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Catalyst control over sixfold stereogenicity

A Publisher Correction to this article was published on 03 June 2021

This article has been updated

Abstract

Achieving control over higher-order stereogenicity is a long-standing goal in stereoselective catalysis to deliberately address more than a twofold number of stereoisomers per stereogenic unit. Current methods allow control over 2n stereoisomers and their configurations are routinely assigned using the descriptors (R) and (S) or related binary codes. In contrast, conformational analysis extends beyond this dualistic treatment of stereoisomerism, which constitutes an unmet challenge for catalyst stereocontrol. Here, we report that sixfold stereogenicity is tractable by stereoselective catalysis. By controlling a configurationally stable stereogenic axis with six large rotational barriers, a catalytic [2 + 2 + 2] cyclotrimerization selectively governs the formation of one of six stereoisomers with up to 0:0:2:98:0:0 stereocontrol. Moreover, the stereoselectivity is redirectable by stereodivergent catalysis, providing four of the six stereoisomers as major stereoisomers. The underpinnings of conformational analysis and stereoselective catalysis are thereby conceptually reunited. Novel molecular architectures featuring distinct chemical topologies and unexplored chemical designs are anticipated from catalyst control over higher-order stereogenicity.

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Fig. 1: Stereogenicity and conformational analysis.
Fig. 2: Sixfold stereogenicity of a transitionally stereodynamic system.
Fig. 3: Development of the catalytic [2 + 2 + 2] cycloaddition governing sixfold stereogenicity.
Fig. 4: Catalyst control over sixfold stereogenicity.
Fig. 5: Stereodivergent catalyst control.

Data availability

Experimental details, supplementary methods, NMR spectra and crystallographic data are available in the main text and the Supplementary Information. Other data are available from the authors upon reasonable request. Supplementary crystallographic data for the quasi-racemate between (+ap)-2c/(−ap)-2d and (±)-3b can also be obtained from the Cambridge Crystallographic Data Center at www.ccdc.cam.ac.uk/structures (CCDC 2004118 and 1999568).

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Acknowledgements

Financial support for this work was provided by the Swiss National Science Foundation (SNSF), award number BSSGI0-155902/1 (C.S.), the University of Basel and the NCCR Molecular Systems Engineering Phase II of the SNSF, award number 182895 (C.S.). We thank A. Prescimone for X-ray crystallography.

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Authors and Affiliations

Authors

Contributions

C.S., R.M.W., X.W., C.F. and R.B. conceived the study, designed the experiments and analysed the data. R.M.W, X.W., C.F. and R.B. performed the experiments and D. H. carried out the NMR studies. C.S. wrote the manuscript with input from all authors.

Corresponding author

Correspondence to Christof Sparr.

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Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature Catalysis thanks Jean Rodriguez and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary methods, Figs. 1–19, Tables 1–10 and references.

Supplementary Data 1

This file contains the crystal data for the quasi-racemate of (+ap)-2c and (−ap)-2d (CCDC 2004118).

Supplementary Data 2

This file contains the rtf data for the quasi-racemate of (+ap)-2c and (−ap)-2d (CCDC 2004118).

Supplementary Data 3

This file contains the crystal data for (±)-3b (CCDC 1999568).

Supplementary Data 4

This file contains the rtf data for (±)-3b (CCDC 1999568).

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Wu, X., Witzig, R.M., Beaud, R. et al. Catalyst control over sixfold stereogenicity. Nat Catal 4, 457–462 (2021). https://doi.org/10.1038/s41929-021-00615-z

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