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The preparation of ferrocenylindium species and palladium-catalyzed cross-coupling reactions for the synthesis of monosubstituted and planar chiral 1,2-disubstituted ferrocenes is described. Triferrocenylindium reagents (Fc3In) are efficiently prepared in a one-pot procedure from ferrocenes by lithiation and transmetallation to indium using InCl3. The palladium-catalyzed cross-coupling reactions of Fc3In (40 mol%) with a variety of organic electrophiles (aryl, heteroaryl, benzyl, alkenyl and acyl halides) in THF at 80 °C overnight provided a wide variety of monosubstituted ferrocenes in good to excellent yields. This methodology allowed the stereoselective synthesis of planar chiral 2-aryl-1-oxazolylferrocenes and 2-aryl-1-sulfinylferrocenes, which are of interest in asymmetric catalysis. [ABSTRACT FROM AUTHOR]

Cross-coupling reaction of organogold(I) phosphanes with organic electrophiles in aqueous media has been investigated. Reactions between isolated aryl-, alkenyl-, or alkynylgold(I) phosphanes and aryl halides or triflates, alkenyl halides, and allyl acetates proceed under palladium catalysis conditions at room temperature or 80 °C in water with THF as a co-solvent. The coupling reactions give good yields and are highly versatile and chemoselective, allowing the presence of free amino or hydroxy groups in the electrophile. This methodology was applied to the preparation of substituted phenylalanine esters in a demonstration that gold(I) organometallics are suitable reagents for metal-catalyzed cross-coupling reactions under protic conditions. [ABSTRACT FROM AUTHOR]

1,1′-Binaphthalenes and heterocyclic analogues can be efficiently prepared by palladium-catalysed cross-coupling reactions between tri(1-naphthyl)indium reagents and 1-halonaphthalenes and haloisoquinolines. The reactions were usually carried out in THF at 80 °C with a slight excess of the indium reagent (40 mol-%) and a low catalyst loading (4 mol-% Pd) to afford the cross-coupling products in good yields (45-99 %). The method allows the synthesis of sterically hindered 2-substituted and 2,2′-disubstituted 1,1′-binaphthalenes and naphthylisoquinolines. In addition, the coupling reactions can be performed enantioselectively and the best enantiomeric excesses were obtained by using the chiral amino-phosphane ferrocenyl ligand ( R, S)-PPFA. [ABSTRACT FROM AUTHOR]

Cross-coupling reactions have played a critical role enabling the rapid expansion of structure–activity relationships (SAR) during the drug discovery phase to identify a clinical candidate and facilitate subsequent drug development processes. The reliability and flexibility of this methodology have attracted great interest in the pharmaceutical industry, becoming one of the most used approaches from Lead Generation to Lead Optimization. In this mini-review, we present an overview of cross-coupling reaction applications to medicinal chemistry efforts, in particular the Suzuki–Miyaura and Buchwald–Hartwig cross-coupling reactions as a remarkable resource for the generation of carbon–carbon and carbon–heteroatom bonds. To further appreciate the impact of this methodology, the authors discuss some recent examples of clinical candidates that utilize key cross-coupling reactions in their large-scale synthetic process. Looking into future opportunities, the authors highlight the versatility of the cross-coupling reactions towards new chemical modalities like DNA-encoded libraries (DELs), new generation of peptides and cyclopeptides, allosteric modulators, and proteolysis targeting chimera (PROTAC) approaches. [ABSTRACT FROM AUTHOR]

Di(hetero)aryl ketones are important motifs present in natural products, pharmaceuticals or agrochemicals. In recent years, Pd(II)-catalyzed acylation of (hetero)arenes in the presence of an oxidant has emerged as a catalytic alternative to classical acylation methods, reducing the production of toxic metal waste. Different directing groups and acyl sources are being studied for this purpose, although further development is required to face mainly selectivity problems in order to be applied in the synthesis of more complex molecules. Selected recent developments and applications are covered in this review. [ABSTRACT FROM AUTHOR]

Borylated aryl alkynes have been synthesized via one-pot iridium catalyzed C–H borylation (CHB)/Sonogashira cross-coupling of aryl bromides. Direct borylation of aryl alkynes encountered problems related to the reactivity of the alkyne under CHB conditions. However, tolerance of aryl bromides to CHB made possible a subsequent Sonogashira cross-coupling to access the desired borylated aryl alkynes. [ABSTRACT FROM AUTHOR]

The inside cover picture, provided by José Pérez Sestelo and co ‐ workers illustrates the preparation of triferrocenylindium reagents and their application in palladium ‐ catalyzed cross ‐ coupling reactions. In the flask, a solution of a triferrocenylindium species is prepared by reaction of a ferrocene, an organolithium reagent and indium trichloride. The subsequent palladium ‐ catalyzed cross ‐ coupling reaction affords a series of substituted ferrocenes. The asymmetric synthesis of planar chiral 1,2 ‐ disubstituted ferrocenes is also represented indicating the ortho ‐ directing groups used during the lithiation step. The planar ‐ chirality of the products depends on the directing group employed and is illustrated with a mirror. The background picture shows part of the sculpture park surrounding the Tower of Hercules in A Coruña, Spain. Details of this work can be found in the update on pages 1388 – 1393 (M. Mato, C. Pérez ‐ Caaveiro, L. A. Sarandeses, J. Pérez Sestelo, Adv. Synth. Catal. 2017, 359, 1388 – 1393; DOI: 10.1002/adsc.201601397). [ABSTRACT FROM AUTHOR]

A wide range of aryl-, heteroaryl-, alkynyl- and alkenylgold(I) organometallics react with aryl and alkenyl halides, aryl triflates, and allyl acetates in aqueous media under palladium catalysis conditions. [ABSTRACT FROM AUTHOR]

A range of biaryl compounds (aryl—aryl, aryl—heteroaryl, and heteroaryl—heteroaryl) can be efficiently prepared by a palladium-catalyzed cross-coupling reaction between ortho-substituted triarylindium reagents and aryl halides. The triarylindium reagents are prepared by directed ortho-lithiation and transmetallation to indium from the corresponding benzene derivatives using various directed metallation groups (DMGs). The reaction proceeds smoothly in high yields and short reaction times with high atom economy (the three aryl groups attached to indium are efficiently transferred). [ABSTRACT FROM AUTHOR]

The palladium(0)-catalyzed cross-coupling reaction of allylic halides and acetates with indium organometallics is reported. In this synthetic transformation, triorganoindium compounds and tetraorganoindates (aryl, alkenyl, and methyl) react with cinnamyl and geranyl halides and acetates to afford the SN2 product regioselectively and in good yield. The reaction proceeds with net inversion of the stereochemical configuration. [ABSTRACT FROM AUTHOR]

Triorganoindium reagents (R3In, R = aryl, heteroaryl, alkynyl) react selectively under palladium catalysis with N-benzyl-2,4,5-triiodoimidazole to afford the C-2 monocoupling products. The reaction proceeds efficiently for a variety of aryl- and heteroarylindium reagents with the transfer of all three organic groups attached to the metal. The coupling products can be used in a subsequent two-fold cross-coupling to give trisubstituted imidazoles in good yields. This approach was employed to synthesize neurodazine and analogues in good yields. [ABSTRACT FROM AUTHOR]

In some cases increasing the amount of triorganyl indium reagent can increase the yields of the products [cf. [ABSTRACT FROM AUTHOR]