Acid-Mediated Transformations

The theme of C-glycosyl compounds is covered by two chapters on free radical- and cwis acid-mediated transformations that address the stereocontrolled synthesis of carbon abstitnents at the anomeric position. 

S.C. PanandB. List s paper spans the whole field of current organocat-alysts discussing Lewis and Brpnsted basic and acidic catalysts. Starting from the development of proline-mediated enamine catalysis— the Hajos-Parrish-Eder-Sauer-Wiechert reaction is an intramolecular transformation involving enamine catalysis—into an intermolecular process with various electrophilic reaction partners as a means to access cY-functionalized aldehydes, they discuss a straightforward classification of organocatalysts and expands on Brpnsted acid-mediated transformations, and describe the development of asymmetric counteranion-directed catalysis (ACDC). 

Last but not least, as easily recoverable and reusable catalysts, zeolites also allow to perform acid-mediated transformations with a clear environmental benefit, since it avoids the formation of huge amounts of salts which is typically encountered in acid catalyzed processes. Noteworthy, zeolites can also host active catalytic species such as metals or organometallic complexes for fine chemical synthesis. 

A rate enhancement effect due to secondary nucleation has been identified in the solution-mediated transformation of the 7-phase of (i)-glutamic acid to its / -phase [82]. In this study, the kinetics of the polymorphic transition were studied using optical microscopy combined with Fourier transform infrared, Raman, and ultraviolet absorption spectroscopies. The crystallization process of n-hexatriacontane was investigated using micro-IR methodology, where it was confirmed that single... 

Microwave heating has also been employed for performing retro-Diels-Alder cycloaddition reactions, as exemplified in Scheme 6.94. In the context of preparing optically pure cross-conjugated cydopentadienones as precursors to arachidonic acid derivatives, Evans, Eddolls, and coworkers performed microwave-mediated Lewis acid-catalyzed retro-Diels-Alder reactions of suitable exo-cyclic enone building blocks [193, 194], The microwave-mediated transformations were performed in dichloromethane at 60-100 °C with 0.5 equivalents of methylaluminum dichloride as catalyst and 5 equivalents of maleic anhydride as cyclopentadiene trap. In most cases, the reaction was stopped after 30 min since continued irradiation eroded the product yields. The use of short bursts of microwave irradiation minimized doublebond isomerization. 

One of the most common approaches to pyrrole synthesis is the Paal-Knorr reaction, in which 1,4-dicarbonyl compounds are converted to pyrroles by acid-mediated dehydrative cyclization in the presence of a primary amine. The group of Taddei has reported a microwave-assisted variation of the Paal-Knorr procedure, whereby a small array of tetrasubstituted pyrroles was obtained (Scheme 6.181) [342], The pyrroles were effectively synthesized by heating a solution of the appropriate 1,4-dicarbonyl compound in the presence of 5 equivalents of the primary amine in acetic acid at 180 °C for 3 min. The same result was obtained by heating an identical mixture under open-vessel microwave conditions (reflux) for 5 min. Interestingly, the authors were unable to achieve meaningful product yields when attempting to carry out the same transformation by oil-bath heating. 

The Fujiwara group reported a transition metal free calcium-mediated transformation of methane into acetic acid, in the presence of S2Og2 (Equation (13)). 

Examples of solvent-mediated transformation monitoring include the conversion of anhydrous citric acid to the monohydrate form in water [235,236], CBZ with water [237] and ethanol-water mixtures [238,239], and cocrystallization studies of CBZ, caffeine, and theophylline with water [240]. Raman spectroscopy was used to monitor the crystallization rate and solute and solvent concentrations as griseofulvin was removed from an acetone solution using supercritical CO2 as an antisolvent [241]. Progesterone s crystallization profile was monitored as antisolvent was added [242]. 

The solvent-mediated transformation of o -L-glutamic acid to the S-form was quantitatively monitored over time at a series of temperatures [248]. The calibration model was built using dry physical mixtures of the forms, but still successfully predicted composition in suspension samples. Cornel et al. monitored the solute concentration and the solvent-mediated solid-state transformation of L-glutamic acid simultaneously [249]. However, the authors note that multivariate analysis was required to achieve this. Additionally, they caution that it was necessary to experimentally evaluate the effect of solid composition, suspension density, solute concentration, particle size and distribution, particle shape, and temperature on the Raman spectra during calibration in order to have confidence in the quantitative results. This can be a substantial experi-... 

