Epoxides cationic intermediates

While generation of a Mn(V)oxo salen intermediate 8 as the active chiral oxidant is widely accepted, how the subsequent C-C bond forming events occur is the subject of some debate. The observation of frans-epoxide products from cw-olefins, as well as the observation that conjugated olefins work best support a stepwise intermediate in which a conjugated radical or cation intermediate is generated. The radical intermediate 9 is most favored based on better Hammett correlations obtained with o vs. o . " In addition, it was recently demonstrated that ring opening of vinyl cyclopropane substrates produced products that can only be derived from radical intermediates and not cationic intermediates. ... 

Scheme 10.5 Tentative mechanism for cytochrome P450-cata-lyzed epoxidation of a double bond. The reactive iron-oxo species VII (see Scheme 10.4) reacts with the olefin to give a charge transfer (CT) complex. This complex then resolves into the epoxide either through a radical or through a cationic intermediate.

DNA binds and reacts with carcinogenic and similar compounds which alkylate it through cationic intermediates, in some cases extraordinarily fast 1371 and can in the process catalyse the hydrolysis of some substrates, like the bay-region diol epoxides derived from benzpyrene.1381 In the context of enzyme mimics these reactions are primarily of curiosity value DNA lacks the conformational flexibility and the chemical functionality to offer the prospect of efficient catalysis for ordinary reactions. 

Although (salen)manganese(III) complexes are widely studied, those with other metals are largely unexplored. The stereochemistry of Cr-salen-catalysed epoxidation of dimethylchromenes and styrenes was found to be highly solvent-dependent, with polar solvents giving the opposite sense of induction to non-polar.17 This may be explained by competitive collapse of diastereomeric metalloxetanes either directly to epoxide or via a cationic intermediate. 

One example of neighboring-group participation without the formation of cationic intermediates is the aminolysis of 2-bromoethanols (last example, Scheme4.49). In this instance epoxide formation and opening must be faster or as fast as direct bimolecular substitution of bromide by the amine otherwise no rearranged product would be observed. 

The process research team also observed that other ambrisentan analogs could be prepared as single enantiomers starting from methyl ester (S)-44 (made from acid salt 50) by treatment with acid and the required alcohol in toluene. Azeotropic removal of methanol drove the reaction to completion, to give products 55 via epoxide 53 or cationic intermediate 54, without racemization.35... 

If a suitable (1,3-di-f-butyl) allene is epoxidized with m-CPBA the unstable allene oxide can actually be isolated. On heating, this epoxide gives a stable fra s-di-f-butylcycl6propanone. It is very difficult to see how this reaction could happen except via the oxyallyl cation intermediate. 

Simple amines in the presence of Oxone oxidize alkenes to oxiranes. For example, Oxone, pyridine, and a 2-pyrrolidine derivative in a medium of aqueous acetonitrile selectively converts the triene in Equation (72) to a single epoxide. This process also proceeds using noncyclic alkenes. The mechanism is believed to proceed via a single-electron transfer (SET) process involving radical cation intermediates <2000JA8317>. 

SnCU is also effective in the opening of cyclopropane rings to produce cationic intermediates useful in cyclization reactions. For example, the cyclization of aryl cyclopropyl ketones to form aryl tetralones, precursors of lignan lactones and aryl naphthalene lignans, is mediated by SnCU (Eq. 60) [93]. The reaction is successful in nitromethane, but not in benzene or dichloromethane. Analogous cyclizations with epoxides result in very low yields (2-5 %). 

Medium and large rings can be made via cationic intermediates which are usually generated by treatment of suitable precursors with acid. Reactions of this class are perchloric acid catalyzed rearrangements of bicyclo[n.l.0]alkan-2-ols (n > 5), solvolysis of the corresponding esters, boron trifluoride-diethyl ether complex catalyzed cleavage of epoxides, and tri-fluoroacetic acid catalyzed reactions of 7-(methylsulfanyl)bicyclo[n.l.0]alkanes. 

A radical-cation Cope rearrangement of 2,5-diphenylhexa-l,5-dienes under electron ionization conditions (by mass spectrometry at 70 eV) has been described to occur in the gas phase. The reaction directionality differs from that in a thermal transformation. The rearrangement of hexamethyl-Dewai-benzene 410 into hexamethylbenzene (equation 156) as well as the closure of the bridged hexahydrodiene 411 into the so-called birdcage hydrocarbon 412 proceed during hemin-catalyzed epoxidation via a radical cation intermediate (equation 157)224. These processes are Cope-like rearrangement because two double bonds are separated by one CHt group in 410 and by three -hybridized C-atoms in 411. 

