Reactions of fluorinated silanes with 2-nitrocinnamates Artem A. Zemtsov, Vitalij V. Levin, Alexander D. Dilman *, Marina I. Struchkova, Vladimir A. Tartakovsky N.D. Zelinsky Institute of Organic Chemistry, 119991 Moscow, Leninsky Prospect 47, Russia 1. Introduction Silicon reagents bearing a fluorinated group have become valuable reagents as synthetic equivalents of fluorinated carba- nions [1]. While the major attention has been devoted to trifluoromethylation reactions using Me 3 SiCF 3 (the Ruppert– Prakash reagent), silanes with other fluorinated or fluorine- containing fragments have also been exploited due to convenience of their handling and mild reaction conditions [2,3]. The reactions are typically carried out in the presence of Lewis basic activator which interacts with the silane to generate five- coordinate species followed by transfer of the fluorinated carbanion from silicon to electrophile. The interaction of silanes with C 55 O and C 55 N bonds is very well developed [1], whereas addition of fluorinated group to C 55 C bond still has a limited scope [4–8]. Thus, recently we have demonstrated that highly electrophilic Michael acceptors such as arylidenemalononitriles [6] and arylidene Meldrum’s acids [7], which bear two electron-with- drawing substituents, serve as suitable substrates for the coupling with Me 3 SiCF 3 . We also showed that a,b-unsaturated nitriles, esters and ketones containing additional activating acetoxy group (acylated Baylis–Hillman adducts) can be pentafluorophenylated with the use of complicated silanes Me n Si(C 6 F 5 ) 4Àn [8]. In continuation of these studies, herein we report the reactions of trimethylsilicon reagents Me 3 SiR f with 2-nitrocinnamates. The products of this reaction can be considered as precursors to a- amino acids bearing a fluorinated group in b-position [9]. 2. Results and discussion 2-Nitrocinnamates 1 were obtained from aldehydes or their N- phenylimines and methyl nitro acetate by Knoevenagel condensa- tion [10] (Scheme 1). Compounds 1 were isolated as mixtures of geometrical isomers. Nitrocinnamate 1a (mixture of isomers 1.6:1) was selected as a model substrate and its reaction with the Ruppert–Prakash reagent was investigated (Table 1). Performing the reaction in DMF with stoichiometric amount of sodium acetate as basic activator provides desired product 2a in reasonable yields as a 1:1 mixture of diastereoisomers (entries 1– 3). The variation of temperature and time had no effect on the product yield. We also tested analogous substrate with the tert- butyl instead of methyl ester group, that gave identical result (68% yield). When the amount of Lewis base was decreased to 10 mol%, virtually no product was formed, suggesting that the nitronate anion, which is produced after the addition of CF 3 -carbanion at C 55 C bond, cannot activate the silicon reagent. For the variation of solvent, we used tetrabutylammonium acetate, which was reported to be effective activator of the Ruppert–Prakash reagent in different media [11]. Thus, we observed that the reaction of 1a with Me 3 SiCF 3 in tetrahydrofuran or toluene promoted by Bu 4 NOAc (1.2 equiv.) occurs rapidly and exothermically, but affords the product 2a in only 70% yield. However, decreasing the reaction temperature significantly slowed down the process (entries 8–11). Finally, the best result was obtained when reaction was performed in dichloromethane at À20 8C furnishing 2a in 82% isolated yield (entry 12). Based on the optimization studies, two procedures were selected for further investigation: method A involving NaOAc in DMF, and method B involving Bu 4 NOAc in dichloromethane. The Journal of Fluorine Chemistry 132 (2011) 378–381 A R T I C L E I N F O Article history: Received 7 February 2011 Received in revised form 10 March 2011 Accepted 12 March 2011 Available online 30 March 2011 Keywords: The Ruppert–Prakash reagent Silanes Conjugate addition Nitro alkenes A B S T R A C T The interaction of 2-nitrocinnamates with silicon reagents Me 3 SiR f (R f = CF 3 , C 2 F 5 , and C 6 F 5 ) promoted either by sodium acetate in DMF or by tetrabutylammonium acetate in dichloromethane has been described. The reactions proceed as conjugate addition of fluorinated carbanion at the C 55 C bond and afford 3-aryl-2-nitrobutanoates bearing a fluorinated substituent in good yields as diastereomeric mixtures in ratio from 1:1 to 1.6:1. ß 2011 Elsevier B.V. All rights reserved. * Corresponding author. Fax: +7 499 135 53 28. E-mail address: adil25@mail.ru (A.D. Dilman). Contents lists available at ScienceDirect Journal of Fluorine Chemistry jo ur n al h o mep ag e: www .elsevier .c om /loc ate/f luo r 0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.jfluchem.2011.03.015