Enantioselective Vinylogous Mannich Reaction of Acyclic Vinylketene Silyl Acetals with Acyclic Ketimines

Abstract

The first enantioselective vinylogous Mannich reaction of acyclic vinylketene silyl acetals with acyclic ketimines derived from alkynyl ketoesters was developed. Excellent yields and enantioselectivities were obtained from the reaction using bis(imidazoline)‐Zn(II) catalyst. Based on experiments and MO calculation, a plausible transition state was proposed to explain the stereoselectivity of the reaction. The obtained products were converted into various amines and a lactam. This process provides an efficient route for the synthesis of acyclic δ‐amino‐α,β‐unsaturated carbonyl compounds and their derivatives.

Accessing unnatural α-amino acids with tetrasubstituted stereogenic centersviacatalytic enantioselective reactions of ketimine-type α-iminoesters/α-iminoamides

“…In 2022, the same group reported similar reaction involving acyclic ketimines 47b derived from α-alkynyl ketoesters catalyzed by a zinc salt and chiral bis(imidazolinyl)pyridine ligand 89b (Scheme 34B). 60 A transition state was proposed for this reaction based on DFT calculation, in which the carbonyl oxygen and imino nitrogen coordinate to the Zn( ii ) cation to form an octahedral complex. The vinylketene silyl acetal attacks the Si -face of 47b to give the ( R )-isomer of product 90 .…”

Cu-Catalyzed Direct Enantioselective Vinylogous Mannich Reaction between β,γ-Unsaturated Pyrazoleamides and Ketimines

“…Despite the achievements, the γ-nucleophiles for these enantioselective direct vinylogous Mannich reactions are limited to dicyanoalkenes and cyclic unsaturated carbonyl compounds. To the best of our knowledge, there are no reports on the enantioselective direct vinylogous Mannich reaction of ketimines with acyclic unsaturated carbonyl compounds as the γ-nucleophile. , On the other hand, transition metal catalysis has not been employed in the enantioselective direct vinylogous Mannich reaction of isatin-based ketimines.…”

Amide phosphonium salt catalyzed enantioselective Mannich addition of isoxazole-based nucleophiles to β,γ-alkynyl-α-ketimino esters

“…Recently, ketimines bearing alkynyl substituents have emerged as versatile electrophiles for the synthesis of chiral tertiary propargylic amines (Scheme 1, eqn (2)). 4 In particular, when alkynyl ketimines bearing an ester group were employed as reaction components, such reactions would lead to α,α-disubstituted α-amino acids, wherein one of the substituents is an alkynyl group, 5 the synthesis of which, especially in an asymmetric way, remains desirable and challenging. 6 To date, only limited progress has been achieved with this type of building block.…”