Zwitterionic Acridinium Amidate: A Nitrogen-Centered Radical Catalyst for Photoinduced Direct Hydrogen Atom Transfer.

The development of small organic molecules that can convert light energy into chemical energy to directly promote molecular transformation is of fundamental importance in chemical science. Herein, we report a zwitterionic acridinium amidate as a catalyst for the direct functionalization of aliphatic C-H bonds. This organic zwitterion absorbs visible light to generate the corresponding amidyl radical in the form of excited-state triplet diradical with prominent reactivity for hydrogen atom transfer to facilitate C-H alkylation with a high turnover number. The experimental and theoretical investigations revealed that the noncovalent interactions between the anionic amidate nitrogen and a pertinent hydrogen-bond donor, such as hexafluoroisopropanol, are crucial for ensuring the efficient generation of catalytically active species, thereby fully eliciting the distinct reactivity of the acridinium amidate as a photoinduced direct hydrogen atom transfer catalyst.

Visible Light Thiyl Radical-Mediated Desilylation of Arylsilanes.

A straightforward, visible-light triggered desilylation of arylsilanes by thiyl radicals is presented. Silyl groups are often used to block a reactive position in multi-step organic synthesis, for which a mild cleavage at a late-stage will provide new possibilities and disconnection routes by CAr -Si cleavage/deprotection. In this work, commercially available and cheap disulfides are employed for the first time in this type of C(sp2 )-Si bond cleavage reactions. Thus, upon irradiation with visible-light, homolytic cleavage of the disulfide give rise to the corresponding thiyl radical that allows for a radical chain mechanism. This methodology represents a mild, fast and simple approach suitable for a broad variety of simply substituted arylsilanes. Moreover, the procedure could be easily extended to natural products and therapeutic derivatives, showing its robustness and synthetic application potential.

Enantioselective vinylogous-Mukaiyama-type dearomatisation by anion-binding catalysis.

The first enantioselective vinylogous Mukaiyama-type dearomatisation of heteroarenes under anion-binding catalysis is presented. A recyclable tetrakistriazole catalyst was used for the enantiocontrol of the remote vinylogous active position of silyl dienol ethers. This approach provided chiral heterocycles bearing α,ß-unsaturated chains with complete regioselectivity and excellent enantioselectivities (up to 97.5 : 2.5 e.r.).

Catalytic Enantioselective Reactions with (Benzo)Pyrylium Salts.

The use of (benzo)pyrylium salts as versatile synthetic building blocks has become an attractive platform for the preparation of valuable heterocyclic compounds. Besides other numerous direct applications of (benzo)pyryliums, the intrinsic electrophilic nature of these species or the dipole character of the related oxidopyrylium derivatives have been exploited towards the development of enantioselective transformations such as nucleophilic dearomatization and cycloaddition reactions. This review aims at providing an overview on the relevant catalytic enantioselective methodologies developed in the past years, which are presented considering the involved metal- and/or organic catalytic system, as well as the type of reaction.

8-Mercaptoquinoline as a Ligand for Enhancing the Photocatalytic Activity of Pt(II) Coordination Complexes: Reactions and Mechanistic Insights.

A family of quinoline-platinum(II) complexes as efficient photocatalysts is presented. Their key characteristic is their easy preparation by coordination of the readily available 8-hydroxy- or 8-thio-quinoline ligands, which are well known for their strong chelating ability to different metal ions. In the different photochemical transformations investigated, such as cross-dehydrogenative coupling, oxidation of arylboronic acids, and asymmetric alkylation of aldehydes, 8-mercaptoquinoline-Pt(II) complex proved to be the most general catalyst. Moreover, quenching experiments showed that, contrary to related methods reported in the literature, these complexes followed an oxidative quenching mechanism in all transformations studied. Besides, simulations performed with high-level ab initio methods of the complexes have helped to understand their photocatalytic activity.

Double Cu-Catalyzed Direct Csp3 -H Azidation/CuAAC Reaction: A Direct Approach towards Demanding Triazole Conjugates.

The first one-pot procedure for the double copper(I)-catalyzed oxidative Csp3 -H azidation-CuAAC process, implying unstable azide intermediates and easy-to-remove reagents under water-tolerant conditions, is presented. The combination of tert-butyl hydroperoxide as oxidant and TMSN3 as azide source for the C-H bond azidation, which produces harmless side-products such as tBuOH and H2 O, probed to be perfectly compatible with the following cycloaddition step. Highly demanding 1,2,3-triazoles could be then directly obtained in good overall yields by extraction or simple crystallization, thus avoiding chromatography purifications. The potential of this methodology, has also being highlighted by the successful reaction of alkynes presenting interesting complex biological moieties based for example on biotin, DNA base or cinchona alkaloid units.

