Harnessing formate as a CO2 surrogate for chiral β-hydroxy acid synthesis by photoredox hydrocarboxylation of alkenyl acetates
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GRAPHICAL ABSTRACT
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PUBLIC SUMMARY
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Formate salt as sustainable C1 synthon for the carbon bond elongation reaction.
Photoredox neutral transformation with no external reductant or oxidant.
Anti-Markovnikov hydrocarboxylation of alkenyl acetates.
Photo-enzymatic cascade catalysis for high value-added compound synthesis.
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ABSTRACT
Chiral β-hydroxy acids are prevalent building blocks for pharmaceuticals, making their synthesis by incorporating simple C1 feedstocks show a significant goal. In this report, we build a chemo-enzymatic cascade process that combines photoredox catalysis with biocatalysis to achieve it. The process begins with a visible-light-driven anti-Markovnikov hydrocarboxylation of diverse alkenyl acetates, formate salt was used as a sustainable C1 source and the precursor of CO2•-. This reaction proceeds with broad functional group tolerance to afford β-acetoxy acids in good yields. Subsequently, these intermediates undergo a lipase-catalyzed kinetic resolution reaction to access valuable chiral β-hydroxy acids with moderate to good enantioselectivity. The practical utility of this strategy is demonstrated through gram-scale synthesis and the preparation of a key intermediate for the drug Ezetimibe. Mechanistic studies support a radical-mediated pathway. -
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REFERENCES
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Xia X., Guo J., Gao Y., et al. (2026). Harnessing formate as a CO2 surrogate for chiral β-hydroxy acid synthesis by photoredox hydrocarboxylation of alkenyl acetates. The Innovation Life 4:100224. https://doi.org/10.59717/j.xinn-life.2026.100224
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Xia X., Guo J., Gao Y., et al. (2026). Harnessing formate as a CO2 surrogate for chiral β-hydroxy acid synthesis by photoredox hydrocarboxylation of alkenyl acetates. The Innovation Life 4:100224. https://doi.org/10.59717/j.xinn-life.2026.100224
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Content
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Figure 1.
The importance of chiral β-hydroxy acid derivatives and our designed photo-enzymatic cascade catalysis system
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Figure 2.
Reaction equation and structure of the reagent used in Table 1.
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Figure 3.
Scope of alkenyl acetates
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Figure 4.
Scope of photoredox-enzymatic cascade catalysis
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Figure 5.
Method application
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Figure 6.
Mechanism study
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Figure 7.
Proposed reaction mechanism.
