Total Synthesis of Paracaseolide A

The total synthesis of paracaseolide A, a valuable cell-cycle progression inhibitor, was accomplished in 8 steps from known compounds, with 6.6% overall yield. The synthetic strategy creates strong potential for diversification

First Inverse Electron-Demand Diels–Alder Methodology of 3‑Chloroindoles and Methyl Coumalate to Carbazoles

The first successful inverse electron-demand Diels–Alder has been demonstrated with the 2-pyrone methyl coumalate in conjunction with substituted indoles. Utilizing 1-alkyl-3-chloroindoles as the electron-rich dienophile efficiently generates carbazoles without the need for additional metal catalysts. Through a thermal, one-pot Diels–Alder/decarboxylation/elimination domino sequence, access to a class of 3-methylcarbazoles is rapidly generated with exclusive regiocontrol in up to 90% yield

Mechanistic Insights into Ring-Opening and Decarboxylation of 2‑Pyrones in Liquid Water and Tetrahydrofuran

2-Pyrones, such as triacetic acid lactone, are a promising class of biorenewable platform chemicals that provide access to an array of chemical products and intermediates. We illustrate through the combination of results from experimental studies and first-principle density functional theory calculations that key structural features dictate the mechanisms underlying ring-opening and decarboxylation of 2-pyrones, including the degree of ring saturation, the presence of CC bonds at the C₄C₅ or C₅C₆ positions within the ring, as well as the presence of a β-keto group at the C₄ position. Our results demonstrate that 2-pyrones undergo a range of reactions unique to their structure, such as retro-Diels–Alder reactions and nucleophilic addition of water. In addition, the reactivity of 2-pyrones and the final products formed is shown to depend on the solvent used and the acidity of the reaction environment. The mechanistic insights obtained here provide guidance for the selective conversion of 2-pyrones to targeted chemicals