Regioselective Crossed Aldol Reactions under Mild Conditions via Synergistic Gold-Iron Catalysis

Teng Yuan, Xiaohan Ye, Pengyi Zhao, Shun Teng, Yaping Yi, Jin Wang, Chuan Shan, Lukasz Wojtas, Jonathan Jean, Hao Chen, Xiaodong Shi

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

A synergistic gold-iron (Au-Fe) catalytic system was developed for sequential alkyne hydration and vinyl Au addition to aldehydes or ketones. Fe(acac)3 was identified as an essential co-catalyst in preventing vinyl Au protodeauration and facilitating nucleophilic additions. Effective C–C bond formation was achieved under mild conditions (room temperature) with excellent regioselectivity and high efficiency (1% [Au], up to 95% yields). The intramolecular reaction was also achieved, giving successful macrocyclization (16–31 ring sizes) with excellent yields (up to 90%, gram scale) without extended dilution (0.2 M), which highlights the great potential of this new crossed aldol strategy in challenging target molecule synthesis. Effective construction of the C–C bond is one of the most important tasks in organic synthesis. Whereas aldol condensation is a classic C–C bond-forming transformation, it requires other chemical promoters, such as strong base and reactive acidic catalysts. As a result, the overall transformation is limited in terms of ideal atom economy and environmentally friendly operation. With the discovery of a gold-iron (Au-Fe) synergistic catalysis system, here we describe a new approach to facilitating alkyne hydration and sequential vinyl Au addition to carbonyls. This approach gives the C–C bond-forming products in excellent yields, wide substrate scope, and great functional-group compatibility under mild conditions. This protocol can also be applied to macrocyclization without extended dilution. This C–C bond-forming strategy could facilitate challenging molecule synthesis in chemical, biological, and medicinal research. We report a synergistic gold-iron (Au-Fe) catalytic system to access vinyl Au reactivity by avoiding frequently occurring protodeauration. Fe(acac)3 was identified as an essential co-catalyst, facilitating vinyl Au addition to aldehydes. A broad substrate scope was obtained under mild conditions (room temperature) with excellent regioselectivity and high efficiency (1% [Au], up to 95% yields). This protocol offers a practical solution for achieving macrocyclization (16–31 ring sizes, up to 90%, gram scale) without extended dilution, highlighting the synthetic utility in complex molecular synthesis.

Original languageEnglish (US)
Pages (from-to)1420-1431
Number of pages12
JournalChem
Volume6
Issue number6
DOIs
StatePublished - Jun 11 2020

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry
  • Environmental Chemistry
  • Chemical Engineering(all)
  • Biochemistry, medical
  • Materials Chemistry

Keywords

  • SDG3: Good health and well-being
  • SDG7: Affordable and clean energy
  • aldol reaction
  • gold catalysis
  • iron catalysis
  • macrocyclization
  • synergistic catalysis
  • vinyl gold
  • β-hydroxy ketone

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