109802-64-4

Upstream product

• 2216-94-6 phenylpropynoic acid ethyl ester 
• 26260-02-6 2-iodobenzaldehyde 
• 212505-57-2 N-(2-iodobenzylidene)-2-methylpropan-2-amine 
• 109802-44-0 {Pd(C(Ph)=C(CO2Et)C6H4CH2NMe2(cyclic))(μ-I)}2 

Downstream Products

• 1401424-87-0 ethyl 3-phenyl-1,2,3,4-tetrahydroisoquinoline-4-carboxylate 

Relevant academic research and scientific papers

Highly Regioselective Isoquinoline Synthesis via Nickel-Catalyzed Iminoannulation of Alkynes at Room Temperature

A simple and cost-efficient nickel catalytic system for the annulation of 2-haloaldimines with alkynes to synthesize 3,4-disubstituted and 3-substituted isoquinolines at room temperature has been developed. The air-stable and inexpensive Ni(dppe)Cl2 was employed as a precatalyst, and Et3N was found to be an essential additive for obtaining high yields. By using this nickel catalytic system one-pot three-component direct synthesis of isoquinolines starting with simple 2-halobenzaldehydes, tert-butylamine, and alkynes were also achieved. These reactions occur in moderate to excellent yields with complete regioselectivity. Moreover, these reactions feature a broad substrate scope, easy scalability, operational simplicity, and excellent practicality.

Assembly of isoquinolines via CuI-catalyzed coupling of β-keto esters and 2-halobenzylamines

(Chemical Equation Presented) CuI-catalyzed coupling of 2-halobenzylamines with β-keto esters or 1,3-diketones in i-PrOH under the action of K 2CO3 produced 1,2-dihydroisoquinolines as the coupling/condensative cyclization products,

Highly efficient synthesis of isoquinolines via nickel-catalyzed annulation of 2-iodobenzaldimines with alkynes: Evidence for dual pathways of alkyne insertion

(Chemical Equation Presented) A wide range of substituted isoquinolines were synthesized via a highly efficient nickel-catalyzed annulation of the tert-butyl imines of 2-iodobenzaldehydes and various alkynes; examination of the regiochemistry of isoquinol

Synthesis of isoquinolines and pyridines by the palladium-catalyzed iminoannulation of internal alkynes

A wide variety of substituted isoquinoline, tetrahydroisoquinoline, 5,6-dihydrobenz[f]isoquinoline, pyrindine, and pyridine heterocycles have been prepared in good to excellent yields via annulation of internal acetylenes with the tert-butylimines of o-iodobenzaldehydes and 3-halo-2-alkenals in the presence of a palladium catalyst. The best results are obtained by employing 5 mol % of Pd(OAc)2, an excess of the alkyne, 1 equiv of Na2CO3 as a base, and 10 mol % of PPh3 in DMF as the solvent. This annulation methodology is particularly effective for aryl- or alkenyl-substituted alkynes. When electron-rich imines are employed, this chemistry can be extended to alkyl-substituted alkynes. Trimethylsilyl-substituted alkynes also undergo this annulation process to afford monosubstituted heterocyclic products absent the silyl group.

Controlled synthesis of heterocyclic compounds through ring enlargement by alkyne insertions into the Pd-C bonds of cyclopalladated amines followed by subsequent ring closure

The chloride-bridged dimer [{Pd(dmba)(μ-Cl)}2] (1) (dmba = C6H4CH2NMe2, 2-((dimethylamino)-methyl)phenyl) reacted with 1 equiv per Pd atom of disubstituted alkynes (R1C≡CR2 in which R1 and/or R2 = CO2R, where R = Me or Et) to afford regiospecifically [{Pd(C(R2)=C(R1)C6H4CH 2NMe2)(μ-Cl)}2] (4a-c) through insertion of the alkyne into the Pd-C bond of 1. Compounds 4a-c underwent a further ring expansion by insertion of a second alkyne to give the monomers [Pd{C(R4)=C(R3)C(R2)=C-(R1)C 6H4CH2NMe2}Cl] (6a-j). The compound [Pd{C(Ph)=C(Ph)C(Ph)=C(Ph)(8-mq)}Cl] (7) (8-mq = CH2C9H6N, 8-quinolylmethyl) rearranged in boiling chlorobenzene to afford [Pd{C(Ph)=C(Ph)CH-(Ph)C(Ph)=CHC9H6N}Cl] (8), via a 1,3-hydrogen shift of the CH2 group on the adjacent olefinic bond, together with trace amounts of [{C(Ph)C(Ph)=C(Ph)C(Ph)CH2C9H6N} 2]Pd2Cl6 (9α), which has been fully characterized by an X-ray diffraction study. It shows that the organic moiety of this salt is a cationic heterocycle in which C-C and C-N bonds have been formed by a depalladation process, affording a substituted cyclobutene adduct of 1H-benzo[ij]quinolizinium. Using [{Pd(8-mq)(μ-I)}2] (2*) as well as [Pd(8-mq)(MeCN)2]BF4 (2**) as starting materials afforded good to excellent yields of cationic heterocycles 9β and 9γ having Pd2I62- and BF4- as the counteranions, respectively. Extending these easily available ligand changes to other cyclopalladated starting materials, i.e., by substitution of chloride for iodide or with cationic derivatives, led efficiently to the synthesis of several heterocyclic products. Thus [Pd-(dmba)(MeCN)2]BF4 (1**) with diphenylacetylene afforded a quantitative yield of the product [C(Ph)-=C(Ph)C(Ph)=C(Ph)C6H4CH2NMe 2]BF4 (13) whereas 1** and 2** with ethyl 3-phenylpropiolate gave the analogous heterocycles 14 and 15, respectively, as zwitterionic species. The complex [Pd(dmna)-(MeCN)2]BF4 (3**) (dmna = C10H6NMe2, 1-(dimethylamino)naphthyl-8) reacted with alkynes of the type R1C≡CR2 to afford cationic benzo[de]quinolizinium [C(R2)=C(R1)C10H6NMe 2]BF4 (17a, R1 = R2 = Ph; 17b, R1 = CO2Et, R2 = Ph). This reaction, when starting from [{Pd(dmna)(μ-I)}2] (3*), led to good yields of neutral benzo[de]quinolines 10a-d via a partial demethylation of the NMe2 group. The thermal decomposition of the monoinserted compound [{Pd(C(Ph)=C(CO2Et)C6H4CH2NMe 2)(μ-I)}2] (4a*) led to the heterocyclic products [{C(Ph)=C(CO2Et)C6H4CH=NMe}2]Pd 2I6 (11) and [C(Ph)=C-(CO2Et)C6H4CH=N] (12). The molecular structure of compound 11 has been ascertained by means of X-ray diffraction.

Control of the Reactivity of Cyclopalladated Complexes for the Synthesis of Heterocyclic Compounds

Reactions between iodide or cationic derivatives of cyclopalladated complexes and alkynes lead to the synthesis of heterocyclic compounds through insertion of one or two alkynes into the Pd-C bonds, the new N-C bonds being formed via reductive elimination