oxetane intermediate was postulated) [775] [Ru(HjO)(EDTA)]7aq. H O /dioxane (ascorbic acid to dehydroascorbic acid and of cyclohexanol to cyclohexanone)... 

The formation of 3-pyrrolylcarbinols (280) from the photochemically induced reaction of pyrrole, or its 1-alkyl derivatives, with aliphatic aldehydes and ketones is thought to proceed via an oxetane intermediate (279) (79JOC2949). In contrast, the analogous reaction of 1 -phenylpyrrole with benzophenone leads to the formation of the diphenyl(2-pyrrolyl)car-binol, whilst the oxetane (281) has been isolated from the photoaddition of 1-benzoylpyrrole and benzophenone (76JHC1037, B-77MI30500). 2-Benzoyl-1-methylpyrrole undergoes a normal Paterno-Buchi photocyclization with 2,3-dimethylbut-2-ene, via the n -> v triplet... 

CPCM) solvation, to study the mechanisms and stereochemistries of this important synthetic reaction. Interestingly, from these calculations, it was concluded that secondary enamine-mediated aldols have high activation energies if there is no proton source, and oxetane intermediates such as 1 can be formed (Equation 1) <2001JA11273>. 

The influence of substituents on the energetics of the uncatalyzed Mukaiyama aldol reaction was studied using ab initio molecular orbital calculations at the G3(MP2) level <2005JOC124>. For the reaction between formaldehyde and trihydrosilyl enol ether, a concerted pathway via a six-membered transition state was favored over a stepwise pathway and an oxetane intermediate. 

Therefore, from epoxide 83 (Scheme 5.38), a 1,2-phenyl shift in intermediate MM would provide oxonium derivative NN, which would furnish, after rearrangement of the oxetane intermediate OO, the desired ketone 84. It is interesting to note that on the same substrates cationic gold derivatives (activated with silver salts) did not lead to the same final compounds, showing the unique reactivity of silver salts. 

The synthesis of the oxetane intermediate (40) en route to the alkaloid gelsemine has been achieved in a straightforward way from a diol precursor <02JACS9812> <02TL545>. 

Other methods for preparing perfluoroalkyl- and perfluoroalkoxy oxetanes intermediates and derivatives of the current invention are described (3,4). 

The oxetane intermediate was isolated independently by two groups. Foote and coworkers identified it with certainly and even determined its molecular weight, by... 

It was noted above that the photolysis of indole and aldehydes in the solid state leads to diindolymethanes by a mechanism postulated to involve an oxetane intermediate (Scheme 14). The reaction also proceeds when aromatic aldehydes and indole or 2-methylindole are irradiated with UV light in acetonitrile solution (Scheme 28) [61]. Under these circumstances, it has been proposed that light-induced electron transfer from the indole to the aldehyde yields a ketyl radical anion and the indole radical cation. Proton transfers, coupling, and elimination of water can then yield an electrophilic alkylidene indolenine 65 which can react with indole thermally to give the observed product. 

Interestingly, an epoxide also forms as a primary reaction product along with the product of its hydrolysis, ethylene glycol, in C(sp )-0 reductive elimination from (dpms)Pt (C2H40H)(OH)2 complex 21 in aqueous solutions (Fig. 13) [34]. No Pt oxetane intermediates could be detected in this system. Even if the oxetane 20 did form, the expected low reactivity of this compound would preclude the epoxide elimination at relatively low temperatures. It was assumed that a three-center C-O elimination mechanism is not involved in this transformation. 

Catalysis by (6—4) photolyase must accomplish two chemical tasks cleavage of the C6—C4 sig a bond, and transfer of the OH (or —NH2) group from the C5 of the 5 base to the G4 of the 3 base. Because formation of the (6—4) photoproduct is presumed to proceed through a four-mem-bered oxetane or azetidine intermediate, it has been proposed that (6—4) photolyase first converts the open form of the (6—4) photoproduct to the four-membered ring by a thermal reaction, and then the four-mem-bered ring is cleaved by retro [2+2] reaction photochemically (Kim et al, 1994 Zhao et aL, 1997). A site-directed mutagenesis study has identified two histidine residues in the active site that may participate in conversion of the (6-4) photoproduct to the oxetane intermediate by general acid-base catalysis (Hitomi et al, 2001). A current model for catalysis by (6-4) photolyase is as follows (Fig. 8) The enzyme binds DNA and flips out the... 

