1198150-38-7Relevant academic research and scientific papers
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
, p. 10570 - 10584 (2009)
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.
