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Herein, we describe a novel Negishi-type cross-coupling of amides employing only cobalt bromide salt as the catalyst. This original reaction is highly tolerant to various glutarimide amides as well as organozinc coupling partners. These conditions also allow the performance of the cross-coupling reaction in an eco-compatible solvent such as ethyl acetate on a large scale.

International audience; Simple N-heteroaromatic Ni(II) precatalysts, (L)NiMe2 (L = bipy, bipym), were used for alkene isomerization. With an original reduction method using a simple borane (HB(Cat)), a low-valent Ni center was formed readily and showed good conversion when a reducing divalent lanthanide fragment, Cp*2Yb, was coordinated to the (bipym)NiMe2 complex, a performance not achieved by the monometallic (bipy)NiMe2 analogue. Experimental mechanistic investigations and computational studies revealed that the redox non-innocence of the L ligand triggered an electron shuttle process, allowing the elusive formation of Ni(I) species that were central to the isomerization process. Additionally, the reaction occurred with a preference for mono-isomerization rather than chain-walking isomerization. The presence of the low-valent ytterbium fragment, which contributed to the formation of the electron shuttle, strongly stabilized the catalysts, allowing catalytic loading as low as 0.5%. A series of alkenes with various architectures have been tested. The possibility to easily tune the various components of the heterobimetallic catalyst reported here, the ligand L and the divalent lanthanide fragment, opens perspectives for further applications in catalysis induced by Ni(I) species.

International audience

An efficient and scalable access to the aeruginosin family of marine natural products, which exhibit potent inhibitory activity against serine proteases, is reported. This synthesis was enabled by the strategic use of two different, recently implemented C(sp3)H activation reactions. The first method led to the common 2-carboxy-6-hydroxyoctahydroindole (Choi) core of the target molecules on a large scale, whereas the second one provided rapid and divergent access to the various hydroxyphenyllactic (Hpla) subunits. This strategy allowed the synthesis of the aeruginosins 98B and 298A, with the latter being obtained in unprecedentedly large quantities.

International audience

The development of methods for the introduction of trifluoromethyl groups into functionalized molecules is of great importance due to their presence in many top-selling pharmaceuticals, agrochemicals, and functional materials. Trifluoromethyl groups are known to impart desirable properties, such as higher metabolic stability, increased lipophilicity, and stronger dipole moments to druglike molecules. Celecoxib, dutasteride, fluoxetine, and sitagliptin are some examples of top-selling pharmaceuticals featuring trifluoromethyl groups, and beflubutamid, diflufenican, and norfluazon examples of agrochemicals. However, traditional methods to access benzotrifluorides, for example, the Swarts reaction, typically require harsh conditions and have a low substrate scope, so that they are confined to the beginning of a synthetic sequence (Scheme 1a). Building on pioneering work on Cu– and Pd–perfluoroalkyl complexes by McLoughlin, Yagupolskii, Burton, Chambers, Grushin, and others, substantial progress has recently been made in the development of trifluoromethylation reactions that allow the selective introduction of CF3 groups into functionalized, late-stage synthetic intermediates. A wealth of new reactions has been disclosed, which can be roughly divided into five categories (Scheme 1b–f). The first are couplings of aryl halides with nucleophilic CF3 reagents (reaction type b), usually copper–CF3 complexes in stoichiometric amounts. These complexes may also be generated in situ from copper salts and Ruppert s reagent (CF3SiMe3), [7] fluoroform, potassium (trifluoromethyl)trimethoxyborate, trifluoroacetate salts, methyl trifluoroacetate, or fluorosulfonyldifluoroacetic acid. Grushin, Sanford, and Buchwald also disclosed trifluoromethylations of aryl halides based on palladium complexes. Palladium complexes also promote C H functionalizations of arenes with trifluoromethylating reagents (reaction type c). Examples are the ortho-trifluoromethylation of donor-substituted arenes with Umemoto s reagent described by Yu et al. and the Pd-catalyzed coupling of arenes with perfluoroalkyl iodides reported by Sanford et al. C H trifluoromethylations of heteroarenes have recently been reported also with nucleophilic trifluoromethylation reagents under oxidative conditions. Examples of couplings of aryl nucleophiles with electrophilic CF3 sources (reaction type d) include the coupling of arylboronic acids with Togni s and Umemoto s reagent disclosed by Shen and Liu, respectively. Sanford et al. employed a copper/ruthenium photocatalyst system to promote a radical trifluoromethylation of boronic acids. The copper-catalyzed syntheses of benzotrifluorides from boronic acids and CF3SiMe3 or K [CF3B(OMe)3] developed by Qing et al. and ourselves exemplify oxidative couplings of aryl nucleophiles with nucleophilic CF3 reagents (reaction type e). The radical trifluoromethylation of arenes (reaction type f) was pioneered by Langlois. Baran and MacMillan recently reported modern variants of this reaction concept based on peroxide or ruthenium initiators. From a practical standpoint, nucleophilic reagents are appealing for the introduction of trifluoromethyl groups for the following reasons. CF3SiMe3 and K [CF3B(OMe)3] are available in large quantities for a reasonable price, and are easy to store and handle. They are accessible not only from halofluorocarbons, but also from fluoroform, a by-product in the production of Teflon. One of the most widely used methods for the introduction of halides and related nucleophiles is the Sandmeyer reaction. Aromatic amines, which are available in great structural diversity, are diazotized using, for example, NaNO2 or organic nitrites. Upon treatment with the appropriate copper(I) halides, nitrogen gas is released, and a halide group is installed regiospecifically in the position Scheme 1. Strategies for the introduction of trifluoromethyl groups.

