Compared to heterogenous Ziegler–Natta systems (ZNS), ansa-metallocene catalysts for the industrial production of isotactic polypropylene feature a higher cost-to-performance balance. In particular, the C₂-symmetric bis(indenyl) ansa-zirconocenes disclosed in the 1990s are complex to prepare, less stereo- and/or regioselective than ZNS, and lose performance at practical application temperatures. The golden era of these complexes, though, was before High Throughput Experimentation (HTE) could contribute significantly to their evolution. Herein, we illustrate a Quantitative Structure – Activity Relationship (QSAR) model trained on a robust and highly accurate HTE database. The clear-box QSAR model utilizes, in particular, a limited number of chemically intuitive 3D geometric descriptors that screen various regions of space in and around the catalytic pocket in a modular way thus enabling to quantify individual substituent contributions. The main focus of the paper is on the methodology, which should be of rather broad applicability in molecular organometallic catalysis. Then again, it is worth emphasizing that the specific application reported here led us to identify in a comparatively short time novel zirconocene catalysts rivaling or even outperforming all previous homologues which strongly indicates that the metallocene story is not over yet.

Highly accurate high-throughput experimentation (HTE) data for a set of 21 silicon-bridged C₂-symmetric ansa-zirconocenes in propene homopolymerization were collected and were used to develop quantitative structure – activity relationship (QSAR) models for several performance indicators at high polymerization temperature (T_p = 100 °C) by using chemically meaningful descriptors. Most notably, stereoselectivity is well described by a two-descriptor model linking the quadrant model for stereoselectivity (sterics) with the chain epimerization model (electronics). The catalysts show widely varying temperature responses, most notably on stereoselectivity and molar mass capability, while the regioselectivity response is uniformly weak. Soft conformational locks lose their performance rapidly while hard conformational locks offer enhanced performance even at high temperatures. The quest for high-temperature stable, well-performing ansa-zirconocenes will unquestionably lead to systems with enhanced rigidity.