A trio of UCLA groups harness solid-state photochemistry for natural product synthesis

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The García-Garibay, Garg, and Houk research groups explored the synthesis of challenging structural motifs with  photochemical reactions in crystals.

An experimental team led by Dr. Jordan Dotson, recent joint graduate student in the Garcia-Garibay and Garg groups, has joined with computational graduate student, Ieva Liepuoniute in the García-Garibay and Houk groups, to show how solid-state photochemistry can be used to synthesize natural products with neighboring fully-substituted stereocenters, so-called vicinal quaternary stereocenters. (J. Am. Chem. Soc. 2021, doi.org/10.1021/jacs.1c01100).  Dotson, now a postdoc with Professor Matt Sigman at the University of Utah, says: “Miguel and his group have pioneered in solid-state photochemistry, and with Neil’s guidance, we were able to apply this to make a natural product; we even discovered a new one! (J. Am. Chem. Soc. 2020, 142, 11685–11690). Making vicinal quaternary centers has long been a challenging problem in synthetic organic chemistry, and the solid state gives us a great way to do this! Ieva joined the team to provide computational evidence for how this happens.” 

The team is shown below:

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First row left to right: Dr. Jordan Dotson, Ieva Liepuoniute, Dr. Logan Bachman, Vince Hipwell, Dr. Saeed Khan.
Second row left to right: Prof. Neil Garg, Prof. Miguel García-Garibay, Prof. Ken Houk

Photochemical reactions conducted in the crystalline solid state have now been shown by the Garcia-Garibay technology to build this daunting motif selectively. The team employed both experimental and computational tools to probe the factors that contributed to the success or failure of the key solid-state photodecarbonylation reaction. This ultimately enabled a crystal engineering-based strategy to optimize this solid-state transformation, marking the first use of crystal engineering to optimize a step in a total synthesis campaign. 

Trio Research

By leveraging these tools in tandem, the team was able to synthesize a bis(cyclotryptamine) alkaloid, psychotriadine, featuring an elusive ring system that has been previously overlooked in nature. 

For further information, contact Miguel García-Garibay, mgg@chem.ucla.edu; Neil Garg, neilgarg@chem.ucla.edu; or Ken Houk, houk@chem.ucla.edu