Schiffbases glycinate

Scheme 4.29 Reaction of the acid chloride of tetrachlorophthaloyl glycine with a Schiffbase.

As a prochiral glycine-derived SchifFbase, not only esters but also amides can be used as suitable substrates for asymmetric alkylation under phase-transfer conditions. 

To a solution of benzaldehyde, N-(tert-butoxycarbonyl)imine (10.7 mg, 52.3 pmol), tert-butyl glycinate benzophenone Schiffbase (14.8 mg, 50.1 pmol) and catalyst (5.0 mg, 5.0 pmol) in fluorobenzene (0.5 mL) was added Cs2C03 (32.6 mg, 100.1 pmol) at -30 °C. After stirring for 19 h, the reaction was quenched by the addition of water. The water layer was extracted three times with EtOAc. The combined organic layer was dried over MgS04 and concentrated. The residue was purified by column chromatography on silica gel (hexane ether, 10 1 as eluent) to give the product (24.5 mg, 98%). 

However, the use of the glycinate Schiffbase imine (17) as a Michael donor provided low to moderate enantioselectivity (60-88% ee). 

Ooi and Maruoka developed an efficient phase transfer catalyst (46a-e), which consisted of chiral N-spiro ammonium salts with binaphthalene skeleton. 3,3 -(3,4,5-Trifluorophenyl)ammonium salt (46e) provided a perfect stereoselection in benzylation of benzophenone Schiffbase of glycine terf-butyl ester (47) (Scheme 5.13, Table 5.5) [19]. The perfect stereoselective alkylation is applicable for a variety of alkyl bromides in the presence of 1 mol% of the catalyst (46e). Not only monoalkylation but also the consecutive double alkylation of 49 was successful to give 50 in excellent enantioselectivities (Scheme 5.14) [20]. The protocol is useful for the enantioselective aldol reaction of 47 with aldehyde (51) [21] and a-imino ester [22], in which catalysts (46f) and (46g) were effective (Scheme 5.15) [23]. 

Table 4.5 Asymmetric Michael reaction between t-butyl glycinate Schiffbase and active vinyl compounds in the presence of the guanidine 77...

One class of application that readily highlights the enormous potential of asymmetric phase-transfer catalysis is the stereoselective ot-alkylation of different carbanion nucleophiles, in particular enolates. Although these types of transformations are most important in organic chemistry, there are stiU only a limited number of stereoselective catalytic methods available and the use of chiral PTCs represents one of the most versatile strategies to achieve such transformations. One example of special interest is the asymmetric a-alkylation of glycine Schiffbase 374 (Scheme 85)... 

Shibuguchi T, Mihara H, Kuramochi A, Ohshima T, Shibasaki M (2007) Catalytic Asymmetric Phase-Transfer Michael Reaction and Mannich-Type Reaction of Glycine SchiffBases with Tartrate-Derived Diammonium Salts. Chem Asian J 2 794... 

In the first step, glycine Schiffbase 1 reacts with the inorganic base at the interface of two phases to give the metal enolate 2, which remains at the interface due to its highly polar character. The metal enolate 2 then exchanges the cation to provide onium enolate 3. The sufficiently lipophilic 3 then moves into the organic phase to react with alkyl halide. After the reaction, onium halide (Q X ) is regenerated and enters the next catalytic cycle. The key issue to be considered here is the possibility of product racemization and dialkylation. In this example, the basicity... 

Representative chiral phase-transfer catalysts (Q X ) for the asymmetric alkylation of glycine Schiffbase 1 are summarized in Figure 14.2a [8-13]. These catalysts were also applied to other asymmetric alkylations with different nucleophiles (Figure 14.2b) [14—17]. 

The fate of the onium carbanion Q R incorporated into the organic phase depends on the electrophilic reaction partner. The most studied area in the asymmetric phase-transfer catalysis is that of asymmetric aikyiation of active methylene or methine compounds with alkyl halides, in an irreversibie manner. The reaction mechanism iiiustrated above is exemplified by the asymmetric alkylation of glycine Schiffbase (Scheme 14.2) [7]. 

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