Project description:A highly enantioselective rhodium-catalyzed [4+2+2] cycloaddition of terminal alkynes and dienyl isocyanates has been developed. The cycloaddition provides a rapid entry to highly functionalized and enantioenriched bicyclic azocines. This reaction represents the first [4+2+2] cycloaddition strategy to construct nitrogen-containing eight-membered rings.
Project description:Amines bearing γ-stereocenters are highly important structural motifs in many biologically active compounds. However, reported enantioselective syntheses of these molecules are indirect and often require multiple steps. Herein, we report a general asymmetric route for the one-pot synthesis of chiral γ-branched amines through the highly enantioselective isomerization of allylamines, followed by enamine exchange and subsequent chemoselective reduction. This protocol is suitable for establishing various tertiary stereocenters, including those containing dialkyl, diaryl, cyclic, trifluoromethyl, difluoromethyl, and silyl substituents, which allows for a rapid and modular synthesis of many chiral γ-branched amines. To demonstrate the synthetic utility, Terikalant and Tolterodine are synthesized using this method with high levels of enantioselectivity.
Project description:The cyclohexenone core of welwitindolinones was synthesized by a Rh(I)-catalyzed [5 + 1]-cycloaddition of an allenylcyclopropane with CO. A pentasubstituted cyclopropane was prepared successfully by a Rh(II)-catalyzed intramolecular cyclopropanation of alkenes with chlorodiazoacetates.
Project description:CO! You had me at hello: The use of chiral biphenyl-based phosphoramidite ligands on rhodium provides an efficient [2+2+2] cycloaddition between terminal alkyl alkynes and alkenyl isocyanates (see scheme). The cycloaddition proceeds through a CO migration pathway, and facilitates a rapid four-step asymmetric synthesis of indolizidine (-)-209D.
Project description:The first decarbonylative cycloaddition of less-strained cyclic ketones (isatins) with isocyanates is reported. Initiated by C-C activation, this distinct [5-2+2] transformation provides a rapid entry to access various benzimidazolidinone derivatives, through which a wide range of isocyanates can be efficiently coupled with broad functional group tolerance. A modified one-pot process, combining Curtius rearrangement and C-C activation, was also achieved by using acyl azides as the starting materials. Detailed mechanistic study revealed a surprising double-decarbonylative reaction pathway. The novel reactivity discovered in this basic research is expected to shed light on developing new heterocycle formation methods through a C-C/isocyanate coupling.
Project description:A rhodium-catalyzed regio- and enantioselective synthesis of silicon-stereogenic silicon-bridged arylpyridinones has been developed through [2 + 2 + 2] cycloaddition of silicon-containing prochiral triynes with isocyanates. High yields and enantioselectivities have been achieved by employing an axially chiral monophosphine ligand, and this process could be applied to catalytic asymmetric synthesis of silicon-stereogenic chiral polymers for the first time. The reaction mechanism of the present catalysis has also been experimentally investigated to establish a reasonable catalytic cycle, advancing the mechanistic understanding of the rhodium-catalyzed pyridinone synthesis by [2 + 2 + 2] cycloaddition reactions.
Project description:The catalytic dearomative cycloaddition of bicyclic heteroaromatics including benzofurans and indoles provides rapid access to functionalized heterocyclic molecules. Because of the inherent stereoelectronic differences, the furan or pyrrole nucleus is more prone to dearomative cycloaddition than the benzene ring. Here, we realized a geometry-based differentiation approach for achieving C6-C7 and C7-C7a regioselectivity. The rotationally restricted σ bond at C7 position respectively placed the C6-C7 and C7-C7a sites of benzofurans or indoles in an optimal spatial orientation toward the axially chiral heterodiene, thus affording two enantioenriched polycyclic compounds from a single racemic heterobiaryl atropisomers. Calculation results of density functional theory interpreted the mechanism of this parallel kinetic resolution. The bioactivity of the dearomatized products was evaluated in cancer cell lines with certain compounds exhibiting interesting biological activities.
Project description:We report a rhodium-catalyzed asymmetric formal intermolecular [4 + 2] cycloaddition reaction of 2-alkylenecyclobutanols with α,β-unsaturated cyclic ketones leading to synthetically useful trans-bicyclic molecules. Three consecutive stereogenic centers are formed in a highly enantio- and diastereoselective manner. Stepwise C-C bond cleavage and annulation are likely involved in the reaction pathway. Here, iPr-Duphos is the viable chiral ligand that promotes excellent enantio-control.
Project description:A short entry to substituted azocanes by a Rh-catalyzed cycloaddition-fragmentation process is described. Specifically, exposure of diverse N-cyclopropylacrylamides to phosphine-ligated cationic Rh(I) catalyst systems under a CO atmosphere enables the directed generation of rhodacyclopentanone intermediates. Subsequent insertion of the alkene component is followed by fragmentation to give the heterocyclic target. Stereochemical studies show, for the first time, that alkene insertion into rhodacyclopentanones can be reversible.