Extended Enolates: Versatile Intermediates for Asymmetric C‐H Functionalization via Noncovalent Catalysis

Abstract

Catalyst-controlled functionalization of unmodified carbonyl compounds is a relevant operation in organic synthesis, especially when high levels of site-and stereoselectivity can be attained. This objective is now within reach for some subsets of enolizable substrates using various types of activation mechanisms. Recent contributions to this area include enantioselective transformations that proceed via transiently generated noncovalent di(tri)enolate-catalyst coor-dination species. While relatively easier to form than simple enolate congeners, di(tri)enolates are ambifunctional in nature and so control of the reaction regioselectivity becomes an issue. This Minireview discusses in some detail this and other problems, and how noncovalent activation approaches based on metallic and metal free catalysts have been developed to advance the field.

Organocatalytic Asymmetric Inverse-Electron-Demand Diels–Alder Reaction between Alkylidene Pyrazolones and Allyl Ketones: Access to Tetrahydropyrano[2,3-c]pyrazoles

“…In 1935, Fuson and co-workers formulated the principle of vinylogy, which states that the electronic effects of a functional group in a molecule can be transmitted, via interposed conjugated multiple bonds, to a distal position in the molecule . In this context, in recent years, enolates with conjugated CC double bond(s), that is, di­(poly)­enolates or π-extended enolates, have received special attention . One of the powerful applications of these extended enolates to employ them in tandem reaction processes characterized by sequential donor–acceptor reactivity (ambivalent reactivity), and consequently a range of organocatalytic asymmetric cyclization reactions have been reported .…”

Site-Selective, Photocatalytic Vinylogous Amidation of Enones

“…In recent years, in addition to the established use of preformed silyl enol ethers, novel activation strategies have been developed for vinylogous transformations. − These include iminium/enamine organocatalysis, ,,,− NHC organocatalysis, ,, cooperative organo/metal catalysis, , and photocatalysis. , Because the application of vinylogy creates an additional reaction site in enolizable π-extended carbonyl systems, it has been widely utilized in the synthesis of distantly substituted carbonyl derivatives. ,,− Among them, γ-amination occupies a particular position as γ-aminocarbonyl motifs are quite ubiquitous in natural compounds, γ-aminobutyric acid (GABA), and bioactive molecules (Scheme ). ,, Currently, the known methods for vinylogous amination mainly utilize tetraazodicarboxylates as a nitrogen source and are often limited in scope.…”

“…The concept of vinylogy, established by Fuson in 1935, postulates that the influence of a functional group can be propagated through a conjugated system of unsaturated bonds. This phenomenon is particularly important for the functionalization of α,β-unsaturated carbonyl compounds, which are versatile starting materials in organic synthesis. − Typically, in vinylogous reactions, π-extended carbonyl derivatives of type I are transformed into dienolates II that contain two nucleophilic sites (Scheme ). Consequently, the addition of electrophiles can occur at either α-position ( III ) or more remote γ-position ( IV ). , The regio- and stereoselectivity of these transformations are affected by multiple factors, such as the presence of bulky substituents, a catalyst (if any), or the electron density at the nucleophilic carbon sites, and remain one of the most challenging issues that have to be addressed. − ,− …”

“…This phenomenon is particularly important for the functionalization of α,β-unsaturated carbonyl compounds, which are versatile starting materials in organic synthesis. 2 − 15 Typically, in vinylogous reactions, π-extended carbonyl derivatives of type I are transformed into dienolates II that contain two nucleophilic sites ( Scheme 1 ). Consequently, the addition of electrophiles can occur at either α-position ( III ) or more remote γ-position ( IV ).…”

“… 29 , 30 Because the application of vinylogy creates an additional reaction site in enolizable π-extended carbonyl systems, it has been widely utilized in the synthesis of distantly substituted carbonyl derivatives. 8 , 15 , 31 − 33 Among them, γ-amination occupies a particular position as γ-aminocarbonyl motifs are quite ubiquitous in natural compounds, γ-aminobutyric acid (GABA), and bioactive molecules ( Scheme 1 ). 16 , 34 , 35 Currently, the known methods for vinylogous amination mainly utilize tetraazodicarboxylates as a nitrogen source and are often limited in scope.…”