Enantio and Diastereoselective Addition of Phenylacetylene to Racemic α-chloroketones.docVIP

Molecules 2011, 16, 5298-5314; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Enantio and Diastereoselective Addition of Phenylacetylene to Racemic α-chloroketones Silvia Alesi, Enrico Emer, Montse Guiteras Capdevila, Diego Petruzziello, Andrea Gualandi and Pier Giorgio Cozzi * Alma Mater Studiorum, Dipartimento di Chimica “G: Ciamician”, Università di Bologna, Via Selmi 2, 40126 Bologna, Italy * Author to whom correspondence should be addressed; E-Mail: piergiorgio.cozzi@unibo.it; Tel.: +39-051-209-9511; Fax: +39-051-209-9456. Received: 26 May 2011; in revised form: 17 June 2011 / Accepted: 22 June 2011 / Published: 23 June 2011 Abstract: In this report, we have presented the first diastereoselective addition of phenylacetylene to chiral racemic chloroketones. The addition is controlled by the reactivity of the chloroketones that allowed the stereoselective reaction to be performed at –20 °C. Chiral racemic chloroketones are used in the reaction. By carefully controlling the temperature and the reaction time we were able to isolate the corresponding products in moderate yields and with good, simple and predictable facial stereoselection. Our reaction is a rare example of the use of chiral ketones in an enantioselective alkynylation reaction and opens new perspectives for the formation of chiral quaternary stereocenters. Keywords: alkynylation; (R,R)-salen; chloroketones; Me2Zn; phenylacetylene 1. Introduction The addition of carbon nucleophiles to reactive electrophilic functions, such as C=O and C=N double bonds, is a process of fundamental importance in the development of chemical synthesis [1,2]. Among the various nucleophilic species available, alkynes are excellent reagents for mild and selective C-C bond forming reactions [3-5]. In 2005, we found that mixtures of Me2Zn and acetylenes are able to promote the room temperature alkynylation of alde