Diastereoselective Synthesis of 1,2-Dihydrobenzofuro[3,2-b]pyridines via a Carbon–Carbon Double-Bond Cleavage/Rearrangement Cascade

Abstract

A new Lewis acid-catalyzed [2 + 2] cycloaddition/ retroelectrocyclization (CA-RE)/1,6-addition relay of aurone-derived 1azadienes and 1-alkynylnaphthalen-2-ols has been reported, leading to the regio-and diastereoselective synthesis of 1,2-dihydrobenzofuro[3,2-b]pyridine with a chiral carbon center and an axial chirality in good yields. This protocol enables the C−C double-bond scission/recombination to rapidly construct aza-heterocyclic architectures and features 100% atom utilization, a wide substrate scope, good compatibility with substituents, and excellent diastereoselectivity.

Iodine-Promoted Thioylation and Dicarbonylation of Enaminone α-C Sites: Synthesis of Fully Substituted Thiazoles via C═C Bond Cleavage

“…On the basis of the results presented above and previous reports, a plausible mechanism for these dicarbonylation and thioylation reactions can be proposed (Scheme ). In this process, benzothioamide 3a is initially converted to iodo species 3a′ by the I 2 /DMSO system.…”

Base-Catalyzed Sequential 1,4-Addition/Intramolecular Cyclization/Aromatization Reaction: Synthesis of Benzofuro[3,2-b]pyridines

“…Polyheterocyclic frameworks are ubiquitous in natural products and pharmacologically active molecules . Among them, benzofuro­[3,2- b ]­pyridines (BFPs) (Figure ) represent an important class of heterocyclic compounds. − Various strategies for their construction have been established. − However, some of these methods suffer from multistep procedures and the limitation of a narrow substrate range. Therefore, it still is highly desirable to develop a simple method for the construction of this important scaffold.…”

“…In recent years, aurone-derived 1-azadienes have been used as highly reactive intermediates in organic synthesis, due to the driving force of aromatization. − With these aurone-derived 1-azadienes as the starting material, several elegant methods for the construction of benzofuro­[3,2- b ]­pyridine were established. In 2019, Chen, Jiang and co-workers developed an intriguing base-promoted [4+1+1] annulation reaction of aurone-derived 1-azadienes with α-bromo carbonyls, providing a complex benzofuro­[3,2- b ]­pyridines scaffold in an efficient manner (Scheme a) .…”

“…By using a copper catalyst, Zhou achieved formal [4+2] cycloaddition of aurone-derived 1-azadienes with terminal alkynes, which elegantly produced 1,2-dihydrobenzofuran­[3,2- b ]­pyridines through a complex nucleophilic addition/cyclization/isomerization process (Scheme b) . In 2021, Jiang, Tu, Hao, and co-workers presented a Lewis acid-catalyzed [2+2] cycloaddition/retroelectrocyclization/1,6-addition relay of aurone-derived 1-azadienes and 1-alkynylnaphthalen-2-ols, resulting in the regio- and diastereoselective synthesis of 1,2-dihydrobenzofuro­[3,2- b ]­pyridine with a chiral carbon center and an axial chirality in good yields (Scheme c) . According to previous studies, it was known that the α-hydrogen of allenoates and allene ketones has a certain acidity, which allows allenoates and allene ketones to be deprotonated and thus act as nucleophiles.…”

“…8 In 2021, Jiang, Tu, Hao, and co-workers presented a Lewis acid-catalyzed [2+2] cycloaddition/retroelectrocyclization/1,6-addition relay of aurone-derived 1-azadienes and 1alkynylnaphthalen-2-ols, resulting in the regio-and diastereoselective synthesis of 1,2-dihydrobenzofuro [3,2-b]pyridine with a chiral carbon center and an axial chirality in good yields (Scheme 1c). 9 According to previous studies, 11 it was known that the α-hydrogen of allenoates and allene ketones has a certain acidity, which allows allenoates and allene ketones to be deprotonated and thus act as nucleophiles. On the basis of this feature, we investigated the base-assisted reaction of allenoates with aurone-derived 1-azadienes, and we herein describe an efficient K 2 CO 3 -catalyzed 1,4-addition/intramolecular cyclization/aromatization reaction of aurone-derived 1-azadienes with trisubstituted allenoates, giving a series of benzofuro [3,2b]pyridines (Scheme 1d).…”