Total Synthesis of the Limonoid Alkaloids with Prof. Alex Schuppe

In this Research Spotlight episode, Prof. Alex Schuppe (doctoral alumnus of Newhouse group, Yale University) joins us to share his work on the total synthesis in the limonoid family of alkaloids.

This episode also has an associated problem set, which focuses on 6π electrocyclizations, which can be found at https://synthesis-workshop.com/#probl....

Key references:
J. Am. Chem. Soc. 2017, 139, 631.
J. Am. Chem. Soc. 2018, 140, 2062.
Chem 2022, 8, 2856.

Other references (in order of appearance):
Reviews on Limonoids: Chem. Rev. 2011,111, 7437. Eur. J. Org. Chem. 2011, 19. Phytochem. 1970, 2, 385.
Limonin Isolation: Experientia 1960, 26, 41.
Biomimetic polyene cyclization: Corey, J. Am. Chem. Soc. 1987, 109, 918. J. Am. Chem. Soc. 2008, 130, 6720. Yamashita, Angew. Chem. Int. Ed. 2015, 54, 8538. Biomimetic Michael additions: Williams, J. Org. Chem. 2012, 77, 8913.
Isolation of limonoid alkaloids: Chem. Eur. J. 2008, 14, 1129. J. Nat. Prod. 2010, 73, 1672. Tetrahedron 2014, 70, 6444.
Pyridine synthesis: Liebeskind, J. Am. Chem. Soc. 2008, 130, 6918.
Conventional approach: Stork, Danheiser, J. Org. Chem. 1973, 38, 1775.; Piers, Can. J. Chem. 1987, 65, 78.
Chen, Y.; Romaire, J. P.; Newhouse, T. R. J. Am. Chem. Soc. 2015, 137, 5875. Chen, Y.; Turlik, A.; Newhouse, T. R. J. Am. Chem. Soc. 2016, 138, 1166. Chen, Y.; Huang, D.; Zhao, Y. Newhouse, T. R. Angew. Chem. Int. Ed. 2017, 56, 8258.
α-Keto Oxime: Yamamoto, J. Am. Chem. Soc. 2011, 133, 13880.
Cr(V) allylic oxidation: Baran, J. Am. Chem. Soc. 2014, 136, 4909.
Cyclopropane opening: Ryu, Organometallics 1991, 10, 528. Organometallics 1996, 15, 3902.
Previous attempted allylic oxidation: Tetrahedron 2006, 62, 7355.
α-ionone enzymatic resolution: J. Chem. Soc. Perkin Trans. 1, 1999, 271. Mn-Salen epoxidation resolution: Jacobsen, J. Org. Chem. 1995, 60, 5380. Katsuki, Tetrahedron Lett. 1996, 37, 4533. Dehydrogenation: Stahl, J. Am. Chem. Soc. 2011, 133, 14566.
Knoevenagel condensation: Mischne, J. Org. Chem. 2015, 80, 6515.
Pyran-to-pyridine byproduct: Oshima, Nat. Chem. 2015, 7, 737.

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