Iron‐Catalyst‐Switched Selective Conjugate Addition of Grignard Reagents: α,β,γ,δ‐Unsaturated Amides as Versatile Templates for Asymmetric Three‐Component Coupling Processes

Abstract

Diene for conjugate addition: Iron(II) chloride switches the reaction course of the three‐component coupling of a Grignard reagent, an alkyl halide, and a dienamide, thus making the amide a simple yet versatile chiral template.

Iron Catalysis in Organic Synthesis

“…1070 Reaction without iron catalyst afforded the 1,4-addition product (eq a). The intermediate enolate could be treated with alkyl halides to afford α,β-disubstituted γ,δ-unsaturated amides.…”

Conjugate addition reactions of carbon nucleophiles to electron-deficient dienes

“…More recently, Urabe et al have reported the diastereoselective addition of a-substituted vinylmagnesium bromides to the chiral dienamides 11 (Scheme 5). 4 The use of a sugarderived pyrrolidine as a chiral inducer allowed simultaneous chelation of the metal to the carbonyl and acetal oxygen atoms (12). Internal delivery of the alkenyl fragment to C b of the diene moiety accounted for the high 1,4-selectivity of the addition.…”

Scandium‐Catalyzed Asymmetric 1,6‐Addition of 3‐Substituted Oxindoles to Linear Dienyl Ketones

“…for the asymmetric 1,6‐addition of organometallic reagents to dienones and dienoates 5. 6 In addition, several examples of organocatalytic 1,6‐addition reactions have been reported by Jørgensen, Melchiorre, and Ooi et al 7. Despite these impressive contributions in the field of regioselective 1,6‐additions, lanthanide complexes have not been developed for this asymmetric transformation.…”

“…[4] Chiral copper complexes were developed by Feringa, Alexakis, and Fillion et al for the asymmetric 1,6-addition of organometallic reagents to dienones andd ienoates. [5,6] In addition, several exampleso fo rganocatalytic 1,6-addition reactions have been reported by Jørgensen, Melchiorre, and Ooi et al [7] Despite these impressive contributions in the field of regioselective 1,6-additions, lanthanide complexes have not been developed for this asymmetrict ransformation.H erein, we report the first example of a N,N'-dioxide-Sc III -catalyzed 1,6-addition of 3-substituted oxindoles to d-unsubstituted dienyl ketones and d-methyl-substitutedd ienyl ketones with excellent enantioselectivities and regioselectivities, giving optically activec hiralo xindoles with quaternary stereocenters (Scheme 1). [8,9] In ap reliminarys tudy,w ee xamined the asymmetric 1,6-addition of 3-benzyloxindole (1a)t od -unsubstituted dienyl ketone 2a promoted by Sc(OTf) 3 -N,N'-dioxide complexes under air.…”