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Published March 27, 2023 | public
Journal Article

Development of a Non‐Directed Petasis‐Type Reaction by an Aromaticity‐Disrupting Strategy


The Petasis-type reaction, which couples an imine and boronic acid, is an important tool for C−C bond formation in organic synthesis. However, the generality of this transformation has been limited by the requirement for a directing heteroatom to enable reactivity. Herein, we report the development of a non-directed Petasis-type reaction that allows for the coupling of trifluoroborate salts with α-hydroxyindoles. By disrupting aromaticity to generate a reactive iminium ion, in conjunction with using trifluoroborate nucleophiles, the method generates a new C−C bond without the need for a directing group. This reaction is operationally simple, providing α-functionalized indoles in up to 99 % yield using sp, sp², and sp³-hybridized trifluoroborate nucleophiles. Finally, this reaction is applied as a novel bioconjugation strategy to link biologically active molecules and toward the convergent synthesis of non-natural heterodimeric bisindole alkaloid analogs.

Additional Information

© 2023 Wiley-VCH. The NIH-NIGMS (R01GM080269), NIH-NIGMS (R35GM145239), Heritage Medical Research Investigators Program, and Caltech are thanked for the support of our research program. K.J.G thanks the NSF GRFP for funding. The authors thank Dr. Scott Virgil (Caltech) for assistance with instrumentation, Dr. Mona Shahgoli (Caltech) for mass spectrometry assistance, Dr. Dave VanderVelde (Caltech) for NMR expertise, and Dr. Michael Takase (Caltech) for X-ray analysis. Data Availability Statement. The data that support the findings of this study are available in the supplementary material of this article. The authors declare no conflict of interest.

Additional details

August 22, 2023
October 18, 2023