The Research Of New Synthetic Methodologies Of Fe (â…¢) Catalyzed Nucleophilic Substitution Of Propargylic Acetates

A direct and reliable approach to a wide variety of allylated products is the allylic substitution reactionof allylic alcohol derivatives with nucleophiles catalyzed by transition metal. In contrast, related transitionmetal-catalyzed propargylic substitution reaction of propargylic alcohol derivatives with nucleophiles arerelatively rare. The flexibility of the alkyne functional group makes propargylic substitution reaction apivotal role in organic synthesis.The Nicholas reaction has been widely accepted as a powerful tool for propargylic substitutionreaction but has some drawbacks: a stoichiometric amount of [Co₂(CO)₈] is required, and several stepsare necessary to obtain propargylic product from propargylic alcohols via cationic propargylic complexes[Co₂(CO)₆(propargyl)]⁺. On the other hand, several transition metal-catalysed propargylic substitutionreactions have been recently reported (Figure 1). Among them, a Ruthenium-catalysed process is aversatile and direct method. A wide variety of nucleophiles such as alcohols, amines, amides and thiolsare available for this reaction. Nevertheless, with this method, the substrate is generally limited to thepropargylic alcohols bearing terminal alkyne group. More recently, Toste and Campagne have describedefficient rhenium [(dppm) ReOCl₃] and Gold [NaAuCl₄·2H₂O] catalysed nucleophilic substitution ofpropargylic alcohols respectively. However, the specific and high cost of such catalysts makes a barrier totheir large-scale use. Therefore, development of a general, efficient, cheap and readily available catalystfor propargylic substitution reaction is highly desirable.Figure 1. Nucleophilic Substitution Reactions of Propargylic Alcohols with Various NucleophilesCatalyzed by Transition-Metal ComplexesRecently, Iron(â…¢) compounds have received attention in organic synthesis due to their low toxicity,low cost and relative insensitivity to air and to small amounts of moisture. Iron(â…¢) compounds exhibitLewis acidity and they have been used in many chemical transformations. Iron trichloride is particularlyattractive for us because it is commercially available and inexpensive, especially its stability. Figure 2. Nucleophilic Substitution Reactions of Propargylic acetates with Various aromatic compoundscatalyzed by FeCl₃Herein, we have developed a general and efficient FeCl₃-catalyzed substitution reaction ofpropargylic acetates with various aromatic compounds nucleophiles (Figure 2). The correspondingpropargylic products were obtained in high yields with complete regioselectivity. In comparison withcobalt, rhenium, ruthenium and gold complexes, which are usually used to catalyse the nucleophilicsubstitution of propargylic alcohols, FeCl₃ as the catalyst offers several relevant advantages includingcheapness and commercial availability, broad scope and mild reaction conditions of this transformation.The acetylenic carbon-carbon triple bond plays a pivotal role in a variety of functional grouptransformations, which has resulted in the steady growth in the synthesis of propargylic derivatives.Unfortunately, the carbon-centered nucleophiles were limited to allyl silanes for the construction ofsp³-sp³ C-C bonds in the reaction. Recently, Matsuda and co-workers reported that Iridium complex[Ir(cod){P(OPh)₃}₂]OTf serves as a catalyst for the transformation toγ-alkynyl ketones by the coupling ofpropargylic esters with enoxysilanes. Nishibayashi team also described an efficient coupling ofpropargylic alcohols with ketones for the formation ofγ-alkynyl ketones in the presence of catalyticamount of a ruthenium catalyst. However, with this method, the propargylic alcohols bearing terminalalkyne group are the exclusive applicable substrate. Even so, the peculiarity and high cost of suchcatalysts make a barrier to their large-scale use. Therefore, development of a general, efficient, cheap andreadily available catalyst for the formation ofγ-alkynyl ketones by propargylic substitution reaction is ofsignificance.Recently, we have developed a highly efficient Iron(â…¢) or Bismuth(â…¢)-catalyzed propargylicsubstitution of propargylic alcohols or acetates with various heteroatom- and carbon-centerednucleophiles. Naturally we attempted to extend the scope of carbon-centered nucleophiles from allyl silane to ketones or enoxysilanes for the formation of y-alkynyl ketones. FeCl₃ as an efficient Lewis acidcatalyst, has been widely used in many organic synthesis. So we employed FeCl₃ to catalyze the reactionof propargylic acetates with enoxysilanes (Figure 3).Figure 3 Nucleophilic Substitution Reactions of Propargylic acetates with enoxysilanes catalyzed byFeCl₃Herein a novel and efficient procedure for the synthesis ofγ-alkynyl ketones by the substitutionreaction of propargylic acetates with enoxysilanes catalyzed by 5 mol % FeCl₃, has been developed. Thereaction completed rapidly within very short time under mild conditions and air or moisture is tolerant.Propargylic acetates bearing terminal alkyne group or internal alkyne group are readily available. Suchrelevant advantages make our procedure an appealing alternative to current available methods toγ-alkynyl ketones.Oligoaryl is an important class of compounds which exhibit a variety of fascinating properties foroptoelectronic interests. Incorporation of five-membered heteroaromatic moieties into these conjugatedmolecules will occasionally increase fluorescence quantum yields and the optoelectronic properties of theoligomers can be tuned. Most syntheses of these heteroaromatic containing oligomers involve thetransition-metal catalyzed cross coupling reactions of the corresponding aryl components. In general, thepresence of a long chain aliphatic substituent in these heteroaromatic rings will increase the solubility inorganic solvent and hence enhance the processibility of these materials. However, introduction of suchalkyl substituent at C₃ and/or C₄ positions in these heteroaromatic rings for further cross couplingreactions is not trivial. Cyclization of the 1,4-dicarbonyl moiety with heteroatom-containing reagentsprovides an alternative procedure for the construction of these five-membered heterocycles. It is knownthat annulation of allenylmethanols can afford the corresponding five-membered oxygen heterocycles. Inaddition, annulation of allenyl carbonyl compounds propargylic acetals or oxiranes furnishes a powerfularsenal for the synthesis of substituted furans. The applications of propargylic metallic species have paveda useful path for the construction of furan skeletons. We recently reported that the carbon-centered nucleophiles from allyl silane to ketones orenoxysilanes for the formation ofγ-alkynyl ketones. FeCl₃ as an efficient Lewis acid catalyst, has beenwidely used in many organic synthesis. So we employed FeCl₃ to catalyze the reaction of propargylicacetates with enoxysilanes to achieve the formation of oligomers (Figure 4).Figure 4 Nucleophilic Substitution Reactions of Propargylic acetates with enoxysilanes catalyzed byFeCl₃The photophysical properties of oligomer were briefly examined. The oligomer exhibitsfluoresecsence in the purple region with high quantum yields in CH₂Cl₂ and EtOAc. The emissionspectrum in the solvents shows vibronic fine structure. Importantly, this oligomer bears a long chainaliphatic moiety which increases the solubility for the convenience of processing leading to devices foroptoelectronic investigations. Synthesis of analogous oligomers by the FeCl₃-catalyzedsubstitution/cyclization sequential process and their potential optoelectronic applications are currentlygoing on in our laboratory.