Three-component reaction of aldehydes, α-haloketones and benzoylacetonitrile and Michael addition of benzoylacetonitrile to chalcones both promoted by samarium triiodide: two routes for preparation of 1-benzoyl-1-cyano-2-aryl-3-aroylpropane derivatives

Two methods are described for preparation of 1-benzoyl-1-cyano-2-aryl-3-aroylpropane derivatives via three-component reaction of aldehydes, α-haloketones and benzoylacetonitrile or via Michael addition of benzoylacetonitrile to chalcones promoted by samarium triiodide.

Compared with the wide application of samarium{ II) species in organic systhesis 1 , less attention was paid to the application of samarium( Ill) species to that effect. However, the reports of using samarium( Ill) in mediating carbon-carbon bond formation reactions have gradually increased recently. For example, it has been reported 2 that a-haloketones could react with aldehydes to give a,P-unsaturated ketones promoted by Sml 3 . Also mediated by Sml 3 , P-diketones or P-ketoesters could condense with aldehydes to form benzylidene-substituted P-diketones or P-ketoesters 3 . Besides, catalyzed by Sml 3 , tetrahydrofuran ring could be opened with acyl chlorides or acid anhydrides to yield 4iodobutyl esters 4 · 5 . The art of performing efficient chemical transformation couflling three or more components in a single operation by a catalytic process avoiding stoichiometric toxic reagents, large amount of solvents and expensive purification technique, represents a fundamental target of the modern organic synthesis 6 • As a result, many reagents have been introduced for this purpose. For example, InC1 3 6 • 7 , ln(OTt) 3 8 , Yb(OTt)/, and BF 3 •Et 2 0 10 etc. are amongst the most commonly used reagents. Recently, Shiraishi et al. 11 have reported that Sm 111 species could mediated three-component coupling reaction of aldehydes, amines, and nitroalkanes to give pyrroles 11 . Now we wish to report that Sml 3 could promote three-component reaction of aldehydes, a-haloketones and benzoylacetonitrile to give l-benzoyl-1-cyano-2-aryl-3-aroylpropane in moderate yields (Scheme I). When aromatic aldehydes I and a-haloketones 2 were treated with 1 equiv. Sml 3 for about 2 h at room temperature, almost all of the starting materials were consumed which indicated that the corresponding intermediate a,Punsaturated ketones were readily prepared, then a solution ofbenzoylacetonitrile 3 was added to the mixture, giving 1benzoyl-1-cyano-2-aryl-3-aroylpropane derivatives 4 in moderate yields. The results are summarized in Table 1. In our experiment, the reaction conditions were well studied. We found that the use of catalytic amount ofSmi 3 (1 0%, 20% mol of Smi 3 based on aldehydes or a-haloketones) only gave lower yields of products, which indicated that use of stoichiometric amount ofSmi 3 seemed necessary for the reaction. Aromatic aldehydes were suited for the reaction while aliphatic ones were unavailable. Moreover, the reaction of aldehydes, acetophone with benzoyl acetonitrile in the same conditions could not give the corresponding adducts.

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According to our previous work 2 , a possible mechanism ofSmi 3 mediated three-component reaction of aldehydes, a-haloketoncs and benzoylacetonitrile is presented in Scheme2.
As shown in Scheme 2, the reaction may firstly form intermediate D, then further Michael addition of benzoylacetonitrile to intermediate D affording ihe product 4 via E and F. Since Sml 3 was needed to activate both a-haloketones and benzoylacetonitrile, therefore, using stoichiometric amount ofSmi 3 seemed reasonable. For comparison, pirect Michael addition of benzoylacetonitrile to chalcones promoted by Sml 3 was also used to prepare 1-benzoyl-1-cyano-2-aryl-3-aroylpropane derivatives. The results are also summarized in Table I. The Michael reaction is one of the most useful methods for the carbon-carbon bond formation and has wide synthetic application. Usually these reactions are carried out under a base condition, thus some side-reactions can not be avoided 12 • The present procedure was carried out under neutral conditions, which may overcome these problems. Besides, the resulting products bearing aroyl and/or cyano groups may be potential useful intermediates in organic synthesis because both aroyl and cyano groups could be conducted a variety of transformations. Further studies on the utilization of products 4 are now in progress.

Experimental
Tetrahydrofuran was distilled from sodium-benzophenone prior to use. All reactions were conducted under anitrogen-atmosphere. M.ps. were obtained on an electrothermal apparatus and are uncorrected. IR spectra (KBr) were recorded on a Shimadzu IR-408 spectrophotometer and 1 H NMR spect (CDCI 3 ) on a Bruker AC-400 ( 400 MHz) spectrometer, chemical shifts being expressed in ppm down field from internal tetramethylsilane.
General procedure for three component reaction of aldehydes, a-haloketones and benzoylacetonitrile : To a pale yellow suspension of Smi 3 (I mmol) in THF was added aldehyde 1 (I mmol) and a-haloketones 2 (I mmol) and stirred until I and 2 were almost consumed (monitored by TLC, about2 h), then a solution ofbenzoylacetonitrile 3 (1 mmol) was added. The mixture was refluxed for 10-12 h, then water was added and the product was extracted with diethyl ether. The organic phase was collected, dried over Na 2 S0 4 and evaporated to afford the crude product, which was purified by preparative TLC on silica gel using cyclohexane and ethyl acetate ( (0.67H,d,J 4.80 Hz,m,ArH); mlz 353 (M+); 4b (Found : C,74.46;H,4.59;N,3.70. C 24 H18CIN02 calcd. for: C,74.32;H,4.68;N,3.