γ-Halo-enones: A Method for their Synthesis from Arylacyl Halides and Their Application to the Preparation of Five-Membered Ring Heterocycles

Abstract

A simple method has been developed for synthesis of γ-halo-enones. The approach employs a sequence involving initial indium-mediated allenylation reactions of phenacyl halides with propargyl bromide. This process is followed by acid-promoted rearrangement reactions of the formed homoallenic halohydrins. The new method can be incorporated into routes for the efficient synthesis of various five-membered heterocyclic compounds.

Silver‐Catalyzed Coupling of Two CH Groups and One‐Pot Synthesis of Tetrasubstituted Furans, Thiophenes, and Pyrroles

“…Polysubstituted furans, thiophenes,and pyrroles are valuable five-membered heterocycles, since they are not only prevalent in natural products,p harmaceuticals,a grochemicals,a nd materials, buta lso useful andv ersatile building blocks in organic synthesis. [5] Despite av ariety of well-documented traditional and modernm ethods developedf or the construction of these five-membered heterocycles and their derivatives, [6][7][8] there is no general approach to access all three compounds. Therefore, ag eneral and flexible approacht os ynthesize the three polysubstituted five-membered heterocycles from easily accessible startingm aterials with as imple operation is of great significance.…”

Synthesis of Hexahydro-1H-isoindole Derivatives from Arylacyl Bromides via Homoallenic Bromohydrins

“…A mixture of homoallenic bromohydrin 2 (0.5 mmol) and FeBr 3 (59 mg, 0.2 mmol) in CH 2 Cl 2 (4 mL) was stirred at ambient temperature (25–28 °C), After 2 h, CH 2 Cl 2 (2 mL) and 2 N HCl aqueous solution (2 mL) were added to the reaction, and the mixture was transferred to a separatory funnel. The aqueous layer was back extracted with CH 2 Cl 2 (2 mL × 2).…”

“…For this purpose, we designed an approach that relies on an intramolecular [4 + 2] cycloaddition reaction of an amine tethered ene-aryldiene. Recently, we described a method for the efficient synthesis of homoallenic halohydrins 2 (Scheme ) that involves an indium-mediated allenylation reaction of arylacyl halides with propargyl bromide in aqueous media . In a manner that is similar to the reported generation of 2-halo-1,3-dienes by using halide-ion-promoted S N 2′-type substitution reactions of allenols, we observed that 2-aryl-1,4-dibromo­penta-2,4-dienes 3 can be prepared by reactions of homoallenic bromohydrins 2 with FeBr 3 .…”

“…The results show that indium-mediated allenylation reactions of arylacyl bromides with propargyl bromide in aqueous media take place to form the desired homoallenic bromohydrins in high yields along with small amounts of both the propargyl analogues and corresponding methylketones, generated by direct reduction of the arylacyl bromides. Pure homoallenic bromohydrins 2a , 2e , and 2g , obtained by using the previously described chromatographic procedure, were observed to undergo FeBr 3 -mediated S N 2′-type substitution reactions to give the respective bromo-dienes 3a , 3e , and 3g in high yields (Table , entries 1, 5, and 7). Alternatively, the crude mixtures generated in the indium-mediated allenylation reactions were subjected to the FeBr 3 -mediated S N 2′-type substitution reaction conditions.…”