Amino catalyzed processes

Notwithstanding the expected and also observed high reactivity of the intermediate immonium ions, the stabilization of the exocyclic double bond in the pyrrolidino derivative evidently prevents rapid nucleophilic attack of water and the hydration of this ion to the amino alcohol becomes a slow general base-catalyzed process in weakly acidic solutions [Eq. (6)]. 

The enhanced chemiluminescence associated with the autoxidation of luminol (5-amino-2,3-dihydro-1,4-phthalazinedione) in the presence of trace amounts of iron(II) is being used extensively for selective determination of Fe(II) under natural conditions (149-152). The specificity of the reaction is that iron(II) induces chemiluminescence with 02, but not with H202, which was utilized as an oxidizing agent in the determination of other trace metals. The oxidation of luminol by 02 is often referred to as an iron(II)-catalyzed process but it is not a catalytic reaction in reality because iron(II) is not involved in a redox cycle, rather it is oxidized to iron(III). In other words, the lower oxidation state metal ion should be regarded as a co-substrate in this system. Nevertheless, the reaction deserves attention because it is one of the few cases where a metal ion significantly affects the autoxidation kinetics of a substrate without actually forming a complex with it. 

Grigg et al. also reported the alkylation of indole at the C3-position with alcohols, catalyzed by the 1/KOH system (Scheme 5.32) [69]. A variety of indole derivatives having an alkyl substituent at the C3-position were synthesized by this methodology. The same group also developed a Cp lr-catalyzed process for successive carbon-nitrogen and carbon-carbon bond formation, starting with 2-amino-phenethyl alcohol (also see Scheme 5.22). 

At present, one of the most successful catalysts for enamine activation has been proline (2). Proline is a cheap, widely and commercially available amino acid that can be found in both enantiomeric forms and, as such, represents a remarkable synthetic alternative to many established asymmetric catalysts. Given such attractive features, it has become the catalyst of choice for many enamine-catalyzed processes. However, various more recent studies have demonstrated that proline is not a universal catalyst for transformations that involve the a-functionalization of ketone or aldehyde carbonyls. Indeed, these studies have demonstrated that the iminium catalysts developed by MacMillan (imidazolidinones) and Jprgensen (pyrrolidines) are also highly effective for enamine activation with respect to... 

Since Wakamatsu serendipitously discovered amidocarbonylation while performing the cobalt-catalyzed hydroformyla-tion of olefins in 1971, this unique carbonylation reaction, affording a-amino acids directly from aldehydes, has been extensively studied.More recently, palladium-catalyzed processes have been developed to expand the scope of this reaction.The Pd-catalyzed amidocarbonylation has been applied to aldehydes,aryl halides, and imines. As a related reaction, lactamization " of aryl halides catalyzed by a rhodium complex has also been developed. 

As Scheme 1 illustrates, the Pd-catalyzed process includes the formation of hemiamidal 1 in the same manner as that in the Co-catalyzed process. However, the unique feature in this process is that hemiamidal 1 is converted to a-bromoamide 2, which is the key intermediate in this process. Then, the oxidative addition of 2 to the Pd(0) species forms alkyl-Pd complex 3. Subsequent insertion of CO to the carbon-Pd bond of 3 gives the acyl-Pd complex 4, which leads to the formation of the A -acyl-a-amino acid 5 through reductive elimination and hydrolysis. 

In addition to deliberate enzyme-catalyzed processes, there are nonenzymatic processes that alter proteins. These include the degradative reactions described in Section 5 and also reversible reactions that may be physiologically important. For example, the N-terminal amino groups of peptides, and other amino groups of low p Ka can form carbamates with bicarbonate (Eq. 2-21 ).301-303 This provides an important mechanism of carbon dioxide transport in red blood cells (Chapter 7) and a way by which C02 pressure can control some metabolic processes. 

