When developing synthetic methodology, chemists invariably subject a single substrate to a set of different reaction conditions, aiming for high yields and selectivity. With optimal conditions in hand, they then explore the substrate scope of their method. This model substrate approach is a time-proven strategy that has led to innumerable and widely-used chemical reactions. However, it frequently provides methods that only work on model substrate-like compounds. Perhaps worse, reaction conditions that would enable the conversion of other substrates may be missed. We now show that a completely different approach, in which a collection of structurally distinct substrates are evaluated in a single reaction vessel, can not only provide information on the substrate scope at a much earlier stage in methodology development, but even lead to a broadly applicable synthetic methodology. Using this multi-substrate screening approach, we have identified an efficient and stereoselective organocatalyst for scalable Diels– Alder reactions of cyclopentadiene with different classes of α,β-unsaturated aldehydes.