The Elusive Seven-Membered Cyclic Imino Ether Tetrahydrooxazepine

Abstract

Cyclic imino ether heterocycles are used as ligands in transition metal catalysis, in various drugs and as reactive monomers in living cationic ring-opening polymerization (CROP). While five-and six-membered cyclic imino ethers, i.e. 2-oxazolines and 4,5-dihydro-1,3-oxazines, have extensively been studied in these areas, their seven-membered ring counterparts have remained unexplored. Herein, we report the synthesis of 2-phenyl-4,5,6,7-tetrahydro-1,3-oxazepine allowing reassignment of the earlier, incorrectly reported 4,5,6,7-tetrahydro-1,3-oxazepines as their N-acylated pyrrolidine isomers. Finally, we also report a comparison of the CROP reactivity of a homologous series of cyclic imino ethers with a 2carbon, 3-carbon and 4-carbon methylene bridge, revealing a remarkable ring size effect.

The DP5 Probability, Quantification and Visualisation of Structural Uncertainty in Single Molecules

“…Not only are the correct and incorrect structures almost indistinguishable to an expert chemist, these structures have already been incorrectly assigned and revised in the literature. 1,[34][35][36][37][38] The results of this study are striking and are presented in Figure 6. In all cases the DP5 probabilities of the incorrect structures are equal to or close to one, illustrating that DP5 can reliably pick out even the most subtle inconsistencies in molecular structures.…”

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

“…PPE and PPSE were then tested for the synthesis of the more challenging seven-membered heterocycles, namely 4,5,6,7-tetrahydro-1,3-oxazepines. Instead of the target compounds, the reactions led to the corresponding N-acylpyrrolidines, as disclosed by Hoogenboom et al [55]. These results were intriguing, since the synthesis of some seven-and even eightmembered 1,3-diheterocycles had already been achieved by our group using the PPA ester/MW system [48,50,52,53].…”

The Future of Retrosynthesis and Synthetic Planning: Algorithmic, Humanistic or the Interplay?

“…trunkamide A (261)), [174] or repeat a synthesis (e.g. tetrahydrooxazepine (262)), [175] that the error is detected and corrected. Compounding this problem, in some cases even achieving a synthesis of the proposed target may not offer any additional information on the proposed structure (e.g.…”