A Gold(I)-Catalyzed Hydroamination/Cycloisomerization Cascade: Concise Synthesis of (±)-seco-Antofine and (±)-Septicine

Abstract

A concise and flexible procedure for the synthesis of highly functionalized N-heterocyclic 1,6-annulated 2-pyridones and 2,3-annulated 4-pyrimidinones has been elaborated through a gold-catalyzed tandem hydroamination/cycloisomerization cascade. This novel and highly efficient method allows the rapid construction of these diverse N-heterocyclic scaffolds starting from readily available building blocks, and shows a wide scope and good functional group tolerance. The total synthesis of (±)-seco-antofine and (±)-septicine were realized employing this strategy.

Total Synthesis of Cryptopleurine and Its Analogues

“…Procedures 2-(1,3-Dioxolan-2-yl)piperidine (10) To a solution of 2-(1,3-dioxolan-2-yl)pyridine 15 (20 g, 132 mmol) in AcOEt (150 mL) was added Pd(OH)2 (5.0 g, 5% on Carbon, 1.8 mmol). After flushing with H2, the solution was stirred for 99 h at 23 °C.…”

“…To a solution of 10 (10.3 g, 65.5 mmol) in CH 2 Cl 2 (150 mL) was added a 1.1 M toluene solution of Et 3 Al (77.4 mL, 85.1 mmol) dropwise at 0 °C under argon atmosphere. After stirring for 30 min, a solution of 2-(3,4-dimethoxybenzyl)oxirane ( 8 ; 10 14.0 g, 72.0 mmol) in CH 2 Cl 2 (150 mL) was added dropwise to the mixture. After stirring for 1.5 h at 23 °C, the reaction mixture was quenched with 10% aq NaOH (150 mL).…”

“…Therefore, the development of a simple, direct approach for the synthesis of cryptopleurine in which the C ring is introduced at the end of the synthesis is highly desirable. 10 Herein we report the total synthesis of cryptopleurine and its derivatives via the late-installation of various C-rings. We proposed retrosynthetic analysis of cryptopleurine as shown in Scheme 2.…”

“…Therefore, the development of a simple, direct approach for the synthesis of cryptopleurine in which the C ring is introduced at the end of the synthesis is highly desirable. 10…”

Nickel-Catalyzed Regioselective Hydroamination of Ynamides with Secondary Amines

“…The development of efficient synthetic methodologies has always been important and attractive to organic chemists, due to their potential use in syntheses of natural products and pharmaceutical drugs . In particular, hydroamination has attracted significant interest because of its utilization in the preparation of heterocyclic compounds, including depsipeptides, pharmaceuticals, and important natural products . Although hydroamination usually involves the challenging formation of enamine-containing heterocyclic compounds, the reaction process can overcome the intriguing selectivity of inter/intramolecular nucleophilic attack and demonstrate exceptional ability to activate π-conjugated systems.…”