# Frugal Sampling Strategies for Navigating Complex Reaction Spaces

May 28, 2026

Vincent Porte, Luca Hepp, Philipp Kollmus, Shizhao Lu, Eloisa Serrano, Daniela Blanco, Marco Santagostino

Posted in **Organic Process Research & Development** On April 13, 2026

#### **Abstract**

As the complexity of the chemical space continues to grow, innovative strategies are required to enhance screening efficiency. With the main goal of identifying overarching trends, we introduce novel high-throughput experimentation (HTE) sampling strategies that explore broader chemical spaces and only require 25% of the experiments compared to full factorial designs. Our carefully designed quasi-random sampling methods maximize plate layout diversity while preserving practicality for 96-well microtiter plates. The frugal samplings were successfully applied to four challenging metal-catalyzed cross-coupling reactions. The resulting screens retained sufficient information to understand the main tendencies and enable informed decision-making for subsequent optimization activities. In one case study, the method was coupled with a Bayesian optimization workflow to enable cost-effective transformations within the explored chemical space by introducing a cost-penalized yield as an optimization objective.

[Click here to read the full article.](https://pubs.acs.org/doi/10.1021/acs.oprd.6c00027)

_Porte, V.; Hepp, L.; Kollmus, P.; Lu, S.; Serrano, E.; Blanco, D.; Santagostino, M. "Frugal Sampling Strategies for Navigating Complex Reaction Spaces." Organic Process Research & Development, 2026. https://doi.org/10.1021/acs.oprd.6c00027_

© 2026 The Authors. Published by American Chemical Society. Licensed under CC BY 4.0.