Acid-promoted Cascade Cyclization to Produce Fused-polycyclic Indole Derivatives

An acid-promoted novel cascade cyclization is described. Using 8 equiv of trifluoroacetic acid or a catalytic amount of Lewis acid as the promoter, structurally diverse polycyclic cyclopenta[<i>b</i>]indoles were obtained in moderate to excellent yield. This cascade process was extremely effective for the synthesis of 8-membered ring-fused cyclopenta[<i>b</i>]indole derivatives

Synthetic Study of Pactamycin: Enantioselective Construction of the Pactamycin Core with Five Contiguous Stereocenters

A synthetic study of pactamycin is described. Enantioselective construction of the aminocyclopentitol core of pactamycin bearing five contiguous stereocenters was achieved based on an organocatalytic asymmetric aziridination of 2-cyclopentene-1-one, a regio- and diastereoselective 1,3-dipolar cycloaddition, and a rhodium-catalyzed C–H amination reaction

Asymmetric Aziridination of Cyclic Enones Using Chiral Diamine Catalysts and Its Application to the Total Synthesis of (−)-Agelastatin A

The asymmetric aziridination of cyclic enones with <i>N</i>-tosyloxycarbamates, using <i>N</i>-neopentyl 1,2-diphenylethylenediamine as a catalyst, and its application to the formal total synthesis of (−)-agelastatin A, using a one-pot silylation-selenylation procedure and the regioselective aziridine-opening by an azide anion as key steps, are described

Construction of Divergent Fused Heterocycles via an Acid-Promoted Intramolecular <i>ipso</i>-Friedel–Crafts Alkylation of Phenol Derivatives

Two different cascade cyclization processes were developed using aryl group-substituted propargyl alcohol derivatives with a <i>p</i>-hydroxybenzylamine unit as common substrates. Using TFA as an acid promoter, an intramolecular <i>ipso</i>-Friedel–Crafts alkylation of phenol derivatives, formation of an iminium cation via a rearomatization-promoted C–C bond cleavage, an aza-Prins reaction, and a 6-membered ring formation proceeded sequentially, producing a variety of fused-tricyclic dihydroquinoline derivatives in 45–99% yield. In addition, a one-pot sequential silver acetate-catalyzed hydroamination/etherification–acid-promoted skeletal rearrangement was examined using the same series of substrates, affording fused-tricyclic indole/benzofuran derivatives in 66–89% yield

Synthetic Study of Pactamycin: Enantioselective Construction of the Pactamycin Core with Five Contiguous Stereocenters

A synthetic study of pactamycin is described. Enantioselective construction of the aminocyclopentitol core of pactamycin bearing five contiguous stereocenters was achieved based on an organocatalytic asymmetric aziridination of 2-cyclopentene-1-one, a regio- and diastereoselective 1,3-dipolar cycloaddition, and a rhodium-catalyzed C–H amination reaction

Pd-Catalyzed Cascade Cyclization by Intramolecular Heck Insertion of an Allene–Allylic Amination Sequence: Application to the Synthesis of 3,4-Fused Tricyclic Indoles

A novel Pd-catalyzed cascade cyclization by intramolecular Heck insertion of an allene–allylic amination sequence was developed. Allenes tethered to <i>ortho</i>-iodoaniline derivatives at the <i>meta</i>-position were reacted with 5–10 mol % of Pd catalyst and 4 equiv of K₂CO₃ in DMSO at 90 °C, producing 3,4-fused tricyclic 3-alkylidene indoline derivatives in moderate to excellent yield. The reaction products were divergently transformed into three types of 3,4-fused tricyclic indole derivatives, successfully demonstrating the versatile properties of the reaction products

Asymmetric Synthesis of Chiral 9,10-Dihydrophenanthrenes Using Pd-Catalyzed Asymmetric Intramolecular Friedel–Crafts Allylic Alkylation of Phenols

We developed a novel asymmetric synthetic method for multisubstituted 9,10-dihydrophenanthrenes based on the Pd-catalyzed asymmetric intramolecular Friedel–Crafts allylic alkylation of phenols, which produces 10-vinyl or 10-isopropenyl chiral 9,10-dihydrophenanthrene derivatives in high yield with up to 94% ee

Asymmetric Synthesis of Chiral 9,10-Dihydrophenanthrenes Using Pd-Catalyzed Asymmetric Intramolecular Friedel–Crafts Allylic Alkylation of Phenols

We developed a novel asymmetric synthetic method for multisubstituted 9,10-dihydrophenanthrenes based on the Pd-catalyzed asymmetric intramolecular Friedel–Crafts allylic alkylation of phenols, which produces 10-vinyl or 10-isopropenyl chiral 9,10-dihydrophenanthrene derivatives in high yield with up to 94% ee

Synthetic Study of Dragmacidin E: Construction of the Core Structure Using Pd-Catalyzed Cascade Cyclization and Rh-Catalyzed Aminoacetoxylation

We developed a novel synthetic method of the core structure of dragmacidin E bearing a 7-membered ring-fused bis­(indolyl)­pyrazinone skeleton. Formation of the 7-membered ring-fused tricyclic indole skeleton was accomplished using a palladium-catalyzed Heck insertion–allylic amination cascade. Vicinal difunctionalization of the 7-membered ring was realized via a rhodium-catalyzed aminoacetoxylation

General Approach to Nitrogen-Bridged Bicyclic Frameworks by Rh-Catalyzed Formal Carbenoid Insertion into an Amide C–N Bond

Various nitrogen-bridged bicyclic skeletons are found in bioactive natural products and pharmaceuticals. The development of a new reaction to construct these molecular frameworks has attracted considerable attention in synthetic organic chemistry. We developed a novel synthetic method for obtaining a wide variety of nitrogen-bridged bicyclic compounds with a catalytic process, Rh-catalyzed formal carbenoid insertion into an amide C–N bond. Using 0.1–0.4 mol % Rh₂(NHCO^<i>t</i>Bu)₄ catalyst, various azabicyclo­[<i>X</i>.<i>Y</i>.<i>Z</i>]­alkane derivatives were obtained in good to excellent yield, successfully demonstrating the broad substrate scope of the developed process. Experimental and computational studies to elucidate the reaction mechanism revealed that the formal insertion reaction of a carbenoid into an amide C–N bond proceeded via the formation of Rh-associated <i>N</i>-ylides, followed by an acyl group-selective Stevens [1,2]-shift through a concerted addition/elimination process on the sp²-hybridized carbon