Organocatalysis in Synthesis L-Proline as an Enantioselective Catalyst in the Synthesis of Pyrans and Thiopyrans 英文参考文献.docVIP

Molecules 2012, 17, 4300-4312; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Organocatalysis in Synthesis: L-Proline as an Enantioselective Catalyst in the Synthesis of Pyrans and Thiopyrans Noha M. Hilmy Elnagdi * and Noura Saad Al-Hokbany Women Students-Medical Studies Sciences Sections, Chemistry Department, College of Science, King Saud University, Riyadh, KSA, P.O. Box 22452, Riyadh 11495, Saudi Arabia * Author to whom correspondence should be addressed; E-Mail: elnagdinoha@; Tel.: +966-50-043-2102; Fax: +966-1-477-2245. Received: 26 January 2012; in revised form: 19 March 2012 / Accepted: 20 March 2012 / Published: 10 April 2012 Abstract: The multicomponent reaction (MCR) of aromatic aldehydes 1 and malononitrile (2) with active methylenes 5a–h in the presence of L-proline produced pyrans and thiopyrans 6a–h stereospecifically and in good yields. Moreover a novel MCR of ethyl propiolate (8) with 1 and 2 in the presence of L-proline to afford (R)-polysubstituted pyran is also reported. X-ray structures, e.e. and optical activity of the synthesized compounds indicated that L-proline as a catalyst is responsible for the observed enantioselectivity in the studied reactions. Keywords: L-proline; pyran; assymetric synthesis; enantioselectivity; ethyl propiolate; optical activity 1. Introduction Polyfunctionally substituted pyrans are no doubt an important class of heterocycles due to their great biological and pharmacological importance [1–6]. The addition of active methylene reagents to arylidenemalononitrile in the presence of homogeneous basic catalysts has been extensively used in the past for the synthesis of these compounds [7–12]. Interest in these reactions has recently been revived [13,14] with the aim of developing green laboratory reaction conditions [15,16], such as replacing homogeneous catalysis with heterogeneou