There is also debate about the nature of the intermediates involved in the second step in the catalytic cycle illustrated in Fig. 19.1, that is, the transfer of oxygen to the alkene to form the epoxide. No intermediates have been detected experimentally, but five different possibilities have been proposed in the literature for the alkene complexed to the oxidized porphyrin [11,25-29]. The five proposed intermediates are radical, cation, concerted, metallaoxetane, and pi-radical-cation species. The literature is rather complicated due to the lack of direct experimental observation, and it is not clear that conclusions from, say, iron and chromium porphyrins also apply to manganese porphyrins [28]. Arasasingham et al. claim unequivocal evidence for a radical intermediate being involved in the oxidation of alkenes by manganese porphyrins [28]. They also discuss a charge-transfer complex that is similar to the concerted intermediate. Recently, density functional theory (DFT) and quantum mechanics/molecular mechanics (QM/MM) calculations were applied to styrene epoxidation by Mn-porphyrins ... 

A group of fungicides that inhibit squalene epoxidation has been developed primarily for use against pathogenic fungi in medicine. Epoxidation of squalene is catalyzed by squalene epoxidase (a flavoprotein) that starts the complicated cyclization of squalene. The squalene-2,3-epoxide formed by this enzyme is further metabolized to a protosterol cation intermediate, which is transformed to either cycloartenol in plants (cycloartenol synthase) or lanosterol (lanosterol synthase). Cycloartenol is the precursor to plant sterols, whereas lanosterol is the precursor of cholesterol and the other sterols in animals, and to ergosterol in plants. 

P-450 has been shown to catalyze epoxidation with retention of the olefin configuration (114). Ortiz de Montellano and co-woiicers have shown that heme N-alkylation accompanies epoxidation when terminal olefins are oxidized by P-450 (775). Further, the oxidation of 1,1,2-trichloroethylene is known to give trichloroacetaldehyde along with epoxide (776, 777). A mechanism that explains simultaneous epoxidation, heme alkylation, and halogen migration is depicted in Scheme XVI (777). In this process, initial electron transfer affords a transient rr-radical cation that can collapse with C-0 bond formation to give either radical or cation intermediates. 

The polarity of the pocket and hydrogenbonding machinery were found to increase the dominance of the LS reactivity in arene hydroxylation and the HS reactivity in sulfoxidation. Similarly, these factors will have a strong impact on the appearance of cationic intermediates during hydroxylation and epoxidation. More intriguing is the result that these properties of the protein pocket have a major impact on the regioselectivity of C-H hydroxylation versus C=C epoxidation as well as on the stereospecificity of both processes. Time will show whether these are generalities or isolated findings. 

If the epoxide moiety is attached to a tertiary carbon, cationic rearrangements can lead to significant amounts of rearranged product. The cationic intermediate generated from the epoxide and MgX2 does not... 

Some of the cyclic species you have seen so far (aziridinium ions, epoxides) are intermediates the intermediate cyclic cation here is probably only a transition state. 

Compounds such as (69) (from gum mastic, Pistacia len-tiscus, Anacardiaceae) and (70) (Fig. 23.24) may be regarded as products of trapping of a cationic intermediate of the cyclization of squalene 2,3-epoxide (2) to tetracyclic and pentacyclic triterpenes (Harrison, 1988). 

A one-step Lewis acid-catalysed intermolecular 4- -3-cycloaddition of aromatic a,)3-unsaturated aldehyde and ketones (105) with epoxides (106) formed seven-membered oxacycles (107) under mild conditions (Scheme 34).The effect of oxygen-, sulfur-, and halogen-substituents on the reactivity of nitrogen-stabilized oxyallyl cations in 4- -3-cycloaddition reactions has been extensively investigated. Aza-oxyallyl cationic intermediates react with cyclopentadiene and furan via an aza-4 -I- 3-cycloaddition reaction to form bicyclic cycloadducts in moderate yields. The intramolecular formal 4- -4-cycloaddition of conjugated enynes with an e-deflcient cyclobutene (108) yielded a strained six-membered cyclic allene (109) that isomerized to a 1,3-cyclohexadiene (110). This intermediate underwent a thermal or acid-promoted six-electron electrocyclic ring opening to yield a 2,4,6-cyclooctatrienone (111) (Scheme 35). ... 

The mechanisms of the epoxidations of olefins have been studied intensively.3 3 -376-378 In general, the reactions of metal-oxo complexes with olefins to form epoxides do not involve intermediates containing metal-carbon bonds. The 0x0 group tends to act as an electrophile and interact with the HOMO of the olefin during the transfer of the 0x0 to the olefin. After this initial interaction, the epoxide may form by a non-radical concerted process or by a stepwise process involving radical or cationic intermediates. ... 

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