Access to Highly Functionalized Cyclopentenones via Diastereoselective Pauson Khand Reaction of Siloxy-Tethered 1,7-Enynes

Abstract

A diastereoselective Co<sub>2</sub>(CO)<sub>8</sub>-mediated Pauson-Khand reaction (PKR) of siloxy-tethered 1,7-enynes for the synthesis of cyclopentaoxasilinones has been developed. This transformation can be performed on a multi-gram scale and is characterized by broad substrate scope, functional group compatibility, and high chemo- and diastereoselectivity. Oxidation of the resulting cyclopentaoxasilinones delivers stereoenriched β-alkylated cyclopentenones, which are inaccessible by intermolecular PKRs. This research provides a practical solution to the challenges associated with the classical intermolecular PKR.

Modular Cyclopentenone Synthesis through the Catalytic Molecular Shuffling of Unsaturated Acid Chlorides and Alkynes

“…11,12 Specific challenges are (1) alkenes show low reactivity; (2) unreliable control of regioselectivity with respect to the alkene component, and (3) the requirement of excess hazardous chemicals (e.g., pressurized CO gas or stoichiometric cobalt− carbonyl complexes). While several creative solutions have been demonstrated to overcome specific challenges, such as the alkene scope being improved by the preinstallation of a cleavable directing group 13,14 and the use of CO surrogates 15 and less toxic metal catalysts/reagents, 16,17 paradigms that are often complementary in nature. One such example is the development of cyclization reactions of unsaturated carbonyl compounds and alkynes to generate cyclopentenones using Co/Rh and Ni catalysts, respectively (Scheme 1a, right).…”

Access to Highly Functionalized Cyclopentenones via Diastereoselective Pauson–Khand Reaction of Siloxy-Tethered 1,7-Enynes

“…We are thankful to Prof. Simon Cocklin (Drexel), Brian M. Stoltz (Caltech), and Prof. Patrick J. Walsh (UPenn) for helpful suggestions during the writing of this manuscript, Dr. Chen Wu (Walsh Group, UPenn) for providing HPLC data, and former Martinez-Solorio research group members: Brendan G. Rackley, Adam W. McLean, Pasquale Carione (Genentech), and Karlo K. Sales. An early preprint of this research appeared on ChemRxiv …”