Mechanistic Analysis and Kinetic Profiling of Soai’s Asymmetric Autocatalysis for Pyridyl and Pyrimidyl Substrates

Mechanistic Analysis and Kinetic Profiling of Soai’s Asymmetric Autocatalysis for Pyridyl and Pyrimidyl Substrates | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Physical Sciences - Article Mechanistic Analysis and Kinetic Profiling of Soai’s Asymmetric Autocatalysis for Pyridyl and Pyrimidyl Substrates Oliver Trapp, Patrick Möhler, Gloria Betzenbichler, Laura Huber, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5918778/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Nonlinear effects in chemical reactions, 1 coupled with amplifying catalysis, give rise to remarkable phenomena such as spontaneous symmetry breaking, 2 a process associated with the emergence of a homochiral world at the origin of life. 3,4 Soai's asymmetric autocatalysis 5 serves as a prototypical reaction that intrinsically integrates these properties. In this reaction, the enantiomeric excess of the added product alcohol is not only preserved during the alkylation of pyridyl and pyrimidyl carbaldehydes with diisopropylzinc but is also amplified. However, elucidating the underlying mechanism is challenging due to complex reaction equilibria, elusive intermediates, and highly sensitive, structure-dependent kinetics. In this study, we utilize in situ high-resolution mass spectrometry (HRMS), kinetic analysis, and reaction profile simulations to unravel the intricate dynamics of these systems. We demonstrate that both the pyrimidyl and pyridyl reaction pathways involve the formation of catalytically active transient hemiacetalate isopropyl zinc complexes via the addition of the alcoholate product to the carbaldehyde reactant. These diastereomeric complexes enable dual stereocontrol, which accounts for the pronounced positive nonlinear effects observed. Furthermore, our comprehensive analysis provides unambiguous structural identification of all reaction intermediates, delivering experimental validation of the proposed autocatalytic cycle. The quantitative insights gained also reveal the impact of substituent variations and system-specific differences on reaction efficiency and enantioselectivity. This mechanistic understanding paves the way for the rational design of novel, highly efficient autocatalytic processes. Physical sciences/Chemistry/Catalysis/Asymmetric catalysis Physical sciences/Chemistry/Supramolecular chemistry/Self-assembly Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SISoaifinal.pdf Supplementary Information Methods, synthetic procedures, analytical data, NMR spectra, in-situ HRMS data, kinetic analysis, additional references are available in the supplementary information. Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5918778","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Physical Sciences - Article","associatedPublications":[],"authors":[{"id":423955916,"identity":"99b6ff57-b882-48f3-a694-52bd1f58547b","order_by":0,"name":"Oliver 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