Periodic Reporting for period 4 - CHAOS (C-H Acids for Organic Synthesis)
Período documentado: 2021-04-01 hasta 2021-09-30
Enantioselective Brønsted and Lewis acid organocatalysis has the potential to revolutionize asymmetric synthesis. However, a common feature of the so far known asymmetric organocatalytic processes was that they require relatively high catalyst loadings of typically 10 to even 20 mol% which hampers their wider use in the chemical and pharmaceutical industries.
We established very acidic and highly active C-H acids (Science 2016) which formed the basis for this research program for the development and investigation of novel catalysts. Here, a research program with three major goals was investigated: 1) broadly conceived synthetic studies were undertaken, which have given access to C–H acids and related catalysts with a wide range of acidity and steric confinement. 2) The newly developed catalysts were applied to address one of the most general limitations currently encountered in organocatalysis: The enantioselective conversion of small and unbiased substrates. 3) The newly developed catalysts, which enable unprecedented acidities and catalytic activities, were employed in the activation of increasingly less reactive electrophiles, for example aliphatic aldehydes but also esters and olefins, for which enantioselective organocatalytic reactions are currently very limited or even unknown. Overall, this research program aimed at the design, synthesis and application of C–H acids and related catalysts as a platform for solving several long standing challenges in asymmetric organocatalysis. The introduction of C–H acids and other highly acidic and confined catalysts for organic synthesis is expected to enrich the toolbox of synthetic chemists in both academic and industrial laboratories.
IDPi catalysts also allow for the enantiocontrol of reactions proceeding via simple aliphatic oxocarbenium ions, a direct diene aldehyde cycloaddition reaction, the utilization of the non-classical 2-norbonyl cation in asymmetric catalysis, Diels–Alder and Mukaiyama–Michael reaction of methyl cinnamates and a regio- and enantioselective catalytic method which affords highly substituted tetrahydrofurans and tetrahydropyrans. Imidodiphosphorimidate catalysts also enabled the synthesis of (+)-2-epi-ziza-6(13)en-3-one, a molecule that could be proved to be the active smelling principle of vetiver oil, an efficient and highly enantioselective asymmetric intramolecular hydroarylation of aliphatic and aromatic olefins with indoles and a scalable, catalytic one-pot approach to enantiopure and unmodified β²-amino acids.