Investigation of Dearomatizing Spirocyclizations and Spirocycle Functionalization En Route to Spirocalcaridines A and B—Some Trials and Tribulations
Year: 2025
Type: article
Abstract: Spirocalcaridines A and B are among the most challenging members of the marine invertebrate derived Leucetta alkaloids. Approaches for construction and elaboration of the highly compact spirocyclic core are described. Synthesis of tricyclic guanidine via a tandem oxidative amination dearomatizing spirocyclization (TOADS) using hypervalent iodine set the stage for total synthesis via migration of the C4/C8 double bond to C4/C5 position followed by oxidation. The undesired but not surprising propensity of the spirocyclic cyclohexadienone to undergo rearrangement to the phenol hindered the desired olefin migration. Furthermore, initial efforts to install the oxidation sequentially first, at C5 followed by C4 of the complete carbon skeleton were fraught with unforeseen challenges and unusual outcomes. In addition, the scope, and limitations of hypervalent iodine mediated tandem oxidative dearomatizing spirocyclization on various substrates were explored. Urethanes and thiourethanes undergo spirocyclization in excellent yield whereas, the reaction with allylic substrates and species lacking the p-methoxy substituent does not proceed. Attempts to prepare other guanidine precursors are briefly discussed.
Source: Molecules
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,258
OpenAlex ID: W4408112897