Organic Chemistry

Temperature-Regulated Regiodivergent Synthesis via Alkene Migratory Hydroalkylation

Authors

  • Jia-Wang Wang University of Science and Technology of China ,
  • De-Guang Liu University of Science and Technology of China ,
  • Zhe Chang University of Science and Technology of China ,
  • Zhen Li University of Science and Technology of China ,
  • Yao Fu University of Science and Technology of China ,
  • Xi Lu University of Science and Technology of China

Abstract

An approach for reliable and predictable carbon-carbon or carbon-heteroatom bond formation that produces either regioisomer starting from the same raw materials, also known as a regiodivergent methodology, is highly desirable. Altering the chemical reaction variables, including catalysts, ligands, solvents, or other additives, were the predominant strategy for the implementation of regiodivergent features in metal-catalysed organic synthesis. The achievement of switchable selectivity using quickly and conveniently controlled physical variables constitutes a desirable goal with an intriguing method of attainment. Herein, we report our discovery that temperature-regulated switchable site-selectivity can be achieved in alkene (migratory) functionalization. Judicious selection of reaction temperatures, one of the most easily changed variables, led to protocols that provide the regiodivergent alkylation products starting from a single alkene substrate. This protocol allows for the convenient synthesis of α- and β-branched protected amines, both of which are substantially important to the pharmaceutical chemistry and biochemistry fields. In addition, enantioenriched β-branched alkyl amines could be accessed in a catalytic asymmetric variant manner. This work may inspire more research interests in metal-catalysed regiodivergent reaction discovery using easily changed physical variables.

Content

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Supplementary material

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Supplementary Information_Temperature-Regulated Regiodivergent Synthesis via Alkene Migratory Hydroalkylation
SI for Temperature-Regulated Regiodivergent Synthesis via Alkene Migratory Hydroalkylation