Cascade Cyclization of Azadienes with Difluoroenoxysilanes: A One-Pot Formal [4 + 2] Approach to Fluorinated Polyfused Heterocycles

Abstract

A TfOH-promoted synthesis of fluorinated polyfused heterocycles via the cascade cyclization of azadienes and difluoroenoxysilanes has been developed, leading to the facile construction of and 5,6-dihydrobenzo[h]quinolines. This one-pot formal [4 + 2] approach involves 1,4-difluoroalkylation, desulfonylation, cyclization, and dehydrated and dehydrofluorinated aromatization and represents the first application of difluoroenoxysilane in cascade transformations. Furthermore, this methodology is highlighted by the synthesis of three fluoro analogues of bioactive molecules with potent topoisomerase inhibitory activities.

Recent Advances in Alkenyl sp2 C–H and C–F Bond Functionalizations: Scope, Mechanism, and Applications

“…More recently, the group of Li and Wang disclosed an effieient one-pot procedure for the rapid preparation of fluorinated polyfused heterocycles such as benzofuro­[3,2- b ]­pyridines, 5 H -indeno-[1,2- b ]­pyridines, and 5,6-dihydrobenzo­[ h ]­quinolines via the TfOH-promoted domino cyclization of azadienes with readily available difluoroenoxysilanes (Scheme ). This formal [4 + 2] cyclization strategy undergoes 1,4-difluoroalkylation, desulfonylation, intramolecular cyclization, and dehydrated and dehydrofluorinated aromatization sequences.…”

Direct benzylic C–H difluoroalkylation with difluoroenoxysilanes by transition metal-free photoredox catalysis

“…11 Among multiple accesses to carbocations from C(sp 3 )–H bonds, 12 the combined principle of hydrogen atom transfer (HAT) with oxidative radical-polar crossover (ORPC) promoted by visible light photoredox catalysis offers a mild and versatile approach. 8 b ,13 Based on our interest in difluoroalkylation 7 b ,14 and C–H functionalization, 15 we herein report a direct benzylic C–H difluoroalkylation with difluoroenoxysilanes by photoredox catalysis via a HAT-ORPC pathway (Scheme 1c). In comparison with transition metal photocatalysts, commonly used in the late-stage difluoroalkylation of organic substrates, 16 transition metal-free photocatalysts are typically low cost, of low toxicity, and easily handled, which show great advantages in environmental friendliness, combined with the green oxidant of air 17 and mild reaction conditions.…”

Palladium(0)-Catalyzed Heteroannulations of Allenamides: General Synthesis of δ-Carbolines and Benzofuro[3,2-b]pyridines

“…In addition to carbolines, other pyridine fused polyheterocycles are also of interest. 6 In particular, benzofuro [3,2b]pyridines (BFPs 2, Figure S1) serve as the core structure in natural products and bioactive compounds. 7 For example, sinensine D 8 (III, Figure S1) is found in fruiting bodies of Ganoderma sinense, a plant credited with beneficial effects in chronic hepatitis and nephritis, while compounds IV 9 (Figure S1) are reported as potent topoisomerase inhibitors.…”

“…In addition to carbolines, other pyridine fused polyheterocycles are also of interest . In particular, benzofuro­[3,2- b ]­pyridines (BFPs 2 , Figure S1) serve as the core structure in natural products and bioactive compounds .…”

“…Only the former approach is known to provide a general synthesis of 2 , though there are also few specific examples . In contrast, the latter approach provides some general methods , (Scheme b), relying on substrates prepared in multiple steps. Therefore, development of a straightforward method using readily available substrates would be worthwhile.…”