Synthesis of Spirocyclic Oxaheterocycles via a Copper-Catalyzed Cyclization Alkene Transposition Sequence

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.

Publication History

Article published online:
25 February 2025