Pd/NHC-Catalyzed Enantiospecific and Regioselective Suzuki–Miyaura Arylation of 2-Arylaziridines: Synthesis of Enantioenriched 2-Arylphenethylamine Derivatives

Abstract

A palladium-catalyzed stereospecific and regioselective cross-coupling of enantiopure 2-arylaziridines with arylboronic acids under mild conditions to construct a tertiary stereogenic center has been developed. N-heterocyclic carbene (NHC) ligands efficiently promote the coupling, suppressing β-hydride elimination. The enantiospecific cross-coupling allowed us for preparation of a series of biologically important 2-arylphenethylamine derivatives in an enantiopure form.

Ring Expansions of Activated Aziridines and Azetidines

“…Minakata and co-workers developed a palladium-catalyzed stereospecific and regioselective ring opening of enantiopure aziridines 405 with arylboronic acids [176]. Combining this strategy with a subsequent Pictet-Spengler reaction, they synthesized hexahydrobenzophenanthridine derivative 407 in excellent yield and enantiomeric excess (Scheme 102).…”

Palladium(II)-Catalyzed Formal [3 + 2] Cycloaddition of Aziridines with 3-Substituted Indoles: Synthesis of Enantioenriched Pyrroloindolines

“…Under strictly oxygen-free conditions, the reaction could go smoothly; while the reaction of C3-methylindole 1a and benzyl-substituted aziridine was examined and no product was observed under the same conditions 14 (Scheme 3a). Using Pd(0) catalysts such as Pd(PPh 3 ) 4 or Pd 2 (dba) 3 , no desired product was observed and the two substrates were recovered quantitatively (Scheme 3b). Furthermore, when the Pd(PPh 3 ) 2 Cl 2 or PdCl 2 coupled with phosphines or amines ligands were used as the catalysts, the reaction did not proceed probably due to the addition of ligands decreasing the Lewis acidity of palladium by resonance of unpaired electrons to the empty orbit of metal palladium (Scheme 3c).…”

“…Recently, Takeda and coworkers developed a Pd-catalyzed enantiospecific crosscoupling of chiral 2-arylaziridines with arylboronic acids for the construction of 2-arylphenethylamines in an enantiopure form using N-heterocyclic carbene (NHC) ligands to promote the coupling. 4 In this context, an efficient method for regioselective and stereospecific ring-opening of chiral aziridines is still in great demand.…”

Organocatalyzed Asymmetric Conjugate Addition of Heteroaryl and Aryl Trifluoroborates: a Synthetic Strategy for Discoipyrrole D

“…[1] Recent stereospecific [2] and enantioselective [3] CÀCb ond-forming methods have been reported for such stereocenters that usually rely on transition metal catalysis,l imiting functional group tolerance.F or example,c ompatibility with nitrogen-containing or electronrich heterocycles is rare,a lthough such compounds are important in pharmaceutical development. [1] Recent stereospecific [2] and enantioselective [3] CÀCb ond-forming methods have been reported for such stereocenters that usually rely on transition metal catalysis,l imiting functional group tolerance.F or example,c ompatibility with nitrogen-containing or electronrich heterocycles is rare,a lthough such compounds are important in pharmaceutical development.…”