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Published November 15, 2019 | Accepted Version + Supplemental Material
Journal Article Open

Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation of 1,4-Diazepan-5-ones


We report the palladium-catalyzed asymmetric allylic alkylation of 1,4-diazepan-5-ones. This reaction proceeds smoothly to give gem-disubstituted diazepanone heterocycles bearing various functional groups in up to >99% yield and up to 95% ee. An electron-rich p-anisoyl lactam protecting group and the use of a nonpolar solvent proved crucial to obtaining high enantioselectivity in most cases. Additionally, we demonstrate the use of our methodology in the synthesis of a gem-disubstituted analogue of the FDA-approved anti-insomnia drug suvorexant.

Additional Information

© 2019 American Chemical Society. Received: October 6, 2019; Published: October 31, 2019. The NIH-NIGMS (R01GM080269) and Caltech are thanked for financial support. Z.P.S. thanks the Rose Hills Foundation for support via a Rose Hills Foundation Graduate Fellowship. A.W.S. thanks the NIH-NIGMS for a predoctoral fellowship (Ruth L. Kirschstein Institutional National Research Service Award F30GM120836) and a UCLA-Caltech Medical Scientist Training Program Fellowship (T32GM008042). Variable-temperature NMR spectra were obtained on a spectrometer funded by the NIH (RR027690). Dr. Scott Virgil (Caltech) and Dr. David VanderVelde (Caltech) are gratefully acknowledged for instrumentation and helpful discussions. Ky Nguyen (Caltech) is thanked for experimental assistance. Author Contributions: Z.P.S. and A.W.S. contributed equally. The authors declare no competing financial interest.

Attached Files

Accepted Version - nihms-1745701.pdf

Supplemental Material - ol9b03530_si_001.pdf


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