Unified Synthesis of 2‐Isocyanoallopupukeanane and 9‐Isocyanopupukeanane through a “Contra‐biosynthetic” Rearrangement

Herein, we describe our synthetic efforts toward the pupukeanane natural products, in which we have completed the first enantiospecific route to 2‐isocyanoallopupukeanane in 10 steps (formal synthesis), enabled by a key Pd‐mediated cyclization cascade. This subsequently facilitated an unprecedented...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2024-01, Vol.63 (4), p.e202317348-n/a
Main Authors: Hardy, Melissa A., Hayward Cooke, Jack, Feng, Zhitao, Noda, Kenta, Kerschgens, Isabel, Massey, Lynée A., Tantillo, Dean J., Sarpong, Richmond
Format: Article
Language:English
Subjects:
Carbocation Rearrangement
Chiral Pool
Cyclization Cascade
Natural Product Synthesis
Natural products
Sesquiterpenes
Synthesis
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Summary:Herein, we describe our synthetic efforts toward the pupukeanane natural products, in which we have completed the first enantiospecific route to 2‐isocyanoallopupukeanane in 10 steps (formal synthesis), enabled by a key Pd‐mediated cyclization cascade. This subsequently facilitated an unprecedented bio‐inspired “contra‐biosynthetic” rearrangement, providing divergent access to 9‐isocyanopupukeanane in 15 steps (formal synthesis). Computational studies provide insight into the nature of this rearrangement. Enantiospecific formal syntheses of 2‐isocyanoallopupukeanane and 9‐isocyanopupukeanane were achieved in 10 and 15 steps, respectively. These short synthetic sequences were enabled by a key palladium‐mediated cyclization cascade and culminated in an unprecedented “contra‐biosynthetic” rearrangement, which was investigated computationally and allows access to the related pupukeanane core as a sultone.
ISSN:1433-7851
1521-3773
1521-3773
DOI:10.1002/anie.202317348