Au(I)-Catalyzed Synthesis of Trisubstituted Indolizines from 2-Propargyloxypyridines and Methyl Ketones

Abstract

A new Au(I)-catalyzed method for the preparation of trisubstituted indolizines from easily accessible 2-propargyloxy-pyridines is reported. The reaction tolerates a wide range of functionality, allowing for diversity to be introduced in four distinct regions of the product (R, R 1 , R 2 , and Ar). The proposed mechanism proceeds via enol addition to an allenamide intermediate and explains the observed increase in yields when electron poor methyl ketones are utilized.

Homogeneous and Heterogeneous Gold Catalysis for Materials Science

“…The reaction system is applicable for a variety of N-, C-, and O-based nucleophiles, even though a scope of substituents on the pyridine ring is not demonstrated. Other gold-catalyzed indolizines syntheses such as the intramolecular cyclization of pyridine derivatives containing an alkyne at an appropriate position , and a three-component reaction of pyridine-2-carboxaldehyde, various secondary amines, and terminal alkynes were also developed.…”

Synthesis of Ester-Substituted Indolizines from 2-Propargyloxypyridines and 1,3-Dicarbonyls

“…Following the general procedure outlined above for the synthesis of compound 5p , catalyst 3 (22 mg, 0.025 mmol), ethanol (0.6 mL), and dimethyl malonate (2.0 mL, 0.25 M) were added to 2-(6-phenyl-2-hexynoxy)­pyridine (123 mg, 0.49 mmol). After 18 h, the reaction was worked up and purified by column chromatography (SiO 2, 19:1 hexanes/ethyl acetate) to afford 125 mg (83% yield) of 5r as a brown syrup.…”

Crystal structure of tris(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl-κP)-μ-oxoethenylidene-triangulo-trigold(I) bis(trifluoromethanesulfonyl)imide

“…The title compound was observed during scope studies related to the gold(I)-catalyzed synthesis of trisubstituted indolizine 2 from 2-propargyloxypyridine 1 (Rossler et al, 2019). While initial studies had shown that treatment of pyridine 1 with methyl ketones in the presence of alcohols and (2-dicyclohexylphosphino-2 0 ,6 0 -dimethoxy-1,1 0 -biphenyl)gold(I) bis(trifluoromethane-sulfonyl)imide could provide trisubstituted indolizines 2 in moderate to good yields, when the methyl ketone was replaced with acetic anhydride, an unknown organic product and the title ketenylidene cluster 3 were observed (Fig.…”