Brønsted Acid-Catalyzed Synthesis of 4-Functionalized Tetrahydrocarbazol-1-ones from 1,4-Dicarbonylindole Derivatives.

A p-toluenesulfonic acid-catalyzed cascade reaction is reported for the synthesis of 4-functionalized tetrahydrocarbazolones via the reaction of 4-(indol-2-yl)-4-oxobutanal derivatives with a variety of nucleophiles in acetonitrile or hexafluoroisopropanol. After the initial intramolecular Friedel-Crafts hydroxyalkylation, the 3-indolylmethanol intermediate is subsequently activated and reacted with the external nucleophile. The reaction conditions are crucial to avoid alternative reaction pathways, allowing direct substitution reaction with thiols, (hetero)arenes, alkenes, or sulfinates. The procedure features high overall yields to access a diverse family of compounds bearing the tetrahydrocarbazole core.

Catalyst- and Substrate-Controlled Regiodivergent Synthesis of Carbazoles through Gold-Catalyzed Cyclizations of Indole-Functionalized Alkynols.

A wide variety of regioselectively substituted carbazole derivatives can be synthesized by the gold-catalyzed cyclization of alkynols bearing an indol-3-yl and an additional group at the homopropargylic positions. The regioselectivity of the process can be controlled by both the oxidation state of the gold catalyst and the electronic nature of the substituents of the alkynol moiety. The 1,2-alkyl migration in the spiroindoleninium intermediate, generated after indole attack to the activated alkyne, is favored with gold(I) complexes and for electron-rich aromatic substituents at the homopropargylic position, whereas the 1,2-alkenyl shift is preferred when using gold(III) salts and for alkyl or non-electron-rich aromatic groups.

Asymmetric Gold(I)-Catalyzed Tandem Hydroarylation-Nazarov Cyclization: Enantioselective Access to Cyclopentenones.

The asymmetric synthesis of cyclopentachromenones from gold-catalyzed reaction of readily available skipped alkenynones is described. This cascade reaction involves an initial anti-Michael hydroarylation of the ynone moiety to form a gold-functionalized dialkenylketone intermediate, followed by a Nazarov cyclization that proceeds in an unprecedented enantioselective manner. Excellent enantiomeric ratios and chemical yields are obtained under mild reaction conditions.

Regiodivergent Hydration-Cyclization of Diynones under Gold Catalysis.

Skipped diynones, efficiently prepared from biomass-derived ethyl lactate, undergo a tandem hydration-oxacyclization reaction under gold(I) catalysis. Reaction conditions have been developed for a switchable process that allows selective access to 4-pyrones or 3(2H)-furanones from the same starting diynones. Further application of this methodology in the total synthesis of polyporapyranone B was demonstrated.

Gold(i)-catalyzed nucleophilic cyclization of ß-monosubstituted o-(alkynyl)styrenes: a combined experimental and computational study.

The stereospecific gold(i)-catalyzed nucleophilic cyclization of ß-monosubstituted o-(alkynyl)styrenes to produce C-1 functionalized 1H-indenes including challenging substrates and nucleophiles, such as ß-(cyclo)alkyl-substituted o-(alkynyl)styrenes and a variety of alcohols as well as selected electron-rich aromatics, is reported. DFT calculations support the stereochemical outcome of the process that involves the formation of a key cyclopropyl gold carbene intermediate through a regiospecific 5-endo cyclization.

Gold(i)-catalyzed diastereoselective synthesis of 1-α-oxybenzyl-1H-indenes.

The gold(i)-catalyzed oxycyclization of ß-aryl monosubstituted o-(alkynyl)styrenes gives rise to 1-α-methoxy or 1-α-hydroxybenzyl-1H-indenes in a diastereospecific way. In contrast to ß,ß-disubstituted o-(alkynyl)styrenes, the stereochemical outcome of this process, diastereospecific reaction supports the higher contribution of a gold intermediate with a cyclopropylcarbene-like character.