to his 75th birthday As ac omplementary approach to current asymmetrics ynthetic methods, ad irect transformation of styrenes into 1-phenylethylamines was developed. The one-pot process represents af ormal hydroamination of an on-activated alkene with ammonia andi sb ased on the combination of aP d/Cu-catalyzed Wacker-oxidation with an enzymatic transamination.Akey feature of this processi st he compartmentation of the catalytic systems, which turned out to be essential to avoid deactivation of the transaminase by the Cu-component. This one-pot synthesis can be applied to ab road substrate range, which leads to the chiral amines with high conversionsa nd excellent enantioselectivities of > 99 % ee.

Ozanimod represents a recently developed, promising active pharmaceutical ingredient (API) molecule in combating multiple sclerosis. Addressing the goal of a scalable, economically attractive, and technically feasible process for the manufacture of this drug, a novel alternative synthetic approach toward (S)-4-cyano-1-aminoindane as a chiral key intermediate for ozanimod has been developed. The total synthesis of this intermediate is based on the utilization of naphthalene as a readily accessible, economically attractive, and thus favorable petrochemical starting material. At first, naphthalene is transformed into 4-carboxy-indanone within a four-step process by means of an initial Birch reduction, followed by an isomerization of the CC double bond, oxidative CC cleavage, and intramolecular Friedel–Crafts acylation. The transformation of the 4-carboxy-indanone into (S)-4-cyano-1-aminoindane then represents the key step for introducing the chirality and the desired absolute S configuration. When evaluating complementary biocatalytic approaches based on the use of a lipase and transaminase, respectively, the combination of a chemical reductive amination of the 4-carboxyindanone followed by a subsequent lipase-catalyzed resolution turned out to be the most efficient route, leading to the desired key intermediate (S)-4-cyano-1-aminoindane in satisfactory yield and with excellent enantiomeric excess of 99%.

An enantioselective chemoenzymatic two-step one-pot transformation of styrene to 1-phenylethylamine has been developed based on combining an initial Pd/Cu-catalyzed Wacker oxidation of styrene with a subsequent reductive amination of the in situ formed acetophenone. As a nitrogen source only ammonia is needed. The incompatible catalysts were separated by means of a polydimethylsiloxane membrane, thus leading to quantitative conversion and an excellent enantiomeric excess of the corresponding amine. The overall one-pot process formally corresponds to an asymmetric hydroamination of styrene with ammonia.

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