ARISING FROM C. Yang et al., Nature Chemistry https://doi.org/10.1038/s41557-023-01212- 2 (2023) In this work Yang et al.  claim that an enantioselective Michael addition reaction with a barrier of 16 kcal/mol occurs at the single molecule level in frozen solvent by measuring fluctuations in current flowing across graphene based molecular devices. If true, such methods would provide a leap forward in understanding reaction mechanisms. However such strong conclusions need strong experimental evidence, which, as we detail in this Matters Arising, is lacking in the work of Yang et al. . Typically, advances in synthetic chemistry have thrived based on a strong tradition of providing analytical evidence for compounds formed using methods such as nuclear magnetic resonance (NMR), high-performance liquid chromatography (HPLC), high resolution mass spectroscopy (HRMS) as well as structure identification using x-ray techniques. These methods often require macroscopic quantities of the products. This makes such characterizations difficult when molecules are synthesized one at a time. Although there are no techniques available for single molecule NMR analysis yet, there are many other experiments that could have been performed to show proof of synthesis at the single molecule level. Unfortunately, as we show here, in the work of Yang et al.  the evidence provided is insufficient, often inconsistent, and even misleading, leaving us to conclude that the results appear to be too good to be true.
On Maintaining Standards in Chemistry
16 November 2023, Version 1
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