Substrate-Controlled Regiodivergent Synthesis of Fluoroacylated Carbazoles via Friedel–Crafts Acylation

Abstract

A general, efficient, and substrate-controlled regiodivergent trifluoroacetylation of carbazoles has been developed through Friedel–Crafts acylation. This strategy was applicable to a wide scope of readily available substituted carbazoles at air atmosphere without using a metal catalyst, affording the corresponding trifluoroacetylated carbazoles in up to 99% yield. The divergency of the products and the orientation rules have been illustrated based on different substituents on carbazole rings. This method could also be extended to the synthesis of chlorodifluoroacetylated and pentafluoropropionylated carbazoles, which have been achieved for the first time.

BF3-Mediated Acetylation of Pyrazolo[1,5-a]pyrimidines and Other π-Excedent (N-Hetero)arenes

“…Acylation reaction is a fundamental and valuable transformation in organic synthesis and is often employed in manufacturing various pharmaceuticals, cosmetics, and agrochemicals. − Furthermore, acylated compounds are of great interest because they have demonstrated utility as functional substrates in constructing more complex structures with remarkable biological and physicochemical properties. − Many strategies have been developed to incorporate the acyl group into aromatic compounds, such as radical transformations, ,, metal acylation, − and the well-established Friedel–Crafts acylation. − However, except for formylation reactions, very few approaches are used to acetylate or acylate N -heteroaromatic rings. These scaffolds are of considerable interest due to their frequent biological and photophysical applications. − …”

One-pot synthesis of tri- and di-fluoromethylated bis(indolyl)methanols via Friedel–Crafts-type acylation and alkylation

“…13 C NMR (126 MHz, acetone-d6): δ ( ppm) = 137.0, 130. 7,129.1,127.2 (q,J = 287.3 Hz),125.0,124.5,113.4,113.1,112.4,75.6 (q,J = 31.5 Hz) 3ka: The general experimental procedure was followed to afford product 3ka as a white solid (41.6 mg, 55% yield). 1 H NMR (500 MHz,: δ ( ppm) = 7.92 (s, 2H), 7.41 (d,J = 8.5 Hz,2H),7.29 (s,2H),7.27 (d,J = 8.5 Hz,2H),5.77 (brs,OH),3.85 (s,6H).…”

“…As part of our ongoing research interest in the synthesis of fluorinated heteroaromatics, 7 we herein report the synthesis of tri- and di-fluoromethylated bis(indolyl)methanols via a one-pot Friedel–Crafts-type acylation–alkylation (Scheme 1c). This simple and efficient methodology employs indoles as the substrates and readily available fluorinated acids as the solvent as well as substrates, requires no metal, additive or toxic solvent, and proceeds smoothly under an air atmosphere.…”

Metal‐Free One‐Pot Synthesis of Tri‐ and Difluoromethylated Bis(carbazolyl)methanes

“…Trifluoromethylated polymers possess impressive high chemical and heat resistance, high flame retardancy and low friction coefficient, which have been widely used in the areas such as microelectronics and aerospace [8] . Despite these notable advantages, methods for combining trifluoromethyl groups with carbazole‐frameworks remain rare [9] . In year 2021, Nguyen, Koenigs and co‐workers reported the only example of the synthesis of trifluoromethylated bis(carbazolyl)phenylmethane with moderate yield in their elegant studies on the multiple C−H functionalization of carbazoles, in which trifluoromethylated diazoalkane was used as the trifluoromethylation reagent to react with 9‐methyl‐carbazole under the promotion of Au and Ag catalysts (Scheme 1a) [10] .…”

“…[8] Despite these notable advantages, methods for combining trifluoromethyl groups with carbazole-frameworks remain rare. [9] In year 2021, Nguyen, Koenigs and co-workers reported the only example of the synthesis of trifluoromethylated bis(carbazolyl)phenylmethane with moderate yield in their elegant studies on the multiple CÀ H functionalization of carbazoles, in which trifluoromethylated diazoalkane was used as the trifluoromethylation reagent to react with 9-methyl-carbazole under the promotion of Au and Ag catalysts (Scheme 1a). [10] Thus, the development of simple and inexpensive methodologies for the efficient and regioselective synthesis of trifluoromethylated bis(carbazolyl)methanes (BCMs) are still highly desirable.…”