An Isolable Vinylidene <i>ortho‐</i>Quinone Methide: Synthesis, Structure and Reactivity

Liu, Hong; Li, Kai; Huang, Shengbing; Yan, Hailong

doi:10.1002/anie.202117063

Cited by 27 publications

(10 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another transformations for the synthesis of allenones include an anionic Oxy‐Cope rearrangement/oxygenation, [54] a vinylidene ortho‐quinone methide synthesis, [55] or a recent approach to a List‐Lerner‐Barbas aldol reaction including examples of allenones in broader scopes [56] …”

Section: Synthesis Of Allenonesmentioning

confidence: 99%

Highlighting the Rich Chemistry of the Allenone Moiety

Almendros

Alonso

2023

Adv Synth Catal

View full text Add to dashboard Cite

Conjugated and non-conjugated allenones appear as recurring motifs in organic synthesis, natural products and mechanistic investigations showing unique properties and applications. The ability of allenones to build cycles has provided a direct access to strained systems, medium-sized rings, arenes, heterocycles and complex polycycles. In addition, allenones have served as models in mechanistic investigations and catalysis. The critic compilation herein presented will provide an exhaustive overview of the synthetic possibilities allenones may offer, which certainly will inspire our community in their search of more efficient synthetic methodologies, preparation of biological and pharmaceutical targets, and improve our knowledge in theoretical organic chemistry. Great part of this review will discuss synthetic aspects, catalysis innovation and mechanistic insights of the chemical transformations implying the allenone motif. In addition, many examples on total synthesis and pharmacologically active compounds will be described. We hope that this overview will be attractive to the organic chemistry, synthetic chemistry, catalysis, theoretical chemistry, natural products and medicinal chemistry communities. 3.5. Synthesis of Spirocycles and Bridged Structures 3.6. Open-Chain Structures from Allenones 3.7. Allenones in Total Synthesis 4.

show abstract

Section: Synthesis Of Allenonesmentioning

confidence: 99%

Highlighting the Rich Chemistry of the Allenone Moiety

Almendros

Alonso

2023

Adv Synth Catal

View full text Add to dashboard Cite

show abstract

“…After adjusting the structure of VQM precursors and tuning the reaction conditions, the isolation and characterization of a VQM intermediate were achieved recently by our group. 25 The tetra-substituted VQM was successfully isolated as a yellow solid and exhibited good thermal stability (Scheme 2c). Structural characterization was achieved including crystallographic analysis; the X-ray structure demonstrated that the neutral nonaromatic representation was the major resonance structure in the solid state.…”

Section: Accounts Of Chemical Researchmentioning

confidence: 99%

Section: Discovery and Identification Of Vinylidene Ortho-quinone Met...mentioning

confidence: 99%

“…Our group has developed novel organocatalytic systems based on tri-and tetra-substituted VQMs to access a wide range of atropisomeric biaryl, hetero-biaryl, and non-biaryl structures and atropisomers with complex stereogenic elements including central chirality or helices. Recently, we have achieved the isolation and characterization of the transient VQM intermediates 25 so as to provide compelling evidence for their existence and also allow reactivity studies. Therefore, we highlight our recent contributions to the enantioselective synthesis of atropisomers through VQM intermediates.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Enantioselective Synthesis of Atropisomers via Vinylidene ortho-Quinone Methides (VQMs)