Parathion (0,0-diethyl 0-/7-nitrophenyl phosphorothioate) is degraded in the near subsurfaee aerobie environment via hydrolysis, where two degradation products are observed, diethylthiophosphoric acid and p-nitrophenol, according to the schematic pathway described in Fig. 16.35. Abiotic hydrolysis of parathion in the subsurface is a result of a surface-mediated transformation (see Sect. 16.1) or a biodegradation process. 

In 2006, Xu and Xia et al. revealed the catalytic activity of commercially available D-camphorsulfonic acid (CS A) in the enantioselective Michael-type Friedel-Crafts addition of indoles 29 to chalcones 180 attaining moderate enantiomeric excess (75-96%, 0-37% ee) for the corresponding p-indolyl ketones 181 (Scheme 76) [95], This constitutes the first report on the stereoselectivity of o-CSA-mediated transformations. In the course of their studies, the authors discovered a synergistic effect between the ionic liquid BmimBr (l-butyl-3-methyl-l/f-imidazohum bromide) and d-CSA. For a range of indoles 29 and chalcone derivatives 180, the preformed BmimBr-CSA complex (24 mol%) gave improved asymmetric induction compared to d-CSA (5 mol%) alone, along with similar or slightly better yields of P-indolyl ketones 181 (74-96%, 13-58% ee). The authors attribute the beneficial effect of the BmimBr-D-CSA combination to the catalytic Lewis acid activation of Brpnsted acids (LBA). Notably, the direct addition of BmimBr to the reaction mixture of indole, chalcone, d-CSA in acetonitrile did not influence the catalytic efficiency. 

Chiral phosphoric acids mediate the enantioselective formation of C-C, C-H, C-0, C-N, and C-P bonds. A variety of 1,2-additions and cycloadditions to imines have been reported. Furthermore, the concept of the electrophilic activation of imines by means of phosphates has been extended to other compounds, though only a few examples are known. The scope of phosphoric acid catalysis is broad, but limited to reactive substrates. In contrast, chiral A-triflyl phosphoramides are more acidic and were designed to activate less reactive substrates. Asymmetric formations of C-C, C-H, C-0, as well as C-N bonds have been established. a,P-Unsaturated carbonyl compounds undergo 1,4-additions or cycloadditions in the presence of A-triflyl phosphoramides. Moreover, isolated examples of other substrates can be electrophil-ically activated for a nucleophilic attack. Chiral dicarboxylic acids have also found utility as specific acid catalysts of selected asymmetric transformations. 

Thus sulfonamides are bacteriostatic drugs that inhibit bacterial growth by interfering with the microbial synthesis of folic acid. More specifically, sulfonamides block the biosynthetic pathway of folic acid synthesis, thus competitively inhibiting the transformation of p-aminobenzoic acid to folic acid (mediated by the enzyme dihydropteroate synthetase), which allows them to be considered as antimetabolites. 

Our initial aim was to prepare the epoxyalkyl glycosides 60 as mixtures of dia-stereoisomers. The literature abounds with methods for such syntheses, ranging from Lewis-acid mediated condensations of the acetate 62 [43,44] to acid-catalyzed additions to the oxazoline 63 [45,46]. All of these transformations seemed rather cumbersome and long-winded to us, especially those involving the separate preparation of the oxazoline ... 

Usually, (he construction of carbocyclic rings requires the preparation of highly functionalized intermediates. Youquan Deng of the Lanzhou Institute of Chemical Physics reports (Tetrahedron Lett. 48 2I91, 2003) that simple acid-mediated equilibration of l-dodecene 12 gives a remarkably efficient conversion to cyclododecane 13. The authors speculate that the peculiar thermodynamic stability of 13 favors this transformation. 

The principal transformations of caffeic acid mediated by microorganisms are reduction of the unsaturated aliphatic side chain, dehydroxylation, and decarboxylation. 

Methylcyclohexenone 281 upon oxidation with Mn(OAc)3 in benzene under reflux gave 282, which reacted with phenylmagnesium chloride and CuBr-Me2S to form two isomeric ketones 283 and 284. Further, 283 has been transformed to vinylsilane 285 followed by its hydrolysis to form the free alcohol 286, which in turn was alkylated with methoxyallyl bromide to give 287. Oxalic acid-mediated deprotection of 287 led to the formation of the ketone 288. Ozonolysis of 288 in methanol afforded the fused 1,2,5-trioxepine 289 in low yields (Scheme 66) <1997BML2357>. 

A DYKAT (dynamic kinetic asymmetric transformation) approach has been taken to de novo synthesis of triketide- and deoxy-sugars from racemic /i-hydroxyal-dehydes.119 Using proline as catalyst, the process involves continuous amino acid-mediated racemization of the acceptor /3-hydroxyaldehydc in combination with direct... 

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