RESUMO
The first Negishi nickel-catalyzed stereospecific cross-coupling reaction of secondary benzylic esters is reported. A series of traceless directing groups is evaluated for ability to promote cross-coupling with dimethylzinc. Esters with a chelating thioether derived from commercially available 2-(methylthio)acetic acid are most effective. The products are formed in high yield and with excellent stereospecificity. A variety of functional groups are tolerated in the reaction including alkenes, alkynes, esters, amines, imides, and O-, S-, and N-heterocycles. The utility of this transformation is highlighted in the enantioselective synthesis of a retinoic acid receptor agonist and a fatty acid amide hydrolase inhibitor.
Assuntos
Derivados de Benzeno/química , Níquel/química , Catálise , Ésteres/química , Metilação , EstereoisomerismoRESUMO
A method for the preparation of highly functionalized 4-iodo-7-azaindazoles is reported. These valuable heterocycles are synthesized via condensation of 2-hydrazineylpyrimidines with various iodoalkynones followed by Diels-Alder/retro-Diels-Alder cyclization. The method is general to the formation of products with a variety of C3, C5, and C6 substituents while preserving the C4 iodide functional handle for further late-stage functionalization. The utility of this transformation is demonstrated through the rapid synthesis of several bioactive azaindazole targets.
RESUMO
Secondary benzylic ethers undergo stereospecific substitution reactions with Grignard reagents in the presence of nickel catalysts. Reactions proceed with inversion of configuration and high stereochemical fidelity. This reaction allows for facile enantioselective synthesis of biologically active diarylethanes from readily available optically enriched carbinols.
RESUMO
A general method to prepare valuable chiral synthon ß-aryl-ß-aryloxy esters from enantioselective hydrogenation of (E)-ß-aryl-ß-aryloxy-α,ß-unsaturated esters is described. The E-isomer was prepared via isomerization of the mixture of E- and Z-isomers using photocatalyst [Ir(ppy)2(dtbbpy)]PF6. A laser as the light source facilitated isomerization with only 0.05 mol % catalyst. The enantioselective hydrogenation was conducted with (NBD)2Rh(BF4) and a commercially available Josiphos ligand to provide the synthons in up to 95% yield with 97% ee.
RESUMO
Copper, an earth-abundant metal, has reemerged as a viable alternative to the versatile Pd-catalyzed C-N coupling. Coupling sterically hindered reaction partners, however, remains challenging. Herein, we disclose the discovery and development of a pyrrole-ol ligand to facilitate the coupling of ortho-substituted aryl iodides with sterically hindered amines. The ligand was discovered through a library screening approach and highlights the value of mining heteroatom-rich pharmaceutical libraries for useful ligand motifs. Further evaluation revealed that this ligand is uniquely effective in these challenging transformations. The reaction enables the coupling of sterically hindered primary and secondary amines, anilines, and amides with broad functional group tolerance.
RESUMO
Impregnation of nickel(II) onto graphite, upon reduction in situ, leads to a reagent that catalyzes both C-H and C-C bond formations between aryl halides, or aryl pseudo-halides, and various organometallics. Cross-couplings, most notably with tosylates, can lead to either reduced aromatics, biaryls, or styrenes as products under the influence of Ni/Cg. The catalyst is inexpensive, non-pyrophoric, and reusable.