A nickel-catalyzed reductive dimerization of bromocyclobutenes to produce unusual and unprecedented cyclobutene dimers was developed. In a stereoconvergent procedure, various bromocyclobutenes were readily dimerized in good yields, with good diastereoselectivities and broad functional group tolerance. Notably, the presence of a carbonyl group in the starting material appears to dictate diastereoselectivity.

The study and application of transition metal hydrides (TMHs) has been an active area of chemical research since the early 1960s1, for energy storage, through the reduction of protons to generate hydrogen2,3, and for organic synthesis, for the functionalization of unsaturated C–C, C–O and C–N bonds4,5. In the former instance, electrochemical means for driving such reactivity has been common place since the 1950s6 but the use of stoichiometric exogenous organic- and metal-based reductants to harness the power of TMHs in synthetic chemistry remains the norm. In particular, cobalt-based TMHs have found widespread use for the derivatization of olefins and alkynes in complex molecule construction, often by a net hydrogen atom transfer (HAT)7. Here we show how an electrocatalytic approach inspired by decades of energy storage research can be made use of in the context of modern organic synthesis. This strategy not only offers benefits in terms of sustainability and efficiency but also enables enhanced chemoselectivity and distinct, tunable reactivity. Ten different reaction manifolds across dozens of substrates are exemplified, along with detailed mechanistic insights into this scalable electrochemical entry into Co–H generation that takes place through a low-valent intermediate. A perspective is given on how an electrocatalytic approach, inspired by decades of energy storage studies, can be used in the context of efficient cobalt-hydride generation with a variety of applications in modern organic synthesis.

A formal enone α-arylation is described. This metal-free transformation relies on the I(III)-mediated skeletal reorganization of silyl enol ethers and features mild conditions, good yields, and high stereoselectivities for β-substituted enones.

This perspective article discusses structural features of iodine(iii) compounds as a prelude to presenting their use as umpolung reagents, in particular as pertains to their ability to promote the selective coupling of two nucleophilic species via 2e(-) oxidation.

The study and application of transition metal hydrides (TMH) has been an active area of chemical research since the early 1960’s. The use of TMHs has been broadly bifurcated into fields focused on energy storage through the reduction of protons to generate hydrogen and in organic synthesis for the functionalization of unsaturated C–C, C–O, and C–N bonds. In the former instance, electrochemical means for driving such reactivity has been commonplace since the 1950’s. In contrast, the use of stoichiometric exogenous organic and metal-based reductants to harness the power of TMHs in synthetic chemistry remains the norm. In particular, Co-based TMHs have found widespread use for the derivatization of olefins and alkynes in complex molecule construction, often via a net hydrogen atom transfer (HAT). Here, we show how an electrocatalytic approach inspired by decades of energy storage precedent can be leveraged in the context of modern organic synthesis. Such an approach not only offers benefits in terms of sustainability and efficiency but also enables enhanced chemoselectivity and unique and tunable reactivity. Ten different reaction manifolds across dozens of substrates are thus exemplified, along with a detailed mechanistic and computational analysis of this scalable electrochemical entry into Co-H chemistry.

AbstractThe reactivity of iodine(III) reagents towards nucleophiles is often associated with umpolung and cationic mechanisms. Herein, we report a general process converting a range of ketone derivatives into α‐cyclopropanated ketones by oxidative umpolung. Mechanistic investigation and careful characterization of side products revealed that the reaction follows an unexpected pathway and suggests the intermediacy of non‐classical carbocations.

The work presented herein describes the synthesis of a formerly inaccessible class of heterocyclic compounds. The reaction relies on α-phthalimido-amides, which are readily prepared from amino acids in 2 simple reactions steps. Under amide activation conditions in which classical keteniminium ions are not formed, the nitrile solvent is incorporated into the new fused 7-membered ring system. Due to the absence of a keteniminium intermediate, the stereogenic information in the α-position is fully retained.

DIESE ARBEIT BESCHREIBT DIE ENTWICKLUNG neuer Synthesemethoden in der organischen Chemie. Das erste Kapitel schildert ein Eintopfverfahren, in welchem eine Hosomi-Sakurai Reaktion mit einer regio- sowie stereoselektiven internen Reduktion der generierten homoallylischen Doppelbindungen durch eine nicht sigmatrope 1,5 Hydridverschiebung, gekoppelt wird. Hierbei werden 1,3-disubstituierte Alkohole vorzugsweise als anti-Diastereoisomere gewonnen. Im zweiten Kapitel wird die Entwicklung einer Ruthenium-katalysierten Olefinierungsreaktion erortert, in der Carbenvorstufen miteinander gekuppelt werden. Die Alkene, welche als Produkt anfallen, werden dabei in hoher Z-Selektivitat gebildet. Das dritte Kapitel setzt sich mit neuartigen Funktionalisierungsreaktionen von tertiaren Amiden auseinander. Diese Reaktionen basieren auf der elektrophilen Aktivierung von Amiden, welche mit weiteren Oxidationschritten kombiniert wird. α,β-Epoxyamide, β-Thioamide α-Ketoamide, β-Ketoamide sowie Furanone konnen dabei in moderaten bis exzellenten Ausbeuten gewonnen werden. Desweitern wurden im Laufe der Studie mehrere unerwartete Nebenreaktionen entdeckt und erforscht. Diese Reaktionen fuhrten zur Bildung heterocyclischer Verbindungen deren Darstellung zuvor schwierig war. Im vierten und letzten Kapitel wird der Gebrauch von Iod(III) Reagenzien zur Oxidation von Keton derivativen beschrieben, um Umlagerungen, welche typischerweise in klassischen und nicht-klassischen Carbokationen beobachtet werden, hervorzurufen. Die erste Methode beschaftigt sich mit einer oxidativen 1,2-Aryl Verschiebung in β-Aryl Ketonderivaten, welche zur Bildung von α-Aryl-β-Mesylat Ketonen fuhrt. Eine asymmetrische Variante dieser Reaktion wurde ebenfalls erfolgreich untersucht. Die zweite Methode nutzt hingegen γ,δ-ungesattigte Ketonderivative als Startmaterialien, welche durch Oxidation in Cyclopropylcarbinylkationen uberfuhrt werden. Diese Kationen konnen dann mit verschiedenen Nukleophilen eingefangen werden, was zur Bildung von disubstituierten trans Cyclopropanen fuhrt.

