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Reinvestigation of a robotically revealed reaction

Nature volume 570, pages E54–E59 (2019)Cite this article

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The Original Article was published on 18 July 2018

ARISING FROM J. M. Granda et al. Nature https://doi.org/10.1038/s41586-018-0307-8 (2018)

We were intrigued by the Cronin group’s report1 of robot-guided discovery, and were particularly attracted to the possibility of using molecules such as compound 1 in biological screening experiments. However, on noting inconsistencies in the product characterization, we calculated the expected nuclear magnetic resonance (NMR) shifts for the minimum-energy diastereomer of 1 (1a; Extended Data Fig. 1) using both a parameterized method (MestReNova) and density functional theory (DFT) calculation (at the B3LYP/6-31G* level of theory). The results (Extended Data Table 1) did not support the assigned product.

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Fig. 1: One of four new reactions reported by Cronin et al.1, and a structural revision of the isolated product.

Data availability

Raw NMR data files for compounds 2a and 2b have been deposited with figshare (https://doi.org/10.6084/m9.figshare.7639703.v1).

References

  1. Granda, J. M., Donina, L., Dragone, V., Long, D.-L. & Cronin, L. Controlling an organic synthesis robot with machine learning to search for new reactivity. Nature 559, 377–381 (2018).

    Article  ADS  CAS  Google Scholar 

  2. Fukazawa, Y., Yang, Y., Hayashibara, T. & Usui, S. Shielding effect of carbonyl group and its application to the conformational analysis of 1,1,10,10-tetramethyl[3.3]metacyclophane-2,11-dione. Tetrahedron 52, 2847–2862 (1996).

    Article  CAS  Google Scholar 

  3. Ayub, K., Li, R., Bohne, C., Williams, R. V. & Mitchell, R. H. Calculation driven synthesis of an excellent dihydropyrene negative photochrome and its photochemical properties. J. Am. Chem. Soc. 133, 4040–4045 (2011).

    Article  CAS  Google Scholar 

  4. Levin, R. H. & Roberts, J. D. Nuclear magnetic resonance spectroscopy. Ring-current effects upon carbon-13 chemical shifts. Tetrahedron Lett. 14, 135–138 (1973).

    Article  Google Scholar 

  5. Constantino, M. G., Júnior, V. L. & da Silva, G. V. J. Detailed assignments of 1H and 13C NMR spectral data of 13 β-substituted cycloenones. Magn. Reson. Chem. 43, 346–347 (2005).

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Chemistry, University of Victoria, Victoria, British Columbia, Canada

    Jonathan K. Sader & Jeremy E. Wulff

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  1. Jonathan K. Sader
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  2. Jeremy E. Wulff
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Contributions

J.K.S. analysed the original spectral data and suggested the structure 2 instead of 1, then carried out all experimental work and constructed the Supplementary Information. J.E.W. did the calculations and prepared the manuscript with advice from J.K.S.

Corresponding author

Correspondence to Jeremy E. Wulff.

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The authors declare no competing interests.

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Extended data figures and tables

Extended Data Fig. 1 Minimum energy diastereomer of compound 1, two diastereomers of an alternative product, and comparison with a known vinyl acetate.

Compound numbering is indicated in red. Chemical shift values (in p.p.m.) are shown in blue.

Extended Data Fig. 2

Proposed mechanism leading to the observed product 2.

Extended Data Fig. 3

Isolation of vinyl esters 2a and 2b, and further evidence for their assignment from hydrolysis.

Extended Data Table 1 Comparison of spectral assignments to calculated 13C NMR shifts for 1aa
Full size table

Supplementary information

Supplementary Information

This file contains Supplementary Text and Data, Supplementary Figures 1-41 and Supplementary Tables 1-3.

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Sader, J.K., Wulff, J.E. Reinvestigation of a robotically revealed reaction. Nature 570, E54–E59 (2019). https://doi.org/10.1038/s41586-019-1176-5

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