Aldol Bronsted acids

Montmorillonite K10 was also used for aldol the reaction in water.280 Hydrates of aldehydes such as glyoxylic acid can be used directly. Thermal treatment of K10 increased the catalytic activity. The catalytic activity is attributed to the structural features of K10 and its inherent Bronsted acidity. The aldol reactions of more reactive ketene silyl acetals with reactive aldehydes proceed smoothly in water to afford the corresponding aldol products in good yields (Eq. 8.104).281... 

It has also been shown that dimethylsilyl enolates can be activated by diisopropylamine and water and exhibit a high reactivity toward iV-tosyl imines to give Mannich-type reaction products in the absence of a Fewis acid or a Bronsted acid.51 For example, the reaction of [(1-cyclohexen-l-yl)oxy]dimethylsilane with 4-methyl-A -(phenylmethylene)benzene sulfonamide gave re/-4-methyl-N- (f )-[(15)-(2-oxocyclohexyl)phenyl-methyl] benzenesulfonamide (anti-isomer) in 91% yield stereoselectively (99 1 anti syn) (Eq. 11.30). On the other hand, Fi and co-workers reported a ruthenium-catalyzed tandem olefin migration/aldol and Mannich-type reactions by reacting allyl alcohol and imine in protic solvents.52... 

During our investigations of the reactions mediated by LASCs, we have found that addition of a small amount of a Bronsted acid dramatically increased the rate of the aldol reaction (Eq. 5).[191 This cooperative effect of a LASC and an added Bronsted acid was also observed in the allylation ofbenzalde-hyde with tetraallyltin in water.1201 Although, from a mechanistic point of view, little is known about the real catalytic function of scandium and proton, this cooperative effect of a Lewis acid and a Bronsted acid provides a new methodology for efficient catalytic systems in synthetic chemistry. 

K. Manabe, Y. Mori, S. Nagayama, K Odashima, S. Kobayashi, Synthetic Readions Using Organometal-lics in Water. Aldol and Allylation Reactions Catalyzed by Lewis Acid-Surfadant-Combined Catalysts/ Bronsted Acids Systems Inorg Chim. Acta in press. 

Examples are reactions initiated by the protonation, as for example carbenium ion formation from — for example—olefins (Bronsted acidic centres) or deprotonation reactions like base-catalysed aldol condensation. 

Sc(() l f) ( is an effective catalyst of the Mukaiyama aldol reaction in both aqueous and non-aqueous media (vide supra). Kobayashi et al. have reported that aqueous aldehydes as well as conventional aliphatic and aromatic aldehydes are directly and efficiently converted into aldols by the scandium catalyst [69]. In the presence of a surfactant, for example sodium dodecylsulfate (SDS) or Triton X-100, the Sc(OTf)3-catalyzed aldol reactions of SEE, KSA, and ketene silyl thioacetals can be performed successfully in water wifhout using any organic solvent (Sclieme 10.23) [72]. They also designed and prepared a new type of Lewis acid catalyst, scandium trisdodecylsulfate (STDS), for use instead of bofh Sc(OTf) and SDS [73]. The Lewis acid-surfactant combined catalyst (LASC) forms stable dispersion systems wifh organic substrates in water and accelerates fhe aldol reactions much more effectively in water fhan in organic solvents. Addition of a Bronsted acid such as HCl to fhe STDS-catalyzed system dramatically increases the reaction rate [74]. 

The diastereoselectivity of the reaction was independent of the catalyst but was affected by the nature of the solvent. The threo isomer was preferentially formed in toluene, while the erythro isomer was formed in 1,2-dimethoxy-ethane. The proton-exchanged montmorillonite (H+-mont) showed similar activity and diasteroselectivity to Al3+-mont. This fact suggests that the exchangeable Al3+ cations in the montmorillonite do not function as Lewis acid sites and it is the Bronsted acid sites that are essential for catalysis of the aldol reaction. 

As a result of the preliminary examples described in Sect. 3.1 and the quest for automation techniques in solution-phase synthesis, various examples of continuous flow processes appeared in the literature lately which utilized solid-phase-bound chemical catalysts. In a simple example, Yamamoto and coworkers studied the use of super Bronsted acids loaded on polystyrene beads 5 for use in a single-pass column system (Fig. 4) [30]. It was shown that these columns are suited for the acetylation of alcohols, acetalization of carbonyl compounds, Sakurai-Hosomi allylation reactions, and Mukaiyama aldol reactions. 

