Enantioselective Reductive Oligomerization of Carbon Dioxide into l-Erythrulose via a Chemoenzymatic Catalysis

A cell-free enantioselective transformation of the carbon atom of CO₂ has never been reported. In the urgent context of transforming CO₂ into products of high value, the enantiocontrolled synthesis of chiral compounds from CO₂ would be highly desirable. Using an original hybrid chemoenzymatic catalytic process, we report herein the reductive oligomerization of CO₂ into C₃ (dihydroxyacetone, DHA) and C₄ (l-erythrulose) carbohydrates, with perfect enantioselectivity of the latter chiral product. This was achieved with the key intermediacy of formaldehyde. CO₂ is first reduced selectively by 4e^- by an iron-catalyzed hydroboration reaction, leading to the isolation and complete characterization of a new bis(boryl)acetal compound derived from dimesitylborane. In an aqueous buffer solution at 30 °C, this compound readily releases formaldehyde, which is then involved in selective enzymatic transformations, giving rise either (i) to DHA using a formolase (FLS) catalysis or (ii) to l-erythrulose with a cascade reaction combining FLS and d-fructose-6-phosphate aldolase (FSA) A129S variant. Finally, the nature of the synthesized products is noteworthy, since carbohydrates are of high interest for the chemical and pharmaceutical industries. The present results prove that the cell-free de novo synthesis of carbohydrates from CO₂ as a sustainable carbon source is a possible alternative pathway in addition to the intensely studied biomass extraction and de novo syntheses from fossil resources.