524696-51-3Relevant articles and documents
Amine-catalyzed direct aldol reactions of hydroxy- and dihydroxyacetone: Biomimetic synthesis of carbohydrates
Popik, Oskar,Pasternak-Suder, Monika,Le?niak, Katarzyna,Jawiczuk, Magdalena,Górecki, Marcin,Frelek, Jadwiga,Mlynarski, Jacek
, p. 5728 - 5739 (2014/07/08)
This article presents comprehensive studies on the application of primary, secondary, and tertiary amines as efficient organocatalysts for the de novo synthesis of ketoses and deoxyketoses. Mimicking the actions of aldolase enzymes, the synthesis of selected carbohydrates was accomplished in aqueous media by using proline- and serine-based organocatalysts. The presented methodology also provides direct access to unnatural l-carbohydrates from the (S)-glyceraldehyde precursor. Determination of the absolute configuration of all obtained sugars was feasible using a methodology consisting of concerted ECD and VCD spectroscopy.
Chiral catalysts dually functionalized with amino acid and Zn2+ complex components for enantioselective direct aldol reactions inspired by natural aldolases: Design, synthesis, complexation properties, catalytic activities, and mechanistic study
Itoh, Susumu,Kitamura, Masanori,Yamada, Yasuyuki,Aoki, Shin
experimental part, p. 10570 - 10584 (2010/05/02)
Aldolases are enzymes that catalyze stereospecific aldol reactions in a reversible manner. Naturally occurring aldolases include class I aldolases, which catalyze aldol reactions via enamine intermediates, and class II aldolases, in which Zn2+ enolates of substrates react with acceptor aldehydes. In this work, Zn2+ complexes of Lprolyl-pendant[15] aneN5 (ZnL3), Lprolyl-pendant[12]aneN4 (ZnL4), and L-valyl-pendant[12]aneN4 (ZnL5) were designed and synthesized for use as chiral catalysts for enantioselective aldol reactions. The complexation constants for L3 to L5 with Zn2+ [logKs(ZnL)] were determined to be 14.1 (for ZnL3), 7.6 (for ZnL4), and 9.6 (for ZnL5), indicating that ZnL3 is more stable than ZnL4 and ZnL 5. The depro-tonation constants of Zn2+-bound water [pKa values] for ZnL3, ZnL4, and ZnL 5 were calculated to be 9.2 (for ZnL3), 8.2 (for ZnL 4), and 8.6 (for ZnL5), suggesting that the Zn 2+ ions in ZnL3 is a less acidic Lewis acid than in ZnL4 and ZnL5. These values also indicated that the amino groups on the side chains weakly coordinate to Zn2+. We carried out aldol reactions between acetone and 2-chlorobenzaldehyde and other aldehydes in the presence of catalytic amounts of the chiral Zn2+ complexes in acetone/H2O at 25 and 37°C. Whereas ZnL3 yielded the aldol product in 43% yield and 1 % ee (R), ZnL4 and ZnL5 afforded good chemical yields and high enantioselectivities of up to 89% ee (R). UV titrations of proline and ZnL4 with acetylacetone (acac) in DMSO/H2O (1:2) indicate that ZnL4 facilitates the formation of the ZnL4.(acac)- complex (Kapp = 2.1X102M-1), whereas L-proline forms a Schiff base with acac with a very small equilibrium constant. These results suggest that the amino acid components and the Zn2+ ions in ZnL4 and ZnL5 function in a cooperative manner to generate the Zn 2+-enolate of acetone, thus permitting efficient enantioselective C-C bond formation with aldehydes.
Dual mechanism of zinc-proline catalyzed aldol reactions in water
Kofoed, Jacob,Darbre, Tamis,Reymond, Jean-Louis
, p. 1482 - 1484 (2008/02/11)
The aldol reaction of acetone with aldehydes in aqueous medium under catalysis by zinc-proline (Zn(l-Pro)2) and secondary amines such as proline, (2S,4R)-4-hydroxyproline (Hyp) and (S)-(+)-1-(2-pyrrolidinomethyl) pyrrolidine (PMP) is shown to proceed by an enamine mechanism, as evidenced by reductive trapping of the iminium intermediate, while the aldol reaction of dihydroxyacetone (DHA) under catalysis by zinc-proline and by general bases such as N-methylmorpholine (NMM) is shown to occur under rate-limiting deprotonation of the α-carbon and formation of an enolate intermediate. The Royal Society of Chemistry 2006.