Some of the catalyst systems used in the asymmetric aldol reaction are also effective in related reactions. Thus, bifunctional catalysts and L-prohne-based organocatalysts have been used to good effect in the nitroaldol reaction and Mannich reaction. The latter process is also effectively catalysed by enantiomeri-cally pure Bronsted acids. Furthermore, much recent progress has been made in the development of a catalytic asymmetric Morita-Baylis-Hillman reaction using Lewis/Bronsted acid catalysts and bifunctional catalysts. 

Some other very important events in the historic development of asymmetric organocatalysis appeared between 1980 and the late 1990s, such as the development of the enantioselective alkylation of enolates using cinchona-alkaloid-based quaternary ammonium salts under phase-transfer conditions or the use of chiral Bronsted acids by Inoue or Jacobsen for the asymmetric hydro-cyanation of aldehydes and imines respectively. These initial reports acted as the launching point for a very rich chemistry that was extensively developed in the following years, such as the enantioselective catalysis by H-bonding activation or the asymmetric phase-transfer catalysis. The same would apply to the development of enantioselective versions of the Morita-Baylis-Hillman reaction,to the use of polyamino acids for the epoxidation of enones, also known as the Julia epoxidation or to the chemistry by Denmark in the phosphor-amide-catalyzed aldol reaction. ... 

Alternatively, the iminium-activation strategy has also been apphed to the Mukaiyama-Michael reaction, which involves the use of silyl enol ethers as nucleophiles. In this context, imidazolidinone 50a was identified as an excellent chiral catalyst for the enantioselective conjugate addition of silyloxyfuran to a,p-unsaturated aldehydes, providing a direct and efficient route to the y-butenolide architecture (Scheme 3.15). This is a clear example of the chemical complementarity between organocatalysis and transition-metal catalysis, with the latter usually furnishing the 1,2-addition product (Mukaiyama aldol) while the former proceeds via 1,4-addition when ambident electrophiles such as a,p-unsaturated aldehydes are employed. This reaction needed the incorporation of 2,4-dinitrobenzoic acid (DNBA) as a Bronsted acid co-catalyst assisting the formation of the intermediate iminium ion, and also two equivalents of water had to be included as additive for the reaction to proceed to completion, which... 

For aldol reactions, typically proline-type catalysts were used. However, Palomo and coworkers reported cross-aldol reactions between unmodified aldehydes and ynals. This transformation was enabled by the cooperative action of newly designed catalyst C7, copper iodide and a Bronsted acid. In this way, remarkably high levels of diastereo- and enantioselectivily were achieved (Scheme 8.32). 

In 2005 Yamamoto et al. reported the first example of asymmetric Bronsted acid-catalysed nitroso-aldol synthesis in particular 1-naphthyl-TADDOL 2a was particularly efficient in promoting the addition of achiral enamines 22 to nitrosobenzene with high regio- and enantioselectivities (Scheme 24.8). ... 

Terada, M. Tanaka, H. Sorimachi, K. Enantioselective Direct Aldol-Type Reaction of Azlactone via Protonation of Vinyl Ethers by a Chiral Bronsted Acid Catalyst. /. Am. Chem. Soc. 2009,131,3430-3431. 

In Mannich-type reactions, too, a certain acceleration was shown by a Brensted add, although a dramatic effect such as that in aldol and aUylation reactions was not observed (Table 3.10, Scheme 3.62). More interestingly, however, a combination of HCl and SDS catalyzed Mannich-type reactions. In view of the above results, it is clear that BASCs can create a hydrophobic reaction environment and provide efficient add catalysis, simultaneously, by acting as both a siufactant and a Bronsted acid. 

The combination of SDS and a Bronsted acid was also investigated in aldol reaction using diphenylboronic add (Scheme 3.71). In this reaction, it should be noted that boron enolates were formed in water, and that high syn selectivity of the product was observed. Boron enolates are known to be water-sensitive, but such species can be successfully used in water imder these reaction conditions. 

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