Roberto Sanz

This work reports a one‐pot Friedländer‐type protocol based on the dioxomolybdenum(VI)‐catalyzed reduction of readily available o ‐nitrobenzaldehydes with pinacol in the presence of external aliphatic aldehydes or acetals and p ‐toluenesulfonic acid as an additive. The tandem process proceeds through Mo‐catalyzed reduction to generate o ‐aminobenzaldehydes in situ, which subsequently undergo Friedländer annulation with the external carbonyl partner, thereby avoiding the isolation of unstable intermediates. The use of an excess of aldehyde suppresses competitive reactions involving acetone generated during the reduction. Under the optimized conditions, a broad range of functionalized o ‐nitrobenzaldehydes and aliphatic aldehydes afforded 3‐substituted quinolines with broad functional‐group tolerance. The use of acetals further expanded the scope, providing improved yields in several cases and enabling the synthesis of valuable 2,4‐unsubstituted quinoline‐3‐carboxylates, as well as 3‐acetyl‐, 3‐cyano‐, 3‐(2‐thienyl)‐, and nitrogen‐functionalized quinolines. The methodology is readily scalable and provides a convenient, chemoselective, and sustainable approach to structurally diverse quinoline scaffolds from inexpensive nitroarene precursors.

An intermolecular hydroxylation of α,β-unsaturated gold carbene intermediates, generated from readily accessible 3-propargylindoles through a tandem 1,2-indole migration–hydroxylation sequence using water as an external nucleophile, has been developed. Under mild reaction conditions and employing gold(I) catalysts bearing bulky and electron-rich phosphine ligands, a significant range of hydroxy-functionalized indole derivatives was synthesized in high yields. Mechanistic studies support the selective addition of water to the β-position of the electrophilic α,β-unsaturated gold carbene intermediate, whereas competing attack at the carbene center or direct hydration of the activated alkyne was not observed.

A formal vinylcyclopropanation of olefins from N ‐allyl N ‐(3‐alkoxymethyl‐2‐lithioallyl) amines acting as carbenoid equivalents is described. The reaction proceeds through a tandem 5‐ exo carbolithiation/3‐ exo S _N ʹ affording 1‐vinylazabicyclo[3.1.0]hexanes. Different substituents can be located at any of the other positions of the azabicycle, leading in most cases to high diastereoselectivities. DFT studies have been performed to account for the observed stereoselectivities that could not be rationalized in all cases through the expected chair‐like transition states.

The direct preparation of nitrogen‐containing polyaromatic heterocycles in a single operational step from readily available nitroarenes represents an attractive and sustainable alternative to traditional multistep approaches. In this context, this work describes an efficient and versatile methodology for the synthesis of fused N ‐polyheterocyclic scaffolds from functionalized nitroarenes and aldehydes catalyzed by dioxomolybdenum(VI) complexes and employing pinacol as a readily available and environmentally benign reductant. The protocol integrates nitro reduction, imine formation, and intramolecular cyclization in a single operational sequence. Careful fine‐tuning of the reaction conditions proved crucial to minimizing competing pathways. This molybdenum‐catalyzed strategy exhibits broad substrate scope, accommodating aromatic, aliphatic, and α,β‐unsaturated aldehydes, and enabling access to a variety of pharmaceutically relevant frameworks, such as pyrrolo[1,2‐ a ]quinoxalines, indoloquinoxalines, γ‐carbolines, imidazoquinolines, and phenanthridines.

Gold(I)-catalyzed tandem cyclization reactions of 3-propargylindoles bearing a hydroxyalkyl substituent at C2 enable rapid access to indole-fused cyclic ethers through the vinylogous reactivity of α,β-unsaturated gold-carbene intermediates. A selective intramolecular Michael-type attack of the hydroxyl group, supported by DFT studies, affords indole-fused six-, seven-, and eight-membered O-heterocycles under mild conditions. A one-pot hydrogen transfer process further delivers reduced pyranoindoles, highlighting the versatility and synthetic potential of this method.

Optimal conditions for the metalation via α-lithiation of 1,2-dimethylindoles were established with nBuLi at room temperature, providing the most effective protocol. The resulting organolithium reagents bearing the structure of 2-lithiomethylindole were efficiently trapped with diverse electrophiles, including Weinreb amides, ketones, alkyl bromides, and epoxides, affording a broad range of C2-functionalized indoles in good yields. The methodology proved general and was successfully applied to 2-methylindoles bearing different substituents at the benzenoid ring, C3, and on the nitrogen atom, as well as to 2-benzylindoles, giving access to new functionalized indole derivatives. Importantly, deep eutectic solvents enabled these transformations under air- and moisture-tolerant conditions, highlighting their greener and operationally simple character. The synthetic utility of the method was further demonstrated through subsequent derivatizations, exemplified by the two-step preparation of 2,4-disubstituted carbazoles.

Sulfur-substituted fulvenes have been synthesized from 1,3-dien-5-ynes via a gold-catalyzed 5- exo-dig cyclization. Activation by the gold and Brønsted acid catalysts generates fulvenium ions, enabling one-pot reaction with indoles.

Viologen derivatives are widely used in the anolytes of aqueous organic redox flow batteries (AORFBs). However, their applications have been restricted to neutral pH systems due to their fast degradation in basic media via a dealkylation process driven by a nucleophilic attack of hydroxide. In this study, a family of viologen-based anolytes suitable for alkaline systems is introduced, demonstrating that properly designed viologens can also be used in alkaline conditions. A variety of N-aryl viologens are prepared and characterized, showing that the dealkylation process is prevented by bonding an aryl group directly to the N-atom of the bipyridine core. Pairing B-2,5-DHPV for the anolyte and K₄Fe­(CN)₆ for the catholyte, a full alkaline AORFB having a nominal cell voltage at 0.98 V maintains stable capacity over 1400 continuous cycles with nearly 0.03%·h^–1 capacity decay, which is a very acceptable value for a viologen in an alkaline medium. Our results enable the broadening of the range of viable organic anolytes for alkaline AORFBs.

A thermally controlled rare chemodivergent mechanistic trifurcation has been found through experimental and computational efforts. Notably, one of the available paths in this three-way mechanism allows for an unprecedented dearomatization reactivity of non-activated 2-arylphenyl benzyl ethers under very mild thermal conditions after Csp³-H bond functionalization through α-lithiation, bringing easy access to regioselectively functionalized dearomatized benzochromene scaffolds via anionic dearomatization enabled by carbolithiation of a non-activated aromatic ring. A [1,2]-Wittig rearrangement and a benzyl migration reaction complete the available product alternatives. Moreover, a delicate but useable balance within this reaction path manifold permits steering the reactivity toward each of the three possible products. A kinetically-, thermodynamically- and quantum tunneling-controlled path can be selected to afford one of its three possible products by only tuning reaction time and temperature.

3-Propargylindoles with a terminal alkyne, efficiently prepared from direct alkylation of indoles, undergo a tandem 1,2-indole migration/cyclopropanation reaction under gold(I) catalysis. Reaction conditions have been developed for suitable access to indole-substituted vinylcyclopropanes from 3-propargyl indoles and olefins. The corresponding 2-alkenyl-functionalized substrates evolve through an intramolecular cyclopropanation allowing the synthesis of various polycyclic indole derivatives. The presence of silver salts modifies the diastereoselectivity observed.