Frontiers in Halogen and Chalcogen-Bond Donor Organocatalysis.

Non-covalent molecular interactions on the basis of halogen and chalcogen bonding represent a promising, powerful catalytic activation mode. However, these "unusual" non-covalent interactions are typically employed in the solid state and scarcely exploited in catalysis. In recent years, an increased interest in halogen and chalcogen bonding has been awaken, as they provide profound characteristics that make them an appealing alternative to the well-explored hydrogen bonding. Being particularly relevant in the binding of "soft" substrates, the similar strength to hydrogen bonding interactions and its higher directionality allows for solution-phase applications with halogen and chalcogen bonding as the key interaction. In this mini-review, the special features, state-of-the-art and key examples of these so-called σ-hole interactions in the field of organocatalysis are presented.

Pd(OAc)2/Ph3P-catalyzed dimerization of isoprene and synthesis of monoterpenic heterocycles.

The palladium-catalyzed dimerization of isoprene is a practical approach of synthesizing monoterpenes. Though several highly selective methods have been reported, most of them still required pressure or costly ligands for attaining the active system and desired selectivity. Herein, we present a simple and economical procedure towards the tail-to-tail dimer using readily available Pd(OAc)2 and inexpensive triphenylphosphine as ligand. Furthermore, simple screw cap vials are employed, allowing carrying out the reaction at low pressure. In addition, the potential of the dimer as a chemical platform for the preparation of heterocyclic terpenes by subsequent (hetero)-Diels-Alder or [4 + 1]-cycloadditions with nitrenes is also depicted.

Recent progress in mild Csp3-H bond dehydrogenative or (mono-) oxidative functionalization.

Over the past few years, the development of oxidative methodologies towards efficient and selective direct Csp3-H bond functionalization processes has attracted tremendous attention from synthetic chemists. However, only a little attention has been given to the key role of the nature of the oxidant. This review aims at providing a brief summary of the recent advances in mild and more benign oxidative Csp3-H bond functionalization reactions, which are classified according to the type of oxidation system employed.

1,2,3,-Triazole-Based Catalysts: From Metal- to Supramolecular Organic Catalysis.

1,2,3-Triazoles are unique heterocycles with intriguing physical properties that allow not only the coordination to metals, but also the establishment of supramolecular interactions based on their polarized C-H bonds. In this account, an extensive work of our group on the design and application of 1,2,3-triazole catalysts is covered. Initially, a family of BINOL triazoles (Click-BINOLs) was synthesized and employed in model test reactions in asymmetric metal catalysis such as the Ti-catalyzed addition of alkylzinc reagents to aldehydes. The evolution from the Click-BINOLs to a novel class of triazole-based anion-binding organocatalysts is further discussed. Consequently, these catalysts were successfully applied in alkylation reactions, as well as asymmetric dearomatizations of diverse N-heteroarenes.

Asymmetric nucleophilic dearomatization of diazarenes by anion-binding catalysis.

The first anion-binding organocatalyzed enantioselective Reissert-type dearomatization of diazarenes has been developed. This reaction represents a synthetic challenge since diazarenes have various reactive sites. The use of a chiral tetrakistriazole as a C-H-based hydrogen-donor catalyst allowed the straightforward highly regio- and enantioselective synthesis of a variety of chiral diazaheterocycles.

Dehydrogenative TEMPO-Mediated Formation of Unstable Nitrones: Easy Access to N-Carbamoyl Isoxazolines.

N-carbamoyl nitrones represent an important class of reagents for the synthesis of a variety of natural and biologically active compounds. These compounds are generally converted into valuable 4-isoxazolines upon cyclization reaction with dipolarophiles. However, these types of N-protected nitrones are highly unstable, which limits their synthesis, storage and practical use, enforcing alternative lengthy or elaborated synthetic routes. In this work, a 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO)-mediated formal "dehydrogenation" of N-protected benzyl-, allyl- and alkyl-substituted hydroxylamines followed by in situ trapping of the generated unstable nitrones into N-carbamoyl 4-isoxazolines is presented. A plausible mechanism is also proposed, in which the dipolarophile shows an important assistant role in the generation of the active nitrone intermediate. This simple protocol avoids the problematic isolation of N-carbamoyl protected nitrones, providing new synthetic possibilities in isoxazoline chemistry.

Oxidative C-H bond functionalization and ring expansion with TMSCHN2 : a copper(I)-catalyzed approach to dibenzoxepines and dibenzoazepines.

