Littlewood-Evans et al. demonstrate that extracellular succinate leads to the propagation of inflammatory macrophage activation, providing translational evidence to support the development of GPR91 antagonists for the treatment of rheumatoid arthritis.
Organomagnesium reagents occupy a central position in synthetic organic and organometallic chemistry. Recently, the halogen-magnesium exchange has considerably extended the range of functionalized Grignard reagents available for synthetic purposes. Functional groups such as esters, nitriles, iodides, imines, or even nitro groups can be present in a wide range of aromatic and heterocyclic organomagnesium reagents. Also various highly functionalized alkenyl magnesium species can be prepared. These recent developments as well as new applications of organomagnesium reagents in cross-coupling reactions and amination reactions will be covered in this Review.
The catalytic enantioselective formation of new C À C bonds is an important class of reactions.[1] Especially attractive are multicomponent reactions which allow the formation of several bonds including new CÀC bonds in a one-pot procedure.[2] For achieving optimum atom economy [3] and avoiding the production of stoichiometric amounts of metal salts as by-products, we [4] and others [5] have examined the use of an alkyne as the precursor for the nucleophilic reaction component. Alkynes of type 1 can be deprotonated catalytically in situ by means of cesium salts and reacted subsequently with aldehydes and ketones, leading to propargyl alcohols. [6] Recently, we have shown that various enamines react with terminal alkynes in the presence of copper(i) salts and quinap (2), [7] providing propargylamines in up to 90 % ee.[4]In order to avoid the generation of sensitive enamines and to extend the scope of this propargylamine synthesis to nonenolizable aldehydes (i.e. aldehydes from which enamines cannot be prepared), we have examined a new threecomponent reaction [8] between an alkyne 1, an aldehyde 3, and a secondary amine 4. We have found that propargylamines of type 5 are formed in toluene at room temperature in the presence of CuBr (5 mol %), (R)-quinap ((R)-2) (5.5 mol %), and molecular sieves 4 in excellent yields (up to 99 %) and good enantioselectivities (up to 96 % ee; Scheme 1 and Table 1).The reaction is usually complete within 12 to 48 h for the racemic reaction without ligand and within one to six days for the enantioselective reaction with high yields in most cases. The alkyne can bear either an aryl substituent (R 1 = Ph) or an alkyl substituent (R 1 = Bu; entries 1 and 2 in Table 1). The resulting propargylamines 5 a and 5 b were obtained in 98 and 85 % yield and 86 and 82 % ee, respectively. Branched aliphatic aldehydes like isobutyraldehyde lead to the expected propargylamines 5 c and 5 d in 60 and 99 % yield and 84 and 83 % ee, respectively (entries 3 and 4). The use of
Magnesiumverbindungen spielen eine zentrale Rolle in der präparativen organischen und metallorganischen Chemie. Seit kurzem ermöglicht der Halogen‐Magnesium‐Austausch den Zugang zu einer Reihe funktionalisierter Grignard‐Reagentien. Ester‐, Nitril‐, Iod‐ und Iminfunktionen und sogar Nitrogruppen können in einer breiten Reihe aromatischer und heterocyclischer Organomagnesiumverbindungen vorhanden sein. Auch hoch funktionalisierte Alkenylmagnesiumspezies können auf diese Weise generiert werden. Diese neuen Entwicklungen sowie die Anwendung von Organomagnesiumreagentien in Kreuzkupplungen und Aminierungsreaktionen werden in diesem Aufsatz eingehend beschrieben.
The one-pot three-component reaction of terminal alkynes, aldehydes and secondary amines in the presence of copper(I) bromide/quinap is reported. The reaction scope has been determined and a broad variety of all three components has been used, which afforded the corresponding propargylamines in good to excellent yields and moderate to very good enantioselectivities. The reaction showed a strong positive nonlinear effect. The transformation of a propargylamine intermediate into the alkaloid (S)-(+)-coniine has also been described.
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