Macrobicyclic compounds 1-3 (Fig. 1. A) have been proposed to interconvert from an in-in (ii) form to an out-out (oo) form via a process named homeomorphic isomerism. This mechanism would require one of the three bridges to be threaded through the ring formed by the remainder of the structure, and proceed via a ''cross-chain'' (cs) intermediate (Fig. 1; 2). Structural evidence for this mechanism has been lacking and our objective was to understand, if using simulated annealing to sample conformations of these macrobicyclic compounds, could lead to the observation of cs isomers. At which cage size is the homeomorphic process feasible? We further sought to gain insight of the relative thermodynamic stability of ii and oo as a function of cage size (n). Additional spectroscopic insight was sought, as this would further support the previous hypothesized spectroscopic assignments. A combination of calculation methods were used. Electronic structure methods (e.g. density functional theory) was used for spectroscopic analysis and to probe stability differences whereas simulated annealing was used to sample the conformational space. We found that the homeomorphic isomerism can be supported but not for all cage sizes. cs are only observed from n &gt; 13 (e.g. Fig. 1, B, red crosses). By expanding the size of the cage, the frequency of cs increased. With respect to the mechanism, cs structures of the type shown in Fig. 1, C-middle, is suggestive of an asynchronous process (Fig 1. D, left). Species of the type shown in Fig. 1, D (right) were never observed. We conclude that pyramidal inversion does not participate in this process or co-occurs based on a frequently observed cs intermediate that is almost isoenergetic with the oo isomers. ii isomers are more stable than oo species by ca. 5 kcal/mol. These investigations will help design container molecules with appropriately sized macrobicycles which can have the homeomorphic mechanism turned on or off based on size.

Computational simulation of homeomorphic isomerism in phosphine macrobicycles: Topology, spectroscopy, and stability of in/out isomers

2019 Spring National Meeting

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