Studies on the Synthesis of DMAP Derivatives by Diastereoselective Ugi Reactions 英文参考文献.docVIP

Molecules 2011, 16, 8815-8832; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Studies on the Synthesis of DMAP Derivatives by Diastereoselective Ugi Reactions Hiroki Mandai *, Shunsuke Irie, Koichi Mitsudo and Seiji Suga * Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan * Authors to whom correspondence should be addressed; E-Mails: mandai@cc.okayama-u.ac.jp (H.M.); suga@cc.okayama-u.ac.jp (S.S.); Tel.: +81-86-251-8604 (H.M.); Fax: +81-86-251-8082 (H.M.). Received: 17 August 2011; in revised form: 11 October 2011 / Accepted: 12 October 2011 / Published: 20 October 2011 Abstract: Diastereoselective Ugi reactions of DMAP-based aldehydes with α-amino acids and tert-butyl isocyanide were examined. The reactions of 4-(dimethylamino)-2-pyridine- carboxaldehyde with various α-amino acids afforded 2-substituted DMAP derivatives with low diastereoselectivity. On the contrary, reactions with 4-(dimethylamino)-3-pyridine- carboxaldehyde delivered 3-substituted DMAP derivatives with moderate to high diastereoselectivity. The combination of α-amino acid and DMAP-based aldehyde is thus important to achieve high diastereoselectivity. Kinetic resolution of a secondary alcohol using a chiral DMAP derivative obtained through these reactions was also examined. Keywords: multicomponent reaction; Ugi reaction; chiral DMAP; kinetic resolution 1. Introduction Multicomponent reactions are highly efficient in atom economical transformations in synthetic organic chemistry [1]. They can be used for constructing various libraries of compounds in medicinal chemistry. Among the multicomponent reactions, Ugi reaction, known as a four-component reaction, combines a carbonyl compound, an amine, a carboxylic acid, and an isonitrile to afford highly functionalized molecu