Chiral Zinc(II)‐Catalyzed Enantioselective Tandem α‐Alkenyl Addition/Proton Shift Reaction of Silyl Enol Ethers with Ketimines

Abstract

An ew catalytic asymmetric tandem a-alkenyl addition/proton shift reaction of silyl enol ethers with ketimines was serendipitously discovered in the presence of chiral N,N'dioxide/Zn II complexes.T he proton shift preferentially proceeded instead of as ilyl shift after a-alkenyl addition of silyl enol ether to the ketimine.Awide range of b-amino silyl enol ethers were synthesized in high yields with good to excellent ee values.C ontrol experiments suggest that the Mukaiyama-Mannich reaction and tandem a-alkenyl addition/proton shift reaction are competitive reactions in the current catalytic system. The obtained b-amino silyl enol ethers were easily transformed into b-fluoroamines containing two vicinal tetrasubstituted carbon centers.

Recent Developments in Enantioselective Domino Reactions. Part B: First Row Metal Catalysts

“…In 2019, this type of ligands was applied to develop the first catalytic enantioselective domino α‐alkenyl addition/proton shift reactions between silyl enol ethers and cyclic ketimines, such as isatin‐ and pyrazolinone‐derived ketimines (Scheme 12). [19] Indeed, silyl enol ethers 43 and 44 reacted at 40 °C with isatin‐derived ketimine 45 in the presence of 2.5–5 mol% of a chiral zinc catalyst in situ generated from Zn(OTf) 2 and chiral N,N’ ‐dioxide ligand 46 to give the corresponding β‐amino silyl enol ethers 47 and 48 , respectively, in high enantioselectivities (87–93% ee ) and low to high yields (21–90%). The scope of this methodology was extended to the reaction of pyrazolinone‐derived ketimines 49 with silyl enol ethers 43 .…”