Mannich catalysts structure

Similar organocatalytic species to those successfully used for the Strecker reaction were used for the asymmetric Mannich reaction. Catalyst structure/ enantioselectivity profiles for the asymmetric Strecker and Mannich reactions were compared by the Jacobsen group [160]. The efficient thiourea... 

Systematic investigations of the catalyst structure-enantioselectivity profile in the Mannich reaction [72] led to significantly simplified thiourea catalyst 76 lacking both the Schiff base unit and the chiral diaminocyclohexane backbone (figure 6.14 Scheme 6.88). Yet, catalyst 76 displayed comparable catalytic activity (99% conv.) and enantioselectivity (94% ee) to the Schiff base catalyst 48 in the asymmetric Mannich reaction of N-Boc-protected aldimines (Schemes 6.49 and 6.88) [245]. This confirmed the enantioinductive function of the amino acid-thiourea side chain unit, which also appeared responsible for high enantioselectivities obtained with catalysts 72, 73, and 74, respectively, in the cyanosilylation of ketones (Schemes 6.84 and 6.85) [240, 242]. 

Trimerization to isocyanurates (Scheme 4.14) is commonly used as a method for modifying the physical properties of both raw materials and polymeric products. For example, trimerization of aliphatic isocyanates is used to increase monomer functionality and reduce volatility (Section 4.2.2). This is especially important in raw materials for coatings applications where higher functionality is needed for crosslinking and decreased volatility is essential to reduce VOCs. Another application is rigid isocyanurate foams for insulation and structural support (Section 4.1.1) where trimerization is utilized to increase thermal stability and reduce combustibility and smoke formation. Effective trimer catalysts include potassium salts of carboxylic acids and quaternary ammonium salts for aliphatic isocyanates and Mannich bases for aromatic isocyanates. 

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. 

Wenzel and Jacobsen, in 2002, identified Schiff base thiourea derivative 48 as catalyst for the asymmetric Mannich addition [72] of tert-butyldimethylsilyl ketene acetals to N-Boc-protected (hetero)aromatic aldimines (Scheme 6.49) [201]. The optimized structure of 48 was found through the construction of a small, parallel... 

Another more efficient catalytic version of the reaction consists of the interaction of ketones with chiral amines [6] to form enolate-like intermediates that are able to react with electrophilic imines. It has been postulated that this reaction takes place via the catalytic cycle depicted in Scheme 33. The chiral amine (130) attacks the sp-hybridized carbon atom of ketene (2) to yield intermediate (131). The Mannich-like reaction between (131) and the imine (2) yields the intermediate (132), whose intramolecular addition-elimination reaction yields the (5-lactam (1) and regenerates the catalyst (130). In spite of the practical interest in this reaction, little work on its mechanism has been reported [104, 105]. Thus, Lectka et al. have performed several MM and B3LYP/6-31G calculations on structures such as (131a-c) in order to ascertain the nature of the intermediates and the origins of the stereocontrol (Scheme 33). According to their results, conformations like those depicted in Scheme 33 for intermediates (131) account for the chiral induction observed in the final cycloadducts. 

The best catalyst for this transformation was AgSbFg (10 mol%), and (3-ketoesters, malonates, and silyl enol ethers have been used for the nucleophilic addition on the pyridinium intermediate DD. The dihydroisoquinolines 48 have been further used in several reactions in order to assemble the framework of various alkaloids. One example is given in the formation of dihydroisoquinoline 49, bearing a pendent a, 3-unsaturated ketone. Compound 49 can rearrange to the tetracycle 50 (related to the core structure of karachine, Scheme 5.23), using TMSOTf, via a tandem Michael addition-Mannich reaction process (intermediates EE and FF). 

Some of them (adhesives, coatings, foam plastics, and resins) use Mannich bases or their derivatives as structural components of the material, whereas all the listed branehes are concerned with the use of important additives (mainly antioxidants) or auxiliaries such as basic catalysts and accelerators. Specific functions are performed, for instance, by agents improving the adhesion of photopolymerizable paints and by accelerator-modified adhesion promoters for mbber-to-wirc adhesion." ... 

Three-component Mannich reactions involving other imines also worked well in [bmim][BF4]/ but even more efficient protocols involve solvent-less conditions, in the presence of water again we deal with aqueous biphasic systems. Catalyst 15a (Table 1.1) is suitable for such an application, as well as siloxytetrazole 18a, derived from a combination of the structural features of 3 (Table 1.1) and tetrazole derivative 18b.Interestingly, while neither 3 nor 18b were suitable for such transformation, the hybrid catalyst 18a gave the excellent results shown in Scheme 1.8. 

