Aldehyde Carboxylation: A Concise DFT Mechanistic Study and a Hypothetical Role of CO₂ in the Origin of Life

^# These authors contributed equally

Abstract

Carbon dioxide is arguably one of the most stable carbon-based molecules, yet enzymatic carbon fixation processes enabled the sustainable life cycle on Earth. Chemical reactions involving CO₂-functionalization often suffer from low efficiency with highly reactive substrates. We recently reported mild carboxylation of aldehydes to furnish α-keto acids – a building block for chiral α-amino acids via reductive amination. Here, we discuss potential reaction mechanisms of aldehyde carboxylation reactions based on two promoters: NHCs and KCN in the carboxylation reaction. New DFT mechanistic studies suggested a lower reaction barrier for a CO₂-functionalization step, implying a potential role of CO₂ in prebiotic evolution of organic molecules in the primordial soup.

1 Introduction: Aldehydes, Benzoins, Carboxylic Acids

2 CO₂-Activation: NHC, Cyanide, Lewis Acid and Water

3 A Breslow Intermediate: Benzoin Reaction vs. Carboxylation with CO₂

4 Carboxylation in the Primordial Soup

5 Conclusion

Key words

carbon dioxide - umpolung - origin of life - cyanide - amino acids

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