Rhodium(III)-Catalyzed Cascade [5 + 1] Annulation/5-exo-Cyclization Initiated by C–H Activation: 1,6-Diynes as One-Carbon Reaction Partners

Abstract

The catalytic [5 + 1] annulation/5-exo-cyclization reaction of amidines with diynes is reported herein. This protocol provides highly atom-economical access to fabricate two nitrogen-containing heterocycles in one step with high efficiency and selectivity. Significantly, this reaction represents the first example of using diyne as a one-carbon reaction partner in C-H functionalization. Kinetic isotope effects suggested that the catalytic cycle of this reaction is initiated by the cleavage of the ortho C-H bond in the N-phenyl ring of amidines, which is likely involved in the rate-limiting step. Calculations based on density functional theory (DFT) indicated that C-H activation and the formation of Rh(V) species via 5-exo-cyclization could be vital processes for this cascade transformation.

Ortho‐Functionalization of Benzimidates and Benzamidines

“…[25] In 2011, Ihara and co-workers reported the annulation of imidates (42) with dimethyl acetylenedicarboxylate ( 44 49) in moderate to good yields (Scheme 20). [26] Based on different controlled experiments, it was revealed that cyclic imidates (imino ether) (42) were isomerized to enaminoethers (43) and attacked to alkene systems to yield the Micheal adducts. The adducts then isomerized to enamino ethers followed by cyclization by eliminating methanol as the by-product.…”

“…[24] A simple class of αolefins are synthesized on a large scale every year industrially, showing the potential of these organic moieties. [25] In 2011, Ihara and co-workers reported the annulation of imidates (42) with dimethyl acetylenedicarboxylate ( 44 49) in moderate to good yields (Scheme 20). [26] Based on different controlled experiments, it was revealed that cyclic imidates (imino ether) (42) were isomerized to enaminoethers (43) and attacked to alkene systems to yield the Micheal adducts.…”

“…Later in the year 2018, Du et al reported a catalytic [5 + 1] cyclization/5-exocyclization of amidines (109) with diynes (110) (Scheme 44). [42] Under the optimized reaction condition, [Cp*RhCl 2 ] 2 (5 mol %), Ag 2 CO 3 (10 mol %), 2,6-dimethylbenzoic acid (1 equiv), H 2 O (4 equiv), Li 2 CO 3 (80 mol %), DMA/EtOH/NMP (6 mL, 2 : 1 : 2), 80 °C for 21 h, the substrate scope of a diversely substituted amidines were investigated. The methodology was tolerable with electron-rich and-poor substituents at the paraposition delivering the products in moderate to good yields (33-91 %).…”

Transition Metal Promoted Cascade Heterocycle Synthesis through C−H Functionalization

“…In 2018, Du and co‐workers, reported the synthesis of substituted quinazolines by one‐pot [5+1] annulation/5‐ exo cyclization initiated by Rh III ‐catalyzed C−H activation . Their protocol involves the reaction of amidines 63 and diynes 64 as one carbon precursor under rhodium catalysis.…”

Titanium Tetraiodide/Trimethylsilyl Iodide Synergistically Induced Cyclization of N-(2-Cyanophenyl)benzamides into 2-Aryl-4-iodoquinazolines

“…11 Xu and co-workers reported the 2-arylquinazoline synthesis by the rhodium(III)-catalyzed cascade [5 + 1] annulation/5-exocyclization reaction of amidines with diynes. 12 Jiang reported the copper-catalyzed synthesis of substituted quinazolines from benzonitriles and 2-ethynylanilines via a carbon–carbon bond cleavage using molecular oxygen. 13 Chen reported the synthesis of quinazolines using the palladium-catalyzed tandem reaction of N -(2-cyanoaryl)benzamides with arylboronic acids.…”