Homolytic N-S Bond Cleavage in Vinyl Triflimides Enabled by Triplet-Triplet Energy Transfer.

Vinyl triflimides are a new compound class with unknown reactivity. A computational analysis identified homolytic cleavage of the N-Tf bond induced by triplet-triplet energy transfer (EnT) as a highly interesting reaction type that might be accessible. A combination of experimental and mechanistic work verified this hypothesis and proved the generated radicals to be amenable to radical-radical coupling. Thereby, vinyl triflimides were transformed into a range of α-quaternary, ß-trifluoromethylated amines in a 1,2-difunctionalization reaction with no need for external CF3 reagents.

Catalyst-Free Reductive Coupling of Aromatic and Aliphatic Nitro Compounds with Organohalides.

A rare reductive coupling of nitro compounds with organohalides has been realized. The reaction is initiated by a partial reduction of the nitro group to a nitrenoid intermediate. Therefore, not only aromatic but also aliphatic nitro compounds are efficiently transformed into monoalkylated amines, with organohalides as the alkylating agent. Given the innate reactivity of the nitrenoid, a catalyst is not required, resulting in a high tolerance for aryl halide substituents in both starting materials.

Vinyl Triflimides-A Case of Assisted Vinyl Cation Formation.

A new concept for selectivity control in carbocation-driven reactions has been identified which allows for the chemo-, regio-, and stereoselective addition of nucleophiles to alkynes-assisted vinyl cation formation-enabled by a Li+ -based supramolecular framework. Mechanistic analysis of a model complex (Li2 NTf2 + ⋅3 H2 O) confirms that solely the formation of a complex between the incoming nucleophile and the transition state of the alkyne protonation is responsible for the resulting selective N addition to the vinyl cation. Into the bargain, a general, operationally simple synthetic procedure to previously inaccessible vinyl triflimides is provided.

Direct Reductive N-Functionalization of Aliphatic Nitro Compounds.

The first general protocol for the direct reductive N-functionalization of aliphatic nitro compounds is presented. The nitro group is partially reduced to a nitrenoid, with a mild and readily available combination of B2 pin2 and zinc organyls. Thereby, the formation of an unstable nitroso intermediate is avoided, which has so far severely limited reductive transformations of aliphatic nitro compounds. The reaction is concluded by an electrophilic amination of zinc organyls.

Are Vinyl Cations Finally Coming of Age?

Ready for the open waters? Recent developments have fundamentally changed our knowledge of vinyl cation reactivity. The myth that they are too reactive for a predictable reaction design has been debunked, and the applicability of their most distinguished feature, namely their carbene-like reactivity, has taken a major leap forwards. Vinyl cations have thus matured into distinct reactive intermediates with a bright future ahead.

O2 -Mediated Oxidation of Aminoboranes through 1,2-N Migration.

In analogy to the classical reaction of C-B bonds with peroxides, the first oxidative functionalization of aminoboranes through a 1,2-N migration was realized. Readily available aliphatic nitro compounds are thereby transformed into N- and O-functionalized hydroxylamines in a single synthetic operation. Addition of hazardous peroxides is avoided. Instead, the insertion of O2 , as the terminal oxidant, into Zn-C bonds provides the necessary peroxides. The required zinc organyls, in turn, are formed through a boron-to-zinc exchange, from an organoboronic ester byproduct of the nitro-to-aminoborane transformation.

Taming a Vinyl Cation with a Simple Al(OTf)3 Catalyst To Promote C-C Bond Cleavage.

A detailed mechanistic investigation identified the stepwise nature of the 1,3-aryl shift, which enables our recently disclosed Al3+ -catalyzed insertion of unactivated alkynes into the sp2 -sp3 C-C bond of benzyl alcohols. The selectivity for the rearranged product was found to be induced by the continued coordination of the aluminum catalyst to the rearranging species, which is encouraged by a reversible background reaction. This participation of the catalyst beyond the ionization step is unique in the realm of carbocation driven reactions and opens up the possibility of a catalyst-induced chiral induction in the future. Furthermore, the study represents a rare example of detailed mechanistic analysis of a reaction with a product selectivity that changes with increasing conversion.

A Vinyl-Cation-Induced 1,3-Aryl Shift.

A net insertion of an unactivated, internal alkyne into a sp2 -sp3 C-C bond of simple benzylic alcohols was achieved using the rearrangement of a highly reactive vinyl cation intermediate to a stabilized allyl cation as the driving force for an unusual 1,3-carbon shift reaction. In the presence of 10 mol % of Al(OTf)3 as a simple, inexpensive, and abundant catalyst, high selectivity for the rearrangement was achieved. The reaction scope proved general with regard to both the alkyne and the benzylic alcohol and a range of 1,2-dihydroquinolines as well as 2H-chromenes were obtained.

Electrophilic Amination with Nitroarenes.

An exceptionally general electrophilic amination, which directly transforms commercially available nitroarenes into alkylated aromatic aminoboranes with zinc organyl compounds was developed. The reaction starts with a two-step partial reduction of the nitro group to a nitrenoid, which is used in situ as the electrophilic amination reagent. To facilitate isolation, the resulting air- and moisture-sensitive aminoboranes were reacted with a range of electrophiles. The method not only represents a direct transformation of nitro compounds into electrophilic amination reagents but also provides an elegant alternative to dehydrocoupling methods for the generation of aminoboranes.

