Mannich Bronsted base

Shibasaki and coworkers have conducted extensive research on the use of hetero-bimetallic complexes as catalysts for asymmetric synthesis [11]. The reactions are catalyzed by heterobimetallic complexes that function as both a Lewis acid and a Bronsted base. Among these, LaLi3tris(binaphthoxide) catalyst 1 (LLB) was proven to be an effective catalyst in direct asymmetric aldol reactions (Fig. 1) [12]. On the basis of this research, Shibasaki et al. reported the first report of a direct catalytic asymmetric Mannich reaction [13],... 

Ishihara developed a highly diastereo- and enantioselective direct Man-nich-type reaction of aldimines with 1,3-dicarbonyl compounds using chiral lithium binaphtholate salts as effective Lewis-acid-Bronsted-base catalysts (Scheme 2.5). ° The stereoselectivity of the Mannich products anti-S and syn-7 ) was reversed when the nucleophile was changed from acyclic 1,3-dicarbonyl compound 4 to cyclic compound 6. The molecular flexibility and acidity of the nucleophiles 4 and 6 would be the major factor in differentiating the two reaction pathways. 

In 2007, Ooi and coworkers introduced chiral tetraaminophosphonium salts as a new class of Bronsted acids [166]. Similar to the guanidine/guanidinium case, these tetraaminophosphonium salts act as Bronsted bases in their neutral/ deprotonated (triaminoiminophosphorane) form, while they can also be used as mono-functional Bronsted acids in their protonated, phosphonium form. Phos-phonium salt 67, when neutralized in situ with KO Bu, was shown to be a highly effective catalyst in the enantioselective Henry reaction of nitroalkanes with various aromatic and aliphatic aldehydes (Scheme 10.65). The same strategy was further applied to the catalytic asymmetric Henry reaction of ynals [167] and hydrophosphonylation of ynones (Scheme 10.66) [168]. Brfunctional catalysis using this scaffold were also obtained using the carboxylate salts of tetraaminophosphoniums in the direct Mannich reaction of sulfonyl imines with azlactones (Scheme 10.67) [169]. 

Tetraaminophosphonium carboxylates and phenoxides have also been developed as chiral Bronsted base catalysts for asymmetric Mannich reachons and conjugate addihons [6c, 33]. These catalysts recognized and achvated the nucleophiles through the hydrogen-bonding network (Scheme 14.10). 

Quaternary ammonium betaines possessing an anion moiety have emerged as Bronsted base catalysts. The C2-symmetric axially chiral ammonium betaine 177 deprotonates the a-substituted a-nitrocarboxylates (176) to form a structured ion pair that reacts with imines (173) to furnish the corresponding anti-Mannich... 

Mannich Reactions in Bronsted Base Catalysis Including Bifunctional Catalysis... 

The vinylogous Mannich reaction of 2 silyloxy furans and imines may also be catalyzed through chiral Brpnsted acids, as shown by Akiyama et al. [10]. Previously, Akiyama [11] and Terada [12] had independently discovered that 3,3 substituted BINOL based phosphoric acids were excellent Bronsted acids for a broad range of mainly imine addition reactions via protonation of the imines and in situ formation of chiral iminium contact ion pairs. Using the slightly modified phosphoric acid 28 as catalyst carrying additional iodine substituents in the 6,6 positions, the y amino substituted butenolides 27 were obtained in excellent enantioselectivity and variable diastereoselectivity (Table 5.4). 

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. 

Direct catalytic asymmetric Maimich-type reactions of various aromatic and heteroaromatic hydroxyke-tones are catalyzed by a Y N(SiMe3)2 3/TMS-linked-BrNOL complex, whereas a heterobimetallic lanthanum arylox-ide/lithium aryloxide/pybox complex catalyzes direct catalytic asymmetric Mannich-type reactions of a-keto anilides as synthetic equivalents of homoenolates. A La(OTf)3/Me-PyBox/amine base/Bronsted acid combination was found to be effective for direct catalytic asymmetric Maiuiich-type reactions of y-butenolides. ... 

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