Diastereodivergent [3 + 2] Annulation of Aromatic Aldimines with Alkenes via C–H Activation by Half-Sandwich Rare-Earth Catalysts

Abstract

Stereodivergent catalysis is of great importance, as it can allow efficient access to all possible stereoisomers of a given product with multiple stereocenters from the same set of starting materials. We report herein the first diastereodivergent [3 + 2] annulation of aromatic aldimines with alkenes via C−H activation by half-sandwich rare-earth catalysts. This protocol provides an efficient and general route for the selective synthesis of both trans and cis diastereoisomers of multisubstituted 1-aminoindanes from the same set of aldimines and alkenes, featuring 100% atom efficiency, excellent diastereoselectivity, broad substrate scope, and good functional group compatibility. The diastereodivergence is achieved by fine-tuning the sterics or ligand/metal combination of the half-sandwich rare-earth metal complexes.

Theoretical Studies of Rare-Earth-Catalyzed [3 + 2] Annulation of Aromatic Aldimine with Styrene: Mechanism and Origin of Diastereoselectivity

“…In those contents, the stereoselectivity of the reactions is usually controlled by changing additives, temperature, solvents, or substrates. , Very recently, some of us reported that the diastereodivergent [3 + 2] annulation of aromatic aldimines with alkenes catalyzed by half-sandwich rare-earth complexes and the diastereodivergence is achieved by fine-tuning ligand/metal combination of the catalysts (Scheme ). As shown in Scheme , in the reaction of N-tert -butyl benzaldimine ( 1a ) with styrene ( 2a ), a cis -diastereoisomer product could be exclusively obtained when the C 5 Me 4 H ligand was used as an yttrium catalyst ( Y-1 , trans - 3a / cis - 3a < 1:19). Intriguingly, the C 5 Me 4 SiMe 3 -ligated scandium catalyst Sc-2 could completely reverse the diastereoselectivity compared to the analogous yttrium catalyst Y-1 , giving a trans -diastereoisomer product exclusively ( trans - 3a / cis - 3a > 19:1).…”

Enantioselective C–H Alkenylation of Ferrocenes with Alkynes by Half-Sandwich Scandium Catalyst

“…We have recently found that half-sandwich rare-earth catalysts can serve as a unique platform for various chemical transformations, − including the enantioselective C–H addition of pyridines to alkenes, , diastereodivergent asymmetric carboamination/annulation of cyclopropenes with aminoalkenes, and enantioselective construction of all-carbon quaternary stereocenters via C–H alkylation of imidazoles with 1,1-disubstituted alkenes . These findings have provoked our interest in exploring the potential of rare-earth catalysts for asymmetric C–H alkenylation with alkynes.…”

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

“…Therefore, as challenging as it seems to be, there is still a demand for applying this relevant methodology to obtain new compounds with known pharmacological properties. However, several molecules based on structural scaffolds related to important biological activities have been successfully achieved via scandium-catalyzed C-H activation [37][38][39][40][41]. Hou's group presented various studies on this theme [42,43], such as a notable work recently published in which they promoted a scandium-catalyzed intramolecular cyclization on benzimidazole substrates, via a C-H activation at the C-2 position (Scheme 2B).…”

“…Recently, Hou and co-workers also explored the utility of a similar catalyst, [Sc-2], which bears a more electron-rich cyclopentadienyl ligand, in a scandium-catalyzed C-H [3 + 2] cyclization (Scheme 5B) [40]. In this transformation, several aminoindane derivatives were obtained from benzylimines in the presence of the catalyst , alkenes and [Ph 3 C][B(C 6 F 5 ) 4 ].…”