Enantioselective Ring-Closing Aminomethylamination of Allylic Aminodienes with Aminals Triggered by C-N Bond Metathesis.

A conceptually novel strategy utilizing a cyclopalladated complex as an electrophile to activate the C-N bond for the C-N bond metathesis between allylamines and aminals is developed, which enables an efficient ring-closing aminomethylamination of allylic aminodienes and aminals. The reaction proceeds under mild reaction conditions and displays a remarkable scope. Utilizing a modified Trost-type diphosphine as the ligand, this method enables the efficient synthesis of 5-10-membered aminoallylated chiral N-heterocycles in good yields with high enantiomeric excess values.

Palladium-Catalyzed Aminoalkylative Cyclization Enables Modular Synthesis of Exocyclic 1,3-Dienes.

A novel and efficient palladium-catalyzed regioselective and stereodivergent ring-closing reaction of aminoenynes with aldehydes and boronic acids or hydrosilane is developed. This three-component reaction allows for the modular synthesis of a series of exocyclic 1,3-dienes bearing 5- to 8-membered saturated N-heterocycles. The reactions utilize a simple Pd-catalyst and work with broad range of aminoenynes, aldehydes and organometallic reagents under mild reaction conditions. The products represent useful intermediates for chemical synthesis due to the versatility of the conjugated diene. Preliminary mechanistic details of the method are also revealed.

Palladium-Catalyzed Ring-Closing Aminoalkylative Amination of Unactivated Aminoenynes.

An efficient strategy for preventing the ß-hydride elimination of alkylpalladium species by ligation of the palladium with adjacent amino-group was developed, which enabled a novel palladium-catalyzed ring-closing aminoalkylative amination of unactivated aminoenynes. The reaction is amenable to aminals, as well as aliphatic aldehydes with secondary amines, which provides straightforward access to structurally diverse exocyclic allenic amines bearing 5 to 12-membered N-heterocycles. With chiral phosphoramidite-ligated palladium complex as the catalyst, an enantioselective variant was achieved with up to 93 % ee. Simultaneously, synthetic transformations of the chiral products were also conducted to afford structurally unique spirodiamines including one pharmaceutically active molecule via axial-to-central chirality transfer.

Highly regioselective and diastereodivergent aminomethylative annulation of dienyl alcohols enabled by a hydrogen-bonding assisting effect.

A ligand-controlled palladium-catalyzed highly regioselective and diastereodivergent aminomethylative annulation of dienyl alcohols with aminals has been established, which allows for producing either cis- or trans-disubstituted isochromans in good yields with complete regioselectivity and good to excellent diastereoselectivity. Moreover, the chiral cis-products were also obtained in good yields with up to 94% ee by using a chiral phosphinamide as the ligand. Mechanistic studies revealed that the hydroxyl group plays a key role in facilitating the Pd-catalyzed Heck insertion regioselectively taking place across the internal C[double bond, length as m-dash]C bond of conjugated dienes.

Palladium-Catalyzed Ring-Closing Reaction for the Synthesis of Saturated N-Heterocycles with Aminodienes and N,O-Acetals.

An efficient palladium-catalyzed ring-closing reaction of aminodienes with N,O-acetals for the synthesis of saturated N-heterocycles is described. The reaction is consistently operated at room temperature and tolerates a wide range of functional groups with volatile MeOH as the sole byproduct. This method provides rapid and practical access to a broad range of saturated N-heterocycles with diverse structural backbones that are useful building blocks in natural product synthesis and drug discovery.

Palladium-Catalyzed Ring-Closing Reaction via C-N Bond Metathesis for Rapid Construction of Saturated N-Heterocycles.

The ring-closing reactions based on chemical bond metathesis enable the efficient construction of a wide variety of cyclic systems which receive broad interest from medicinal and organic communities. However, the analogous reaction with C-N bond metathesis as a strategic fundamental step remains an unanswered challenge. Herein, we report the design of a new fundamental metallic C-N bond metathesis reaction that enables the palladium-catalyzed ring-closing reaction of aminodienes with aminals. The reactions proceed efficiently under mild conditions and exhibit broad substrate generality and functional group compatibility, leading to a wide variety of 5- to 16-membered N-heterocycles bearing diverse frameworks and functional groups.

Carbonylative cycloaddition between two different alkenes enabled by reactive directing groups: expedited construction of bridged polycyclic skeletons.

A novel palladium-catalyzed highly selective hydrocarbonylative cycloaddition reaction with two different alkenes in the presence of CO enabled by a reactive directing-group is developed, which offers efficient and convenient access to lactone-containing bridged polycyclic compounds in high yield with high chemo- and stereoselectivities.

Transition-metal-catalyzed reactions involving reductive elimination between dative ligands and covalent ligands.

Reductive elimination is a crucial bond-forming elementary reaction in various transition-metal mediated reactions. Apart from the well-developed classic reductive elimination, the non-classic reductive elimination occurring between a covalent ligand and a dative ligand, which has been known for over 50 years, has gradually attracted much attention from the organic community. By avoiding pπ-dπ repulsion between the filled metal d-orbital and the filled ligand p-orbital and forming a cationic-type molecule, non-classic reductive elimination could facilitate many catalytic reactions that were difficult to be realized via classic reductive elimination. In this review, transition-metal catalyzed C-P, C-S, C-N, and C-C bond-forming reactions with non-classic reductive elimination as the key elementary step are summarized.

Palladium-Catalyzed Hydrocarbonylative Cyclization of 1,5-Dienes.

A novel and atom-economic palladium-catalyzed isomerization-hydrocarbonylative cyclization reaction of 1,5-dienes to 2-alkylidenecyclopentanones has been developed, which provides a rapid and straightforward approach to 2-alkylidenecyclopentanones with high stereoselectivity. The reaction was found to proceed via alkene isomerization and selective hydrocarbonylative cyclization to generate 2-alkylidenecyclopentanones with high selectivity.

Catalyst-Free Aminomethylamination of o-Hydroxystyrenes with Aminals to 1,3-Diamines.

A new catalyst-free protocol for aminomethylamination of o-hydroxystyrenes with simple aminals is described. This direct and operationally simple method provides a fundamentally novel and rapid approach for the synthesis of 1,3-diamines. This novel reaction occurs under mild reaction conditions and provides a fundamentally unique and efficient strategy for the synthesis of 1,3-diamines with good to excellent yields.