Periodic Reporting for period 1 - SusCat (Stereoselective CO2 Capture through Sustainable Organocatalytic Alkene Activation)
Periodo di rendicontazione: 2020-04-01 al 2022-03-31
Asymmetric hydroalkoxylation of alkenes constitutes a redox-neutral and 100% atom-economical strategy toward enantioenriched oxygenated building blocks from readily available starting materials. Despite their great potential, catalytic enantioselective additions of alcohols across a C–C multiple bond are particularly underdeveloped, especially compared to other hydrofunctionalization methods such as hydroamination. The activation of olefins for asymmetric chemical synthesis traditionally relies on transition metal catalysts. Although chemists have long designed chiral Brønsted acid catalysts to activate imines and carbonyl compounds, however achieving stereoselective protonation of simple unbiased olefins has posed a significant synthetic challenge. SusCat proposes a combined theoretical and experimental approach to develop a new catalytic, asymmetric hydro-carbamation and hydro-carbonation methodology using CO2 and alkenes as building blocks. One of the major discovery during this period was the discovery of asymmetric protolactonization reaction. Since its initial report in 1883, electrophilic lactonization has remained at the forefront of catalytic endeavors resulting in a wealth of literature. Despite the overwhelming success, achieving stereocontrol using simple proton (H+) as an electrophile for analogous lactonization has long recognized an unsolved challenge. We developed a general catalytic asymmetric protolactonization using a newly designed chiral imidodiphosphorimidate (IDPi) Brønsted acid catalyst. This method is operationally simple, scalable, and compatible with a wide variety of substrates. Through in-depth physical organic and DFT analyses, we also derive a nuanced picture of the mechanism and enantioselectivity of these reactions. So far, our work has resulted 8 (eight) high-impact papers and many more will follow soon. These work not only represent the frontier of catalysis but also offer highly innovative ways to access the useful structural motifs and drug molecules. Although one of the key objective (organocatalytic CO2 fixation) yet to be achieved, the preliminary results obtained during this fellowship, offers a clear blueprint how this challenge might be addressed in the near future. Overall, our work will lay a foundation for sustainable novel catalytic discoveries and spur further innovation in asymmetric organocatalytic hydrofunctionalizations.
Major discoveries during the fellowship time:
• Asymmetric Catalytic Protolactonization
• Asymmetric (4+3) Cycloaddition of 2-Indolylalcohols with Dienolsilanes
• Catalytic Asymmetric Spirocyclizing DielsAlder Reactions of Enones
• Catalytic Asymmetric Intermolecular Prins Reaction
• Confinement-Controlled, Either syn- or anti-Selective Catalytic Asymmetric Mukaiyama Aldolizations of Propionaldehyde Enolsilanes
Progress beyond the state of the art, expected results until the end of the project and potential impacts (including the socio-economic impact and the wider societal implications of the project so far)
The activation of olefins for asymmetric chemical synthesis traditionally relies on transition metal catalysts. Although chemists have long designed chiral Brønsted acid catalysts to activate imines and carbonyl compounds, however achieving stereoselective protonation of simple unbiased olefins has posed a significant synthetic challenge. A realization of such method offers a sustainable alternative to the existing strategy and revolutionize the drug discovery landscape.
• Asymmetric Catalytic Protolactonization
• Asymmetric (4+3) Cycloaddition of 2-Indolylalcohols with Dienolsilanes
• Catalytic Asymmetric Spirocyclizing DielsAlder Reactions of Enones
• Catalytic Asymmetric Intermolecular Prins Reaction
• Confinement-Controlled, Either syn- or anti-Selective Catalytic Asymmetric Mukaiyama Aldolizations of Propionaldehyde Enolsilanes
Progress beyond the state of the art, expected results until the end of the project and potential impacts (including the socio-economic impact and the wider societal implications of the project so far)
The activation of olefins for asymmetric chemical synthesis traditionally relies on transition metal catalysts. Although chemists have long designed chiral Brønsted acid catalysts to activate imines and carbonyl compounds, however achieving stereoselective protonation of simple unbiased olefins has posed a significant synthetic challenge. A realization of such method offers a sustainable alternative to the existing strategy and revolutionize the drug discovery landscape.
The activation of olefins for asymmetric chemical synthesis traditionally relies on transition metal catalysts. Although chemists have long designed chiral Brønsted acid catalysts to activate imines and carbonyl compounds, however achieving stereoselective protonation of simple unbiased olefins has posed a significant synthetic challenge. A realization of such method offers a sustainable alternative to the existing strategy and revolutionize the drug discovery landscape.