Asymmetric Aldol Reactions between Acetone and Benzaldehydes Catalyzed by Chiral Zn2+ Complexes of Aminoacyl 1, 4, 7, 10‐Tetraazacyclododecane: Fine‐Tuning of the Amino‐Acid Side Chains and a Revised Reaction Mechanism. Issue 9 (18th June 2013)

• Record Type: Journal Article
• Authors: Itoh, Susumu; Tokunaga, Takuya; Sonoike, Shotaro; Kitamura, Masanori; Yamano, Akihito; Aoki, Shin
• Is Part Of: Chemistry, an Asian journal. Volume 8:Issue 9(2013:Sep.)
• Page Start: 2125
• Page End: 2135
• Publication Date: 2013-06-18
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1002/asia.201300308
• Languages: English
• ISSNs: 1861-4728

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>We previously reported that chiral Zn<sup>2+</sup> complexes that were designed to mimic the actions of class‐I and class‐II aldolases catalyzed the <named-content id="d387e1195" content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">enantioselective aldol reactions</named-content> of acetone and its analogues thereof with benzaldehyde derivatives. Herein, we report the synthesis of new chiral Zn<sup>2+</sup> complexes that contain Zn<sup>2+</sup>tetraazacyclododecane (Zn<sup>2+</sup>[12]aneN<sub>4</sub>) moieties and <named-content id="d387e1214" content-type="chemicalTechnology" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">amino acids</named-content> that contain aliphatic, aromatic, anionic, cationic, and dipeptide side chains. The chemical and optical yields of the <named-content id="d387e1217" content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">aldol reaction</named-content> were improved (up to 96 % <italic>ee</italic>) by using ZnL complexes of <sc>L</sc>‐decanylglycyl‐pendant [12]aneN<sub>4</sub> (<sc>L</sc>‐ZnL<sup>7</sup>), <sc>L</sc>‐naphthylalanyl‐pendant [12]aneN<sub>4</sub> (<sc>L</sc>‐ZnL<sup>10</sup>), <sc>L</sc>‐biphenylalanyl‐pendant [12]aneN<sub>4</sub> (<sc>L</sc>‐ZnL<sup>11</sup>), and <sc>L</sc>‐phenylethylglycyl‐pendant [12]aneN<sub>4</sub> ligands (<sc>L</sc>‐ZnL<sup>12</sup>). UV/Vis and circular dichroism (CD) titrations of acetylacetone (acac) with ZnL complexes confirmed that a ZnL(acac)<sup>−</sup> complex was exclusively formed and not the enaminone of ZnL and acac, as we had previously proposed. Moreover, the results of stopped‐flow experiments indicated that the <named-content id="d387e1280" content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">complexation</named-content> of (acac)<sup>−</sup> with ZnL was complete within milliseconds, whereas the formation of an enaminone required several hours. X‐ray crystal‐structure analysis of <sc>L</sc>‐ZnL<sup>10</sup> and the ZnL complex of <sc>L</sc>‐diphenylalanyl‐pendant [12]aneN<sub>4</sub> (<sc>L</sc>‐ZnL<sup>13</sup>) shows that the NH<sub>2</sub> groups of the amino‐acid side chains of these ligands are coordinated to the Zn<sup>2+</sup> center as the fourth coordination site, in addition to three nitrogen atoms of the [12]aneN<sub>4</sub> rings. The reaction mechanism of these <named-content id="d387e1315" content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">aldol reactions</named-content> is discussed and some corrections are made to our previous mechanistic hypothesis.</p> </abstract>