Enol ethers hydrolysis, mechanism

On the other hand, in view of important analogies in kinetic behaviour between enol ketonisation and enol ether hydrolysis, the HA [HA,] terms cannot correspond to a concerted mechanism. Lienhard and Wang (1969) and this author (Dubois and Toullec, 1969b Toullec and Dubois, 1974) have pointed out that the rate-limiting step of enol ketonisation is closely similar to that of enol ether hydrolysis if the two-step mechanism for acid-catalysed enolisation is valid. The two reactions occur by rate-limiting proton transfer to the double bond with formation of either a hydroxycarbenium ion (19) or an alkoxycarbenium ion (20). However, in the latter reaction, in contrast to the... 

Danishefsky also investigated the development of a trans Diels-Alder reaction in seeming violation of the inherent stereoselectivity of the reaction mechanism. The key to this process was the use of 1-nitrocyclohexene (80) as the dienophile. After a standard intermolecular Diels-Alder reaction with diene 79, cis cycloadduct 81 could be transformed preferentially into trans-fused product 82 upon radical denitration and enol ether hydrolysis. ... 

The mechanism of the reaction can be explained by protonation of 9 followed by cationic cyclization to afford an intermediate of type 7. After electrocyclization, intermediate 10 is converted by hydrolysis into enone 11. The ease with which the cationic cyclization occurred (compared to direct enol ether hydrolysis) testifies to the rate-accelerating effect of the electron-rich a-substituent. 

Enol ethers are readily hydrolyzed by acids the rate-determining step is protonation of the substrate. However, protonation does not take place at the oxygen but at the p carbon, because that gives rise to the stable carbocation 104. After that, the mechanism is similar to the A1 mechanism given above for the hydrolysis of acetals. 

The acid-catalyzed hydrolysis of enol esters (RCOOCR =CR) can take place either by the normal Aac2 mechanism or by a mechanism involving initial protonation on the double-bond carbon, similar to the mechanism for the hydrolysis of enol ethers given in 10-6, ° depending on reaction conditions. In either case, the products are the carboxylic acid RCOOH and the aldehyde or ketone R2" CHCOR. ... 

The reaction mechanism proposed for the addition of organostannanes [29] is similar to that for organoboronic acids. An example of the reaction of methyl vinyl ketone 42 is outlined in Scheme 3.15. The catalytic cycle involves a cationic rhodium complex G, phenylrhodium H, and oxa-n -allylrhodium I. Stannyl enol ether 44 is formed by the reaction of oxa-n -allylrhodium I with Me3SnBF4, which upon hydrolysis gives the ketone 43. The lower yields in the absence of water were explained by the further reaction of 44 with methyl vinyl ketone 42. The rapid hydrolysis with water may prevent such oligomerization. 

The formation and the hydrolysis of acyclic and cyclic acetals have been studied in rather great detail [91]. Several reviews on this topic are available [92] and some comments have been made [13] concerning the carbohydrate series. We have shown in Schemes 1,2, and 3 that a common feature of this reaction seems to be the intermediacy of an oxocarbenium ion. However, the cyclization of such an intermediate has been questioned more recently [93] in the light of the Baldwin s rules for ring closure [94]. At least for the five-membered ring, an SN2-type displacement mechanism far the protonated form (B) of die hemiacetal (A) (favorable 5-exo-tet cyclization) has been proposed rather than the unfavorable 5-endo-trig cyclization of the oxocarbenium ion (C) (Scheme 5). Except when the formation of the enol ether (D) is structurally impossible, the intermediacy of such a compound remains feasible. 

The stereoselectivity of the gas-phase 1,2-eliminations of deuterium-labelled 392 and of 393 with several bases have been studied470. The SDIE has been used471 to study the mechanism of hydrolysis of the enol ether, 2-MeOC=CHC6H4COOH, which yields the acylal, 394, rather than the formal product of hydrolysis. 

Following the mechanism given in Figure 12.23, the addition of an acetal to a simple enol ether (in contrast to the dienol ether B shown above) leads to a /3-alkoxy acetal. This reaction is known as the Mukaiyama aldol addition. If this is followed by a hydrolysis (of the... 

A similar reaction occurs when enol ethers react with alcohols in acid solution and in the absence of water, but now we are starting in the middle of the acetal hydrolysis mechanism and going the other way, in the direction of the acetal A useful example is the formation of THP (= TetraHydroPyranyl) derivatives of alcohols from the enol ether dihydropyran. You will see THP derivatives of alcohols being used as protecting groups in Chapter 24. 

