A new method has been introduced that is able to tackle the complexities of N-C(O) activation in amide moieties through utilization of pyrylium tetrafluoroborate in a mechanochemical setting, where amide bonds undergo activation and subsequent conversion to biaryl ketones. Due to the employment of a mechanochemical setting, the reaction conforms to green chemistry principles, offering an environmentally friendly approach to traditional amide derivatization techniques that rely on transition metals to achieve further functionalization.

A convenient one-pot procedure for the mechanochemical nanocellulose-supported synthesis of trifluoromethyl arenes has been developed through the selective transformation of an aromatic amino group into the trifluoromethyl functionality using pyrylium tetrafluoroborate (Pyry-BF4) and trifluoromethyltrimethylsilane (TMSCF3) via in situ formation of the pyridinium salt intermediate under transition metal-free conditions. The nanocellulose acts here as a green reaction medium, and the reaction does not occur without this additive. The scope of the present protocol includes synthesis of 28 trifluoromethyl arenes in excellent yields via a selective (ipso-)substitution (SNAr) of aromatic amino group with CF3 functionality. This method could have a great significance in pharmaceutical industries for the late-stage functionalization of active pharmaceutical ingredients (APIs)/drugs.

Aryl trifluoromethyl ethers (ArOCF₃) are important structural motifs in pharmaceuticals, agrochemicals, and functional materials. However, the methods reported for the efficient synthesis of these scaffolds are extremely underdeveloped and limited. Here, we report a highly efficient mechanochemical approach for the selective transformation of aryltrimethylammonium triflates, aryldiazonium tetrafluoroborates, and aryl pinacolboranes to aryl trifluoromethyl ethers via in situ-generated OCF₃ source using triphosgene and Co(II) fluoride (CoF₂). The proposed synthetic protocol also shows potential for the selective transformation of other groups such as arylsulfonium and diaryliodonium functionalities. The present trifluoromethoxylation strategy exhibited a broad functional group tolerance and found to be superior over other existing protocols in terms of substrate scope, yields, operational simplicity, and reaction times.

The development of an efficient alternative to the widely employed Balz-Schiemann deaminative fluorination method (i. e. without using aryl diazonium tetrafluoroborate salt) is a challenging task. Herein, we report a convenient one-pot method for the FeCl3-nanocellullose mediated mechanochemical synthesis of fluoroarenes through the selective substitution of an aromatic amino group by fluorine group using pyrylium tetrafluoroborate (Pyry-BF4) and sodium fluoride (NaF) via in situ formation of pyridinium salt intermediate. The scope of the present protocol includes synthesis of thirty-four organofluorine compounds with excellent yields via a selective substitution (SNAr) of an amino group by fluorine. The presented concise methodology opens a pathway to access new chemical spaces for the late-stage functionalization in pharmaceutical industries.

Direct and selective transformation of the phenolic hydroxy group in a concise way without prior derivatization is relevant in many industrial processes, particularly late-stage modification of pharmaceuticals and for lignin-material treatment. The introduction of fluorine has a profound impact on the molecular properties of both small molecules and biopolymers. Herein, we report a Ru-catalyzed transformation of phenols into trifluoromethyl-arenes under mechanochemical conditions. The protocol accepts a wide scope of starting materials and allows for gram-scale synthesis in excellent yields. The developed approach may offer an important alternative to known methods in the context of PASE (pot, atom, and step economy) synthesis and, therefore, green chemistry.

Activation of phenols by a Ru-catalyst allows for the resulting η⁵-phenoxo complex to selectively react with a variety of nucleophiles under mechanochemical conditions. Conversion of phenolic hydroxy groups without derivatization is important for late-stage modifications of pharmaceuticals and in the context of lignin-material processing. We present a one-step, Ru-catalyzed cross-coupling of phenols with boronic acids, aryl trialkoxysilanes and potassium benzoyltrifluoroborates under mechano-chemical conditions. The protocol accepts a wide scope of starting materials and allows for gram-scale synthesis in excellent yields. The developed approach constitutes a very interesting and waste-limiting alternative to the known methods.

Since the introduction of the TM-catalyzed cross-couplings their scope of starting materials has been growing systematically, allowing for more flexible design of synthetic routes with the coupling as a key step, particularly late-stage modifications. Herein we present the use of trifluoromethoxyarenes as halide surrogates in Ni-catalyzed couplings with arylboronic acids, potassium aryl trifluoroborates and aryl trialkoxysilanes, under mechanochemical conditions. In total, 22 biphenyl structures were obtained in good yields. Successful gram scale experiments confirm the usefulness of our protocol. The developed transformations’ mechanism was discussed in relation to the experimental and literature data and DFT calculations. The unusual reactivity of potassium benzoyltrifluoroborates was uncovered. 6 examples of resulting benzophenones were obtained in very good yields and the protocol was extended to gram scale. The described methods present a powerful tool when combined with the recent advances in organofluorine chemistry.

An alternative strategy for the mechanochemical defluorinative acylation of ortho-hydroxyarylenaminones has been developed to synthesise 3-acylchromones utilizing CF3-compounds via activation of the C−F bound of the trifluoromethyl group in the presence of ytterbia (Yb2O3). The current protocol tolerated a wide range of coupling substrates to access a library of diversely substituted 3-acylchromones under the mechanochemically induced domino cyclisation mode. This is the first report for the deflourinative transformation of the inert CF3 group to the corresponding carbonyl functionality under the mechanochemical conditions.

The amide bond is prominent in natural and synthetic organic molecules endowed with activity in various fields. Among a wide array of amide synthetic methods, substitution on a pre-existing (O)C-N moiety is an underexplored strategy for the synthesis of amides. In this work, we disclose a new protocol for the defluorinative arylation of aliphatic and aromatic trifluoroacetamides yielding aromatic amides. The mechanochemically induced reaction of either arylboronic acids, trimethoxyphenylsilanes, diaryliodonium salts, or dimethyl(phenyl)sulfonium salts with trifluoroacetamides affords substituted aromatic amides in good to excellent yields. These nickel-catalyzed reactions are enabled by C-CF3 bond activation using Dy2O3 as an additive. The current protocol provides versatile and scalable routes for accessing a wide variety of substituted aromatic amides. Moreover, the protocol described in this work overcomes the drawbacks and limitations in the previously reported methods.

Among a wide array of synthetic amides, N-aryl/alkyl amides are an important class of structural motifs having significant importance in pharmaceutical and agrochemical industries. In this regard, a rapid, low-cost, and environmentally friendly synthesis of N-aryl/alkyl amides still remains in a high demand. Herein, we report a convenient route for the mechanochemical synthesis of N-aryl/alkyl amides via FeCl3-catalyzed reductive amidation of nitro compounds, as well as acylation of aliphatic/aromatic amines with carboxylic acids using nanocellulose as the reaction media/stoichiometric reducing agent. The protocol was found to be simple, efficient, and environmentally benign to obtain a diverse array of the respective amides with good to excellent yields. Furthermore, the use of nitro compounds, amines, and carboxylic acids as cheap and readily available starting materials, FeCl3 as a nontoxic catalyst, and nanocellulose as the biodegradable reaction media as well as the stoichiometric reducing agent makes this protocol in the category of a green chemical transformation.