Gold-Mediated Cascade Cyclization on-route to the Total Synthesis of (−)‑Presilphiperfolan-1-ol
Abstract
We report a concise and convergent total synthesis of (−)-presilphiperfolan-1-ol, a highly strained tricyclic sesquiterpene bearing five contiguous stereocenters. Central to our strategy is a gold(I)-catalyzed cascade cyclization of a silyl enol ether containing an enyne motif, which simultaneously constructs the fused tricyclo[5.3.1.04,8]undecane core and sets three remote stereocenters. A systematic ligand screening revealed that, in contrast to prior reports, both NHC-type ligands and bulky Buchwald-type phosphines promoted exclusive 5-exo-dig cyclization, indicating a strong substrate-controlled preference that overrides steric and electronic ligand effects. The full sequence proceeds in nine steps from commercially available materials, and the key cyclization step was successfully scaled up to the gram scale. Access to enantioenriched material was achieved via a stereoselective methylcuprate addition catalyzed by a chiral NHC-Ag complex. This work establishes a practical and modular strategy for the synthesis of complex terpenoids and offers new mechanistic insight into ligand-substrate interplay in gold-catalyzed enyne cyclizations.
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BibTeX
@misc{wicks2026goldmediated,
title = {{Gold-Mediated Cascade Cyclization on-route to the Total Synthesis of (−)‑Presilphiperfolan-1-ol}},
author = {Christopher Wicks and Timothée Stoerkler and Louis Barriault},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010883/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010883/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Gold-Mediated Cascade Cyclization on-route to the Total Synthesis of (−)‑Presilphiperfolan-1-ol
AU - Christopher Wicks
AU - Timothée Stoerkler
AU - Louis Barriault
PY - 2026
DA - 2026/10/22
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010883/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010883/v1
AB - We report a concise and convergent total synthesis of (−)-presilphiperfolan-1-ol, a highly strained tricyclic sesquiterpene bearing five contiguous stereocenters. Central to our strategy is a gold(I)-catalyzed cascade cyclization of a silyl enol ether containing an enyne motif, which simultaneously constructs the fused tricyclo[5.3.1.04,8]undecane core and sets three remote stereocenters. A systematic ligand screening revealed that, in contrast to prior reports, both NHC-type ligands and bulky Buchwald-type phosphines promoted exclusive 5-exo-dig cyclization, indicating a strong substrate-controlled preference that overrides steric and electronic ligand effects. The full sequence proceeds in nine steps from commercially available materials, and the key cyclization step was successfully scaled up to the gram scale. Access to enantioenriched material was achieved via a stereoselective methylcuprate addition catalyzed by a chiral NHC-Ag complex. This work establishes a practical and modular strategy for the synthesis of complex terpenoids and offers new mechanistic insight into ligand-substrate interplay in gold-catalyzed enyne cyclizations.
ER -