Bronsted base moiety

The use of alkali metal-containing, heterobimetallic lanthanoid complexes as catalysts in asymmetric synthesis is reviewed. This new and innovative type of chiral catalyst, which was recently developed by Shibasaki et al., contains a Lewis acid as well as a Bronsted base moiety, thereupon showing a similar mechanistic effect as observed in enzyme chemistry. The heterobimetallic complexes have been successfully applied as highly stereoinducing catalysts in many different types of asymmetric reactions, including the stereoselective formation of C-C, C-O, and C-P bonds. 

Therein, the lanthanum center ion (III) should function as a Lewis acid activating the aldehyde, whereas the lithium binaphthoxide moiety act as Bronsted base moiety. The synergetic effect of both groups, as can be seen in intermediate III, appeared to be responsible that the reaction proceeds without any activation of the starting materials, especially the ketone component. 

LA represents Lewis acid in the catalyst, and M represents Bren sled base. In Scheme 8-49, Bronsted base functionality in the hetero-bimetalic chiral catalyst I can deprotonate a ketone to produce the corresponding enolate II, while at the same time the Lewis acid functionality activates an aldehyde to give intermediate III. Intramolecular aldol reaction then proceeds in a chelation-controlled manner to give //-keto metal alkoxide IV. Proton exchange between the metal alkoxide moiety and an aromatic hydroxy proton or an a-proton of a ketone leads to the production of an optically active aldol product and the regeneration of the catalyst I, thus finishing the catalytic cycle. 

Shibasaki et al. also developed a barium complex (BaB-M, 14, Scheme 5) for the aldol reaction of acetophenone (la), making use of the strongly basic characteristic of barium alkoxide. The catalyst was prepared from Ba(0-z-Pr)2 and BINOL monomethyl ether, and the products were obtained in excellent yield with up to 70% ee (Scheme 6) [8], Shibasaki et al. attempted to incorporate a strong Bronsted base into the catalyst and developed a lanthanide heterobime-tallic catalyst (15) possessing lithium alkoxide moieties, which promoted the aldol reaction with up to 74% ee (Scheme 6) [9]. Noyori and Shibasaki et al. reported a calcium alkoxide catalyst (16) that was prepared from Ca[N(SiMe3)2]2,... 

The roles of the catalytic functions are not necessarily opposite or limited to Lewis acid/base pairs. For example, amine thiourea derivatives like Takemoto s catalyst 4 merge the hydrogen bond donor capability of the thiourea moiety with Bronsted base functionality of the amine function and revealed itself particularly efficient organocatalysts for Michael reactions of various 1,3-dicarbonyl compounds with nitroolefins (Scheme 3) [17-19]. 

Free alkoxide and aryloxide anions are Bronsted bases with pK values of the corresponding alcohols ranging from 5 to 20 in water. The basicity is highly dependent on the electronic properties of the alkyl or aryl moieties. For example, the pK value of hexafluoro-tert-butanol, (CF3)jMeCOH, is 9.6, which is considerably lower than the pK value of tert-butanol (19.2), but roughly the same as that of phenol (9.9). Such differences in electronic, as well as steric, environments often leads to the different structures and reactivity patterns for compounds containing similar ancillary ligands, but different alkoxides or aryloxides. 

The postulated catalytic cycle of the asymmetric epoxidation reaction is shown in Figure 13.10. A lanthanide metal alkoxide moiety changes to a rare earth metal-peroxide through proton exchange (I). In this step, lanthanide metal alkoxide moiety functions as a Bronsted base. The rare earth metal-BINOL complex also functions as a Lewis acid to activate electron-deficient olefins through monoden-tate coordination (II). Enantioselective 1,4-addition of rare earth metal-peroxide gives intermediate enolate (III), followed by epoxide formation to regenerate the catalyst (IV). 

Calixarene Catalysts Containing Bronsted Acid/Base Moieties... 

The mechanistic role played by Bronsted bases involves either a pro-nucleophile or a stabilized, charged nucleophUe-electrophile adduct both species lose a proton to the amine moiety of the Bronsted base, resulting in newly activated intermediates with basic character (Figure 13.1). The activated intermediate species during the course of the reaction are involved in a second proton transfer event from the protonated Bronsted base, which frees up the Bronsted base for subsequent cycles of activity. 

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... 

Figure 13.16 Correlation (Bronst-ed plot) of base-catalyzed hydrolysis rates (log kB) of carbamates as a function of the pKa of the alcohol moiety for a series of N-phenyl carbamates. Data from references given in Table 13.11.

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