Organocatalyst-Controlled Stereoselective Macrocyclizations (Supplementary Materials)

This repository provides supplementary information for the manuscript: J. W. Rackl, L. B. Boll, H. Wennemers, Organocatalyst-controlled stereoselective head-to-tail macrocyclizations, Science 2026, 391, 931-936. DOI: 10.1126/science.aec8992 The ring strain of some of the macrocycles reported in the manuscript was estimated following a workflow described by Houk and James (A. R. Bogdan et al., J. Am. Chem. Soc. 2012, 134, 2127.). Briefly, enthalpies of hydrogenation of the macrocycles were related to the enthalpy of hydrogenation of an acyclic analog. To obtain enthalpies of hydrogenation, lowest-energy conformers of the macrocycles, the hydrogenation products, and the acyclic analogs were obtained by conformational sampling using CREST. Ensembles were reranked using CENSO. Final geometry optimization, single-point energy, and frequency calculations (298.15 K) were performed at the B3LYP-D3/def2-TZVP(CPCM(CHCl3)) level of theory using ORCA. Zipped folders contain conformer-rotamer ensembles after CREST and CENSO, geometries from ORCA runs, as well as some input and output files for each step of the workflow. All calculations were performed on the Euler high-performance computing cluster of ETH Zürich using the following program versions: xTB: Version 6.6.0 // CREST: Version 2.12 or 3.0.2 // CENSO: Version 1.2.0 or 2.1.3.dev9+geae4274 // ORCA: Version 5.0.3/5.0.4 or 6.0.0