Au(I)-Catalyzed Cascade Reaction Involving Formal Double Hydroamination of Alkynes Bearing Tethered Carboxylic Groups: An Easy Access to Fused Dihydrobenzimidazoles and Tetrahydroquinazolines

Abstract

A process involving gold(I)-catalyzed formal double hydroamination of alkynes, bearing a tethered carboxylic group, for the synthesis of fused dihydrobenzimidazoles and tetrahydroquinazolines has been developed. A series of transition metal catalysts have been screened for this transformation, and a catalyst system consisting of Ph(3)PAuCl (1 mol %) and AgOTf (1 mol %) was found to be the best. The procedure entails the reaction of easily accessible starting materials such as alkynoic acids and 1,2-diaminobenzenes/2-aminobenzylamines in the presence of the catalyst in 1,2-dichloroethane at 100 degrees C. In the case of alpha-substituted alkynoic acids, the corresponding products were obtained in high diastereoselectivities; the structure of the diastereomers has been unambiguously characterized by NMR techniques. The mechanism of the reaction is discussed, and the origin of the diastereoselectivities is addressed. It was observed that under the microwave irradiation conditions, the reaction time is significantly shortened (0.5 h).

Transition‐Metal‐Catalyzed Hydroamination Reactions

“…Patil and coworkers [360][361][362][363] has published a series of papers that exploits the so-called tandem hydroamination-hydroarylation of nitrogen-containing arenes, such as pyrroles, to establish one-pot reactions for the synthesis of multicyclic frameworks with two nitrogens incorporated. Substrate scope investigations suggest that formal hydroamination processes are not involved and the approach is related to similar cyclizations achieved using iminium ions generated in situ from alkynylacids [364,365].…”

Alkyne hydroamination triggered cyclizations: A powerful tool for the construction of biologically important structural motifs

“…The method involves the treatment of diamines 123 with alkynoic acids 124, in the presence of 1 mol% Ph 3 PAuOTf, to give fused dihydrobenzimidazoles/tetrahydroquinazolines 125 in high yields and excellent diastereo-/regioselectivities (Table 14) [71]. Concerning mechanism, the reaction involves gold-catalyzed hydrocarboxylation of alkynoic acids 124 leading to the formation of exocyclic vinyl lactones 126.…”

Recent advances in the gold-catalyzed additions to C–C multiple bonds

“…These cascades are proposed to occur from an initial enol lactone intermediate via an intramolecular cycloaddition [165]. A subsequent intermolecular hydroamination of the intermediate, followed by a cyclization, leads to the observed products.…”