Fig. 8. Reaction mechanism of (6-4) photolyase. The enzyme binds to DNA containing a (6-4) photoproduct and flips out the dinucleotide adduct into the active site cavity, where the open form of the photoproduct is converted to the oxetane intermediate by a light-independent general acid-base mechanism. Catalysis is initiated by light MTHF absorbs a photon and transfers energy to FADH , which then transfers an electron to the oxetane intermediate bond rearrangement in the oxetane radical regenerates two canonical pyrimidines, and back-electron transfer restores the flavin radical to catalytically competent FADH form. The repaired dipyrimidine flips back into the DNA duplex, and the enzyme is dissociated from the substrate.

Clearly, all indications are that (6—4) photolyase binds DNA and repairs its substrate by a mechanism quite similar to that of classical photolyase. However, there appears to be a fundamental difference in the photochemical reaction catalyzed by the two enzymes. The quantum yield of repair by excited singlet-state flavin by classical photolyase is near unity, whereas the quantum yield of repair by excited flavin in (6-4) photolyase is 0.05-0.10. Whether this low quantum yield of repair by (6—4) photolyase is a result of the low efficiency of formation of the oxetane intermediate thermally, low efficiency of electron transfer from the flavin to the photoproduct, or low efficiency splitting of the oxetane anion coupled with high rate of back electron transfer is not known at present. Furthermore, it was found that (6-4) photolyase can photorepair the Dewar valence isomer of the (6-4) photoproduct (Taylor, 1994) that cannot form an oxetane intermediate, casting some doubt about the basic premise of the retro [2+2] reaction. However, the Dewar isomer is repaired with 300-400 lower quantum yield than the (6-4) photoproduct, and it has been proposed (Zhao et ai, 1997) that the Dewar isomer may be repaired by the enzyme through a two-photon reaction in which the first photon converts the Dewar isomer to the Kekule form and a second electron transfer reaction initiated by the second photon promotes the retro [2+2] reaction. 

One of the most prevalent examples of reaction involving DNA excited states is pyrimidine-pyrimidine dimer formation. Thymine and cytosine are the two pyrimidine bases present in DNA, and pyrimidine-pyrimidine dimers can form between any combination of these two bases. The most common of these is the thymine-thymine (TT) dimer [4-7]. Two types of TT dimers are known (shown in Fig. 13.1). The first, and sole focus of this chapter due to its prevalence, is called cyclobutane pyrimidine dimer (CPD) and is formed by the [2-1-2] addition of the C5-C6 double bonds. The second is called the 6 photoadduct and is formed by the addition of the C5-C6 double bond on one thymine to the C4-04 double bond on the other. This leads to an oxetane intermediate that subsequently rearranges to form the 6-4 product. Both of these photoproducts are thought to form starting with initial excitation to a state. There is some debate in the literature... 

The typical example of 1,2-addition reaction with singlet oxygen is the photosensitized oxidation of isoeugenol (Eskin, 1979). On sensitized photo-irradiation in sodium a solution of hydroxide, the isoeugenol molecule is attacked by singlet oxygen to form a di-oxetane intermediate 28, which is then converted to a vanillin (Scheme 26). Methylene blue is the most effective sensitizer in terms of vanillin yield. 

Funher details have appeared on the synthesis and reactivity of I(TPP)RuPh2], which decomposes thermally to I(TPP)RuPh] and oxidizes to ( (TPP)RuPh)20i-O)]. A ruthena-oxetane intermediate has been proposed to account frn- the kinetics of C-H bond activation by Ru(VI) dioxo porphyrin complexes. 1 2... 

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