Intramolecular addition reactions tetrahydroquinolines

Intramolecular addition reactions of arenes and aryl olefins with secondary and primary amines have proven to be of broader scope than the analogous reactions with tertiary amines. The intramolecular addition of nonconjugated o-allylanilines 51 to yield the 2-methylindolines 52 was reported by Koch-Pomeranz et al. in 1977. Intramolecular electron transfer from the singlet aniline to the ground state alkene followed by N-H proton transfer to the alkene terminal carbon was proposed to account for the regioselective formation of indolines. Proton transfer to the internal carbon would yield tetrahydroquinolines, which were... 

Gold(lII) chloride and silver hexafluoroantimonate can also be used as catalyst for addition reactions of electron-rich arenes and heteroarenes to olefins. In a similar fashion, the intramolecular hydroarylation of aryl homoallyl ethers and related substrates takes place upon heating with AuCb and AgOTf in dichloroethane to 80 °C and affords dihydrobenzopyrans, tetrahydroquinolines, and tetralins with good yield (Scheme 4-18). ... 

Palladium chemistry has been used in the synthesis of tetrahydroisoquinolines. Different combinations of iodoaryl-amine-alkene can be used in these multicomponent reactions. For example, the metal-mediated o-alkylated/alkenyl-ation and intramolecular aza-Michael reaction (Scheme 109) give moderate yields of heterocycle <2004TL6903>, whereas the palladium-catalyzed allene insertion-nucleophilic incorporation-Michael addition cascade (Equation 172) produces good yields of tetrahydroisoquinolines in 15 examples <2003TL7445> with further examples producing tetrahydroquinolines (Scheme 110) <2000TL7125>. 

Baylis-Hillman adducts such as 55 and 56 derived from 2-nitrobenzaldehydes were shown to function as useful precursors to functionalized (1H)-quinol-2-ones and quinolines. Treatment of 55 and 56 with iron and acetic acid at 110 °C afforded 57 and 58, respectively <02T3693>. A variety of other cyclization reactions utilized in the preparation of the quinoline scaffold were also reported. An iridium-catalyzed oxidative cyclization of 3-(2-aminophenyl)propanols afforded 1,2,3,4-tetrahydroquinolines <02OL2691>. The intramolecular cyclization of aryl radicals to prepare pyrrolo[3,2-c]quinolines was studied <02T1453>. Additionally, photocyclization reactions of /rans-o-aminocinnamoyl derivatives were reported to provide 2-quinolones and quinolines <02JHC61>. Enolizable quinone and mono- and diimide intermediates were shown to provide quinolines via a thermal 6jt-electrocyclization <02OL4265>. Quinoline derivatives were also prepared from nitrogen-tethered 2-methoxyphenols. The corresponding 2-methoxyphenols were subjected to a iodine(III)-mediated acetoxylation which was followed by an intramolecular Michael addition to afford the quinoline OAc O... 

The initial attack in the anodic oxidation of papaverine [75] probably involves a similar attack further oxidation and dimerization leads to the isolated product, 12,12 -bis-(2,3,9,10-tetramethoxyindolo[2,l-fl]isoquinolyl). An analogous reaction is the electrooxidation of a tetramethoxy-substituted 2-methyl-l-phenethyl-l,2,3,4-tetrahydroisoquinoline to a dibenzoquinolizinium derivative [76] and the oxidation of A,A -triphenyl-( -phenyle-nediamine to 9,10-diphenylphenazine [77]. Intramolecular Michel addition of nitrogen in a tetrahydroquinoline derivative to an o-quinone moity have resulted in the formation of a 5,6-dihydrodibenz[6,d]indolizine derivative [78]. A similar ring closure occurs during the oxidation of various catecholamines [79] and similar compounds [79] to indoles. Cyclic a-carbonylazo compounds, generated by anodic oxidation of the hydrazines, may be trapped by reaction with dienes to the expected heterocycles [80]. 

Oxidation of benzoylacetanilide in MeCN gives a good yield of 2,4-dioxo-l-phenyl-1,2,3,4-tetrahydroquinoline. The reaction is reported to be an intramolecular coupling between an amidyl radical and the radical cation of the benzoyl group [83], but an electrophilic aromatic substitution by the amidyl cation or an addition of the amidyl radical to the phenyl ring (followed by an oxidation) could also be considered. 

S02-extrusion affords the electrophilic radical 49 (Scheme 10). Intramolecular homolytic substitution eventually gives tetrahydronaphthalene 50 (92%). Beckwith showed that the A-(o-bromophenyl)amide 51 can be transformed into the corresponding oxindole 54 (70%) at high temperatures using BusSnH via tandem radical translocation of the initially formed aryl radical 52 to form 53 with subsequent intramolecular homolytic substitution [77]. The nucleophilic a-aminomethyl radical 55 reacted in a tandem addition/homolytic aromatic substitution reaction via radical 56 to tetrahydroquinoline 57 [78]. Radical 55 can either be prepared by oxida-... 

The [Ir(ppy)2bpy] complex photo-catalyses inter- and intramolecular C-H functionalisation reactions of tertiary amines under the visible light irradiation. Oxygen behaves as a chemical switch, triggering different reaction pathways and leading to different products from the same starting material. In anaerobic conditions, the intermolecular addition of iV,iV-dimethyl-anilines to electron-deficient alkenes yields y-amino nitriles. Aerobic conditions, on the other hand, favour a radical addition/ cyclisation reaction, leading to tetrahydroquinoline derivatives. The intramolecular version of the radical addition produces unexpectedly indole-3-carboxaldehyde derivatives. ... 

In a same area, an efficient and simple method for the enantioselective synthesis of indolines, isoindolines, tetrahydroquinolines and tetraisoquino-lines was achieved by means of the organocatalytic intramolecular aza-Michael reaction of the corresponding aniline and benzylamine derivatives. " This process was catalysed by a diarylprolinol silyl ether used in the presence of benzoic acid as an additive, which provided the Michael adducts in good yields and excellent enantioselectivities of up to 99% ee (Scheme 1.85). This methodology was applied to the synthesis of the biologically active tetra-hydroquinoline alkaloid (-l-)-angustureine. 

In addition to the activity, the selectivity of the two zincates was also different in some cases [12]. In a representative example, addition of LiZnMes to aryl iodide 17 resulted in intramolecular epoxide ring-opening reaction in 86% yield with 96% en o-selectivity. In sharp contrast, when Li2Zn(SCN)Me3 was used, the selectivity changed and the exo-product became the major one (Eq. 12). Dihydroindole 18 and tetrahydroquinoline 19 stmctures exist widely in natural products and pharmaceuticals. Hence, combining the complementary results obtained with zincate-wa and zincate-i a would provide an efficient and practically useful protocol for preparation of aryl zincates as well as for further derivatization ... 

---