One-step synthesis of indolizino[3,4,5-ab]isoindoles by manganese(I)-catalyzed C-H activation: structural studies and photophysical properties.

Herein, a regioselective synthesis of indolizino[3,4,5-ab]isoindoles, a valuable class of heterocycles with interesting luminescence properties, is described using manganese(I)-catalyzed C-H activation. The reported transformation proceeds in one-step and employs readily available 2-phenylpyridines as starting materials. Furthermore, the obtained single products exhibit blue-greenish fluorescence with high quantum yields.

Organic Electrosynthesis Towards Sustainability: Fundamentals and Greener Methodologies.

The adoption of new measures that preserve our environment, on which our survival depends, is a necessity. Electro-organic processes are sustainable per se, by producing the activation of a substrate by electron transfer at normal pressure and room temperature. In the recent years, a highly crescent number of works on organic electrosynthesis are available. Novel strategies at the electrode are being developed enabling the construction of a great variety of complex organic molecules. However, the possibility of being scaled-up is mandatory in terms of sustainability. Thus, some electrochemical methodologies have demonstrated to report the best results in reducing pollution and saving energy. In this personal account, these methods have been compiled, being organized as follows: • Direct discharge electrosynthesis • Paired electrochemical reactions. and • Organic transformations utilizing electrocatalysis (in absence of heavy metals). Selected protocols are herein presented and discussed with representative recent examples. Final perspectives and reflections are also considered.

Site-selective C-H activation and regiospecific annulation using propargylic carbonates.

Herein we describe an unprecedented RuII-catalyzed site-selective and regiospecific annulation of benzoic acids with propargylic carbonates. The weakly coordinating carboxylic acid moiety outperformed other typically used directing groups in C-H activation, including ketone, nitrile, sulfonamide, amide and strongly coordinating nitrogen heterocycles. This is an important step towards the application of C-H activation reactions in complex (functional) real-world molecules.

MnI /AgI Relay Catalysis: Traceless Diazo-Assisted C(sp2 )-H/C(sp3 )-H Coupling to ß-(Hetero)Aryl/Alkenyl Ketones.

An unprecedented MnI /AgI -relay-catalyzed C(sp2 )-H/C(sp3 )-H coupling of (vinyl)arenes with α-diazoketones is reported, wherein the diazo group was exploited as a traceless auxiliary for control of regioselectivity. Challenging ß-(hetero)aryl/alkenyl ketones were obtained through this operationally simple approach. The cascade process merges denitrogenation, carbene rearrangement, C-H activation, and hydroarylation/hydroalkenylation. The robustness of this method was demonstrated at preparative scale and applied to late-stage diversification of natural products.

Manganese(I)-Catalyzed C-H (2-Indolyl)methylation: Expedient Access to Diheteroarylmethanes.

An unprecedented MnI -catalyzed (2-indolyl)methylation of heteroarenes is reported. This method makes use of an aromatizing cascade strategy to install a (2-indolyl)methyl group into target molecules, thereby leading to the expedient synthesis of previously challenging and important unsymmetrical diheteroarylmethanes, in particular bis(2-indolyl)methanes. The proposed cascade process comprises the reorganization of multiple bonds with controlled regioselectivity and high atom economy and can be performed on a gram-scale. Furthermore, a metal-free C-H propargylation is observed. The diverse application of this method is also demonstrated.

Highly Selective Manganese(I)/Lewis Acid Cocatalyzed Direct C-H Propargylation Using Bromoallenes.

A manganese(I)/Lewis acid cocatalyzed direct C-H propargylation with high selectivity has been developed. BPh3 was discovered to not only promote the reactivity, but also enhance the selectivity. Secondary, tertiary, and even quaternary carbon centers at the propargylic position could be directly constructed. Both internal and terminal alkynes are easily accessible. The chirality was successfully transferred from an axially chiral allene to central chirality. The reactivity of the manganese catalyst in this reaction was found to be unique among transition metal catalysts.

Redox-Neutral Manganese(I)-Catalyzed C-H Activation: Traceless Directing Group Enabled Regioselective Annulation.

A strategy is reported in which traceless directing groups (TDGs) are used to promote the redox-neutral MnI -catalyzed regioselective synthesis of N-heterocycles. Alkyne coupling partners bearing a traceless directing group, which serves as both the chelator and internal oxidant, were used to control the regioselectivity of the annulation reactions. This operationally simple approach is highly effective with previously challenging unsymmetrical alkyne systems, including unbiased dialkyl alkynes, with perfect regioselectivity. The simple conditions and the ability to carry out synthesis on a gram scale underscore the usefulness of this method. The application of this strategy in the concise synthesis of the bioactive compound PK11209 and the pharmaceutical moxaverine is also described.

Allenols versus Allenones: Rhodium-Catalyzed Regiodivergent and Tunable Allene Reactivity with Triazoles.