The Cover Feature shows the reaction of an amino acid derivative with acetonitrile to form a formally unknown heterocyclic compound. The reaction is mediated by trifluoro-methanesulfonic anhydride, which unlashes this unconventional reactivity and is illustrated by the scissors, which cut the rope holding the weight of CH3CN. The background shows a 3D model of the product, which is based on the X-ray diffraction analysis of its single crystal. More information can be found in the Communication by N. Maulide et al.

A regio- and chemoselective preparation of bicyclic alkoxyoxazolium salts from amide derivatives of proline and pipecolic acid by electrophilic amide activation is reported. Mechanistic NMR experiments suggest an unusual role for the base and highlight the effect of substitution pattern of the substrates.

A quantitative synthesis of piperine from commercially available starting material is presented. The synthesis relies on a stereoselective nucleophilic attack of an in situ generated cuprate onto a cyclobutene lactone. The so-formed aryl-substituted cyclobutene spontaneously undergoes a conrotatory 4π-electrocyclic ring opening to form the 4-aryl pentadienoic acid as a single diastereoisomer. The high-yielding synthesis can be easily modulated on the aryl and on the amide moiety for the synthesis of a wide range of piperine analogues.

Aliphatic C-H functionalization is a topic of current intense interest in organic synthesis. Herein, we report that a facile and stereoselective dehydrogenation event enables the functionalization of aliphatic amides at different positions in a one-pot fashion. Derivatives of relevant pharmaceuticals were formally functionalized in the β-position in late-stage manner. A single-step synthesis of incrustoporine from a simple precursor further showcases the potential utility of this approach.

A synthetically useful approach for the direct α-arylation of carbonyl compounds through a novel oxidative C-C bond activation is reported. This mechanistically unusual process relies on a 1,2-aryl shift and results in all-carbon quaternary centers. The transformation displays broad functional-group tolerance and can in principle also be applied as an asymmetric variant.

AbstractEine synthetisch nützliche Methode für die direkte α‐Arylierung von Carbonylverbindungen mittels einer neuartigen, oxidativen C‐C‐Bindungsaktivierung wird vorgestellt. Dieser mechanistisch unübliche Prozess baut auf einer 1,2‐Aryl‐Umlagerung auf, welche zur Bildung von quaternären, vollständig mit Kohlenstoff substituierten Zentren führt. Die Umsetzung weist eine breite Toleranz gegenüber funktionellen Gruppen auf und ist prinzipiell auch in einer asymmetrischen Variante möglich.

AbstractEine neuartige Ruthenium‐katalysierte Kreuz‐Olefinierung von Diazoverbindungen und Sulfoxonium‐Yliden wird vorgestellt. Unser Reaktionsdesign nutzt den intrinsischen Reaktivitätsunterschied von Diazoverbindungen und Sulfoxonium‐Yliden als maskierte Carbene und Nukleophile, welche hohe Selektivitäten in der Reaktion ermöglichen.

A novel reductive variant of the classical Hosomi-Sakurai reaction is reported. This transformation hinges on a redox-neutral, stereoselective internal reduction event under mild conditions. This operationally simple reaction relies on readily available starting materials and leads to useful products in diastereoselectivities of up to 7:1. The versatility of this new method is demonstrated through the stereoselective one-step synthesis of an AChE inhibitor.

Herein we present a full account on the reductive Hosomi-Sakurai reaction along with some insight into the reaction mechanism. Stereoselectivity appears to be highest when the crucial carbocation intermediate, derived by protonation of the homoallylic ether, is sufficiently stabilized to ensure that the hydride transfer becomes rate-determining. This hypothesis is supported by experiment and mechanistic analysis.

It is textbook knowledge that carboxamides benefit from increased stabilisation of the electrophilic carbonyl carbon when compared to other carbonyl and carboxyl derivatives. This results in a considerably reduced reactivity towards nucleophiles. Accordingly, a perception has been developed of amides as significantly less useful functional handles than their ester and acid chloride counterparts. However, a significant body of research on the selective activation of amides to achieve powerful transformations under mild conditions has emerged over the past decades. This review article aims at placing electrophilic amide activation in both a historical context and in that of natural product synthesis, highlighting the synthetic applications and the potential of this approach.

A ruthenium-catalysed cross-olefination of diazo compounds and sulfoxonium ylides is presented. Our reaction design exploits the intrinsic difference in reactivity of diazo compounds and sulfoxonium ylides as both carbene precursors and nucleophiles, which results in a highly selective reaction.

The first catalytic kinetic resolution by N-sulfonylation is described. 2-Substituted indolines are resolved (s=2.6-19) using an atropisomeric 4-dimethylaminopyridine-N-oxide (4-DMAP-N-oxide) organocatalyst. Use of 2-isopropyl-4-nitrophenylsulfonyl chloride is critical to the stereodiscrimination and enables facile deprotection of the sulfonamide products with thioglycolic acid. A qualitative model that accounts for the stereodiscrimination is proposed.