Bioinspired Asymmetric Synthesis of (−)-Gymnothelignan V

A bioinspired asymmetric total synthesis of a structurally unique subtype of lignan, namely, (−)-gymnothelignan V, was achieved. The key synthetic sequences involved reduction of the eupomatilone skeleton leading to (−)-gymnothelignan J followed by the formation of the corresponding oxocarbenium ion and stereoselective intramolecular Friedel–Crafts reaction. Our synthetic approach provides the information to support the plausible biosynthetic pathway of this structurally unusual lignan. On a similar basis, other structurally related natural and non-natural gymnothelignans including (−)-gymnothelignan D, 6,9-bis-<i>epi</i>-gymnothelignan V, and 5-<i>epi</i>-gymnothelignans D and J were readily prepared

Oxidative Difluoromethylation of Tetrahydroisoquinolines Using TMSCF₂SPh: Synthesis of Fluorinated Pyrrolo[2,1‑<i>a</i>]isoquinolines and Benzo[<i>a</i>]quinolizidines

An efficient <i>C</i>1-difluoromethylation of tetrahydroisoquinolenes was achieved using TMSCF₂SPh as a difluoromethylating agent and 2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (TEMPO⁺BF₄^–) as an oxidant. The process provides an access to a variety of <i>C</i>1-difluoro­(phenylsulfanyl)­methylated tetrahydroisoquinoline adducts in good yields. These adducts were employed as key precursors for preparing fluorinated pyrrolo­[2,1-<i>a</i>]­isoquinoline and benzo­[<i>a</i>]­quinolizidines

Synthesis of <i>C</i>₂‑Symmetric <i>gem</i>-Difluoromethylenated Angular Triquinanes

A synthesis of symmetrical <i>gem</i>-difluoromethylenated angular triquinanes is described. The synthetic strategy involved sequential fluoride-catalyzed nucleophilic addition of PhSCF₂SiMe₃ (<b>1</b>) to 2,2-diallylated or 2,2-dipropargylated indane-1,3-diones <b>2</b> followed by stereoselective radical cyclization of the resulting adducts <b>3</b> to provide the cyclized <i>gem</i>-difluoromethylenated diquinanes <b>4</b> as a mixture of stereoisomers. Repeated addition of <b>1</b> to <b>4</b> followed by cyclization resulted in the stereoselective synthesis of the desired <i>C</i>₂-symmetric <i>gem</i>-difluoromethylenated angular triquinanes <b>6</b> in good yields with high stereoselectivity

Stereoselective Synthesis of 1‑Fluoro-<i>exo</i>,<i>exo</i>-2,6-diaryl-3,7-dioxabicyclo[3.3.0]octanes: Synthesis of (±)-1-Fluoromembrine

Stereoselective synthesis of 1-fluoro-<i>exo</i>,<i>exo</i>-2,6-diaryl-3,7-dioxabicyclo­[3.3.0]­octanes is described. The synthetic strategy involves stereoselective fluorination of 3,4-<i>trans</i>-4,5-<i>cis</i>-3-aroyl-5-arylparaconic esters using Selectfluor to afford the corresponding fluorinated paraconic esters in good yields as a single isomer, which are subjected to reduction employing LiAlH₄ or DIBALH followed by furofuran formation under acidic or Lewis acid conditions to afford a series of 1-fluoro-<i>exo</i>,<i>exo</i>-furofurans in moderate yields. The synthetic protocol also provides an access to (±)-1-fluoromembrine

Intramolecular Conjugate Ene Reaction of γ‑Difluoromethyl- and γ‑Trifluoromethyl-α,β-Unsaturated γ‑Butyrolactones

A general synthetic strategy to cis-fused bicyclic γ-butyrolactones via the retro-Diels–Alder reaction/intramolecular conjugate ene cascade (RDA/ICE) reaction under the flash-vacuum pyrolysis of maleic anhydride adducts is developed. The reaction gave high yields of products with high stereoselectivity. The existence of the difluoromethyl or trifluoromethyl group at the γ-position of the in situ-generated homoalkenyl- or homoalkynyl-α,β-unsaturated γ-butyrolactones was found to accelerate the rate of the intramolecular conjugate ene reaction leading to γ-difluoromethylated and γ-trifluoromethylated cis-fused bicyclic γ-butyrolactones

Regioselective <i>C</i>2 Sulfonylation of Indoles Mediated by Molecular Iodine

A facile and general method for regioselective <i>C</i>2 sulfonylation reaction of indoles mediated by iodine is described. The 2-sulfonylated products were obtained up to 96% yield under mild reaction conditions (room temperature, 2 h)

TBAI/TBHP-Mediated Cascade Cyclization toward Sulfonylated Indeno[1,2‑<i>c</i>]quinolines

Treatment of <i>ortho</i>-amino-substituted aryldiyne derivatives with sulfonyl hydrazides in the presence of tetrabutylammonium iodide (TBAI) and <i>tert</i>-butyl hydroperoxide (TBHP) led to a cascade cyclization reaction to yield sulfonylated indeno­[1,2-<i>c</i>]­quinolines in moderate to good yields. The features of the methodology include metal-free reaction, the ease of reagent handling, and a broad functional group tolerance

Iodine-catalyzed Sulfonylation of Arylacetylenic Acids and Arylacetylenes with Sodium Sulfinates: Synthesis of Arylacetylenic Sulfones

A highly efficient and generally applicable iodine-catalyzed reaction of arylacetylenic acids and arylacetylenes with sodium sulfinates for the synthesis of arylacetylenic sulfones was developed. The methodology has the advantages of a metal-free strategy, easy to handle reagents, functional group tolerance, a wide range of arylacetylenic acids and arylacetylenes, and easy access to arylacetylenic sulfones

Synthesis of <i>gem</i>-Difluoromethylenated Polycyclic Cage Compounds

The synthesis of <i>gem</i>-difluoromethylenated polycyclic cage compounds, utilizing PhSCF₂SiMe₃ as a <i>gem</i>-difluoromethylene building block, is described. The fluoride-catalyzed nucleophilic addition of PhSCF₂SiMe₃ to both maleic anhydride–cyclopentadiene and maleic anhydride–cyclohexadiene adducts was accomplished with high stereoselectivity to provide the corresponding adducts that were treated with Grignard reagents, followed by acid-catalyzed lactonization to afford the corresponding γ-butyrolactones, each as a single isomer. These γ-butyrolactones underwent intramolecular radical cyclization to give the corresponding tetracyclic cage γ-butyrolactones, which were employed as precursors for the synthesis of <i>gem</i>-difluoromethylenated tetracyclic cage lactols or tetracyclic cage furans, upon treatment with Grignard reagents

Electrophilic Difluoro(phenylthio)methylation: Generation, Stability, and Reactivity of α‑Fluorocarbocations

Electrophilic difluoro(phenylthio)methylation of allylsilanes has been achieved using bromodifluoro(phenylthio)methane (PhSCF₂Br) and silver hexafluoroantimonate (AgSbF₆). The structural assignment and observation of α-fluorocarbocation were substantiated by NMR and theoretical calculations. Detailed mechanistic and electronic studies have provided a fundamental understanding of the reactivity and stability of the difluoro(phenylthio)methylium cation (PhSCF₂⁺)