2-Pyrrolines and 6-oxo-hexa-2,4-dienals have been prepared through the divergent reactions of 1-benzenesulfonyl-4-aryl-1,2,3-triazoles with functionalized allenes. The rhodium-catalyzed reactions between allenols and 1-benzenesulfonyl-4-aryl-1,2,3-triazoles yielded 2-pyrrolines. This transformation is compatible with the presence of aliphatic, aromatic, heterocyclic, amide, and halogen functional groups. Interestingly, a reactivity switch took place when the allene-tethered alcohol substrate was replaced by its ketone counterpart. When the rhodium-catalyzed reaction of 1-benzenesulfonyl-4-phenyl-1,2,3-triazole was performed with allenones, acyclic 6-oxo-hexa-2,4-dienals were stereoselectively formed as (2Z,4E) isomers.

Cationic AuIII versus AuI : Catalyst-Controlled Divergent Reactivity of Alkyne-Tethered Lactams.

Switchable reactivity through cationic gold-based catalyst control built on the oxidation state, namely cationic AuIII versus AuI , has been achieved in the direct functionalization of 2-azetidinone-tethered alkynyl indoles.

Metal-Catalyzed Cyclization Reactions of 2,3,4-Trien-1-ols: A Joint Experimental-Computational Study.

Controlled preparation of tri- and tetrasubstituted furans, as well as carbazoles has been achieved through chemo- and regioselective metal-catalyzed cyclization reactions of cumulenic alcohols. The gold- and palladium-catalyzed cycloisomerization reactions of cumulenols, including indole-tethered 2,3,4-trien-1-ols, to trisubstituted furans was effective, due to a 5-endo-dig oxycyclization by attack of the hydroxy group onto the central cumulene double bond. In contrast, palladium-catalyzed heterocyclization/coupling reactions with 3-bromoprop-1-enes furnished tetrasubstituted furans. Also studied was the palladium-catalyzed cyclization/coupling sequence involving protected indole-tethered 2,3,4-trien-1-ols and 3-bromoprop-1-enes that exclusively generated trisubstituted carbazole derivatives. These results could be explained through a selective 6-endo-dig cumulenic hydroarylation, followed by aromatization. DFT calculations were carried out to understand this difference in reactivity.

Stereoselective synthesis of strained cage compounds via gold-catalyzed allene functionalization.

The diastereoselective synthesis of strained adducts that show cage-like structures has been accomplished directly from allenyl-ß-lactams through gold catalysis.

Iron-catalyzed domino indole fluorination/allenic aza-Claisen rearrangement.

The synthesis of 2-allenyl-2-substituted-3,3-difluoroindolines has been accomplished, taking advantage of the reaction between N-allenyl-indoles and Selectfluor under iron catalysis.

tBuLi-Mediated One-Pot Direct Highly Selective Cross-Coupling of Two Distinct Aryl Bromides.

A Pd-catalyzed direct cross-coupling of two distinct aryl bromides mediated by tBuLi is described. The use of [Pd-PEPPSI-IPr] or [Pd-PEPPSI-IPent] as catalyst allows for the efficient one-pot synthesis of unsymmetrical biaryls at room temperature. The key for this selective cross-coupling is the use of an ortho-substituted bromide that undergoes lithium-halogen exchange preferentially.

Gold as Catalyst for the Hydroarylation and Domino Hydroarylation/N1-C4 Cleavage of ß-Lactam-Tethered Allenyl Indoles.

Gold-catalyzed hydroarylation reaction of ß-lactam-tethered allenyl indoles gives azeto-oxepino[4,5-b]indol-2-ones, tetrahydroazeto-azocino[3,4-b]indol-2-ones, and hexahydroazeto-azepino[3,4-b]indol-2-ones with very high levels of stereo- and regioselectivity, the 7-exo and 8-endo carbocyclization modes by attack of the indole group toward either the internal or the terminal allene carbon, respectively, being favored. Hydroarylation across the central carbon of the allene moiety has not been detected. The controlled gold-catalyzed annulations allowed the formation of fused ß-lactams without harming the sensitive four-membered heterocycle. Besides, a novel gold-catalyzed domino process, namely, the allenic hydroarylation/N1-C4 ß-lactam bond breakage to afford dihydro-oxepino[4,5-b]indole-4-carboxamides, has been discovered.

Iodine recycling via 1,3-migration in iodoindoles under metal catalysis.

3-Substituted (indol-2-yl)-α-allenols show divergent patterns of reactivity under metal catalysis. An unprecedented intramolecular 1,3-iodine migration is described.

Gold-catalysed tuning of reactivity in allenes: 9-endo hydroarylation versus formal 5-exo hydroalkylation.

The divergent gold-catalysed reactivity (C(sp(2))-H versus C(sp(3))-H) of aryloxy-tethered allenes has been uncovered.

Controlled rearrangement of lactam-tethered allenols with brominating reagents: a combined experimental and theoretical study on α- versus ß-keto lactam formation.

N-Bromosuccinimide (NBS) smoothly promotes the ring expansion of lactam-tethered allenols to efficiently afford cyclic α- or ß-ketoamides with good yields and high chemo-, regio-, and diastereoselectivity, through controlled C-C bond cleavage of the ß- or γ-lactam nucleus. Interestingly, in contrast to the rearrangement reactions of 2-azetidinone-tethered allenols, which lead to the corresponding tetramic acid derivatives (ß-keto lactam adducts) as the sole products, the reactions of 2-indolinone-tethered allenols under similar conditions give quinoline-2,3-diones (α-keto lactam adducts) as the exclusive or major products. To rationalize the experimental observations, theoretical studies have been performed.