Enantioselective, Organocatalytic Morita-Baylis-Hillman and Aza-Morita-Baylis-Hillman Reactions Stereochemical Issues.docVIP

Molecules 2010, 15, 709-734; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Review Enantioselective, Organocatalytic Morita-Baylis-Hillman and Aza-Morita-Baylis-Hillman Reactions: Stereochemical Issues Javier Mansilla and José M. Saá * Departamento de Química, Universidad de las Islas Baleares, 07122, Palma de Mallorca, Spain * Author to whom correspondence should be addressed; E-Mail: jmsaa@uib.es. Received: 19 January 2010; in revised form: 25 January 2010 / Accepted: 29 January 2010 / Published: 1 February 2010 Abstract: Conscious of the importance that stereochemical issues may have on the design of efficient organocatalyts for both Morita-Baylis-Hillman and aza-Morita-Baylis-Hillman reaction we have analyzed them in this minireview. The so-called standard reactions involve “naked” enolates which therefore should lead to the syn adducts as the major products, irrespective of the E, Z stereochemistry of the enolate. Accordingly, provided the second step is rate determining step, the design of successful bifunctional or polyfunctional catalysts has to consider the geometrical requirements imposed by the transition structures of the second step of these reactions. On the other hand, MBH and aza-MBH reactions co- catalyzed by (S)-proline and a secondary or tertiary amine (co-catalyst) involve the aldol- type condensation of either a 3-amino-substituted enamine, dienamine, or both, depending on the cases. A Zimmerman-Traxler mechanism defines the stereochemical issues regarding these co-catalyzed condensations which parallel those of the well established (S)-proline catalyzed aldol-like reactions. Keywords: Morita-Baylis-Hillman reaction; aza-Morita-Baylis-Hillman reaction; stereochemistry; bifunctional catalysts; polyfunctional catalysts; (S)-proline-amine co- catalysis  Molecules 2010, 15 710 1. Introduction The original Morita-Baylis-Hillman (MBH) react