Tricyclic dibenzoxepines and dibenzazepines are important therapeutic agents for the pharmaceutical industry and academic research. However, their syntheses are generally rather tedious, requiring several steps that involve a Wagner-Meerwein-type rearrangement under harsh conditions. Herein, we present the first copper(I)-catalyzed oxidative CH bond functionalization and ring expansion with TMSCHN2 to yield these important derivatives in a facile and straightforward way.

Chiral helical oligotriazoles: new class of anion-binding catalysts for the asymmetric dearomatization of electron-deficient N-heteroarenes.

Helical chirality and selective anion-binding processes are key strategies used in nature to promote highly enantioselective chemical reactions. Although enormous efforts have been made to develop simple helical chiral systems and thus open new possibilities in asymmetric catalysis and synthesis, the efficient use of synthetic oligo- and polymeric helical chiral catalysts is still very challenging and rather unusual. In this work, structural unique chiral oligotriazoles have been developed as C-H bond-based anion-binding catalysts for the asymmetric dearomatization of N-heteroarenes. These rotational flexible catalysts adopt a reinforced chiral helical conformation upon binding to a chloride anion, allowing high levels of chirality transfer via a close chiral anion-pair complex with a preformed ionic substrate. This methodology offers a straightforward and potent entry to the synthesis of chiral (bioactive)heterocycles with added synthetic value from simple and abundant heteroarenes.

Highly enantioselective synthesis of chiral 7-ring O- and N-heterocycles by a one-pot nitro-Michael-cyclization tandem reaction.

A concise enantioselective approach to synthesise medium-sized 7-ring O- and N-heterocycles has been developed. The synthetic strategy relies on an organocatalytic nitro-Michael-nitrile oxide cycloaddition tandem reaction, leading to the corresponding chiral benzoxe- and benzazepine derivatives containing an additional fused dihydroisoxazoline ring in good yields and excellent enantioselectivities (up to 97% ee).

Iron(II) triflate as an efficient catalyst for the imination of sulfoxides.

The challenging imination of benzyl-, sterically demanding alkyl-, and heteroaryl-substituted sulfoxides has been studied. Iron(II) triflate was identified as a highly efficient and robust catalyst for sulfur imination reactions. A variety of sulfoxides and sulfides were efficiently iminated with sulfonyliminoiodinanes (PhI=NSO(2)R) at room temperature to give the corresponding sulfoximines and sulfilimines in good yields and with short reaction times.

Catalytic enantioselective approach to the stereodivergent synthesis of (+)-lasubines I and II.

A concise and efficient approach to the stereodivergent synthesis of (+)-lasubines I and II is described. The key common intermediate is a chiral N-sulfonyl 2,3-dihydropyridone obtained by a novel Cu-catalyzed asymmetric formal aza-Diels-Alder reaction between N-tosyl aldimines and Danishefsky's diene.

Synthesis of sulfonimidamides from sulfinamides by oxidation with N-chlorosuccinimide.

BACKGROUND: The synthesis of sulfonimidamides involves the nucleophilic substitution of a sulfonimidoyl chloride with an amine. However, only four chlorinating systems have been reported for the preparation of the sulfonimidoyl chloride intermediates. Whereas some of them have shown a rather limited substrate spectrum, the most versatile and commonly used tert-butyl hypochlorite is known to be explosive. To establish alternative methods for the synthesis of these molecules is therefore desirable. RESULTS: The preparation of various p-tolylsulfonimidamides through the reaction of the corresponding N-protected p-tolylsulfinamides and a number of amines in the presence of N-chlorosuccinimide was achieved at room temperature in 50-97% yield. CONCLUSION: A convenient alternative procedure for the synthesis of sulfonimidamides from sulfinamides and various amines and sulfonamides using N-chlorosuccinimide as halogenating agent has been developed.

Iodinane- and metal-free synthesis of N-cyano sulfilimines: novel and easy access of NH-sulfoximines.

The synthesis of N-cyanosulfilimines can readily be achieved by reaction of the corresponding sulfides with cyanogen amine in the presence of a base and NBS or I2 as halogenating agents. Oxidation followed by C-N bond cleavage affords synthetically useful NH-free sulfoximines.

Synthesis of N-(1H)-tetrazole sulfoximines.

N-(1H)-Tetrazole sulfoximines are readily available by addition of sodium azide to the corresponding N-cyano derivatives in the presence of ZnBr2. The use of these N-(1H)-tetrazoles as intermediates in the synthesis of other N-heterocyclic sulfoximines is demonstrated.