The development of efficienta nd mild methods for the synthesis of organofluorine compounds is of foremost interest in various fields of chemistry.Adirect pyrimidine-based selective meta-CÀHp erfluoroalkenylationo f arenes involving several commerciallya vailable perfluoroolefins is described. The synthetic versatility of the protocol is demonstrated by an extensive substrate scopei ncludingd ifferent benzylsulfonyl, alkylarene and phenylacetic acid scaffolds. The generality of this methodology includingt he meta-CÀHp erfluoroalkenylation of Ibuprofen, the facile cleavageo ft he directing group and gram-scale reactions are presented.Fluorine-containingc ompounds are knownt op lay ap ivotal role in pharmaceutical/medicinal chemistry,b ut also in agrochemicala nd material sciences.F luorinea nd in particular the incorporation of CÀFb onds into organic molecules strongly influence their properties such as thermals tability,h igh chemical inertness ands olubility in organic solvents. [1] Bioavailability and metabolic stabilitya re commonlyi ncreased by substitution with fluorine atoms. [2] Alkenes and aromatic moieties bearing perfluorinated tails are widely used as as table isosterica nd isoelectronic mimics of the amide bond, and bioisosteres in structure-activity relationships tudies. [3] Althougho fg reat importance,t he synthesiso fp erfluoroalkenylated arenes through the incorporationo ff luoroalkyl chains has remained an out-standingc hallenge. Few strategies for the preparation of these structuralm otifs, such as the classical cross-couplingr eaction have been shown to be effective. [4,5] The existing methods usually require prefunctionalization of substrates or employment of non-readilya vailable starting materials, and these methods often suffer from low regio-or stereoselectivity and poor functionalg roup toleranced ue to the employmento fs ensitive reagents. [6] Therefore, new synthetic strategies featuring high efficiency and mild conditions are highly desirable.Over the past decades, transition-metal-catalyzed CÀHb ond functionalization has been establisheda sa ne ffectives trategy in late-stage functionalization of pharmaceuticals and bioactive molecules. [7] To achieve site-selective CÀHb ond functionalization at ad esired position, directing group (DG) approaches [8] have been employede xtensively for the ortho-CÀHb ond, [9] whereasd istal meta-a nd para-CÀHb onds have been much less addressed. In the past few years, meta-selective CÀHf unctionalizations of arenes have been accomplishedb ye xploiting the inherent steric and electronic properties of substrates, or by designing suitablet emplates. [10] In this context, direct CÀH perfluoroalkenylation of arenes is an important route in terms of both atom and step economy.V ery recently,L oh, Wang, and Ackermann elegantly reported ortho-CÀHf luoroalkenylation of arenest hrough CÀFb ond activation. [11] Intriguingly,t he metafunctionalization of arenes using sterically demanding electrophilic perfluoroalkenes remainsad ifficult task, due to th...

A silver(I) catalyzed regioselective trifluoromethylation of allenes using Langlois's salt (NaOSOCF3) is demonstrated. This transformation enables direct expedient access to α‐trifluoromethylated acroleins, which are valuable synthons for a number of pharmaceuticals and agrochemicals containing vinyl‐CF3 moieties. Versatility of this trifluoromethylation method has been established with good yield and excellent regioselectivity. Preliminary experiments and computational studies were carried out to elucidate the mechanistic insight of this protocol.

A regioselective meta-C–H activation strategy for benzophenone was successfully developed by overriding the inherent ketone-directed ortho-selectivity.