One-step reduction of chalcones to saturated alcohols by ammonium

Transcription

1 ne-step reduction of chalcones to saturated alcohols by ammonium formate/palladium on carbon: a versatile method. arlos Kleber Z. Andrade *, Wender A. Silva Laboratório de Química Metodológica e rgânica Sintética (LaQMS), Instituto de Química, Universidade de Brasília,.P. 4478, , Brasília, DF, Brazil Fax: ckleber@unb.br Abstract: Several chalcones are reduced directly to the corresponding saturated alcohols, in a catalytic transfer hydrogenation process, by use of the ammonium formate/palladium on carbon system in very good yields. Key words: halcones, catalytic transfer hydrogenation (T), ammonium formate.

2 Introduction Molecular hydrogen is widely used in catalytic hydrogenation of double bonds despite the risks associated with this gas. Also, this reaction usually requires high pressure equipments. These drawbacks can be overcome in catalytic transfer hydrogenations (T) in which a stable hydrogen donor is used instead of hydrogen gas [1]. ne of the most common hydrogen donors is ammonium formate [2], a versatile inexpensive and nontoxic reagent already employed in the reduction of compounds such as azides [3], nitriles [4] or aldehydes and ketones [5]. These reductions can proceed under homogeneous or heterogeneous conditions. In the latter case, palladium on carbon is usually used as catalyst. The ammonium formate/palladium on carbon system has been recently described to effectively reduce carbon-carbon double bonds in steroidal olefins [6]. In this paper, we wish to describe a versatile method for the one-step reduction of chalcones using ammonium formate and Pd/ 5%, in methanol at room temperature. halcones are an interesting class of α,β-unsaturated carbonyl compounds for which several methods of selective reduction of either the carbonyl [7] or the = double bond [8] have been accomplished. Nevertheless, to the best of our knowledge, there is only one report of a systematic study on the one-step reduction of chalcones, which employs the Inl 3 /NaB 4 system [9]. ther systems have also been found to completely reduce chalcones but only isolated examples were reported [7,10]. Results and Discussion Several chalcones were prepared under basic conditions using a known procedure [11]. The results of the reductions are shown in Table 1 [12,13].

3 Table 1. Reductions of chalcones by ammonium formate/ palladium on carbon [12,13]. R 2 R 3 2 N 4 Pd/ 5%, Me r.t. R 2 R 3 Entry halcone Time (h) Product Yield (%) a N N N N 95 7 Me 3 Me 95

4 8 2 Me Me Fe Fe 11 Ph 12 Ph a Isolated Yields of the chromatographically pure products. Excellent yields were obtained in all cases and the reactions went to completion in short times furnishing the corresponding saturated alcohols (entries 1-8). eteroaromatic chalcones and chalcones with either electron withdrawing or electron donating substituents attached to the aromatic rings underwent reduction easily. Sensitive groups such as nitro and fufuryl were not affected (entries 3-6). The ferrocenyl substituted chalcone was also smoothly reduced (entry 10). It is worth mentioning that the reduction of chalcones by conventional reducing agents such as NaB 4 in Me and LiAl 4 in ether gave the allyl alcohols or a mixture of products, respectively [9]. This reduction was also problematic when indium metal was used [14].

5 A different outcome was achieved when the analogue derived from cinnamaldehyde was used. In this case, both = double bonds were reduced furnishing the saturated ketone in almost quantitative yield (entry 11). At least two other methods have been shown to produce the same result [8b,c]. This is in sharp contrast to the reduction of this same compound using the Inl 3 /NaB 4 system in which the γ,δ-unsaturated alcohol was obtained as the only product [9]. The proposed mechanism for this reaction is depicted in Scheme 1, based on the work of Ram and Spicer [15]. R + R Pd Pd 0 R Pd R 2 2 Pd 0 R Pd 2 - R 2 2 Pd + R Pd 0 Scheme 1

6 onclusion In summary, the ammonium formate/palladium on carbon system proved to be very efficient and versatile for the one-step reduction of chalcones. The reaction workup is simple and the products were easily obtained in excellent yields under mild conditions at room temperature, in short reaction times and without the need for high pressures and explosive hydrogen gas. Acknowledgment The authors thank the Instituto de Química, Universidade de Brasília, for financial support, FINEP-T INFRA nº 0970/01, and APES for fellowship. References [1] a) Brieger, G.; Nestrick, T.J. hem. Rev. 1974, 74, 657. b) Johnstone, R. A. W.; Wilby, A..; Entwistle, I. D. hem. Rev. 1985, 85, 129. [2] Ram. S.; Ehrenkaufer, R. E. Synthesis 1988, 91. [3] Gartiser, T.; Selve,.; Delpuech, J. J. Tetrahedron Lett. 1983, 24, [4] Brown, G. R.; Foubister, A. J. Synthesis 1982, [5] Ram, S.; Spicer, L. D. Tetrahedron Lett. 1988, 29, [6] Paryzek, Z.; Koenig,.; Tabaczka, B. Synthesis 2003, [7] Alonso F.; Yus, M. Tetrahedron 1998, 54, [8] a) Basu, B.; Bhuiyan, M..; Das, P.; ossain, I. Tetrahedron Lett. 2003, 44, b) Tian, F.; Lu, S. Synlett 2004, c) Sajiki,.; Ikawa, T.; Yamada,.; Tsubouchi, K.; irota K. Tetrahedron Lett. 2003, 44, 171. d) Nielsen, S. F.; Kharazmi, A.; hristensen, S.

7 B. Bioorg. Med. hem. Lett. 1998, 6, 937. e) Keinam, E.; Greenspoon, N. J. Am. hem. Soc. 1986, 108, [9] Ranu, B..; Samanta, S. Tetrahedron 2003, 59, [10] a) Alonso F.; Vitale,.; Radivoy, G.; Yus, M. Synthesis 2003, 443. b) attori, K.; Sajiki,.; irota, K. Tetrahedron 2001, 57, [11] [12] Typical experimental procedure: to a solution of the chalcone (1.00 mmol) in Me (3 ml) at room temperature, was added Pd/ 5% (0.15 mmol). The resulting suspension was stirred vigorously and ammonium formate (8.00 mmol) was then added portionwise. Stirring was continued until no starting material has left as confirmed by TL. The reaction was filtered and the organic phase was dried with Na 2 S 4 and concentrated at reduced pressure to furnish the crude product, which was purified by silica gel chromatography (30% EtAc in hexanes). [13] All the compounds gave satisfactory spectroscopic data. Data for selected compounds are given below: [14] a) Ranu, B..; Dutta, J.; Guchhait, S. K. rg. Lett. 2001, 3, b) Pitts, M. R.; arrison, J. R.; Moody,. J. J. hem. Soc., Perkin Trans , 955. [15] a) Ram, S.; Spicer, L. D. Synth. ommun. 1992, 22, b) Ram, S.; Spicer, L. D. Synth. ommun. 1992, 22, 2683.