A general synthetic sequence involving simply prepared starting materials provides rapid access to diverse, novel tricyclic architectures inspired by pleuromutilin. Sm^II-mediated radical cyclization cascades of dialdehydes, prepared using a new, one-pot, copper-catalyzed double organomagnesium addition to β-chlorocyclohexenone, proceed with complete sequence selectivity and typically with high diastereocontrol to give analogues of the target core. Our expedient approach (ca. 7 steps) allows non-traditional, de novo synthetic access to analogues of the important antibacterial that can′t be prepared from the natural product by semisynthesis.

A copper-catalyzed three-component coupling of allenes, bis(pinacolato)diboron, and imines allows regio-, chemo-, and diastereoselective assembly of branched α,β-substituted-γ-boryl homoallylic amines, that is, products bearing versatile amino, alkenyl, and borane functionality. Alternatively, convenient oxidative workup allows access to α-substituted-β-amino ketones. A computational study has been used to probe the stereochemical course of the cross-coupling.

A copper-catalyzed three-component coupling of allenes, bis(pinacolato)diboron, and imines allows regio-, chemo-, and diastereoselective assembly of branched α,β-substituted-γ-boryl homoallylic amines, that is, products bearing versatile amino, alkenyl, and borane functionality. Alternatively, convenient oxidative workup allows access to α-substituted-β-amino ketones. A computational study has been used to probe the stereochemical course of the cross-coupling.

A sulfoxide-directed, metal-free ortho-propargylation of aromatics and heteroaromatics exploits intermolecular delivery of a propargyl nucleophile to sulfur followed by an intramolecular relay to carbon. The operationally simple cross-coupling procedure is general, regiospecific with regard to the propargyl nucleophile, and shows complete selectivity for products of ortho-propargylation over allenylation. The use of secondary propargyl silanes allows metal-free ortho-coupling to form carbon–carbon bonds between aromatic and heteroaromatic rings and secondary propargylic centres. The ‘safety-catch’ nature of the sulfoxide directing group is illustrated in a selective, iterative double cross-coupling process. The products of propargylation are versatile intermediates and they have been readily converted into substituted benzothiophenes.

Invited for the cover of this issue is the group of David J. Procter at the University of Manchester (UK). The image illustrates a new, metal-free direction for cross-coupling technology by taking signage from the University of Manchester campus. Read the full text of the article at 10.1002/chem.201406424.

The mechanism of the SmI₂-mediated reduction of unactivated esters has been studied using a combination of kinetic, radical clocks and reactivity experiments. The kinetic data indicate that all reaction components (SmI₂, amine, H₂O) are involved in the rate equation and that electron transfer is facilitated by Brønsted base assisted deprotonation of water in the transition state. The use of validated cyclopropyl-containing radical clocks demonstrates that the reaction occurs via fast, reversible first electron transfer, and that the electron transfer from simple Sm(II) complexes to aliphatic esters is rapid. Notably, the mechanistic details presented herein indicate that complexation between SmI₂, H₂O and amines affords a new class of structurally diverse, thermodynamically powerful reductants for efficient electron transfer to carboxylic acid derivatives as an attractive alternative to the classical hydride-mediated reductions and as a source of acyl-radical equivalents for CC bond forming processes.

Copper-catalyzed silylation of aryl allenes using a silylborane reagent affords vinyl silane building blocks with high efficiency. The use of a seven-membered NHC ligand proved crucial for high regioselectivity. The catalytically generated allylcoppper intermediates were intercepted by aldehydes in a diastereoselective three-component coupling to furnish homoallylic alcohols.

The first enantiospecific total synthesis of the antibacterial natural product (+)-pleuromutilin has been achieved. The approach includes the synthesis of a non-racemic cyclisation substrate from (+)-trans-dihydrocarvone, a highly selective SmI₂-mediated cyclisation cascade, an electron transfer reduction of a hindered ester, and the first efficient conversion of (+)-mutilin to the target.

Reactions proceeding through open-shell, single-electron pathways offer attractive alternative outcomes to those proceeding through closed-shell, two-electron mechanisms. In this context, samarium diiodide (SmI₂) has emerged as one of the most important and convenient-to-use electron-transfer reagents available in the laboratory. Recently, significant progress has been made in the reductive chemistry of other divalent lanthanides which for many years had been considered too reactive to be of value to synthetic chemists. Herein, we illustrate how new samarium(II) complexes and nonclassical lanthanide(II) reagents are changing the landscape of modern reductive chemistry.

Reaktionen, die über offenschalige Einelektronenmechanismen ablaufen, führen zu interessanten alternativen Resultaten gegenüber solchen Reaktionen, die Zweielektronenmechanismen mit geschlossenen Schalen gehorchen. In diesem Zusammenhang entwickelte sich Samariumdiiodid zu einem der wichtigsten Elektronentransferreagentien. In letzter Zeit wurde ein signifikanter Fortschritt auf dem Gebiet der reduktiven Chemie anderer zweiwertiger Lanthanoide erzielt, die viele Jahre lang als zu reaktiv erachtet worden waren, um von Nutzen für Synthesechemiker zu sein. Wir beschreiben hier, wie neue Samarium(II)-Komplexe und nichtklassische Lanthanoid(II)-Reagentien die moderne reduktive Chemie verändern.

SmI₂/H₂O reduces cyclic 1,3-diesters to 3-hydroxyacids with no over reduction. Furthermore, the reagent system is selective for cyclic 1,3-diesters over acyclic 1,3-diesters, and esters. Radicals formed by one-electron reduction of the ester carbonyl group have been exploited in intramolecular additions to alkenes. The ketal unit and the reaction temperature have a marked impact on the diastereoselectivity of the cyclizations. Cyclization cascades are possible when two alkenes are present in the starting cyclic diester and lead to the formation of two rings and four stereocenters with excellent stereocontrol.

Since the early 1960s the Pummerer reaction has evolved to become an indispensable tool for synthesis, and continues to serve as a source of inspiration for organic chemists. In recent years, many exciting advances have demonstrated the broad scope and synthetic utility of Pummerer methodology and the versatility of thionium ion intermediates.

Seit den frühen 1960er Jahren hat sich die Pummerer-Reaktion zu einem unentbehrlichen Syntheseverfahren in der organischen Chemie entwickelt. Viele interessante Fortschritte in den vergangenen Jahren unterstreichen die breite Anwendbarkeit und den Nutzen dieser Methode sowie die Vielseitigkeit von Thioniumionen als Intermediate.