Joachim Loup

A reductive cyclization to prepare a variety of N ‐heterocycles, through the use of ortho ‐vinylanilides, is reported. The reaction is catalyzed by an inexpensive and bench‐stable iron complex and generally occurs at ambient temperature. The transformation likely proceeds through hydromagnesiation of the vinyl group, and trapping of the in situ generated benzylic anion by an intramolecular electrophile to form the heterocycle. This iron‐catalyzed strategy was shown to be broadly applicable and was utilized in the synthesis of substituted indoles, oxindoles and tetrahydrobenzoazepinoindolone derivatives. Mechanistic studies indicated that the reversibility of the hydride transfer step depends on the reactivity of the tethered electrophile. The synthetic utility of our approach was further demonstrated by the formal synthesis of a reported bioactive compound and a family of natural products.

A reductive cyclization to prepare a variety of N‐heterocycles, through the use of ortho‐vinylanilides, is reported. The reaction is catalyzed by an inexpensive and bench‐stable iron complex and generally occurs at ambient temperature. The transformation likely proceeds through hydromagnesiation of the vinyl group, and trapping of the in situ generated benzylic anion by an intramolecular electrophile to form the heterocycle. This iron‐catalyzed strategy was shown to be broadly applicable and was utilized in the synthesis of substituted indoles, oxindoles and tetrahydrobenzoazepinoindolone derivatives. Mechanistic studies indicated that the reversibility of the hydride transfer step depends on the reactivity of the tethered electrophile. The synthetic utility of our approach was further demonstrated by the formal synthesis of a reported bioactive compound and a family of natural products.

Publication Date: 18 May 2021 (online) © 2021. Thieme. All rights reserved Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

The utilization of the Bpin group as a pronucleophile to facilitate the assembly of cyclic carbamates has been achieved. This one-pot process involves an initial copper-catalyzed borylation, a subsequent C–B bond oxidation to generate the reactive alcohol intermediate, and a cyclization. We report the use of this efficient, scalable, and simple method toward the synthesis of a wide range of benzoxazinone scaffolds, including enantioselective results. Subsequent transformations into useful scaffolds showcase the utility of this strategy.

Copper-catalyzed enantio- and diastereoselective conjugate borylation across Michael acceptors, with subsequent Mannich-type cyclization, was utilized to construct tetrahydroquinoline scaffolds containing three contiguous stereocenters.

Molecular syntheses largely rely on time‐ and labour‐intensive prefunctionalization strategies. In contrast, C−H activation represents an increasingly powerful approach that avoids lengthy syntheses of prefunctionalized substrates, with great potential for drug discovery, the pharmaceutical industry, material sciences, and crop protection, among others. The enantioselective functionalization of omnipresent C−H bonds has emerged as a transformative tool for the step‐ and atom‐economical generation of chiral molecular complexity. However, this rapidly growing research area remains dominated by noble transition metals, prominently featuring toxic palladium, iridium and rhodium catalysts. Indeed, despite significant achievements, the use of inexpensive and sustainable 3d metals in asymmetric C−H activations is still clearly in its infancy. Herein, we discuss the remarkable recent progress in enantioselective transformations via organometallic C−H activation by 3d base metals up to April 2019.

Molekulare Synthese basiert größtenteils auf zeit‐ und arbeitsintensiven Präfunktionalisierungsstrategien. Demgegenüber bietet die C‐H‐Aktivierung ein leistungsstarkes Hilfsmittel, das ohne lange Synthesen präfunktionalisierter Substrate auskommt und großes Potenzial für z. B. die Wirkstoffentwicklung, die pharmazeutische Industrie, die Materialwissenschaften und die Synthese von Pflanzenschutzmitteln hat. Die enantioselektive Funktionalisierung omnipräsenter C‐H‐Bindungen hat sich zu einer etablierten Methode für die stufen‐ und atomökonomische Synthese komplexer chiraler Moleküle entwickelt. Allerdings ist dieses rasant wachsende Feld größtenteils durch die Verwendung edler Übergangsmetalle geprägt, mit besonderer Präsenz toxischer Palladium‐, Iridium‐ und Rhodiumkatalysatoren. Trotz bedeutender Errungenschaften befindet sich die asymmetrische C‐H‐Aktivierung unter Verwendung kostengünstiger und nachhaltiger 3d‐Metalle noch im Anfangsstadium. In diesem Kurzaufsatz diskutieren wir die neuen, herausragenden Fortschritte bei enantioselektiven Transformationen über metallorganische C‐H‐Aktivierungen durch 3d‐Basismetalle bis April 2019.

A combination of electrospray-ionization mass spectrometry and Mössbauer spectroscopy was used to investigate the species generated in situ in highly enantioselective Fe/NHC-catalyzed C–H alkylations. The findings indicate an organometallic iron(II)–NHC species to be of key relevance in the asymmetric catalysis.

Air- and moisture-stable secondary phosphine oxides (SPOs) enabled nickel-catalyzed Kumada–Corriu cross-couplings of various arylmethyl ethers at room temperature by challenging C–O activation.

Highly enantioselective nickel‐catalyzed alkene endo‐hydroarylations were accomplished with full selectivity by organometallic C−H activation. The asymmetric assembly of chiral six‐membered scaffolds proved viable in the absence of pyrophoric organoaluminum reagents within an unprecedented nickel/JoSPOphos manifold.