Ag(I)-Catalyzed/Acid-Mediated Cascade Cyclization of ortho-Alkynylaryl-1,3-dicarbonyls to Access Arylnaphthalenelactones and Furanonaphthol Libraries via Aryl-Disengagement

ortho-Alkynylarylketone derivatives were employed as key precursors for a one-pot synthesis of arylnaphthalenelactone and furanonaphthol libraries. In this work, we discovered a cost-effective protocol to prepare arylnaphthalenelactones in one-pot using inexpensive starting material, malonate ester, which was conveniently functionalized leading to a variety of structures. Moreover, we also found an unexpected oxy-dearylation reaction which could be used to synthesize furanonaphthol analogs. These novel methods could be applied to a broad range of substrates to give the corresponding products in up to 83% yield. Notably, these classes of compounds exhibited more significant inhibition against protein-tyrosine phosphatase 1B (PTP1B) enzyme than a standard compound, ursolic acid.     

Pt(IV)-catalyzed generation and [4+2]-cycloaddition reactions of o-quinone methides

Novel intermolecular and intramolecular generations of ortho-quinone methides and their formal [4+2]-cycloaddition reactions with olefins catalyzed by PtCl₄ and AuCl₃ under mild conditions have been developed. Good to excellent yields (up to 99%) and diastereoselectivity (up to >99:1) of the chromans were obtained. PtCl₄ was found to be effective and compatible with various functional groups present in the substrates. A mechanism accounting for its catalytic cycle is proposed and discussed.     

Convenient synthetic route to a dehydrorotenoid via selective intramolecular aldol condensation of 1,2-diaryl diketone

Synthesis of dehydrorotenoid (1) was successfully achieved via an intramolecular aldol reaction of the corresponding 1,2-diaryl diketone intermediate. The 1,2-diaryl diketone was prepared using a ruthenium-catalyzed oxidation of the corresponding substituted diaryl acetylene. Treatment of this 1,2-diketone with l-proline induced a selective intramolecular aldol condensation reaction, forming the desired benzopyranone over the alternative benzofuran. Deprotection, cyclization, and dehydration gave the target compound in good overall yield.     

PtCl4-catalyzed cyclization of N-acetyl-2-alkynylanilines: A mild and efficient synthesis of N-acetyl-2-substituted indoles

An efficient synthesis of N-acetyl-2-substituted indole derivatives via direct intramolecular hydroamination of N-acetyl-2-alkynylaniline derivatives was developed. The reaction could be applied to a wide range of substrates employing only 1–2?mol% of PtCl₄ as the catalyst to furnish the desired indole products in moderate to excellent yields. The current protocol is efficient, reliable and scalable, and could serve as an important tool for convenient and rapid access to this important class of N-heterocyclic skeleton from readily available substrates.     

Synthesis of the tricyclic core of aldingenin B by oxidative cyclo-ketalization of an alkyne-diol

The preparation and selenium-mediated cyclo-ketalization of an alkyne-diol is described as a model study for the synthesis of aldingenin B. The oxidative cyclization is a simplifying transformation for aldingenin B, as it provides a convenient method for generating the tricylic core of the natural product from a functionalized cyclohexane.     

Acid-promoted rearrangement of arylmethyl azides: applications toward the synthesis of N-arylmethyl arenes and polycyclic heteroaromatic compounds

An acid-promoted Aubé–Schmidt's rearrangement of arylmethyl azides provides a useful in situ iminium ion intermediate, which can be efficiently trapped by various nucleophiles. We report here the reaction of this iminium ion with aromatic nucleophiles to give N-arylmethyl arenes and the reaction with heteroaromatic compounds to give fused polycyclic heteroaromatic products in a formal [4+2] cycloaddition. The short synthesis of isocrytolepine, an antimalarial agent, further demonstrated the utility of this process.     

Generation of medium-ring cycloalkynes by ring expansion of vinylogous acyl triflates

Reductive cyclization of aryl and vinyl iodides tethered to vinylogous acyl triflates (VATs) induces a ring-expanding fragmentation to provide cyclic alkynyl ketones, including strained nine-membered cycloalkynes, in fair to excellent yield. The tandem cyclization/C-C bond-cleavage is initiated under carefully optimized conditions by halogen-metal exchange in the presence of carbonyl and vinyl triflate functionality. A modified protocol for alkylation of 1,3-cyclohexanedione is described for preparing the relevant VAT substrates.     

Stereodefined homopropargyl amines by tandem nucleophilic addition/fragmentation of dihydropyridone triflates

Dihydropyridone (DHPD) triflates undergo nucleophile-triggered fragmentation to provide homopropargyl amine derivatives, the stereochemistry of which is defined by starting from readily available β-amino esters.