Stereodivergent Synthesis of 1,4-Dicarbonyl Compounds through Sulfonium Rearrangement: Mechanistic Investigation, Stereocontrolled Access to γ-Lactones and γ-Lactams, and Total Synthesis of Paraconic Acids.

Although simple γ-lactones and γ-lactams have received considerable attention from the synthetic community, particularly due to their relevance in biological and medicinal contexts, stereoselective synthetic approaches to more densely substituted derivatives remain scarce. The in-depth study presented herein, showcasing a straightforward method for the stereocontrolled synthesis of γ-lactones and γ-lactams, builds on and considerably expands the stereodivergent synthesis of 1,4-dicarbonyl compounds by a ynamide/vinyl sulfoxide coupling. A full mechanistic and computational study of the rearrangement was conducted, uncovering the role of all of the reaction components and providing a rationale for stereoselection. The broad applicability of the developed tools to streamlining synthesis is demonstrated by concise enantioselective total syntheses of (+)-nephrosteranic acid, (+)-rocellaric acid, and (+)-nephromopsinic acid.

Sulfonium Rearrangements Enable the Direct Preparation of Sulfenyl Imidinium Salts.

Sulfenyl imidinium salts are a virtually unexplored class of intermediates in organic chemistry. Herein, we demonstrate how sulfonium rearrangements can be deployed to access these versatile synthetic intermediates, bearing three contiguous (and congested) stereogenic centers, with high levels of selectivity. The synthetic value of the scaffold was unraveled by selective transformations into a range of building blocks, including 1,4-dicarbonyl derivatives and sulfonolactones.

Inverse hydride shuttle catalysis enables the stereoselective one-step synthesis of complex frameworks.

The rapid assembly of complex scaffolds in a single step from simple precursors identifies as an ideal reaction in terms of efficiency and sustainability. Indeed, the direct single-step synthesis of complex alkaloid frameworks remains an unresolved problem at the heart of organic chemistry in spite of the tremendous progress of the discipline. Herein, we present a broad strategy in which dynamically assembled ternary complexes are converted into valuable azabicyclic scaffolds based on the concept of inverse hydride shuttle catalysis. The ternary complexes are readily constructed in situ from three simple precursors and enable a highly modular installation of various substitution patterns. Upon subjection to a unique dual-catalytic system, the transient intermediates undergo an unusual hydride shuttle process that is initiated by a hydride donation event. Furthermore, we show that, in combination with asymmetric organocatalysis, the product alkaloid frameworks are obtained in excellent optical purity.

Straightforward Access to Thiocyanates via Dealkylative Cyanation of Sulfoxides.

Thiocyanates, versatile building blocks in organic synthesis, are shown to be easily accessible via an interrupted Pummerer reaction of sulfoxides. This facile dealkylative functionalization proceeds under mild conditions through electrophilic activation of the sulfoxide partner. The resulting thiocyanate itself can serve as a handle for diversification in a straightforward one-pot procedure.

As Similar As Possible, As Different As Necessary - On-Site Laboratory Teaching during the COVID-19 Pandemic.

Most of the available information on studying under the challenging conditions brought about by the COVID-19 pandemic emphasizes a variety of aspects on how to digitalize the whole teaching process. Thus, several useful and potentially game-changing strategies have been reported recently. In contrast to the digitalization of teaching, in this article, we focus on the reverse process: transitioning back to offline teaching, which is unavoidable especially for the acquisition of practical skills during chemistry studies. In this work, we describe our own experience acquired during the Organic Chemistry practical course at the University of Vienna, which was held in June 2020 and onwards. The article contains descriptions of precautions and measures that were taken, additional materials, and necessary changes made in order to safely continue on-site course teaching. We anticipate that this set of precautions can be used in an adapted fashion for any type of laboratory course. Further, we offer a critical analysis of students' and instructors' opinions concerning the changes and well-being during the course. Those opinions were collected via a detailed survey. From our experience, with careful planning and responsible behavior, a return to on-site education is possible and warmly welcomed by all involved participants. The detailed description of our course may also be useful for those who need to start a new organic laboratory course or want to improve an existing one.

Bond-Forming and -Breaking Reactions at Sulfur(IV): Sulfoxides, Sulfonium Salts, Sulfur Ylides, and Sulfinate Salts.

Organosulfur compounds have long played a vital role in organic chemistry and in the development of novel chemical structures and architectures. Prominent among these organosulfur compounds are those involving a sulfur(IV) center, which have been the subject of countless investigations over more than a hundred years. In addition to a long list of textbook sulfur-based reactions, there has been a sustained interest in the chemistry of organosulfur(IV) compounds in recent years. Of particular interest within organosulfur chemistry is the ease with which the synthetic chemist can effect a wide range of transformations through either bond formation or bond cleavage at sulfur. This review aims to cover the developments of the past decade in the chemistry of organic sulfur(IV) molecules and provide insight into both the wide range of reactions which critically rely on this versatile element and the diverse scaffolds that can thereby be synthesized.

Stereodivergent synthesis of 1,4-dicarbonyls by traceless charge-accelerated sulfonium rearrangement.

The chemistry of the carbonyl group is essential to modern organic synthesis. The preparation of substituted, enantioenriched 1,3- or 1,5-dicarbonyls is well developed, as their disconnection naturally follows from the intrinsic polarity of the carbonyl group. By contrast, a general enantioselective access to quaternary stereocenters in acyclic 1,4-dicarbonyl systems remains an unresolved problem, despite the tremendous importance of 2,3-substituted 1,4-dicarbonyl motifs in natural products and drug scaffolds. Here we present a broad enantioselective and stereodivergent strategy to access acyclic, polysubstituted 1,4-dicarbonyls via acid-catalyzed [3,3]-sulfonium rearrangement starting from vinyl sulfoxides and ynamides. The stereochemistry at sulfur governs the absolute sense of chiral induction, whereas the double bond geometry dictates the relative configuration of the final products.

Unusual mechanisms in Claisen rearrangements: an ionic fragmentation leading to a meta-selective rearrangement.

A mechanistic investigation of the acid-catalysed redox-neutral oxoarylation reaction of ynamides using electrospray ionisation mass-spectrometry (ESI-MS) and quantum chemical calculations (DFT and MP2) is presented. This study reveals the diversity of pathways and products available from an otherwise deceptively simple-looking, classical transformation: fragmentation, an unusual meta-arylation and competing α-carbonyl cation pathways are some of the alternatives unveiled by ESI-MS and mechanistic experiments. Detailed calculations explain the observed trends and rationalise the results.

Synthesis and Photocatalytic Reactivity of Vinylsulfonium Ylides.

Although sulfur ylides are textbook reagents in organic synthesis, surprisingly little variation of substituents on sulfur is usually observed. In particular, vinylsulfonium ylides have been neglected so far. Herein, we present a study on their synthesis and reactivity, including interesting behavior under photocatalytic conditions.