Regioselective C−H Hydroarylation of Internal Alkynes with Arenecarboxylates: Carboxylates as Deciduous Directing Groups

Abstract

In the presence of catalytic [Ru(p-cym)I 2 ] 2 and the base guanidine carbonate,b enzoica cids react with internal alkynes to give the corresponding 2-vinylbenzoic acids.T his alkyne hydroarylation is generally applicable to diversely substituted electron-rich and electron-poor benzoic and acrylic acids.A ryl(alkyl)acetylenes react regioselectively with formation of the alkyl-branched hydroarylation products,a nd propargylic alcohols are converted into g-alkylidene-d-lactones.T he hydroarylation can also be conducted decarboxylatively with ad ifferent choice of catalyst and reaction conditions.T his reaction variant, which does not proceed via intermediate formation of 2-vinylbenzoic acids,o pens up ar egioselective,w aste-minimized synthetic entry to vinylarenes.Given the prevalence of vinylarene moieties in functional materials,p harmaceuticals,a nd natural products, [1] efficient methods for the construction of this structural motif are constantly sought. Established synthetic approaches include Mizoroki-Heck [2] and Fujiwara-Moritani reactions, [3] as well as various catalytic cross-couplings of organometallic reagents with alkynes. [4] C À Hh ydroarylations of alkynes are advantageous over these processes,b ecause they require neither prefunctionalized substrates nor oxidants.S ince the pioneering studies by Murai and co-workers, [5] various metals have been found to efficiently catalyze the hydroarylation of alkynes,for example Ru, [6] Rh, [7] Re, [8] Co, [9] and others.[10] However, these CÀH functionalizations are highly regioselective only when directed by ketone,p yridine,a mide,s ulfoxide,o ro ther strong directing groups,groups which need to be synthesized in additional reaction steps and are not easily removed.Arguably,t he most advantageous directing groups in ortho-functionalizations are carboxylates,b ecause benzoic acids are widely available in great structural diversity and at low cost, and can subsequently be derivatized further, utilized as leaving groups in decarboxylative couplings, [11] or removed tracelessly by protodecarboxylation.[12] However,t he weak coordinating ability of this group poses additional challenges in the development of regiospecific CÀH-activating processes. In recent years,s ubstantial advances in carboxylate-directed CÀHa ctivation have been made, [13] for example,b yt he groups of Yu, [14] Miura, [15] Ackermann, [16] and Larrosa, [12b,c] as well as our own group. [12d, 17] In this context, oxidative couplings of benzoic acids with alkynes to form isocoumarins,naphthalenes,and other cyclic structures have intensively been studied. These reactions involve carboxylate-directed CÀHa ctivation to give vinylmetal intermediates,w hich immediately undergo cyclization steps before either reductive elimination or protonolysis can occur (Scheme 1a). [15,18] Moreover,i nt he presence of electron-deficient transition-metal catalysts or ruthenium(II), alkynes preferentially react with the nucleophilic carboxylate, to form enol esters,rather than with the CÀHmoiety...

Nickel-Catalyzed Hydroarylation of Alkynes under Reductive Conditions with Aryl Bromides and Water

“…The compound was isolated as a clear oil (176 mg, 0.619 mmol, 55%). The analytical data matched that reported in the literature: 42 1 H NMR (600 MHz, CDCl 3 , (E) and (Z) diastereomers): δ 7.41 −7.22 (m, 6H), 7.21−7.12 (m, 5H), 7.12−7.05 (m, 3H), 7.01 (s, 1H, alkene H, (Z) diastereomer), 6.99 (s, 1H, alkene H, (E) diastereomer), 2.68 (q, J = 7.6 Hz, 2H, single diastereomer), 2.62 (q, J = 7.6 Hz, 2H, single diastereomer), 1.27 (t, J = 7.6 Hz, 3H, (E) diastereomer), 1.19 (t, J = 7.6 Hz, 3H, (Z) diastereomer).…”

C–H Activation: Toward Sustainability and Applications

“…In 2016, Gooßen accomplished a regioselective C–H hydroarylation of internal alkynes with benzoic acid derivatives using a Ru-based catalyst ( Scheme 13 ). 79 Facile liberation of carbon dioxide (CO 2 ) revealed the product. In the same year, Zhao published a similar method to convert lignin-derived 4-hydroxybenzoic acid into the corresponding meta -substituted alkenyl arene.…”

N‐Methoxybenzamide: A Versatile Directing Group for Palladium‐, Rhodium‐ and Ruthenium‐Catalyzed C−H Bond Activations

“…Ru‐catalyzed C−H bond functionalization has undergone very recent progress like C−H alkynylation, C−H oxygenation of sulfoximine benzamide, bromination of purine based on the meta position, C−H arylation of azoarenes, C−H alkenylation of aryl carboxylic acids with alkynes via decarboxylations, C−H activations of various aromatics, alkenes and heteroaromatics with alkenes to form C−H olefination products . meta ‐Selective C−H functionalizations continue to be scarce, but syntheses of chalcogenoxanthones, chlorination and sulfonation reactions of 2‐phenoxypyrimidines at ortho and meta positions, respectively, C−H activation of indoles with arylsilanes in water, hydroarylations of alkynes by using ball‐milling conditions, meta ‐carboxylation of arenes containing pyridine and other azine‐directing groups, and sulfonylation of N ‐aryl‐2‐aminopyridines have been reported. Some representative C−H activations of various aromatic compounds are discussed here.…”