Enol sulfonates Mannich reaction

Bismuth triflate was found to be an efficient catalyst in the Mannich-type reaction of silyl enolates with N-alkoxycarbonylamino sulfones. The reaction proceeded smoothly with a low catalyst loading of bismuth triflate (0.5-1.0 mol%) to afford the corresponding protected -aminocarbonyl compounds in very good yield (Equation 7) [29]. 

A nanostructured scandium-containing polymer was also successfully used in the condensation of aldehydes, aromatic amines, and silyl enol ethers to give the corresponding /3-aminoketones, but the observed diastereoselectivities were moderate. Cai and coworkers reported the use of sulfonated amino acids as efficient Bronsted catalysts in direct diastereo-and regioselective Mannich reactions in water. ... 

An improved procedure for the chlorosulfonation of substituted diaryl sulfones involves heating the appropriate 4,4 -dialkyl or dihalodiaryl sulfone with chlorosulfonic acid (2-4 equivalents) at 140-150 °C and subsequent treatment with thionyl chloride (6-10 equivalents). The action of chlorosulfonic acid on propiophenone (ethyl phenyl ketone 226) results in a novel cyclization reaction yielding 3-chloro-2-methylbenzothiophene-1,1-dioxide 227 (Scheme 2). The reagent similarly caused smooth cyclization of Mannich bases 228, the reaction again proceeding via the enolic sulfonic acid to yield the cyclic sulfone 229 (Equation 72). ... 

Aldol addition and related reactions of enolates and enolate equivalents are the subject of the first part of Chapter 2. These reactions provide powerful methods for controlling the stereochemistry in reactions that form hydroxyl- and methyl-substituted structures, such as those found in many antibiotics. We will see how the choice of the nucleophile, the other reagents (such as Lewis acids), and adjustment of reaction conditions can be used to control stereochemistry. We discuss the role of open, cyclic, and chelated transition structures in determining stereochemistry, and will also see how chiral auxiliaries and chiral catalysts can control the enantiose-lectivity of these reactions. Intramolecular aldol reactions, including the Robinson annulation are discussed. Other reactions included in Chapter 2 include Mannich, carbon acylation, and olefination reactions. The reactivity of other carbon nucleophiles including phosphonium ylides, phosphonate carbanions, sulfone anions, sulfonium ylides, and sulfoxonium ylides are also considered. 

Several examples of Bi(0Tf)34H20-catalyzed Mannich-type reactions of various A-benzyloxycarbonylamino sulfones 1 with silyl enol ethers are summarized in Table 5. A-Benzyloxycarbonylamino sulfones 1 derived from differently substituted benzaldehydes were reacted with trimethyl(l-phenylvinyloxy)silane in dichloromethane at room temperature. The corresponding (3-amino ketones 24 were smoothly obtained (Table 5, entries 1-6). The reaction was efficient using electron-deficient benzaldehyde-derived sulfones, and the corresponding (3-amino ketones 24... 

Table 5 Bi(0Tf)3-4H20-catalyzed Mannich-type reactions with various N-benzyloxycarbo-nylamino sulfones and silyl enol ethers...

In order to obtain further insight into the mechanism of the Mannich-type reaction, sulfone IP and silyl enol ether derived from acetophenone were reacted in the presence HOTf or TMSOTf, which could be produced in the reaction medium when using Bi(0Tf)3-4H20 as catalyst. It appeared that these two compounds efficiently catalyze the Mannich-type reaction (Table 7, entries 2 and 3). The reaction does not occur in the presence of 2,6-di-/<7V-buty I-4-methyl-pyridine [DTBMP] (1.0 equiv. of lp, 1.3 equiv. of silyl enol ether, 0.5 mol% of Bi(0Tf)34H20, 1.5 mol% of 2,6-di-/c/V-buty l-4-methy I-pyridine, 22 °C, 20 h, 99% recovery of lp), which indicates that triflic acid is involved in the mechanism (Table 7, entry 4). 

Another catalytic application of chiral ketene enolates to [4 + 2]-type cydizations was the discovery of their use in the diastereoselective and enantioselective syntheses of disubstituted thiazinone. Nelson and coworkers described the cyclocondensations of acid chlorides and a-amido sulfones as effective surrogates for asymmetric Mannich addition reactions in the presence of catalytic system composed of O-TM S quinine lc or O-TMS quinidine Id (20mol%), LiC104, and DIPEA. These reactions provided chiral Mannich adducts masked as cis-4,5 -disubstituted thiazinone heterocycles S. It was noteworthy that the in situ formation of enolizable N-thioacyl imine electrophiles, which could be trapped by the nucleophilic ketene enolates, was crucial to the success of this reaction. As summarized in Table 10.2, the cinchona-catalyzed ketene-N-thioacyl-imine cycloadditions were generally effective for a variety of alkyl-substituted ketenes and aliphatic imine electrophiles (>95%ee, >95%cis trans) [12]. 

Three-component Mannich-type reactions of aldehydes, amines, and silicon enolates also proceeded smoothly using PS-SO3H in water (Scheme 3.37). In general, ketene silyl acetals are known to be easily hydrolyzed in the presence of water however, such water-labile compounds could be successfully used in this reaction. Moreover, a remarkable effect of the loading levels of the polystyrene-supported sulfonic acid on yields was observed. It was suggested that the hydrophobic environment created by the catalyst might suppress hydrolysis of ketene silyl acetals. 

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