Concerted reactions epoxidation

An alternative to fluorohydrin formation is observed with the 6/ -methyl-5a,6a-epoxide (30), which rearranges, possibly in a concerted reaction, to the A-homo-B-norsteroid (31) (cf, chapter 14, Vol. II). 

Schechter 55) proposed that the catalytic effect of hydroxyl groups on the epoxide-amine addition reaction involved a termolecular activated complex formed in the concerted reaction of amine, epoxide and hydroxyl. Smith 57) suggested a modified mechanism in which the same activated complex is formed in a bimolecular reaction between an adduct formed from epoxide (E) and the proton donor (HX), and the amine ... 

The recent developments in homogenous Mn(salen)- and Cr(salen)-mediated asymmetric epoxidation, with a variety of co-oxidants, have been reviewed. The possible mechanistic pathways (including concerted reaction and metallooxetane intermediate formation) and trajectory of alkene approach are discussed on the basis of experimental results and theoretical calculations.18... 

The epoxidation takes place in a one-step, concerted reaction that maintains the stereochemistry of any substituents on the double bond. 

In practice the first two classes merge into a single concept of structural rearrangement concerted with epoxide opening, because no attempt seems to have been made to detect an-chimeric assistance by kinetic studies. The reactions which follow a concerted pathway are recognised when product studies show a stereospecific involvement of bonding electrons trans to the breaking epoxide bond. 

In the ( A") case a concerted reaction occurs resulting in the elimination of HO2 and possible formation of a van der Waals complex. The ( A ) state, on the other hand, yields QOOH, the intermediate required for epoxide formation. 

The pH-independent reaction of diol epoxide 81 is quite different from that of diol epoxide 80, although their chemical structures are similar. Subtle differences in conformation clearly are sufficient to cause different pH-independent mechanisms. Whereas one of the pH-independent reaction pathways of 80 involves a carbocation intermediate, carbocation 83 cannot be detected in the pH-independent reaction of 81.89 The mechanism of the diol-forming reactions in the pH-independent reactions of 81 are not clear, but may involve concerted reactions of 81 with solvent. 

General acid catalysis in the hydrolysis of 81 is quite facile. This reaction, as discussed in Section Benzylic epoxides and arene oxides and shown in Scheme 39, involves proton transfer to the epoxide oxygen concerted with epoxide C-O bond breaking to form a carbocation 83. For primary ammonium ions with pKa < 8, only the acid form of the amine is reactive, and carbocation formation is irreversible,... 

The oxygen atom of the OH group of the peroxyacid accepts a pair of electrons from the TT bond of the alkene, causing the weak O — O bond to break heterolytically. The electrons from the O—O bond are delocalized onto the carbonyl group. The electrons left behind as the O—H bond breaks add to the carbon of the alkene that becomes electron deficient when the rr bond breaks. Notice that epoxidation of an alkene is a concerted reaction All the bond-forming and bond-breaking processes take place in a single step. 

Figure 21.29 shows the conversion of squalene to cholesterol. The details of this conversion are far from simple. Squalene is converted to squalene epoxide in a reaction that requires both NADPH and molecular oxygen (O2). This reaction is catalyzed by squalene monooxygenase. Squalene epoxide then undergoes a complex cyclization reaction to form lanosterol. This remarkable reaction is catalyzed by squalene epoxide cyclase. The mechanism of the reaction is a concerted reaction—that is, one in which each part is essential for any other part to take place. No portion of a concerted reaction can be left out or changed because it all takes place simultaneously rather than in a sequence of steps. The conversion of lanosterol to cholesterol is a complex process. It is known that 20 steps are required to remove three methyl groups and to move a double bond, but we shall not discuss the details of the process. 

Surely the carbocation intermediate is planar and the product would be racemic Answer. This was the purpose of the investigation. One chiral centre is lost in the reaction so only absolute stereochemistry is relevant. One explanation is that the cation is short-hved and that bond rotation is fast in the direction shown (the C02Et group is already down and has to rotate by only 30 to get to the right position for migration). The other is that migration is concerted with epoxide opening. This looks unUkely as the overlap is poor. 

With alkyl-substituted terminal alkenes various degrees of porphyrin N-alkylation accompany epoxidation. The N-alkylation take place exclusively at the unsubstituted terminus of the double bond and could be a concerted or non-concerted reaction. Formation of an intermediate carbocation on the path to N-alkylation can be excluded because it would require the preferential formation of a primary carbocation. Radicals, on the other hand, show much lower preference for substituted unsubstituted carbon, suggesting that an initial formation of a carbon radical, followed by its collapse to the N-alkyl porphyrin is possible. While carbon radicals cannot be discrete intermediates in the epoxidation reaction vide supra), they can be intermediates in N-alkylation, if N-alkylation is a side reaction to epoxidation. 

Collman et al. " summarized and discussed the competition between epoxide formation and N-alkylation and the numerous mechanistic possibilities. They concluded in part that "Mechanisms ranging from a fully concerted reaction to a stepwise reaction involving an initial electron transfer may all be possible depending on the nature of the system." The theoretical results, summarize in a recent review, reflect this mechanistic multiplicity by suggesting a concerted mechanism for the low-spin doublet state and a stepwise process for the quartet state, just as was proposed for the hydroxylation of alkanes. 

The addition of a peroxyacid to an alkene to form an epoxide is a concerted reaction the oxygen atom adds to the two sp carbons at the same time (Section 6.10). Therefore, it must be a syn addition. 

Substituent effects on this kind of concerted, stereospecific epoxidation indicate that the peroxy-acid functions as an electrophile electron-donating groups activate the olefin vhile electron-withdrawing groups strongly deactivate it. When the electron flow at the transition state is reversed by using electron-poor olefins and peroxy anions for epoxidation, the reaction is stepwise and stereo-equilibrating and both cis- and trans-olefins (e.g., benzalacetophenone) yield trans-epoxide. (13. 14)... 

Formation of sterols from squalene involves cyclization. First a microsomal mixed-function oxidase (squalene epoxidase) forms squalene-2,3-oxide in the presence of NADPH, FAD and O2 (there is no requirement for cytochrome P450 in this reaction). The cyclization of the oxide to lanosterol then takes place by a concerted reaction without the formation of any stable intermediates. This conversion, which has been described as the most complex known enzyme-catalysed reaction, depends on a cyclase with a molecular mass of only 90kDa. In plants and algae squalene-2,3-epoxide is cyclized to cycloartenol which is the precursor of stigmasterol whereas lanosterol is the precursor of cholesterol and ergosterol (Figure 7.19). 

A concerted [2 + 2] cycloaddition pathway in which an oxametallocycle intermediate is generated upon reaction of the substrate olefin with the Mn(V)oxo salen complex 8 has also been proposed (Scheme 1.4.5). Indeed, early computational calculations coupled with initial results from radical clock experiments supported the notion.More recently, however, experimental and computational evidence dismissing the oxametallocycle as a viable intermediate have emerged. In addition, epoxidation of highly substituted olefins in the presence of an axial ligand would require a seven-coordinate Mn(salen) intermediate, which, in turn, would incur severe steric interactions. " The presence of an oxametallocycle intermediate would also require an extra bond breaking and bond making step to rationalize the observation of trans-epoxides from dy-olefms (Scheme 1.4.5). 

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