α-Carbonyl Cations in Sulfoxide-Driven Oxidative Cyclizations.

The selective, metal-free generation of α-carbonyl cations from simple internal alkynes was accomplished by the addition of a sulfoxide to a densely substituted vinyl cation. The high reactivity of the α-carbonyl cations was found to efficiently induce hydrogen and even carbon shift reactions with unusual selecivities. Complex compounds with highly congested tertiary and all-carbon-substituted quartenary carbon centers can thus be accessed in a single step from simple precursors. Mechanistic analysis strongly supports the intermediacy of the title compounds and provides a simple predictive scheme for the migratory aptitude of different substituents.

Calcium-catalyzed carboarylation of alkynes.

The first transition-metal-free carboarylation of alkynes with commercial and readily available alcohols as alkylating agents was realized in the presence of an environmentally benign calcium catalyst. Thereby, a novel protocol for the one-step synthesis of highly congested, all-carbon tetrasubstituted alkenes, as incorporated in potentially bioactive, complex dihydronaphthalene, chromene and dihydroquinoline structures, is provided. The reaction features an unprecedented, particularly wide substrate scope, good functional-group tolerance and simple experimental operation under mild reaction conditions.

Calcium-catalyzed carboarylation of alkynes.

Invited for the cover of this issue is the group of Meike Niggemann at the RWTH Aachen University. The image depicts a calcium catalyst brewing a magic potion-a carefully balanced choice of ingredients results in a new one-pot procedure for the carboarylation of internal alkynes. Read the full text of the article at 10.1002/chem.201406503.

Cooperative Catalysis: Calcium and Camphorsulfonic Acid Catalyzed Cycloisomerization of Diynols.

The first transition metal-free cycloisomerization of easily accessible diynols is presented as a novel approach to bicyclic 2H-pyrans. As a one-step protocol, the reaction proceeds in a single reaction cascade by intertwining mechanistic fragments borrowed from transition metal-catalyzed Claisen rearrangment of vinyl ethers with our own work on allenyl/propargyl cation rearrangements and a 6π-oxo-electrocylization. It is enabled by a new cooperative catalytic system that combines a simple Ca(2+) catalyst with camphorsulfonic acid.

Calcium-catalyzed formal [2+2+2] cycloaddition.

A formal intermolecular [2+2+2] cycloaddition reaction of enynes to aldehydes is presented, which can be realized in the presence of a simple and benign calcium catalyst. The reaction proceeds with excellent chemo, regio- and diastereoselectivity and leads to a one-step assembly of highly interesting bicyclic building blocks containing up to three stereocenters from simple precursors via a new type of skeletal rearrangement of enynes. The observed diastereoselectivity is accounted for by two different mechanistic proposals. The first one engages mechanistic prospects arising from a gold catalyzed reaction in the absence of the stabilizing gold substituent. The second proposal involves an unprecedented cyclization-carbonyl allene ene reaction-hydroalkoxylation cascade.

Calcium-based Lewis acid catalysts.

Recently, Lewis acidic calcium salts bearing weakly coordinating anions such as Ca(NTf2)2, Ca(OTf)2, CaF2 and Ca[OCH(CF3)2]2 have been discovered as catalysts for the transformation of alcohols, olefins and carbonyl compounds. High stability towards air and moisture, selectivity and high reactivity under mild reaction conditions render these catalysts a sustainable and mild alternative to transition metals, rare-earth metals or strong Brønsted acids.

Highly chemoselective calcium-catalyzed propargylic deoxygenation.

A calcium-catalyzed direct reduction of propargylic alcohols and ethers has been accomplished by using triethylsilane as a nucleophilic hydride source. At room temperature a variety of secondary propargylic alcohols was deoxygenated to the corresponding hydrocarbons in excellent yields. Furthermore, for the first time, a catalytic deoxygenation of tertiary propargylic alcohols was generally applicable. The same protocol was suitable for an efficient reduction of secondary as well as tertiary propargylic methyl, benzyl and allyl ethers. Substrates containing an additional keto-, ester or secondary hydroxyl function were reduced with exceptional chemoselectivity at the propargylic position.

A general, iterative, and modular approach toward carbohydrate libraries based on ruthenium-catalyzed oxidative cyclizations.

Carbohydrates are an omnipresent class of highly oxygenated natural products. Due to their wide spectra of biological activities, they have been in the center of synthetic organic chemistry for more than 130 years. During the past 50 years non-natural carbohydrates attracted the interest of various chemists in the fields of organic, biological, and medical chemistry. Especially desoxygenated sugars proved to be an important class of compounds. Up to date, most non-natural analogues are synthesized starting from natural, enantiomerically pure carbohydrates in multistep synthesis. In this report, we present a synthetic strategy that allows the selective modular synthesis of natural and non-natural carbohydrates within five synthetic steps starting from readily available starting materials. Due to a sequential introduction of O- or N-functionalities, a regioselective protection of each new functional group is possible. The key step in the carbohydrate synthesis is a RuO4-catalyzed oxidative cyclization via a pH-dependent dehydrogenation-dihydroxylation-cyclization or an oxidative fragmentation-cyclization, leading to highly substituted new carbohydrates, in which each functional group is orthogonally protected and accessible for further synthetic operations.