As stated above, aliphatic amines are potent ligands for electrophilic transition metals and are efficient catalyst poisons in attempted alkene animation reactions. However, tosylation of the basic amino group greatly reduces its complexing ability, yet does not compromise its ability to nucleophilically attack complexed alkenes. Thus, a variety of alkenic tosamides efficiently cyclized under palladium(II) catalysis producing N-tosylenamines in excellent yield (equations 17 and 18).32 Again, this alkene amination proceeded through an unstable a-alkylpalladium(II) species, which could be intercepted by carbon monoxide, to result in an overall aminocarbonylation of alkenes. With ureas of 3-hydroxy-4-pentenyl-amines (Scheme 7), this palladium-catalyzed process was quite efficient but it was somewhat less so with... 

A kinetic resolution is a chemical reaction in which one enantiomer of a racemate reacts faster than the other. Most kinetic resolutions of pharmaceutical compounds are catalyzed processes. Catalysts used in a kinetic resolution must be chiral. Binding of a chiral catalyst with a racemic material can form two different diastereomeric complexes. Since the complexes are diastereomers, they have different properties different rates of formation, stabilities, and rates of reaction. The products form from the diastereomeric substrate-catalyst complexes at different rates. Therefore, a chiral catalyst is theoretically able to separate enantiomers by reacting with one enantiomer faster than the other. The catalysts used in kinetic resolutions are often enzymes. Enzymes are constructed from chiral amino acids and often differentiate between enantiomeric substrates. 

Addition of HaS to nitriles (73) represents an important method for the synthesis of primary thioamides (74 equation 33). The reaction is carried out under base or acid catalysis. The base-catalyzed process is particularly useful in the preparation of aromatic thioamides, i.e. for R = aryl, hetaryl in (73) triethylamine in molar proportion or pyridine, which at the same time also serves as solvent, are employed most commonly. The approach tolerates the presence of various other functionalities such as an amide, hydrazone, enamine, a-oxo, a-acetoxy ° or a-amino group. Moreover, the reaction has been applied to the synthesis of thioasparagine as such or incorporated into a dipeptide, as shown... 

Cytochrome P450 electron transport systems are an important feature of biotransformation in animal bodies. Biotransformation is a series of enzyme-catalyzed processes in which potentially toxic and usually hydrophobic substances are converted into less toxic water-soluble derivatives that can then be more easily excreted. Substrates for biotransformation include endogenous substances, such as cholesterol, and foreign molecules, called xenobiotics, such as drugs and nonnutritive components of food (e.g., glycosides and numerous fatty acid and amino acid derivatives). 

The C-terminal amino acid appears to be universally heterocyclic. The heterocycle is either Pro or derived from Cys, Ser, or Thr by an enzyme-catalyzed process. 

A chiral Ir(I) catalyst derived from the amino-(2,2 -biphenoxy)phosphine 37 promotes the synthesis of optically active 3-amino-l-alkenes from 2-alkenols, which are activated by (Eto)5Nb/ l-Vinyl-l,2,3,4-tetrahydroisoquinolines are obtained in good yields in the Pd-catalyzed process. Enantioselectivity is induced by the atropisomeric 38. ... 

Bis[dicarbonylchlororhodium(I)] and bis[(l,5-cyclooctadiene)chlororhodium(I)], Epoxide opening. The monoepoxide of a diene is regioselectively attacked by nucleophile (ArNHR, ROH) at the allylic position using [Rh(CO)2Cl]2 as catalyst, affording anil-1,2-amino alcohols and alkoxy alcohols. The results are apparently complementary to those obtained from the Pd-catalyzed process. 

Arai et al. [141] described a particular enzymatic reaction for producing a surface-active protein. A highly hydrophobic amino acid was covalently bound to a hydrophilic protein in an enzyme-catalyzed process for this purpose. The covalent attachment of L-Leu n-alkyl ester to gelatin in the presence of papain as catalyst resulted in a proteinaceous surfactant [141,142] with very good emulsifying properties. 

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