Daniel Hack

Asymmetric Synthesis of Spiropyrazolones by Sequential Organo‐ and Silver Catalysis

A stereoselective one-pot synthesis of spiropyrazolones through an organocatalytic asymmetric Michael addition and a formal Conia-ene reaction has been developed. Depending on the nitroalkene, the 5-exo-dig-cyclization could be achieved by silver-catalyzed alkyne activation or by oxidation of the intermediate enolate. The mechanistic pathways have been investigated using computational chemistry and mechanistic experiments.

Asymmetric domino synthesis of indanes bearing four contiguous stereocentres catalyzed by sub-mol% loadings of a squaramide in minutes

An efficient diastereo- and enantioselective synthesis of polyfunctionalized indanes bearing four contiguous stereogenic centres in generally very short reaction times and sub-mol% squaramide catalyst loadings has been developed. The novel methodology creates a maximum of two stereocentres per bond formation via an organocatalytic Michael-Henry domino reaction.

Combining Silver Catalysis and Organocatalysis: A Sequential Michael Addition/Hydroalkoxylation One-Pot Approach to Annulated Coumarins

A highly stereoselective one-pot procedure for the synthesis of five-membered annulated hydroxycoumarins has been developed. By merging primary amine catalysis with silver catalysis, a series of functionalized coumarin derivatives were obtained in good yields (up to 91%) and good to excellent enantioselectivities (up to 99% ee) via a Michael addition/hydroalkoxylation reaction. Depending on the substituents on the enynone, the synthesis of annulated six-membered rings is also feasible.

Asymmetric, Three‐Component, One‐Pot Synthesis of Spiropyrazolones and 2,5‐Chromenediones from Aldol Condensation/NHC‐Catalyzed Annulation Reactions

A novel one-pot, three-component diastereo- and enantioselective synthesis of spiropyrazolones has been developed involving the aldol condensation of an enal to generate α,β-unsaturated pyrazolones, which react with a second equivalent of enal through an N-heterocyclic carbene (NHC)-catalyzed [3+2] annulation. The desired spirocyclopentane pyrazolones are obtained in moderate to good yields and good to excellent stereoselectivities. Alternatively, starting from cyclic 1,3-diketones, 2,5-chromenediones are available through [2+4] annulation.

Merging Gold and Organocatalysis: A Facile Asymmetric Synthesis of Annulated Pyrroles

The combination of cinchona-alkaloid-derived primary amine and AuI–phosphine catalysts allowed the selective C—H functionalization of two adjacent carbon atoms of pyrroles under mild reaction conditions. This sequential dual activation provides seven-membered-ring-annulated pyrrole derivatives in excellent yields and enantioselectivities.