Diverting the 5-<i>exo</i>-Trig Oxypalladation to Formally 6-<i>endo</i>-Trig Fluorocycloetherification Product through 1,2-O/Pd(IV) Dyotropic Rearrangement

Pd-catalyzed cyclizative functionalization of γ-hydroxyalkenes affords tetrahydrofuran derivatives via a key 5-exo-trig oxypalladation step. Herein, we report a palladium(II)-catalyzed, Selectfluor-mediated formal 6-endo-trig fluorocycloetherification of γ-hydroxyalkenes for the synthesis of functionalized tetrahydropyrans. Mechanistically, an σ-alkyl-Pd(II) intermediate resulting from the 5-exo-trig oxypalladation process is isolated and characterized by X-ray crystallographic analysis. Its oxidation with Selectfluor to Pd(IV) triggers the chemoselective 1,2-O/Pd(IV) dyotropic rearrangement affording, after C–F bond-forming reductive elimination, the tetrahydropyrans with concurrent generation of a tertiary carbon–fluorine bond. The occurrence of this 1,2-positional interchange is further evidenced by trapping the rearranged quaternary C(sp3)–Pd bond by an internal nucleophile that is materialized by the development of a Pd(II)-catalyzed oxidative bis-heterocyclization of alkenes

Cooperative Pd/Cu Catalysis: Multicomponent Synthesis of Tetrasubstituted Imidazolones from Methyl α‑Isocyanoacetates, Primary Amines, and Aryl(vinyl) Iodides

Three-component reaction of methyl α,α-disubstituted α-isocyanoacetates, primary amines, and aryl­(vinyl) halides in the presence of Pd­(OAc)₂ (0.05 equiv) and Cu₂O (1.0 equiv) provided 2,3,5,5-tetrasubstituted imidazolones via the formation of three chemical bonds. A copper-mediated migratory insertion of the isocyano group into the N–H bond of the amine followed by lactamization and Pd-catalyzed cross-coupling of the in situ generated amidinyl copper species with aryl­(vinyl) halides accounted for the reaction outcome

Three-Component Povarov Reaction–Heteroannulation with Arynes: Synthesis of 5,6-Dihydroindolo[1,2‑<i>a</i>]quinolines

A reaction of 2-acyl substituted tetrahydroquinolines, prepared by Lewis acid-catalyzed three-component reaction of α-oxo aldehydes, anilines, and dienophiles, with in situ generated arynes afforded 5,6-dihydroindolo­[1,2-<i>a</i>]­quinolines in good to excellent yields

Enantioselective Total Syntheses of Leuconolam–Leuconoxine–Mersicarpine Group Monoterpene Indole Alkaloids

A unified strategy allowing enantioselective total syntheses of (−)-mersicarpine, (−)-scholarisine G, (+)-melodinine E, (−)-leuconoxine, and (−)-leuconolam from a common cyclohexenone derivative was reported. The Suzuki–Miyaura reaction was used to couple two simple fragments incorporating the key elements for total synthesis, and unprecedented oxidation/reduction/cyclization processes were developed that converted the substituted cyclohexenone to either a mersicarpine or leuconoxine skeleton. In a reverse biomimetic synthesis fashion, (+)-melodinine E was converted to (−)-leuconolam under acidic conditions

A Concise Total Synthesis of (±)-Trigonoliimine B

Trigonoliimine B, a hexacyclic alkaloid, is synthesized in seven steps from simple starting materials. The synthesis features the use of an α-isocyanoacetate as a glycine template for the preparation of an α,α-disubstituted α-amino ester that is appropriately functionalized for the construction of C, D, and E rings. Sulfolane was found to be the solvent of choice for the unprecedented Bischler–Napieralski reaction implemented for the construction of a seven-membered ring with concurrent formation of an <i>exo</i>-imine function

Enantioselective Total Syntheses of Leuconolam–Leuconoxine–Mersicarpine Group Monoterpene Indole Alkaloids

A unified strategy allowing enantioselective total syntheses of (−)-mersicarpine, (−)-scholarisine G, (+)-melodinine E, (−)-leuconoxine, and (−)-leuconolam from a common cyclohexenone derivative was reported. The Suzuki–Miyaura reaction was used to couple two simple fragments incorporating the key elements for total synthesis, and unprecedented oxidation/reduction/cyclization processes were developed that converted the substituted cyclohexenone to either a mersicarpine or leuconoxine skeleton. In a reverse biomimetic synthesis fashion, (+)-melodinine E was converted to (−)-leuconolam under acidic conditions

Ugi Four-Component Reaction of Alcohols: Stoichiometric and Catalytic Oxidation/MCR Sequences

A new, simple, and efficient procedure for the one-pot Ugi four-component reaction of alcohols instead of aldehydes is described. Using a stoichiometric amount of IBX or only 1–2% of sodium 2-iodobenzenesulfonate in the presence of Oxone, a wide range of primary alcohols were oxidized to the aldehyde that were directly engaged in the Ugi four-component reaction to afford α-acetamidoamides in good to excellent yields

Triple Role of Phenylselenonyl Group Enabled a One-Pot Synthesis of 1,3-Oxazinan-2-ones From α‑Isocyanoacetates, Phenyl Vinyl Selenones, and Water

Reaction of α-substituted α-isocyanoacetates with phenyl vinyl selenones in the presence of a catalytic amount of base (DBU or Et₃N, 0.05–0.1 equiv) followed by addition of <i>p</i>-toluenesulfonic acid (PTSA, 0.1–0.2 equiv) afforded 4,4,5-trisubstituted 1,3-oxazinan-2-ones in good to excellent yields. Enantiomerically enriched heterocycles can also be prepared using a <i>Cinchona</i> alkaloid-derived bifunctional organocatalyst for the Michael addition step. The phenylselenonyl group served as an activator for the Michael addition, a leaving group and a latent oxidant in this integrated reaction sequence

Palladium-Catalyzed Enantioselective Domino Heck/Intermolecular C–H Bond Functionalization: Development and Application to the Synthesis of (+)-Esermethole

Intramolecular asymmetric carbopalladation of <i>N</i>-aryl acrylamides followed by intermolecular trapping of the resulting σ-C­(sp³)–Pd complex by azoles afforded 3,3-disubstituted oxindoles in good yields with excellent enantioselectivities. Two C–C bonds were created with concurrent formation of an all-carbon quaternary stereocenter. Oxadiazole substituted oxindoles were subsequently converted to pyrroloindolines by an unprecedented reductive cyclization protocol. The utility of this chemistry was illustrated by an enantioselective synthesis of (+)-esermethole

Three-Component Povarov Reaction–Heteroannulation with Arynes: Synthesis of 5,6-Dihydroindolo[1,2‑<i>a</i>]quinolines

A reaction of 2-acyl substituted tetrahydroquinolines, prepared by Lewis acid-catalyzed three-component reaction of α-oxo aldehydes, anilines, and dienophiles, with in situ generated arynes afforded 5,6-dihydroindolo­[1,2-<i>a</i>]­quinolines in good to excellent yields