By propoxylation of the resulting polyols (trimethylolisocyanurate and the Mannich base (15.44), in the presence of a tertiary amine as catalyst (for example dimethylaminoethanol) new heterocyclic polyols for rigid PU foams with a triazinic structure are obtained (reactions 15.45 and 15.46). 

Another alkaline catalyst applied for the preparation of resoles is ammonia It is well known that ammonia can dissociate in aqueous solution to form ammonium hydroxide which can also function as a catalyst. Furthermore, the anunonium ion has a comparable ionic radius to the potassium ion. However, ammonia also catalyses the formation of Mannich-bases, Schiffsch-bases, and other structures that are represented as by-products in the mixture of resoles formed. These by-products contribute to a coloring ofthe... 

Chiral disulfonimides of the general structure 236 have been used as highly efficient catalysts for reactions such as an asymmetric Mannich reaction of silyl ketene acetals with A/-Boc-amino sulfones (13JA15334) as well as an asymmetric three-component synthesis of homoaUylic amines (13AGE2573). Analogs of pyrrolo[l,2,5]benzothiadiazepine 237a and the... 

Ricci and coworkers [64] studied oxazoline moiety fused with a cyclopenta[P]thio-phene as ligands on the copper-catalyzed enantioselective addition of Et2Zn to chalcone. The structure of the active Cu species was determined by ESI-MS. Evans and coworkers [65] studied C2-symmetric copper(II) complexes as chiral Lewis acids. The catalyst-substrate species were probed using electrospray ionization mass spectrometry. Comelles and coworkers studied Cu(II)-catalyzed Michael additions of P-dicarbonyl compounds to 2-butenone in neutral media [66]. ESI-MS studies suggested that copper enolates of the a-dicarbonyl formed in situ are the active nucleophilic species. Schwarz and coworkers investigated by ESI-MS iron enolates formed in solutions of iron(III) salts and [3-ketoesters [67]. Studying the mechanism of palladium complex-catalyzed enantioselective Mannich-type reactions, Fujii and coworkers characterized a novel binuclear palladium enolate complex as intermediate by ESI-MS [68]. 

An asymmetric one-pot sequential Mannich/hydroamination sequence involves a three-catalyst system a chiral organocatalyst, BF3 and a gold complex. It converts an indole-imine into privileged spiro[pyrrolidin-3,2 -oxindole] structures in up to 91/97% yield/ee. 

The author next envisioned the preparation of benzothiazine-1,1-dioxide derivatives 15 through domino MCR and cyclization. Since benzo[e][l,2]thiazine-1,1-dioxides are widely found in biologically active compounds including nonsteroidal anti-inflammatory drugs (NSAIDs) [15-22], various approaches to construct this structure have been reported [23-33]. The author expected that the use of such a sulfonamide as 14, an aldehyde, and a secondary amine in the presence of a copper catalyst would bring about a Mannich-type reaction followed by 6-endo-dig cyclization (related synthesis of thiazines has been already reported, see [34, 35]) to afford a benzo[e][l,2]thiazine 15. The reaction of A-methyl and N-ethylsulfonamides 14a and 14b under standard conditions gave the desired ben-zothiazines 15a and 15b, respectively, but in low yields (34 and 37%, respectively, entries 1 and 2, Table 8). Considering that acidity of the amide proton in 14a and... 

On the basis of ESl-MS observation as well as positive nmilinear effects of this system, we assumed that p-oxo-p-aiyloxy-trimer complex is the most enantiose-lective active species (Fig. 3). Therefore, Sm50(0-/Pr)i3 with a well-ordered structure would have beneficial effects for the formation of desired trimer species. Postulated catalytic cycle of the reaction based on the initial rate kinetic studies and kinetic isotope effect studies is shown in Fig. 4. In this catalyst system, both Cu and Sm are essential. We assume that the cooperative dual activation of nitroalkanes and imines with Cu and Sm is important to realize the syn-selective catalytic asymmetric nitro-Mannich-type reaction. The Sm-aryloxide moiety in the catalyst would act as a Brpnsted base to generate Sm-nitronate. On the other hand, Cu(ll) would act as a Lewis acid to control the position of iV-Boc-imine. Among possible transition states, the sterically less hindered TS-1 would be more favorable. Thus, the stereoselective C-C bond formation via TS-1 followed by protonation with phenolic proton affords syn product and regenerates the catalyst. 

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