Convergent Synthesis of Diverse Tetrahydropyridines via Rh(I)-Catalyzed C–H Functionalization Sequences

Abstract

A Rh-catalyzed C–H bond activation/alkenylation/electrocyclization cascade reaction provides diverse 1,2-dihydropyridines from simple and readily available precursors. The reaction can be carried out at low (<1%) Rh-catalyst loadings, and the use of the robust, air-stable Rh precatalyst, [RhCl(cod)]2, enables the cascade reaction to be easily performed on the benchtop. The 1,2-dihydropyridine products serve as extremely versatile synthetic intermediates for further elaboration often without isolation. The addition of electrophiles under kinetic or thermodynamic conditions provides a wide range of iminiums. Subsequent addition of a nucleophile then generates a diverse array of differently substituted piperidine products. Additionally, [3 + 2] and [4 + 2] cycloadditions of the 1,2-dihydropyridine intermediate provides access to bridged bicyclic structures such as tropanes and isoquinuclidines. These concise reaction sequences enable the formation of highly substituted piperidines in synthetically useful yields with excellent diastereoselectivity.

Advancements in the Synthesis and Applications of Cationic N‐Heterocycles through Transition Metal‐Catalyzed C−H Activation

“…[46] Ah ighly regioselective formation of isoquinoliniums alt B1 from the reaction between 2,3-dimethoxybenzaldehyde, methylamine, and 4-(benzo[d] [1,3]dioxol-5-yl)but-3-yn-1-ol resulted in ah igh Chien-Hong Cheng, former Director General of the Department of NaturalS ciences, National Science Council;P resident of Chemical Society,T aiwan;a nd Vice President for Academic Affairs of National Tsing Hua University (NTHU), currently serves as aC hair Professor at the Department of Chemistry,a nd, since 2009, also holds aN ationalC hair in chemistry.H is research interests includet he development of new synthetic methods using organometallic compounds as catalysts and the synthesisoforganic materials and the fabrication of devices using these materials for organic light-emitting diodes. [46] Ah ighly regioselective formation of isoquinoliniums alt B1 from the reaction between 2,3-dimethoxybenzaldehyde, methylamine, and 4-(benzo[d] [1,3]dioxol-5-yl)but-3-yn-1-ol resulted in ah igh Chien-Hong Cheng, former Director General of the Department of NaturalS ciences, National Science Council;P resident of Chemical Society,T aiwan;a nd Vice President for Academic Affairs of National Tsing Hua University (NTHU), currently serves as aC hair Professor at the Department of Chemistry,a nd, since 2009, also holds aN ationalC hair in chemistry.H is research interests includet he development of new synthetic methods using organometallic compounds as catalysts and the synthesisoforganic materials and the fabrication of devices using these materials for organic light-emitting diodes.…”

“…[1][2][3][4][5][6][7][8][9][10] Due to the importance and potentialo fC ÀHa ctivation reactions,m any reviewse xist to outline achievements in these organic syntheses. This synthetic approach has been widely applied in the synthesis of naturala nd bioactive compounds, heterocycles and functional materials.…”

“…This synthetic approach has been widely applied in the synthesis of naturala nd bioactive compounds, heterocycles and functional materials. [1][2][3][4][5][6][7][8][9][10] Due to the importance and potentialo fC ÀHa ctivation reactions,m any reviewse xist to outline achievements in these organic syntheses. [11][12][13][14][15][16][17][18][19][20][21][22][23][24] In recent years, transition metal-catalyzedC ÀHa ctivation reactionsh ave made significant advances in the synthesis of planar ammonium salts such as isoquinolinium, cinnolinium, quinolizinium, pyridinium,a nd other relateds alt compounds.…”

Manganese‐Catalyzed Synthesis of cis‐β‐Amino Acid Esters through Organometallic CH Activation of Ketimines

“…In recent years, catalyzed C À H activation reactions have emerged as an increasingly viable method for improving the step economy of organic syntheses. [2] During the past decade, progress has largely relied on complexes of expensive 4d or 5d noble metals, such as palladium, iridium, or rhodium. In stark contrast, the potential of naturally abundant 3d metal complexes as catalysts for C À H functionalizations is largely untapped.…”

Ruthenium(II)-Catalyzed C–H Arylation of Azoarenes by Carboxylate Assistance

“…2 Because these methods strongly rely on the synthesis and use of prefunctionalized starting materials, direct C−H arylations 3 have received significant recent attention as environmentally benign and economically superior alternatives. 4 Hence, the step-economy of biaryl synthesis has been significantly improved with the aid of versatile transition metal complexes for C−H functionalizations.…”