Funapide is a 3,3’-spirocyclic oxindole with promising analgesic activity. A reported pilot-plant scale synthesis of this chiral compound involves an asymmetric aldol reaction, catalyzed by a common bifunctional thiourea structure. In this work, we show that the swapping of the thiourea unit of the catalyst for a tailored squaramide group provides an equally active, but rewardingly more selective, catalyst for this aldol reaction (from 70.5 to 85 % ee). The reaction was studied first on a model oxindole compound. Then, the set of optimal conditions was applied to the target funapide intermediate. The applicability of these conditions seems limited to oxindoles bearing the 3-substituent of funapide. Exemplifying the characteristics of target-focused methodological development, this study highlights how a wide-range screening of catalysts and reaction conditions can provide non-negligible improvements in an industrially viable asymmetric transformation
