Merging High-Pressure Syngas Metal Catalysis and Biocatalysis in Tandem One-Pot Processes for the Synthesis of Nonchiral and Chiral Alcohols from Alkenes in Water.

While simultaneously proceeding reactions are among the most fascinating features of biosynthesis, this concept of tandem processes also offers high potential in the chemical industry in terms of less waste production and improved process efficiency and sustainability. Although examples of one-pot chemoenzymatic syntheses exist, the combination of completely different reaction types is rare. Herein, we demonstrate that extreme "antipodes" of the "worlds of catalysis", such as syngas-based high-pressure hydroformylation and biocatalyzed reduction, can be combined within a tandem-type one-pot process in water. No significant deactivation was found for either the biocatalyst or the chemocatalyst. A proof-of-concept for the one-pot process starting from 1-octene was established with >99 % conversion and 80 % isolated yield of the desired alcohol isomers. All necessary components for hydroformylation and biocatalysis were added to the reactor from the beginning. This concept has been extended to the enantioselective synthesis of chiral products by conducting the hydroformylation of styrene and an enzymatic dynamic kinetic resolution in a tandem mode, leading to an excellent conversion of >99 % and an enantiomeric ratio of 91 : 9 for (S)-2-phenylpropanol. The overall process runs in water under mild and energy-saving conditions, without any need for intermediate isolation.