Asymmetric Lewis acid-catalyzed 1,3-dipolar cycloadditions

Highly tuned, one-point binding chiral iron and ruthenium complexes selectively coordinate and activate α,β-unsaturated aldehydes and ketones toward asymmetric catalytic Diels-Alder cycloaddition reactions. Here we focus on the application of these transition-metal Lewis acids to asymmetric catalytic 1,3-dipolar cycloaddition reaction between enals and cyclic and acyclic nitrones as well as aryl nitrile oxides to give isoxazolidines and isoxazolines, respectivel

Asymmetric Pd-NHC*-catalyzed coupling reactions

Very high asymmetric inductions result in the Pd-catalyzed intramolecular arylation of amides to give 3,3-disubstituted oxindoles when new in situ-generated chiral N-heterocyclic carbene (NHC*) ligands are employed. Structural studies show that conformational locking to minimize allylic strain is the key to understanding the function of these ligands. New applications of these ligands in the frontier area of asymmetric coupling reactions involving C(sp3)-H bonds are detailed. Highly enantioenriched fused indolines are accessible using either preformed- or in situ-generated Pd-NHC* catalysts. Remarkably, this occurs at high temperature (140-160 °C) via excellent asymmetric recognition of an enantiotopic C-H bond in an unactivated methylene uni

Inflammation in acute myocardial infarction: the good, the bad and the ugly.

Convergent experimental and clinical evidence have established the pathophysiological importance of pro-inflammatory pathways in coronary artery disease. Notably, the interest in treating inflammation in patients suffering acute myocardial infarction (AMI) is now expanding from its chronic aspects to the acute setting. Few large outcome trials have proven the benefits of anti-inflammatory therapies on cardiovascular outcomes by targeting the residual inflammatory risk (RIR), i.e. the smouldering ember of low-grade inflammation persisting in the late phase after AMI. However, these studies have also taught us about potential risks of anti-inflammatory therapy after AMI, particularly related to impaired host defence. Recently, numerous smaller-scale trials have addressed the concept of targeting a deleterious flare of excessive inflammation in the early phase after AMI. Targeting different pathways and implementing various treatment regimens, those trials have met with varied degrees of success. Promising results have come from those studies intervening early on the interleukin-1 and -6 pathways. Taking lessons from such past research may inform an optimized approach to target post-AMI inflammation, tailored to spare 'The Good' (repair and defence) while treating 'The Bad' (smouldering RIR) and capturing 'The Ugly' (flaming early burst of excess inflammation in the acute phase). Key constituents of such a strategy may read as follows: select patients with large pro-inflammatory burden (i.e. large AMI); initiate treatment early (e.g. ≤12 h post-AMI); implement a precisely targeted anti-inflammatory agent; follow through with a tapering treatment regimen. This approach warrants testing in rigorous clinical trials

Organic Chemistry à la Genevoise

This article describes the situation of Department of Organic Chemistry in the year of the 450th anniversary of the University of Geneva

Stereoselective chromium-and molybdenum- mediated transformations of arenes*

Abstract: Tricarbonylchromium-mediated dearomatization provides a rapid access to substituted cyclohexadienes. Efficient asymmetric routes to planar chiral arene complexes and to substituted cyclohexadienes have been developed. The article sums up the main features of this chemistry. Highly enantiomerically enriched ortho-substituted benzaldehyde complexes are accessible via asymmetric lithiation followed by trapping with electrophiles. In different solvents, the trimethylsilyl complex exhibits [α] values ranging from -174 to +108 for the same enantiomer. Details of two asymmetric syntheses of natural products are given: the alkaloid lasubine I starting from a highly enantiomerically enriched planar chiral arene complex and the marine furanosesquiterpene acetoxytubipofuran. The latter is assembled via asymmetric dearomatization of a benzaldehyde imine complex. Other key steps include an Eschenmoser-Claisen rearrangement and a regio-and diastereoselective Pd-catalyzed allylic substitution. The final section deals with labile arene metal complexes. For the first time, dearomatization reactions mediated by the Mo(CO) 3 group have been realized. The reactions show strong analogies to the Cr(CO) 3 -mediated reactions, but exhibit also marked differences: the arene-Mo bond is stronger, but more labile, and the sequential double additions show different selectivities compared to the chromium analogs. The search for ever more efficient chemo-, regio-, and stereoselective routes to complex molecules from simple starting materials is an important task in organic synthesis. Progress in this area continues to advance at a fast pace. Arenes, the subject of this article, are widely available, highly stable, and readily derivatized through reactions such as electrophilic and nucleophilic aromatic substitution [1], ortholithiation followed by reaction with electrophiles [2], or metal-catalyzed substitution and coupling reactions This notwithstanding, the synthesis of complex organic molecules via elegant dearomatization chemistry has undergone intensive investigation. Examples involve the Birch reduction, which achieves *Plenary and invited lectures presented at th

Catalysis with Complexes Containing Stereogenic Metal Centers

Alfred Werner, one of the founders of the Swiss Chemical Society and its first president and the first Nobel Prizewinner for Chemistry in Switzerland, established the stereochemistry of coordination complexes. As an important element in the verification of his hypothesis he demonstrated the existence of two enantiomeric forms of [Co(ethylenediamine)3][Cl3]. The present article briefly examines the question of the use in asymmetric catalysis of catalysts possessing a stereogenic metal center

Tateshina: Swiss Inspiration!

The Tateshina conference celebrates its 20th anniversary this year. Its founder, Eiichi Nakamura, modeled the conference after the Bürgenstock conference where he was a speaker in April 2000. This short account highlights this event