2022

Self Cite

View full text Add to dashboard Cite

Conspectus Atropisomers, arising from conformational restriction, are inherently chiral due to the intersecting dissymmetric planes. Since there are numerous applications of enantiopure atropisomers in catalyst design, drug discovery, and material science, the asymmetric preparation of these highly prized molecules has become a flourishing field in synthetic chemistry. A number of catalysts, synthetic procedures, and novel concepts have been developed for the manufacture of the atropisomeric molecules. However, due to the intrinsic properties of different types of atropisomers featuring biaryl, hetero-biaryl, or non-biaryl architectures, only very few methods pass the rigorous inspection and are considered generally applicable. The development of a broadly applicable synthetic strategy for various atropisomers is a challenge. In this Account, we summarize our recent studies on the enantioselective synthesis of atropisomers using the vinylidene ortho-quinone methides (VQMs) as pluripotent intermediates. The most appealing features of VQMs are the disturbed aromaticity and axial chirality of the allene fragment. At the outset, the applications of VQMs in organic synthesis have been neglected due to their principal liabilities: ephemeral nature, extraordinary reactivity, and multireaction sites. The domestication of this transient intermediate was demonstrated by in situ catalytic asymmetric generation of VQMs, and the reactivity and selectivity were fully explored by judiciously modifying precursors and tuning catalytic systems. A variety of axially chiral heterocycles were achieved through five-, six-, seven- and nine-membered ring formation of VQM intermediates with different kinds of branched nucleophilic functional groups. The axially chiral C–N axis could be constructed from VQM intermediates via N-annulation or desymmetrization of preformed C–N scaffolds. We take advantage of the high electrophilicity of VQMs toward a series of sulfur and carbon based nucleophiles leading to atropisomeric vinyl arenes. Furthermore, chiral helical compounds were realized by cycloaddition or consecutive annulation of VQM intermediates. These achievements demonstrated that the VQMs could work as a nuclear parent for the collective synthesis of distinct and complex optically active atropisomers. Recently, we have realized the isolation and structural characterization of the elusive VQMs, which were questioned as putative intermediates for decades. The successful isolation of VQMs provided direct evidence for their existence and an unprecedented opportunity to directly investigate their reactivity. The good thermal stability and reserved reactivity of the isolated VQMs demonstrated their great potential as synthetic reagents and expanded the border of VQM chemistry.

show abstract

“…Very recently, we reported the isolation of stable VQM with a bulky phenylsulfonyl group on the allene motif . The isolation and characterization of the VQM intermediate provided an unprecedented opportunity to directly interrogate the two sequential mechanistic events in VQM-involved reactions.…”

mentioning

confidence: 99%

Mechanistic Features of Asymmetric Vinylideneortho-Quinone Methide Construction and Subsequent Transformations

Chang

Liu

et al. 2023

ACS Catal.

Self Cite

View full text Add to dashboard Cite

Vinylidene ortho-quinone methide (VQM), an elusive dearomatized intermediate, is widely used in asymmetric catalysis. Due to its transient nature, the current understanding of VQM was largely acquired based on computational studies and trapping experiments. Herein, the enantioselective construction of stable VQM intermediates by an organocatalyzed bromination was achieved. Kinetic studies, control experiments, and nonlinear effects were realized to obtain insights into the two sequential mechanistic events in VQM-involved reactions. The results elucidated that the stereocontrol was enforced by one catalyst molecule in the generation of the axially chiral VQM, but the subsequent transformation was independent of the catalyst. The efficiency of the VQM as axially chiral synthetic reagents was demonstrated by its reactions with carboxylic acids, cyclo-1,3-diones, and nitrone. In all cases, the VQM reacted smoothly to provide the axially chiral esters and ethers via an axial-to-axial chirality transfer, as well as the chiral α-bromo ketones through an axial-to-central chirality conversion. The properties of the isolated VQM exhibited its high potential in organic chemistry.

show abstract

An Isolable Vinylidene ortho‐Quinone Methide: Synthesis, Structure and Reactivity

Cited by 27 publications

References 62 publications

Highlighting the Rich Chemistry of the Allenone Moiety

Highlighting the Rich Chemistry of the Allenone Moiety

Enantioselective Synthesis of Atropisomers via Vinylidene ortho-Quinone Methides (VQMs)

Mechanistic Features of Asymmetric Vinylideneortho-Quinone Methide Construction and Subsequent Transformations

Contact Info

Product

Resources

About