Asymmetric Synthesis of 3‐Pyrrolines through an Aryne‐Induced Domino Process

Abstract

Production of chiral compounds by green processes like domino reactions is of importance to environmental protection and sustainable development. Nevertheless, finding an appropriate catalyst to control enantioselectivity with satisfaction is a major challenge. Here, we report the accomplishment of a newly developed domino reaction for synthesizing optically active 3-pyrrolines, a class of compounds with various biological properties. The reaction involves the use of (trimethylsilyl)aryl triflates, Schiff bases, and alkynes in the presence of a chiral catalyst (R)-(À )-1,1'binaphthyl-2,2'-diyl hydrogenphosphate. The key features of this new reaction include the generation of a single product in very good yields (75-85%) with high stereo-and enantioselectivity; the enantiomeric ratio reaches as high as 98.5 : 1.5. Moreover, it involves an aryne-induced domino reaction and an unusual 1,4-intramolecular proton transfer, which overwhelms the well-established 1,5-proton transfer.

Three-Component, Diastereoselective [6 + 3] Annulation of Tropone, Imino Esters, and Arynes

“…In 2015, Hwu and co-workers generated the nitrogen ylides by the reaction of Schiff base (imino ester) with aryne, and the formed ylide was intercepted with excess Schiff base present in the medium resulting in the direct access of imidazolidines (Scheme , eq 1) . Moreover, the ylides can be trapped with activated alkenes leading to the synthesis of pyrrolidines . We have recently demonstrated the generation of strained aziridinium ylide A by the reaction of arynes with N -substituted aziridines, and the formed ylide was trapped with aldehydes for the diastereoselective synthesis of 2-amino epoxides (eq 2). , Inspired by the work of Hwu and co-workers, we envisioned that the nitrogen ylide generated from the Schiff base and aryne could be intercepted with tropone in a [6 + 3] annulation reaction for convenient access to azabicyclo[4.3.1]­decadienes.…”