*Article* **Catalysis of an Aldol Condensation Using a Coordination Cage**

### **Cristina Mozaceanu, Christopher G. P. Taylor, Jerico R. Piper, Stephen P. Argent and Michael D. Ward \***

Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK; Cristina.Mozaceanu@warwick.ac.uk (C.M.); C.Taylor.10@warwick.ac.uk (C.G.P.T.); Jerico.Piper@warwick.ac.uk (J.R.P.); stephen.argent@nottingham.ac.uk (S.P.A.) **\*** Correspondence:m.d.ward@warwick.ac.uk

Received: 7 January 2020; Accepted: 24 January 2020; Published: 25 January 2020

**Abstract:** The aldol condensation of indane-1,3-dione (**ID**) to give 'bindone' in water is catalysed by an M8L12 cubic coordination cage ( **H w**). The absolute rate of reaction is slow under weakly acidic conditions (pH 3–4), but in the absence of a catalyst it is undetectable. In water, the binding constant of **ID** in the cavity of **H w** is ca. 2.4 (±1.2) × 10<sup>3</sup> <sup>M</sup>−1, giving a ΔG for the binding of −19.3 (±1.2) kJ mol−1. The crystal structure of the complex revealed the presence of two molecules of the gues<sup>t</sup> **ID** stacked inside the cavity, giving a packing coe fficient of 74% as well as another molecule hydrogen-bonded to the cage's exterior surface. We sugges<sup>t</sup> that the catalysis occurs due to the stabilisation of the enolate anion of **ID** by the 16+ surface of the cage, which also attracts molecules of neutral **ID** to the surface because of its hydrophobicity. The cage, therefore, brings together neutral **ID** and its enolate anion via two di fferent interactions to catalyse the reaction, which—as the control experiments show—occurs at the exterior surface of the cage and not inside the cage cavity.

**Keywords:** host–guest chemistry; coordination cage; catalysis; crystal structure; supramolecular chemistry