The first cobalt-catalyzed amide activation of N-Boc-amides, and their conversion into esters, is reported herein. This new methodology presents a very practical process, that does not require an inert atmosphere, uses an inexpensive cobalt catalyst, and proceeds under mild reaction conditions. This catalytic system has a broad substrate scope and has been shown to be highly efficient, with catalyst loadings as low as 1 mol%.

International audience; Dedicated to the memory of Professor Jean F. Normant; a brilliant scientist and a great person air or BQ r.t. CoBr 2 , cat. Zn Ar Br Ar ZnBr Ar Ar 18 examples 0-95% Ar = aryl or heteroaryl with FG = o-MeO, m-MeO, p-MeO, Me, NMe 2 , H, Cl, COMe, CN, CF 3 , CO 2 Et Reductive Process Oxidative Process Abstract A novel procedure for the synthesis of functionalized symmetrical biaryl compounds is described. The reaction proceeds via the oxidative homocoupling of arylzinc species formed by cobalt catalysis in the presence of air or p-benzoquinone depending on the nature of the functional group.

A general and scalable access to the aeruginosin family of marine natural products, exhibiting potent inhibitory activity against serine proteases, is reported. This was enabled by the strategic use of two recently implemented Pd-catalyzed C(sp(3))-H activation reactions. The first method allowed us to obtain the common 2-carboxy-6-hydroxyoctahydroindole (Choi) core of the target molecules on a large scale, whereas the second method provided a rapid and divergent access to various hydroxyphenyllactic (Hpla) subunits, including halogenated ones. This unique strategy, together with an optimization of the fragment coupling sequence allowed the synthesis of four aeruginosins, that is, 98A-C and 298A from the chiral pool. Among them, aeruginosin 298A was synthesized on an unprecedentedly large scale. In addition, halogenated aeruginosins 98A and 98C were synthesized for the first time, thanks to a fine-tuning of the final hydrogenation step.

An efficient and scalable access to the aeruginosin family of marine natural products, which exhibit potent inhibitory activity against serine proteases, is reported. This synthesis was enabled by the strategic use of two different, recently implemented C(sp(3))-H activation reactions. The first method led to the common 2-carboxy-6-hydroxyoctahydroindole (Choi) core of the target molecules on a large scale, whereas the second one provided rapid and divergent access to the various hydroxyphenyllactic (Hpla) subunits. This strategy allowed the synthesis of the aeruginosins 98B and 298A, with the latter being obtained in unprecedentedly large quantities.

In the presence of copper thiocyanate, sodium thiocyanate and the inexpensive, easy-to-use trifluoromethylating reagent Me3Si–CF3, diazonium salts are smoothly converted into the corresponding aryl trifluoromethyl thioethers. Combined with diazotisation, this convenient and inexpensive method allows the straightforward synthesis of aryl or heteroaryl trifluoromethyl thioethers from the corresponding anilines.

The newly developed Sandmeyer trifluoromethylation is applicable to differently substituted arenediazonium salts.

The catalyst [Rh(cod)Cl]2 is found to direct the acylation of benzoic acids with anhydrides into the ortho position.

This is the first efficient α-arylation of non-activated deoxybenzoin derivatives with simple aryl iodides.

International audience; The first efficient method for direct α-arylation of non-activated or non-protected family of enolizable ketones with simple aryl iodides employs a catalytic copper system. The method shows potential for the easy and step-economical synthesis of tamoxifen, the most commonly administrated drug for the management of breast cancer.

A highly efficient non-chiral-pool synthesis of (+)-1-deoxynojirimycin has been realized (24 % overall yield, 11 steps, complete stereocontrol). A novel one-pot enol ether metathesis/hydroboration/oxidation sequence is used for the selective formation of the all-trans cyclic triol. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

In the presence of copper thiocyanate, sodium thiocyanate and the inexpensive, easy-to-use trifluoromethylating reagent Me3Si–CF3, diazonium salts are smoothly converted into the corresponding aryl trifluoromethyl thioethers. Combined with diazotisation, this convenient and inexpensive method allows the straightforward synthesis of aryl or heteroaryl trifluoromethyl thioethers from the corresponding anilines.

An asymmetric synthesis of (+)-castanospermine is presented in which enol ether metathesis-hydroboration/oxidation is used for stereoselective installation of the trans-trans hydroxyl groups on the piperidine ring of the alkaloid.