Perhaps the simplest example of this reaction sequence is the hydrolysis of enamines, shown in equation 2. It is the purpose of this chapter to consider in detail the mechanism(s) of enamine hydrolysis. Comparison between enamines and other nucleophilic alkenes, among them enolates, enols and enol ethers, will also be made. 

Allylic azides, e.g., 1, were produced by treatment of the triisopropylsilyl enol ethers of cyclic ketones with azidotrimethylsilane and iodosobenzene78, but by lowering the temperature and in the presence of the stable radical 2,2,6,6-tetramethylpiperidine-/V-oxyl (TEMPO), 1-triso-propylsilyloxy-l,2-diazides, e.g., 2, became the predominant product79. The radical mechanism of the reaction was demonstrated. A number of 1,2-diazides (Table 4) were produced in the determined optimum conditions (Method B 16h). The simple diastereoselectivity (trans addition) was complete only with the enol ethers of unsubstituted cycloalkanones or 4-tert-butylcy-clohexanone. This 1,2-bis-azidonation procedure has not been exploited to prepare a-azide ketones, which should be available by simple hydrolysis of the adducts. Instead, the cis-l-triiso-propylsilyloxy-1,2-diazides were applied to the preparation of cw-2-azido tertiary cyclohexanols by selective substitution of the C-l azide group by nucleophiles in the presence of Lewis acids. 

Many other metabolic degradation pathways are either initiated by reactions involving generation of transient carbocations or pass through a transition state with highly positive charge density on a carbon center. Reactions in this category are the acidic hydrolysis of acetals, aminals, or enol ethers, and the oxidation of alcohols to ketones via a hydride-transfer mechanism. 

Sodium Azide/Ammonium Cerium(IV) Nitrate. Silyl enol ethers give a-azido ketones on treament with sodium azide and anhydrous ammonium cerium(IV) nitrate in anhydrous acetonitrile (see Eq. 97).297 325 33i With a glycal, the 2-azido-1-hydroxy nitrate derivative is formed.332 Low yields due to hydrolysis of the silyl enol ether may be improved by use of the triisopropylsilyl (TIPS) derivatives,331 although with a sterically encumbered taxane-derived enol ether the TMS derivative gives higher yields than the TIPS derivative.325 The mechanism is believed to involve addition of an azide radical to the double bond. 

N-Chlorocarbamate/Chromium(II) Chloride. Enol ethers (see Eq. 80) and glycals (see Eq. 84) react with N-chlorocarbamates in the presence of chromous chloride to produce a-amino carbonyl derivatives.343 Trimethylsilyl enol ethers give low yields because of their ease of hydrolysis. A radical chain mechanism has been proposed with the N-haloamide acting as the transfer agent (Eq. 32).344... 

A similar rearrangement to a [4.4.0] carbocyclic skeleton was observed by Harmata upon treatment of 146 with bromine. The proposed mechanism involves formation of a bromonium ion which rearranges and loses a proton to form an enol ether, which reacts with a second mole of bromine to give, after hydrolysis, an excellent yield of the rearranged product (Scheme 9) [148]. 

The pH dependence of the hydrolysis of all compounds studied is, in principle, consistent with the mechanism of Scheme 6 that applies to the alkoxyphenylcarbene complexes, and so are the products of the reactions of 68, 66 and 8. However, the products obtained in the hydrolysis of 144 and the fact that in basic solution the hydrolysis of all the compounds is subject to a substantial kinetic solvent isotope effect are inconsistent with Scheme 6, at least at pH >8.5. The mechanism that accounts best for all experimental observations at pH >8.5, including the isotope effect, is shown in Scheme 17 for the example of 68. It involves rapid deprotonation of 68 followed either by slow protonation of 135 with water ( 2 )) or a buffer acid (fe [BH]) and subsequent rapid conversion of 161 to 162, or slow concerted water (fe2c) or buffer acid catalyzed (fe [BH]) conversion of 135 to 162 (more on these two alternatives below). Complexation between (CO)sCr and the enol ether activates the latter toward basic hydrolysis which rapidly leads to the vinyl alcohol and tautomerization to the aldehyde. Control experiments demonstrated that the kind of complexation indicated by 162 indeed promotes rapid hydrolysis of the enol ether. ° In the reactions of 144 complexation of the enol ether ()8-methoxystyrene) appears to be weak, presumably because of steric crowding, and hence the reaction... 

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