Retro-aldol fragmentation

Scheme 8.52 Retro-aldol fragmentation of an epoxide-derived hemiacetal.

The reaction conditions where the interaction terms are required to explain the 2-acetoxy-3-pentanone content occur in portions of the experimental space at low rhamnose concentration and at temperatures where the combination-heterocyclic compounds are not formed in large quantity. This also represents experimental points where DMHF had greater stability and thus the pool of retro-aldol fragments was lower. 

Base-catalyzed hydration of conjugated carbonyls, followed by retro-aldol fragmentation has been a common strategy for studying the reaction cascade (1-4). The kinetically important step in the base-catalyzed hydration of an alpha/beta unsaturated carbonyl is similar to a nucleophilic substitution reaction at carbon 3. The reaction cascade proceeds rapidly from the conjugated carbonyl through its hydration and subsequent fragmentation. 

Upon [2 + 2]-photocycloaddition to product E and protecting group removal, the retro-aldol fragmentation can be initiated by base or acid treatment (Scheme 6.18). Under basic conditions, alkoxide F generates an enolate which is subsequently protonated to the 1,5-diketone G. 

A very useful extension of the de Mayo reaction has been recently introduced by Blechert et al. (Scheme 6.26) [78]. The retro-aldol fragmentation was combined with an intramolecular enantioselective allylation (asymmetric ring-expanding allylation) catalyzed by a chiral Pd complex. Bicycloheptane 68, for example, was accessible by intermolecular [2 + 2]-photocycloaddition of cyclopentenone 67 with allene. Further transformation in the presence of Pd2(dba)3 (dba = dibenzylideneacetone) and the chiral oxazoline ligand 69 (tBu-phox) resulted in the enantioselective formation of cycloheptadione 70. 

A key step in the synthesis of 12-epi-lycopodine reported by Wiesner and coworkers is the intramolecular [2 + 2] photocycloaddition of a vinylogous imide and an allene. Irradiation of photosubstrate 46 produced a single cyclobutane 47, in which the allene added to the vinylogous imide anti to the methyl group (Scheme 13)31. Photoadduct 47 was converted to ketal-alcohol 48 via a three-step sequence of ketalization, epoxida-tion and reduction. Hydrolysis of the ketal unmasked the /Miydroxy ketone functionality. Retro-aldol fragmentation followed by aldol closure gave hydroxyketone 49, which was readily converted to the polycyclic alkaloid 12-epi-lycopodine. 

Irradiation at 254 nm of the imidate (Scheme 2) in aqueous solutions results in the formation of 4-cyanophenol and A -isopropylbenzamide. The photochemical step involved in the formation of the products has been shown to be C-O bond fission with the production of the phenoxide and the benzonitrilium ion. Mariano and co-workers have reported a detailed study of the electron-transfer photochemistry of a-anilino carboxylates, p-anilinoalcohols and a-an-ilinosilanes. This study has measured the rates of decarboxylation of aniliniumcarboxylate radicals. The base induced retro-Aldol fragmentations of the radical-cations formed from the p-anilinoalcohols and the influence of substituents on the nitrogen on the desilylation of the a-anilinosilanes was also investigated. In addition, the synthetic potential of some of the electron-transfer photochemistry of the carboxylate salts (181) and (182) has been examined. In these examples irradiation, using DCA in methanol or acetoni-... 

Oxidative Cleavage Reactions. Among the numerous methods for 1,2-diol cleavage there exist only a few that involve catalytic ruthenium reagents, for example Ruthenium(III) Chloride with Sodium Periodate Attempted selective monooxidation of a 1,2-diol to the hydroxy aldehyde with catalytic TPAP and NMO resulted in carbon-carbon bond cleavage to provide the aldehyde (eq 11). Furthermore, attempted oxidation of an anomeric a-hydroxy ester failed instead, in this case decarboxy-lation/decarbonylation and formation of the lactone was observed (eq 12). However, Dimethyl Sulfoxide-Acetic Anhydride provided the required a-dicarbonyl unit. Retro-aldol fragmentations can also be a problem. ... 

Dimethyl-4//-l,3-dioxin-4-one 139 has been used as the photochemical equivalent of formylacetate, which is inactive as the enone partner in the photoaddition with alkenes. Irradiation of dioxinone 139 in the presence of symmetrical cyclopentene 140 leads to the cyclobutane adduct 141. This intermediate upon subjection to hot water undergoes retro-aldol fragmentation and spontaneous lactonization to give lactone 143, a useful prostaglandin intermediate. Enantiomerically pure lactone 143 is prepared by using a chiral version of dioxinone 139. ... 

The conversion of ball-milled cellulose, glucose and fructose into micro-ciystalline lactic acid and 5-hydro g methylfurfural in water, catalysed by lead(ii) nitrate, has been reported (Scheme 22.5). The process involves a multistep cascade including the hydrolysis of cellulose to glucose, the isomerisation of glucose to fructose, retro-aldol fragmentation of fructose to trioses and their subsequent conversion to lactic acid lead(ii) catalyses both the conversion of glucose to fructose and the multistep cascade from fructose to lactic acid. The capacity of lead(ii) to be chelated by... 

A study of the oxidation of /3-hydroxyketones has shown that Collins reagent and dimethylsulphoxide-oxalyl chloride are suitable oxidants for the preparation of l,3-diketones. Using these reagents, neither /3-elimination nor retro-aldol fragmentation were observed. a-Diazo-/3-hydroxyketones are transformed into diketones on treatment with acid, but the need for an acidic medium can limit the generality of the method. However, it has been reported that this transformation occurs rapidly under neutral conditions in the presence of a catalytic amount of rhodium(ii) acetate. ... 

Toluene-p-sulphonic acid monohydrate promotes hydration of imine double bonds, providing a method for the ready regeneration of ketones from their 2,4-dinitrophenylhydrazones this method is unsuitable for regeneration of a S-unsaturated ketones, where extensive retro-aldol fragmentation occurs. Imines can be oxidized photochemically to ketones. In a re-investigation of the acid-catalysed conversion of ew-bromonitro-compounds into ketones, loss of a bromonium ion followed by a Nef reaction is postulated (Scheme 70). ... 

Kuninobu and Takai developed a rhenium-catalyzed reaction of ketoester 43 with an alkyne, leading to cyclooctenone 44, in which an alkyne is formally inserted into a C-C=0 bond (Eq. (6.10)) [22, 23]. This ring-expansion reaction is applicable to the synthesis of up to 10-membered carbocycles. The C-C bond cleavage is proposed to proceed via retro-Aldol fragmentation of intermediate 45 or 46. 

Carbon-carbon bond cleavage is important in the retro-aldol fragmentation of 2-aminoethanol and in the decarboxylation of a-aminoacids. As an example, decarboxylation in a-anilinocarboxyhc acid has been shown to be an unusually fast process (10 to 10 seer ) and to occur unimolecularly, differently from deprotonation and desilylation from structurally related anilines. The decarboxylation of the N-phthaloyl derivatives of a-amino acids has been extensively investigated (see e.g., Equation 4.21). 

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