Asymmetric Bio- and Organocatalysis: Historical Aspects and Concepts

For those who did not follow the invention and development of enantioselective catalysis, this review introduces pertinent historical aspects of the field and presents the scientific concepts of asymmetric bio- and organocatalysis. They are powerful technologies applied in organic laboratories and industry. They realize chiral amplification by converting inexpensive achiral substrates and reagents into enantiomerically enriched products using readily recoverable solvents, if any are used. Racemic substrates can also be deracemized catalytically. More sustainable fabrications are now available that require neither toxic metallic species nor costly reaction conditions in terms of energy, atmosphere control, product purification, and safety. Nature has been the source of the first asymmetric catalysts (microorganisms, enzymes, alkaloids, amino acids, peptides, terpenoids, sugars, and their derivatives). They act as temporary chiral auxiliaries and lower the activation free energy of the reaction by altering the reaction mechanism. Reductions, oxidations, carbon-carbon and carbon-heteroatom bond-forming reactions are part of the process panoply. Asymmetric catalyzed multicomponent and domino reactions are becoming common. Typical modes of activation are proton transfers, hydrogen bonded complex formation, charged or uncharged acid/base pairing (e.g., σ-hole catalysts), formation of equilibria between achiral aldehydes and ketones with their chiral iminium salt or/and enamine intermediates, umpolung of aldehydes and ketones by reaction with N-heterocyclic carbenes (NHCs), phase transfer catalysis (PTC), etc. Often, the best enantioselectivities are observed with polyfunctional catalysts derived from natural compounds, but not always. They may combine to form chiral structures containing nitrogen, phosphorus, sulfur, selenium, and iodine functional moieties. Today, man-made enantiomerically enriched catalysts, if not enantiomerically pure, are available in both enantiomeric forms. Being robust, they are recovered and reused readily.