Enantioselective Construction of Vicinal Tetrasubstituted Stereocenters by the Mannich Reaction of Silyl Ketene Imines with Isatin‐Derived Ketimines

Abstract

A highly enantioselective Mannich reaction of silyl ketene imines with isatin-derived ketimines has been realized by using a chiral N,N'-dioxide/Zn(II) catalyst. A variety of β-amino nitriles containing congested vicinal tetrasubstituted stereocenters were obtained with excellent outcomes (up to 98 % yield, >19:1 d.r. and 99 % ee). Based on the experimental investigations, a possible transition state has been proposed to explain the origin of the asymmetric induction.

Catalytic Enantioselective and Diastereoselective Allylic Alkylation with Fluoroenolates: Efficient Access to C3‐Fluorinated and All‐Carbon Quaternary Oxindoles

“…[6] Thes ynthesis of C3-substituted oxindoles carrying two or more contiguous stereogenic centers is equally demanding,although afew impressive examples are known. [7] Ac atalytic method that affords 3-fluorooxindoles exhibiting vicinal chiral centers with one being fluorinated would achieve both tasks at once and significantly widen the scope and availability of this important class of compounds. [8] In this regard, Trostsasymmetric allylic alkylation (AAA) would be afavorable reaction owing to its outstanding value in natural product synthesis.…”

Efficient Catalytic Enantioselective Hydroxyamination of α‐Aryl‐α‐Cyanoacetates with 2‐Nitrosopyridines

“…By treatment of 3.6 mmol of 1 a and 3.5 mmol of 2 a in the presence of 0.01 mol % L 2 ‐RaPr 3 /Mg(OTf) 2 complex, 1.08 g 3 a was obtained with 92 % ee (95 % yield, Scheme a). The product could also be reduced by Cp 2 TiCl 2 in situ, and then further converted efficiently to α‐amino amide 5 a and 1,2‐diamine 6 a by treating with H 2 O 2 and NaBH 4 , respectively (Scheme b). The convenient gram‐scale synthesis in low catalyst loading and useful transformations indicated a potential of this methodology in medicinal chemistry.…”

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

“…As an example, in 2015 Feng et al reported the enantioselective Mannich reaction of N- Boc-isatin imines 3 with silyl ketene imines 27 catalyzed using a combination of Zn(OTf) 2 and chiral N,N’- dioxide ligand 28 [48]. As shown in Scheme 9, this remarkable process afforded a wide range of chiral β-amino nitriles 29 exhibiting two vicinal tetrasubstituted stereocenters as almost single diastereomers (>90% de) in both uniformly excellent yields (90–98%) and enantioselectivities (94–99% ee).…”