Tian-Ren Li

Catalytic Asymmetric [4 + 1] Annulation of Sulfur Ylides with Copper–Allenylidene Intermediates

The first copper-catalyzed asymmetric decarboxylative [4 + 1] cycloaddition of propargylic carbamates and sulfur ylides was successfully developed. This strategy led to a series of chiral indolines with synthetically flexible alkyne groups in good yields and with high enantio- and diastereoselectivities (up to 99% yield, 98% ee, and >95:5 dr). A possible mechanism and stereoinduction mode with copper-allenylidenes were proposed as the possible dipolar intermediate.

Asymmetric trapping of zwitterionic intermediates by sulphur ylides in a palladium-catalysed decarboxylation-cycloaddition sequence

Through nearly 50 years of development, sulphur ylides have been established as versatile and powerful reagents for the construction of carbocycles and heterocycles. Despite advances, two important and yet elusive bottlenecks continue to inhibit the advancement of this chemistry: a limited number of reagents with polar groups to react with sulphur ylides, and the wide utilization of chiral auxiliaries or substrates to achieve asymmetric cycloaddition processes in the majority of known reports. Herein, we apply an asymmetric palladium catalysis strategy to the chemistry of sulphur ylides to address these two fundamental problems. We thus achieve an unprecedented decarboxylation-cycloaddition sequence of cyclic allylic esters with sulphur ylides through the enantioselective trapping of Pd-stabilized zwitterionic intermediates by the ylides. As a result, a series of biologically and synthetically important 3-vinyl indolines are rapidly assembled with a high reaction efficiency and stereoselectivity.

P,S Ligands for the Asymmetric Construction of Quaternary Stereocenters in Palladium‐Catalyzed Decarboxylative [4+2] Cycloadditions

A new hybrid P,S ligand was exploited by combining a chiral β-amino sulfide and a simple diphenyl phosphite. The resultant ligand performs extremely well in a palladium-catalyzed asymmetric decarboxylative [4+2] cycloaddition reaction, thus generating multiple contiguous stereocenters and a chiral quaternary center. By doing so, a straightforward route to highly functionalized tetrahydroquinolines was developed with yields of up to 99 %, as well as 98 % ee and greater than 95:5 d.r. Moreover, mechanistic insights into this transformation and the possible stereocontrol are discussed.

Iron-Catalyzed Decarboxylative (4+1) Cycloadditions: Exploiting the Reactivity of Ambident Iron-Stabilized Intermediates.

The first example of iron-catalyzed decarboxylative (4+1) cycloaddition reactions is described in this publication. By using this method, a wide range of functionalized indoline products were prepared from easily available vinyl benzoxazinanones and sulfur ylides in high yields and selectivities. A possible reaction pathway involving an allylic iron intermediate is discussed based on a series of control experiments and density-functional theory calculations.

A Copper‐Catalyzed Decarboxylative Amination/Hydroamination Sequence: Switchable Synthesis of Functionalized Indoles

A copper-catalyzed decarboxylative amination/hydroamination sequence of propargylic carbamates with various nucleophiles is described for the first time. It features an earth-abundant metal catalyst, mild reaction conditions, and high efficiency. Further treatments of the resultant key intermediates using an acid or a base in one pot enable the controllable and divergent synthesis of two types of functionalized indoles. Moreover, experiments to demonstrate the synthetic potential of this methodology are performed.

Divergent Synthesis of Polycyclic Indolines: Copper-Catalyzed Cascade Reactions of Propargylic Carbamates and Indoles

Polycyclic indolines are the common and core structural motif of many indole alkaloids that usually exhibit biological activities. Here, we describe two copper-catalyzed cascade reactions between propargylic carbamates and indoles. By doing so, one-step and divergent synthesis of structurally distinct polycyclic indolines, quinoline-fused indolines, C(3a)-indolyl furoindolines, and pyrroloindolines was achieved in high synthetic efficiency and selectivity.

Hydrogen Bond Direction Enables Palladium-Catalyzed Branch- and Enantioselective Allylic Aminations and Beyond

The palladium-catalyzed branch- and enantioselective allylic amination of vinyl benzoxazinones was accomplished through controlling the hydrogen bond direction. This protocol provides a rapid and efficient route for synthesizing an important building block, chiral amino alkene, from widely available aliphatic amines in 64 → 99% yields with up to 99% ee. Furthermore, this transformation and the accompanying products were utilized to develop one-pot reactions through dual catalysis, affording chiral indolines with good synthetic efficiency and excellent enantiocontrol.

Synthesis of Polysubstituted Pyrroles through a Formal [4 + 1] Cycloaddition/E1cb Elimination/Aromatization Sequence of Sulfur Ylides and α,β-Unsaturated Imines

A reaction sequence comprising a formal [4 + 1] cycloaddition, an E1cb elimination, and an aromatization process is described in this work. By doing so, polysubstituted pyrroles were achieved from easily available chemicals, sulfur ylides, and α,β-unsaturated imines. This protocol features mild conditions, high efficiency, and wide substrate scopes.

Stereospecific Decarboxylative Benzylation of Enolates:Development and Mechanistic Insight

A palladium-catalyzed decarboxylative coupling of enol carbonates with diarylmethyl electrophiles that are derived from secondary benzylic alcohols has been developed. This method allows the generation of a variety of β-diaryl ketones through an efficient and highly stereospecific coupling. In addition, detailed mechanistic insight into the coupling suggests that the reaction is a rare example of an intramolecular decarboxylative coupling that proceeds without crossover between reactants.