Systematic, computational discovery of multicomponent and one-pot reactions
Discovery of new types of reactions is essential to organic chemistry because it expands the scope of accessible molecular scaffolds and can enable more economical syntheses of existing structures. In this context, the so-called multicomponent reactions, MCRs, are of particular interest because they can build complex scaffolds from multiple starting materials in just one step, without purification of intermediates. However, for over a century of active research, MCRs have been discovered rather than designed, and their number remains limited to only several hundred. This work demonstrates that computers taught the essential knowledge of reaction mechanisms and rules of physical-organic chemistry can design - completely autonomously and in large numbers - mechanistically distinct MCRs. Moreover, when supplemented by models to approximate kinetic rates, the algorithm can predict reaction yields and identify reactions that have potential for organocatalysis. These predictions are validated by experiments spanning different modes of reactivity and diverse product scaffolds.
Authors
- Agnieszka Wołos (ORCID: https://orcid.org/0000-0001-9881-1634)
- Karol Molga (ORCID: https://orcid.org/0000-0003-4808-7910)
- Barbara Mikulak-Klucznik (ORCID: https://orcid.org/0000-0001-5263-0731)
- Martyna Moskal
- Olena Vakuliuk (ORCID: https://orcid.org/0000-0002-6930-8383)
- Sebastian Baś (ORCID: https://orcid.org/0000-0003-4692-5757)
- Jacek Młynarski (ORCID: https://orcid.org/0000-0002-1794-306X)
- Daniel T. Gryko (ORCID: https://orcid.org/0000-0002-2146-1282)
- Sara Szymkuć (ORCID: https://orcid.org/0000-0002-3475-3663)
- Tomasz Klucznik (ORCID: https://orcid.org/0000-0001-9375-9945)
- Louis Gadina (ORCID: https://orcid.org/0000-0002-4090-0789)
- Patrycja Gołębiowska
- Bartosz A. Grzybowski (ORCID: https://orcid.org/0000-0001-6613-4261)
- Oskar Popik (ORCID: https://orcid.org/0000-0003-4224-5850)
- Rafał Roszak (ORCID: https://orcid.org/0000-0003-1915-1717)
- Ahmad Makkawi
- Yasemin Bilgi (ORCID: https://orcid.org/0000-0002-5318-3360)
- Rafał Frydrych
Institutions
- Jagiellonian University (PL)
- Institute for Basic Science (KR)
- Institute of Organic Chemistry (PL)
- Highland Community College - Illinois (US)
- Ulsan National Institute of Science and Technology (KR)
- Polish Academy of Sciences (PL)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-27
- DOI
- https://doi.org/10.1038/s41467-024-54611-5
- Citations
- 17
- Primary Topic
- Multicomponent Synthesis of Heterocycles
- Type
- article
- Field-Weighted Citation Impact
- 4.25
Funders
- European Commission
- Fundacja na rzecz Nauki Polskiej
- Narodowym Centrum Nauki
- Institute for Basic Science
- HORIZON EUROPE Framework Programme