Proline and its derivatives

FIGURE 4.1 Anatomy of an amino acid. Except for proline and its derivatives, all of the amino acids commonly found in proteins possess this type of structure. 

The problem of competitive reactions can also be overcome by the use of specific catalysts proline and its derivatives proved to be effective and enantiomeric-specific organic catalysts [80-83],... 

Proline and its derivatives also catalyze the classical asymmetric Mannich reaction between aqueous formaldehyde, anilines, and ketones. This was the first successful direct catalytic a-hydroxymethylation of ketones, and the corresponding a-aminomethyl ketones were isolated in excellent yields with up to >99 % ee (Scheme 4) [34]. 

Numerous 2-substituted pyrrolidine organocatalysts have been prepared from L-proline and its derivatives, and have been proven to be highly efficient for many asymmetric reactions. Representative organocatalysts have been selected and categorised on the basis of the 2-substituted group that includes di- and tri-amine (la-m), dithioacetal (2a-f), guanidine (2g-i), sulfonamide (3a-j), amide and thioamide (3k-n), urea (4a and 4e), thiourea (4b-d, f-j) and heterocycles such as tetrazole (5a,b), triazole (5c-g), imidazole (5h-j) and benzoimidazole (5k) (Figure 9.1). 

Several syntheses have appeared in which pyrrolidine carboxylic acids other than proline have been prepared. Refunctionalization of proline is an also excellent route to "non-proline" amino acids, however, because of the ready availability of proline and its derivatives. Proline (7.250) was converted to aldehyde 7.25J by standard procedures, and Wittig olefination lej to 7.252.133 In an interesting transforma-... 

Chiral 1,2,3-triazolium ionic liquid tethered pyrrolidine catalysts built from (S)-proline and its derivatives have been successfully ap>plied in various catalytic reactions (Khan, Shah et al. 2010 Khan, Shah et al. 2010 Maltsev, Kucherenko et al. 2010 Yacob, Shah et al. 2008). The 1,2,3-triazolium ionic liquid-tagged organocatalysts derived from proline and its derivatives are mostly viscous liquids at room temperature and are completely miscible with polar solvents such as methanol, chloroform, acetonitrile, dimethylsulfoxide, dimethylformamide and water. They are insoluble in less-polar solvents such as n-hexane and diethyl ether. In some cases, the ionic liquid sub-unit serves not only as a phase tag for efficient recycling but also as an effective chiral amplifier through polar interactions and steric shielding. 

FIGURE 15.1 Anatomy of an AA. Except for proline and its derivatives, all of the amino acids commonly found in proteins possess this type of structure. Illustration, Irving Geis Garrett RH, Grisham CM, Biochemistry, 3rd ed, Belmont, CA Thomson Brooks/Cole, 2005. Rights owned by Howard Hughes Medical Institute. Not to be reproduced without permission. 

L-Proline and its derivatives are often used as stereoselective catalysts in the Biginelli reactions [29-31]. This amino acid leads to the formation of enamines, key intermediates involved in the formation of Biginelli adducts (Table 4) [29]. 

FIGURE 7 Three possible key steps involved in the transfer of chirality in the BigineUi reaction catalyzed by L-proline and its derivatives. A Activation of acyHrnine by the chiral Bronsted acid B Stereoselectivy attack of chiral enamine to the acylimine C Involvement of both (A and B) activation properties on the asymmetric induction to provide chiral BigineUi adducts. 

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