Wei W-X,
Kuang Y,
Tomanik M *.
New York University, USA
Copper-Catalyzed Cyclization and Alkene Transposition Cascade Enables a Modular Synthesis
of Complex Spirocyclic Ethers.
J. Am. Chem. Soc. 2025;
147: 1034-1041
DOI:
10.1021/jacs.4c14418
Keywords
base metal - spirocycles - annulation
Significance
Spirocyclic heterocycles represent a complex three-dimensional structure found in
various biologically active compounds. Traditional cyclization methods from alkenyl
alcohols result in the loss of the olefin in the final product. Tomanik and co-workers
report a cyclization and alkene transposition to access spirocyclic oxaheterocycles
while retaining the synthetically useful alkene functionality for downstream reactivity.
Comment
The authors performed radical trapping experiments to probe for a radical mechanism.
Upon the addition of TEMPO, the TEMPO adduct bound to the primary radical was isolated.
Further mechanistic studies involving a radical clock experiment resulted in an additional
downstream cyclization with a second alkene prior to oxidative elimination, corroborating
a radical-based mechanism.
