Dynamic covalent scrambling has been shown to dramatically increase POC solubility. This involves reacting more than one vicinal diamine with TFB, to form a statistical distribution of different periphery functionalised cages, without affecting the tetrahedral cage structure. Usually, scrambling is favoured over both self-sorting into the two parent cages or social self-sorting into a new threecomponent species; in the majority of cases where a mixture of vicinal diamines is used, the outcome is a statistical distribution of POCs, no matter what the diamine feed ratio is. In more recent studies using high-throughput robotics to automate the synthesis of scrambled POC mixtures, it was found that mixtures of vicinal diamines did not always lead to the formation of a statistical distribution of cage species. In particular, one combination involving 2-methylpropane-1,2-diamine (MPDA, used in the synthesis of CC13, 1 equiv.) and (3R,4R)-2,5-dimethylhexane-3,4-diamine (DMHDA, 5 equiv.) led to the isolation of a novel isopropyl decorated parent cage, CC21, albeit in a low 5% yield (Figure ). When the direct synthesis of CC21 was then attempted using 6 equivalents of DMHDA in CHCl3, and in the absence of MPDA, the parent cage was not isolated. Instead, an alternative tri-aminal sideproduct (1,3,5-tris(4,5-diisopropyl-imidazolidin-2-yl)benzene, Figure ) was formed and isolated in 33% yield. These preliminary results prompted us to carry out further investigations into the formation of CC21. Here, we report the synthesis, characterisation, and investigation into the formation and properties of this new POC, which proved to be both highly soluble and have unusual crystal packing, likely due to the presence of the sterically bulky isopropyl functionalities on the cage vertices. First, a series of 1 H NMR experiments were carried out probing the neat reaction between TFB and DMHDA, and the reaction in the presence of the ditopic amine MPDA or a mono-amine, namely isobutylamine, which would avoid the formation of a competing cage and avoid the risk of scrambling occurring (SI, Figures & S5). The reaction mixtures were also analysed by high-resolution massspectrometry (HRMS) at different time points to aid in the identification of key reaction intermediates (SI, Figures &). In each of the conditions investigated, no insoluble precipitate formed over the course of the reaction, and common intermediates formed from the reaction of TFB with DMHDA could be identified and persisted throughout the reactions (Figure ; SI, Table & S5, Figure ) - To investigate if these identified intermediates were kinetic traps during the reaction and preventing the formation of CC21, we modelled each intermediate and determined their formation energy using GFN2-xTB (see Supporting Information for details). This was compared against the same intermediates for other structurally analogous and previously synthesised cages, in particular CC1 (formed using ethylenediamine, EDA), CC3 (formed using cyclohexyldiamine, CHDA) and CC13 (formed using MPDA), to evaluate if there were significant differences that might explain the observed behaviour in CC21 formation (Figure ). Importantly, we do not model the barriers between intermediates, which are a key factor in determining the influence of kinetic trapping. Overall, the general trends across the reaction pathways were comparable for all four cages (Figure ), suggesting that the formation of CC21 should be theoretically viable based purely on imine-derived intermediates and the successful formation of the other three cages. Even though we used a semiempirical method, the trend we obtain in formation energies agree with those of Sholl and co-workers. However, given the isolation and identification of the tri-aminal species in the preliminary studies (Figure ), and the fact that the identified intermediates from the HRMS could also correspond to intramolecularly cyclised aminals (SI, Figure ), it was theorised that perhaps the formation of competing aminal intermediates were acting as traps along the reaction pathway to CC21. Therefore, a series of control reactions were carried out between the different di-topic amines (DMHDA, EDA, CHDA, & MPDA) and benzaldehyde, alongside further investigation of the formation energies for the aminal derivatives of the intermediates for CC21. In the series of control reactions (Figure ), when either 1 or 2 equivalents of benzaldehyde were reacted with EDA, CHDA or MPDA, the mono-or bis-imines were formed, respectively (SI, Figure -S10). However, when DMHDA was used, clean conversion to the aminal was observed in the presence of 1 equivalent of benzaldehyde, and a mixture of aminal, residual aldehyde, and partial imine formation was observed in the presence of 2 equivalents (SI, Figure ). The preference for this vicinal diamine to form aminals over di-imines can be further rationalised by looking at the preferred configurations of the different diamines. Therefore, we studied the distribution of structural parameters of the four diamines (EDA, CHDA, MPDA and DMHDA) using the conformer generation algorithm ETKDG (in the RDKit software) to generate 500 conformers, and the semiempirical density functional tight-binding method, GFN2-xTB, to geometry optimise each conformer. We suggest that the distribution of the N-C-C-N dihedral angles and N-N distances for the four amines will infer their preference for aminal reactivity, where dihedrals nearer 0° and shorter N-N distances imply better kinetics for aminal formation due to the closer proximity of the N atoms. Figure shows the distribution of the N-C-C-N dihedral angles over the conformers are within 10 kJ.mol -1 of the lowest energy conformer, where the preference for close N-N positioning in DMHDA is clearly shown. Figure shows the complete set of N-N distance and N-C-C-N dihedral data. This can also be visualised with Newman projections (Figure ) -the steric bulk of the isopropyl functionality likely forces the amines closer together compared to MPDA and EDA and the highly pre-configured CHDA with its chair conformation. This closer proximity of the amines is expected to favour aminal formation kinetics. In addition, a comparison of the formation energies for the aminal intermediates versus the imine analogues (Figure ) clearly shows that the aminal intermediates would be thermodynamically preferred over the imine intermediates, subsequently preventing conversion to CC21. Based on this knowledge, we hypothesised that the presence of an additional diamine in the initial studies promoted the formation of CC21 by acting as an intermediary species to disrupt the aminal reaction pathway. Therefore, a series of reactions was carried out to determine if formal transimination was occurring, a strategy previously applied in the synthesis of imine-linked covalent organic frameworks (COFs), and to investigate if an increased quantity of an additional mono-amine would improve conversion to the desired POC (see SI for further details). Interestingly, when a large excess of isobutylamine (12.0 equiv.), or a pre-formed tri-imine intermediate from the reaction of TFB with isobutylamine was used as a formal transimination precursor, a 'scrambled' statistical distribution of tritopic species containing both isobutylamine and DMHDA was formed (SI, Figures ), analogous to the side-product formed on direct reaction of TFB with DMHDA (Figure ), rather than the desired CC21. As might be expected, the use of 1 equivalent of isobutylamine in the presence of either 5 or 6 equivalents of DMHDA mainly led to the same oligomer distribution observed in the initial screen (Figure ). In contrast, the use of 3 equivalents of isobutylamine with 6 equivalents of DMHDA and 4 equivalents of TFB led to CC21 being isolated in a much more reasonable 29% yield after 14 days (SI, Figures ). This suggests that a balance is required in relation to the quantity of additional mono-amine used, with enough amine present to drive formation towards the desired cage species, but not such a large excess that would result in the formation of a thermodynamic statistical distribution of products.