New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

Abstract

The principle of vinylogy states that the electronic effects of a functional group in a molecule are possibly transmitted to a distal position through interposed conjugated multiple bonds. As an emblematic case, the nucleophilic character of a π-extended enolate-type chain system may be relayed from the legitimate α-site to the vinylogous γ, ε, ..., ω remote carbon sites along the chain, provided that suitable HOMO-raising strategies are adopted to transform the unsaturated pronucleophilic precursors into the reactive polyenolate species. On the other hand, when “unnatural” carbonyl ipso -sites are activated as nucleophiles (umpolung), vinylogation extends the nucleophilic character to “unnatural” β, δ, ... remote sites. Merging the principle of vinylogy with activation modalities and concepts such as iminium ion/enamine organocatalysis, NHC-organocatalysis, cooperative organo/metal catalysis, bifunctional organocatalysis, dicyanoalkylidene activation, and organocascade reactions represents an impressive step forward for all vinylogous transformations. This review article celebrates this evolutionary progress, by collecting, comparing, and critically describing the achievements made over the nine year period 2010–2018, in the generation of vinylogous enolate-type donor substrates and their use in chemical synthesis.

Direct, Asymmetric Synthesis of Carbocycle‐Fused Uracils via [4+2] Cycloadditions: a Noncovalent Organocatalysis Approach

“…In tackling this issue, one obvious problem emerges related to the inherent thermodynamic stability of (hetero)aromatic molecules, whose functionalization often requires harsh reaction conditions hardly compatible with sophisticated transformations. In this context, the benzylic C( sp 3 ) sites of ortho ‐alkyl substituted aromatic carbaldehydes of type I (Figure 1A) may be envisaged as remotely enolizable sites of vinylogous aldehyde systems, [3] which can engage in remote benzylic functionalization with suitable electrophiles III , leading to functionally rich, fused (hetero)cycles of type IV via [4+2] cyclization.…”

Unlocking Access to Enantiopure Fused Uracils by Chemodivergent [4+2] Cross‐Cycloadditions: DFT‐Supported Homo‐Synergistic Organocatalytic Approach

“…The application of the principle of vinylogy—which states that the electronic properties of a functional group within a molecule are possibly transmitted to a remote position through interposed conjugated multiple bonds—has become an appealing opportunity in organic synthesis for the predictable and selective functionalization of remote C(sp 3 )−H bonds [7] . In particular, the benzylic site of ortho ‐methyl (hetero)aromatic carbaldehydes IV and VIII or extended polyenals of type I (Scheme 1) may be envisaged as a remotely enolizable position of the vinylogous aldehyde system, so that useful functionalization chemistry with suitable acceptor components may be fostered.…”

Unlocking Access to Enantiopure Fused Uracils by Chemodivergent [4+2] Cross‐Cycloadditions: DFT‐Supported Homo‐Synergistic Organocatalytic Approach

“…Theapplication of the principle of vinylogy-which states that the electronic properties of af unctional group within am olecule are possibly transmitted to ar emote position through interposed conjugated multiple bonds-has become an appealing opportunity in organic synthesis for the predictable and selective functionalization of remote C(sp 3 ) À H bonds. [7] In particular, the benzylic site of ortho-methyl (hetero)aromatic carbaldehydes IV and VIII or extended polyenals of type I (Scheme 1) may be envisaged as aremotely enolizable position of the vinylogous aldehyde system, so that useful functionalization chemistry with suitable acceptor components may be fostered. However,d eprotonation of these benzylic vinylogous sites is not simple,since it generates highly reactive ortho-quinodimethane species (oQDMs)indeed truly polyenolate donors-where the aromatic character of the original ring is temporarily lost.…”