Application Of FeCl₃ In The Synthesis Of Propargylic Derivatives

Because an acetylenic carbon-carbon triple bond plays a pivotal role in variety of transformations, interests in the synthesis of propargylic derivatives has been steadily growing. The Nicholas reaction has been widely accepted as a powerful tool for propargylic substitution reaction but has some drawbacks: a stoichiometric amount of [Co₂(CO)₈] is required, and several steps are necessary to obtain propargylic substances from propargylic alcohols via cationic propargylic complexes [Co₂(CO)₆(propargyl)]⁺. On the other hand, several transition metal compounds such as ruthenium, rhenium, gold and titanium have been recently developed to catalyzed propargylic substitution reactions. However, all of them have some disadvantage such as the substrate is generally limited to the propargylic alcohols bearing terminal alkyne group, or catalysts are specific and high cost and not environmentally friendly, and difficult to handle. Therefore, development of a general, efficient, cheap, and commercially available catalyst for propargylic substitution reaction is highly desirable.Herein, we describe an efficient FeCl3-catalyzed nucleophilic substitution reaction of propargylic acetates with alcohols, thiols, sp³-C-O sp³-C-S bonds were formed after the etherification event. The reaction was carried out at room temperature in the presence of catalytic amount of FeCl₃ in acetonitrile, high yields were obtained with complete regioselectivities and the reaction proceeded smoothly without exclusion of moisture or air (Figure 1). Because the alkyne moiety offers a handle for transformation into various other functional groups, the propargylic substitution reactions have became an important and powerful tool for the construction of complex molecules. Some transition-metal complexes were developed to catalyze the propargylic substitution reactions of propargylic alcohols with nucleophiles, where most of the nucleophiles were heteroatom-centered such as alcohols, thiols, amides and so on; In contrast, the carbon-centered nucleophiles were unfortunately limited to allyl silanes for the construction of sp³-sp³ C-C bonds in the reaction.Becauseγ-alkynyl ketones with sp³-sp³ C-C bonds play an very important role in the organic synthesis. We found that when employing enoxysilanes as the carbon-centered nucleophiles, propargylic acetates displacing propargylic alcohols as the substrates, the reaction proceeded rapidly in the presence of 5 mol % FeCl₃ and efficiently afforded correspondingγ-alkynyl ketones in high yields. Herein we reported the successful results and scope of the reactions.Indolylglycines are an important class of non-proteinogenic amino acids, which are very useful building blocks for the synthesis of many biologically important compounds such as dragmacidins, cephalosporin, andemedolac. Several methods for the synthesis of a range of indolylglycine derivatives have appeared. The Friedel–Crafts alkylation reaction is one of the most efficient methods for the construction of carbon–carbon bonds to aromatics and heteroaromatics. In general, the reaction requires a stoichiometric amount or catalytic amount of Lewis acid, Bronsted acid, or organocatalyst, as well as organic solvents. Recently, organic reactions under solvent-free conditions have attracted considerable attention due to the advantages in terms of green chemistry. Furthermore, recently, the development of solvent- free and multicomponentreactions is also of great concern. However, in most cases, the solvent-free reaction requires microwave or ultrasound irradiation. Palmieri reported a solvent solventfree asymmetric three-component aminoalkylation reaction for the synthesis of aminoalkylnaphthols by heating the reaction mixture at 60°C. Herein, we would like to report our initial results on the three component Friedel-Crafts reaction of indoles, glyoxylate, and amines under solvent- and catalyst-free conditions at ambient temperature for the convenient synthesis of (3-indolyl)glycine derivatives.