Stereo-Differentiating Asymmetric Rh(I)-Catalyzed Pauson–Khand Reaction: A DFT-Informed Approach to Thapsigargin Stereoisomers
Year: 2024
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide We report a stereo-differentiating dynamic kinetic asymmetric Rh(I)-catalyzed Pauson–Khand reaction, which provides access to an array of thapsigargin stereoisomers. Using catalyst-control, a consistent stereochemical outcome is achieved at C2─for both matched and mismatched cases─regardless of the allene-yne C8 stereochemistry. The stereochemical configuration for all stereoisomers was assigned by comparing experimental vibrational circular dichroism (VCD) and 13 C NMR to DFT-computed spectra. DFT calculations of the transition-state structures corroborate experimentally observed stereoselectivity and identify key stabilizing and destabilizing interactions between the chiral ligand and allene-yne PKR substrates. The robust nature of our catalyst-ligand system places the total synthesis of thapsigargin and its stereoisomeric analogues within reach.
DOI: 10.1021/jacs.4c11661
Institution: University of Pittsburgh
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Awards: G1309160875, Category I. Computing without Boundaries: Cyberinfrastructure for the Long Tail of Science, MRI: Acquisition of Cutting-Edge GPU and MPI Nodes for the Interdisciplinary Pitt Center for Research Computing, Category I: Bridges-2: Scalable Converged Computing, Data, and Analytics for Rapidly Evolving Science and Engineering Research
OpenAlex ID: W4405649148