| For their unique structure and reactivity, propargylic derivatives are accepted as useful synthetic intermediates. The acetylenic carbon-carbon triple bond can be flexibly converted to many other functional groups. Propargylic substitution occurs when propargylic position is activated by the coordination of carbon-carbon triple with transition metals. These make them important in organic synthesis.Nucleophilic substitution of propargylic alcohols with aromatic compounds is a very useful reaction. The Nicholas reaction has been widely accepted as a powerful tool for this transformation but has some drawbacks: a stoichiometric amount of [Co2(CO)8] is required, and several steps are necessary to obtain propargylic product from propargylic alcohols via cationic propargylic complexes [Co2(CO)6(propargyl)]+. On the other hand, several transition metal- or acid-catalyzed propargylation of aromatic compounds has been recently reported. Among them, a Ruthenium-catalyzed process is a versatile and direct method. Nevertheless, with this method, the substrate is generally limited to the propargylic alcohols bearing terminal alkyne group. More recently, Toste and Campagne have described efficient rhenium [(dppm) ReOCl3] and Gold [NaAuCl4·2H2O] catalyzed nucleophilic substitution of propargylic alcohols respectively. However, the specific and high cost of such catalysts makes a barrier to their large-scale use. Therefore, development of a general, efficient, cheap and readily available catalyst for propargylation of aromatic compounds is of importance.Herein, we report a general and efficient FeCl3-catalyzed substitution reaction of propargylic alcohols with aromatic compounds (Figure 1). The corresponding propargylic aromatic compounds were obtained in high yields under very mild reaction conditions. In comparison with cobalt, rhenium, ruthenium and gold complexes, which are usually used in such reactions, FeCl3 as the catalyst offers several relevant advantages including cheapness and commercial availability, operational simplicity and mild reaction conditions of this transformation. The alkylation of 1,3-dicarbonyl compounds represents one of the most useful methodologies for carbon-carbon bond formation. Usually, this process requires the use of a stoichiometric amount of base and an organic halide as the alkylating agent. An alternative approach, via acid-catalyzed addition of active methylenes to alcohols, would provide a more atom-economical process. However, this strategy still remains a major goal of modern organic synthesis.Recently, some catalytic methodologies for the direct substitution of propargylic alcohols in the presence of ruthenium, rhenium, or gold catalysts have been reported. Nevertheless, the use of 1,3-dicarbonyl compounds as nucleophiles has not been well established in any of these works. Of late, nucleophilic substitution of 1,3-dicarbonyl compounds with propargylic alcohols promoted by trifluoroacetic acid or p-toluenesulfonic acid monohydrate were reported. However, many sensitive functional groups are not tolerant in acidic conditions.We have disclosed that FeCl3 is an efficient catalyst for the propargylic substitution of propargylic alcohols with carbon-, oxygen-, nitrogen- or sulfur-centered nucleophiles. The efficiency of this environmentally friendly methodology led us to explore the scope of such a substitution reaction on propargylic derivatives. Herein, we described a rapid entry toγ-alkynyl ketones by the direct substitution of propargylic acetates with 1,3-dicarbonyl compounds in the presence of catalytic amount of FeCl3.γ-Alkynyl ketones were obtained in good yields under mild conditions (Figure 2). Polysubstituted furans represent an important class of five-membered heterocycles that can be broadly found as structural elements of many natural products and pharmaceutically important substances. Furthermore, they can be employed as useful intermediates in synthetic chemistry. Therefore, a tremendous number of synthetic methods to approach substituted furans are known.Classical approaches to substituted furans have involved the cyclocondensation of dicarbonyl compounds or equivalents, or the substitution of an existing furan ring. Alternative strategies have explored the cycloisomerization of alkyne- and allene-containing compounds. However, there are some limitations, including ease of access to allenyl substrates that contain sensitive functional groups and the inability to provide furans with high flexibility regarding their substitution pattern. For these reasons, the development of routes that allow the facile assembly of substituted furans under mild conditions from simple readily available starting materials remains an important objective.It has been knownγ-alkynyl ketones may be cyclized to furans under acidic conditions. It seems that this route to furans has been limited by ready access toγ-alkynyl ketones and by moderate yields in the cyclization step. We now report an approach to furans fromγ-alkynyl ketones which addresses both of these issues (Figure 3).γ-Alkynyl ketone intermediates were firstly obtained by the nucleophilic substitution of propargylic acetates with enoxysilanes or 1,3-dicarbonyl compounds in the presence of catalytic amount FeCl3; and then without isolation, the intermediates were converted to polysubstituted furans promoted by p-toluenesulfonic acid. Functional groups, such as chloro, cyano and methoxyl were tolerant in the tandem process, which allow an access to other functionalized furans. Acyl furans were obtained whenβ-dicarbonyl compounds act as nucleophiles. Figure 3. Synthesis of polysubstituted furans promoted by FeCl3/PTSA...
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