Mukaiyama-type Mannich reaction

Scheme 3.3 Mukaiyama type Mannich reaction of imines with ketene silyl acetals.

Mannich reaction. Mukaiyama-type Mannich reaction can be effected by LiCl (0.2 equiv.) in DMF. 

Synthetic strategy Mukaiyama-type Mannich reaction Catalyst Lithium chloride (LiCl)... 

Keywords Arylaldemines, trimethylsilyl ketene acetal, lithium chloride, DMF, room temperature, Mukaiyama-type Mannich reaction, p-amino esters... 

Hagiwara, H., lijima, D., Awen, B. Z. S., Hoshi, T., and Suzuki, T. (2008). Expedient Mukaiyama-type Mannich reaction catalyzed by lithium chloride. Synlett, 1520-1522. 

In this review we will attempt to highlight the most important contributions toward the realization of a catalytic, enantioselective, vinylogous Mannich reaction and show the current state of the art. This chapter is organized in such a way that vinylogous Mannich reactions of preformed silyl dienolates in Mukaiyama type reactions will be discussed first followed by direct vinylogous Mannich reactions of unmodified substrates. 

The catalytic, enantioselective, vinylogous Mannich reaction has recently emerged as a very powerful tool in organic synthesis for the assembly of highly functionalized and optically enriched 6 amino carbonyl compounds. Two distinctly different strategies have been developed. The first approach calls for the reaction of preformed silyl dienolates as latent metal dienolates that react in a chiral Lewis acid or Bronsted acid catalyzed Mukaiyama type reaction with imines. Alternatively, unmodified CH acidic substrates such as a,a dicyanoalkenes or 7 butenolides were used in vinylo gous Mannich reactions that upon deprotonation with a basic residue in the catalytic system generate chiral dienolates in situ. 

The development of a catalytic, enantioselective Mannich-type reaction of si-lyl ketene acetals lagged far behind the now-well-established enantioselective Mukaiyama directed aldol addition. The major consideration for the invention of such a transformation is obviously the selection of an appropriate Lewis acid activator. This is a challenging problem in view of the basicity of the imine nitrogen, the ambiguity in complexation geometry, and most importantly the release of the catalyst to effect turnover. Thus, it is not surprising that the first successful catalytic, enantioselective Mannich reaction was reported only in 1997. 

While several resin- or polymer-supported Sc(OTf)3 catalysts have been developed and some of them are commercially available, a drawback of these catalysts is that their catalytic ability and reusability are still not satisfactory. Conceptually new methods, polymer incarcerated (PI) method and polymer-micelle incarcerated (PMI) have been developed to immobilize Sc(OTf)3 [100]. PMI Sc(OTf)3 is highly effective in several fundamental carbon-carbon bond-forming reactions, including Mukaiyama aldol, Mannich-type and Michael reactions. It is noted that the high catalytic activity in terms of TON (>7500) has been attained in Michael reaction. The catalyst was recovered quantitatively by simple filtration and reused several times without loss of catalytic activity, and no Sc leaching was observed in all the reactions (<0.1 ppm). 

Keywords Aza-Sakurai allylationreaction Bismuth triflate C-C bond formation Mannich-type reaction Mukaiyama aldol reaction /V-AI koxycaihony I am ino sulfones Silyl nucleophiles... 

Three-component coupling reaction of a-enones, silyl enolates, and aldehydes by successive Mukaiyama-Michael and aldol reactions is a powerful method for stereoselective construction of highly functionahzed molecules valuable as synthetic intermediates of natural compounds [231c]. Kobayashi et al. recently reported the synthesis of y-acyl-d-lactams from ketene silyl thioacetals, a,/l-urisalu-rated thioesters, and imines via successive SbCl5-Sn(OTf)2-catalyzed Mukaiyama-Michael and Sc(OTf)3-catalyzed Mannich-type reactions (Scheme 10.87) [241]. 

In recent years, catalytic asymmetric Mukaiyama aldol reactions have emerged as one of the most important C—C bond-forming reactions [35]. Among the various types of chiral Lewis acid catalysts used for the Mukaiyama aldol reactions, chirally modified boron derived from N-sulfonyl-fS)-tryptophan was effective for the reaction between aldehyde and silyl enol ether [36, 37]. By using polymer-supported N-sulfonyl-fS)-tryptophan synthesized by polymerization of the chiral monomer, the polymeric version of Yamamoto s oxazaborohdinone catalyst was prepared by treatment with 3,5-bis(trifluoromethyl)phenyl boron dichloride ]38]. The polymeric chiral Lewis acid catalyst 55 worked well in the asymmetric aldol reaction of benzaldehyde with silyl enol ether derived from acetophenone to give [i-hydroxyketone with up to 95% ee, as shown in Scheme 3.16. In addition to the Mukaiyama aldol reaction, a Mannich-type reaction and an allylation reaction of imine 58 were also asymmetrically catalyzed by the same polymeric catalyst ]38]. 

