This multiauthor review article aims to bring readers up to date with some of the current trends in the field of process analytical technology (PAT) by summarizing each aspect of the subject (sensor development, PAT based process monitoring and control methods) and presenting applications both in industrial laboratories and in manufacture e.g. at GSK, AstraZeneca and Roche. Furthermore, the paper discusses the PAT paradigm from the regulatory science perspective. Given the multidisciplinary nature of PAT, such an endeavour would be almost impossible for a single author, so the concept of a multiauthor review was born. Each section of the multiauthor review has been written by a single expert or group of experts with the aim to report on its own research results. This paper also serves as a comprehensive source of information on PAT topics for the novice reader.

The ease of separation, simple regeneration, and the usually high stability of solid catalysts facilitating continuous production processes have stimulated the development of heterogeneous asymmetric hydrogenation catalysis. The simplest and so far most promising strategy to induce enantioselectivity to solid metal catalysts is their modification by chiral organic compounds, as most prominently represented by the cinchona-modified Pt and Pd catalysts for the asymmetric hydrogenation of activated C═O and C═C bonds. In this Review, we provide a systematic account of the research accomplished in the past decade on noble metal-based heterogeneous asymmetric hydrogenation of prochiral C═O and C═C bonds, including all important facets of these catalytic systems. The advances made are critically analyzed, and future research challenges are identified.

Surface processes occurring at the catalytic chiral surface of a cinchona-modified Pt catalyst during the asymmetric hydrogenation of activated ketones have been monitored for the first time using operando ATR-IR spectroscopy. Fundamental information about this catalytic system could be gained, including the chiral modification process of the catalyst, the surface interaction of reactant ketone with preadsorbed chiral modifier, the role of hydrogen as well as the influence of the product enantiomers in the catalytic cycle. The formation of a diastereomeric transient surface complex between ketone and chiral modifier was found to be related to the ketone consumption. Among the studied activated ketones, a correlation between stereoselection and the strength of the intermolecular hydrogen bond was identified. Dissociated hydrogen from the catalytic surface is found to play a crucial role in the formation of the diastereomeric surface complex.

Kinetics and parametric sensitivity of the asymmetric hydrogenation and deuteration of the trifluoro-activated ketone, 2,2,2-trifluoroacetophenone (TFAP), to (R)-1-phenyl-2,2,2-trifluoroethanol have been studied on an alumina supported Pt catalyst modified by cinchonidine (CD). The observed catalytic behavior is explained by a reaction network consisting of three catalytic cycles which are mutually interconnected: asymmetric hydrogenation of TFAP on CD-modified sites (Pt-CD), asymmetric hydrogenation on Pt-CD sites interfering with the acidic product alcohol Pt-CD-P, and the racemic hydrogenation occurring on unmodified Pt sites. The contributions of these reaction cycles change with progress of TFAP conversion. The catalytic performance is shown to depend strongly on various factors such as the concentrations of ketone and modifier, catalyst amount, solvent, and hydrogen pressure. Depending on reaction conditions, addition of CD can induce considerable rate enhancement (r modified > r unmodifed). Particularly striking is the influence of hydrogen pressure (coverage) on enantioselection, as higher coverage diminishes the ee, which contrasts the corresponding behavior of α-ketoesters. The special role of hydrogen is investigated by substituting H2 by its heavier isotope D2. With the aid of time-resolved attenuated total reflection infrared spectroscopy the kinetic effects of the isotopic substitution along with other reaction parameters are studied and a kinetic isotope effect for unmodified and modified reactions is determined, which suggests that hydrogen is involved in the rate-determining step.