Amino acid-derived catalysts catalysis

In 1992, O Donnell succeeded in obtaining optically active a-methyl-a-amino acid derivatives 49 in a catalytic manner through the phase-transfer alkylation of p-chlorobenzaldehyde imine of alanine tert-butyl ester 48 with cinchonine-derived la as catalyst (see Scheme 4.16) [46]. Although the enantioselectivities are moderate, this study is the first example of preparing optically active a,a-dialkyl-a-amino acids by chiral phase-transfer catalysis. 

The synthesis of quaternary amino acids 86 have been shown using azlac-tones 85 as nucleophiles and the Trost ligand 39 under palladium [179] or molybdenum catalysis (Scheme 8) [180]. The allylic alkylation of glycine imino esters under biphasic conditions has also been achieved using a chiral phase-transfer catalyst in combination with an achiral Pd catalyst producing the unnatural amino acid derivatives [181]. 

Analytical evaluation is of great importance for stereoselective catalysis. Much of the success in recent years has its origin in new tools such HPLC and GC with modified celluloses, cyclodextrins, or siloxane-bound amino acid derivatives as chiral stationary phases. As described in Chapter 21, it has been shown that upon use of polymer-bound chiral catalysts or selectors, the kinetic parameters of stereoselective reactions can be determined in a parallel mode with high precision. 

N-heterocyclic carbene catalysis has become one of the major categories in orga-nocatalysis. Azolium salts are ready deprotonated by weak bases to generate a carbene, which then adds to an aldehyde to form an acyl anion equivalent, generally called the Breslow intermediate. The reactive acyl anion attacks an electrophile to promote the various transformations such as benzoin, Stetter, and redox reactions [107]. Recently, an interesting approach for NHC-catalyzed generation of an enol/enolate intermediate was reported. Enantio-enriched (i-amino acid derivatives (217) are formed by the reaction between the a-aryloxyaldehyde 214 and N-tosyl-imines (215) in the presence of phenyalanine-derived azoUum salt 216 as a pre-catalyst and aryl phenoxide as a base (Scheme 28.28) [108]. 

Carreira et al. used their experience in the addition of simple silyl ketene acetals to aldehydes under Lewis acid catalysis [15]. In these experiments their 2-amino-2 -hydroxy-l,rbinaphthyl-derived catalyst (19) was used to provide aldol products with very high enantioselectivity (Scheme 8, Table 7). 

Derivatives of the steroids androstene and pregnene have been transformed directly into A-acyl amino acids by an orthogonal catalysis procedure, utilizing [RhCl(nbd)]2 and Co2(CO)8 (Scheme 11). The rhodium phosphine catalyst (generated in situ in the presence of syn-gas and phosphine) affects hydroformylation of the internal olefin to generate aldehyde. In the presence of Co2(CO)8, A-acyl amino acids are obtained as the major products. An unstable amido alcohol intermediate, formed by reaction of the amide with aldehyde, is proposed to undergo cobalt-catalyzed GO insertion to yield the desired A-acyl amino acid. 

Enantioselective Michael addition of glycine derivatives by means of chiral phase-transfer catalysis has been developed to synthesize various functionalized a-alkyl-a-amino acids. Corey utilized 4d as catalyst for asymmetric Michael addition of glycinate Schiff base 1 to a,(3-unsaturated carbonyl substrates with high enantioselectivity (Scheme 2.15) [35,36]. With methyl acrylate as an acceptor, the a-tert-butyl-y-methyl ester of (S)-glutamic acid can be produced, a functionalized glutamic acid... 

In particular, it is not only the cinchona alkaloids that are suitable chiral sources for asymmetric organocatalysis [6], but also the corresponding ammonium salts. Indeed, the latter are particularly useful for chiral PTCs because (1) both pseudo enantiomers of the starting amines are inexpensive and available commercially (2) various quaternary ammonium salts can be easily prepared by the use of alkyl halides in a single step and (3) the olefin and hydroxyl functions are beneficial for further modification of the catalyst. In this chapter, the details of recent progress on asymmetric phase-transfer catalysis are described, with special focus on cinchona-derived ammonium salts, except for asymmetric alkylation in a-amino acid synthesis. 

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