Scandium triflate-catalyzed aldol reactions of silyl enol ethers with aldehyde were successfully carried out in micellar systems and encapsulating systems. While the reactions proceeded sluggishly in water alone, strong enhancement of the reactivity was observed in the presence of a small amount of a surfactant. The effect of surfactant was attributed to the stabiMzation of enol silyl ether by it. Versatile carbon-carbon bondforming reactions proceeded in water without using any organic solvents. Cross-linked Sc-containing dendrimers were also found to be effective and the catalyst can be readily recycled without any appreciable loss of catalytic activity.Aldol reaction of 1-phenyl-l-(trimethylsilyloxy) ethylene and benzaldehyde was also conducted in a gel medium of fluoroalkyl end-capped 2-acrylamido-2-methylpropanesulfonic acid polymer. A nanostmctured, polymer-supported Sc(III) catalyst (NP-Sc) functions in water at ambient temperature and can be efficiently recycled. It also affords stereoselectivities different from isotropic solution and solid-state scandium catalysts in Mukaiyama aldol and Mannich-type reactions. 

After pioneering work on the Lewis base-catalysed Mukaiyama aldol reaction, Mukaiyama-Michael reaction, and Mukaiyama-Mannich-type reaction with the use of lithium acetate, Mukaiyama also demonstrated the same reactions using simple sodium salts (Scheme 2.28). For example, a catalytic Mukaiyama aldol reaction between benzaldehyde and trimethylsilyl enolate using sodium methoxide in DMF proceeded smoothly under mild conditions. Moreover, the Mukaiyama-Michael reaction between chalcone and trimethylsilyl enolates using sodium acetate in DMF provided the desired Michael adduct as the major product in 92% yield along with the 1,2-adduct in 8% yield. ... 

Ishihara developed a highly efficient Mukaiyama aldol reaction between ketones and trimethylsilyl enolates catalysed by sodium phenoxide-phosphine oxides (46) as simple homogeneous Lewis-base catalysts (0.5-10 mol%) (Scheme 2.29). For a variety of aromatic ketones and aldimines, aldol and Mannich-type products with an a-quaternary carbon centre were obtained in good to excellent yields. Remarkably, a retro-aldol reaction was not observed. On a scale of up to 100 mmol, benzophenone and trimethylsilyl enolate gave the product in 97% yield (34.8 g) using 0.5 mol% of catalyst. 

Quite recently, cross-linked dendrimer was also found to be a good support for Sc(III) catalyst [101]. The resultant material could be used in water as a catalyst for three-component Mannich-type reactions and Mukaiyama aldol reactions. A simple immobilization method of Sc species by using montmorillonite as a support has also been reported recently [102]. This method provides a highly active heterogeneous catalyst for Michael reactions under aqueous or solvent-free conditions. 

Kobayashi and coworkers further developed a new immobilizing technique for metal catalysts, a PI method [58-61]. They originally used the technique for palladium catalysts, and then applied it to Lewis acids. The PI method was successfully used for the preparation of immobilized Sc(OTf)3. When copolymer (122) was used for the microencapsulation of Sc(OTf)3, remarkable solvent effects were observed. Random aggregation of copolymer (122)-Sc(OTf)3 was obtained in toluene, which was named as polymer incarcerated (PI) Sc(OTf)3. On the other hand, spherical micelles were formed in THF-cyclohexane, which was named polymer-micelle incarcerated (PMI) Sc(OTf)3.. PMI Sc(OTf)3 worked well in the Mukaiyama-aldol reaction of benzaldehyde with (123) and showed higher catalytic activity compared to that of PI Sc(OTf)3 mainly due to its larger surface area of PMI Sc(OTf)3. This catalyst was also used in other reactions such as Mannich-type (123) and (125) and Michael (127) and (128) reactions. For Michael reactions, inorganic support such as montmorilonite-enwrapped Scandium is also an efficient catalyst [62]. 

Sc(0Tf)3 as a water-compatible Lewis acid catalyst has been reported to exhibit particularly high catalytic performances for a series of Lewis acid-catalyzed reactions the Friedel-Crafts alkylation, allylation reactions, Mukaiyama aldol condensation, and Mannich-type reaction [3,49,50]. The same metal triflate was reported to show catalytic activity for other Lewis acid-catalyzed reactions with carhonyl compounds (Equation (8.23)) in water. Its activity was indicated to he far superior to the other metal triflates, which was suggested as an indication that the high stahiUty of metal triflate-carhonyl compound complexes causes high catalytic performance for these reactions [7]. 

Finally, Mukaiyama-Mannich-type reactions can also be induced and mediated by proton activation of the imine component, which thereby obtains a sufficient degree of reactivity to be attacked by highly nucleophilic silicon enolates. Thus, Wenzel and Jacobsen have shown that the specific protection by N-aryl substituents with a pendant ortho-hydioxy or ortho-methoxy chelating group is not required, if the acetate-derived sHyl ketene acetals 362 are reacted with simply BOC-protected aryl and hetaryl imines 361. Thus, P-amino esters 364 are obtained in excellent enantiomeric excess, if the reaction is catalyzed by the chiral urea derivative 363 that is assumedto act by activation through hydrogen bonding (Scheme 5.95) [181]. 

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