Dihydroquinoline system

EEDQ is a valuable reagent for carboxyl activation in the coupling of amino acids [55]. Ideal d-a pairings of various reactive moieties facilitate the formation of the semicarbonate intermediates. Of course, a major driving force for this transformation is the aromatization of the dihydroquinoline system. 

Apparently, the amine does not undergo Michael addition to the enone system in 107, but (due to the high electrophihcity of its a-C=0 group) prefers imine formation (—> 109). In the strongly acidic medium, 109 is cyclized (presumably via cation 110 and its SeAc cycloalkylation) to the 1,4-dihydroquinoline system 111, which is oxidized to the quinohne-2-carboxylate 108. 

Larock has developed a new catalyst system for the Pd-catalyzed cyclization of olefinic tosylamides. Whereas typical conditions require either stoichiometric amounts of Pd(II) salts or catalytic amounts of Pd(II) in the presence of benzoquinone as a reoxidant, the new catalyst system utilizes catalytic Pd(OAc)2 under an atmosphere of O2 in DMSO with no additional reoxidant <96JOC3584>. Although o-vinylic tosylamides 76 can be cyclized to Af-tosylindoles 77 using this catalyst system, PdCla/benzoquinone is more effective for such cyclizations. Interestingly, in the case of o-allylic tosylanilides, the cyclization can be modulated to afford either dihydroindole or dihydroquinoline products. In a related approach involving a common 7i-aUyl Pd-intermediate, 2-iodoanilines were coupled with vinylic cyclopropanes or cyclobutanes in the presence of a Pd catalyst to afford dihydroindoles <96T2743>. 

Rosche B, B Tshisuaka, S Fetzner F Lingens (1995) 2-Oxo-l,2-dihydroquinoline 8-monooxygenase, a two-component enzyme system from Pseudomonas putida 6. J Biol Chem 270 17836-17842. 

Rosche, B. Tshisuaka, B. Fetzner, S., et al., 2-Oxo-l,2-Dihydroquinoline 8-Monooxygenase, A 2-Component Enzyme-System From Pseudomonas-Putida-86. J. Biol Chem, 1995. 270(30) pp. 17836-17842. 

Cycloadditions are in general an effective way of constructing cyclobutane rings. A wide variety of heterocyclic systems dimerize in this way. 1,3-Diacetylindole, for example, affords the head-to-tail dimer 242 on irradiation in ethanol.185 Ethyl 2-ethoxy-l,2-dihydroquinoline-l-carboxy-late is similarly converted in diethyl ether into the trans head-to-head dimer.186 Notable among many analogous photodimerizations are those reported in 1,4-dihydropyridines,187 in furo[3,2-b]pyridin-2(4//)-ones,188 in 8-methyl-s-triazolo[4,3-a]pyridine,189 and in 2H-2-benzazepine-1,3-diones.190 The [ 2 + 2] dimerization of amidopyrine is the first reported example of a photocycloaddition in a 4-pyrazolin-3-one.191... 

The formation of cyclic nitrones (150) from pericyclic mechanism. Kinetic and computational studies have provided evidence for the involvement of a novel pseudo-pericyclic electrocyclization in the conversion of o-vinylphenyl isocyanates into quinolin-2-ones. " Such reactions have also provided evidence of torquoselectivity in a 6jt system. Hash vacuum thermolysis of triazoles (151) has been found to afford dihydroquinolines (155), presumably by generation of a-oxoketenimines (152) which can undergo a [1,5]-hydrogen shift to the o-quinoid imines (153)7(154) and subsequent electrocyclization (see Scheme 57). 

The system Ru2(OAc) Cl/O2/toluene/50°C oxidisedR CH NHR to imines R CH=NR converted 1,2,3,4-tetrahydroisoquinoline to the 3,4-dihydroisoquinoline with isoquinoline, and 6,7-dimethoxy-l,2,3,4-tetrahydroisoquinoline to 6,7-dimethoxy-3,4-dihydro-iso-qninoline (cf. mech. Ch. 1) [18], Such oxidations were also catalysed by TPAP/NMO/PMS/CH3CN, e.g. the conversion of indoline to indole (in which indoline nndergoes a donble-bond shift and aromatisation), and the oxidation of 1,2,3,4-tetrahydroqninoline to 3,4-dihydroquinoline (Fig. 5.1, Table 5.1) [19]. 

Alkylpyridines are aminated preferentially at the 2-position, but reaction is slower than in the parent system. Quinoline is difficult to aminate and only a low yield of 2-aminoquinoline (32%) is obtained from reaction with sodamide in toluene. When dimethylaniline is employed as solvent, 2-amino-3,4-dihydroquinoline (24%) becomes the major product, and the yield of 2-aminoquinoline drops to 7%. The best yields of 2-aminoquinoline (53-69%) have been obtained by using barium or potassium amide in liquid ammonia. Use of the potassium salt also produces a 10% yield of the 4-amino isomer. The... 

Bodor, N., et al. 2002. In vitro and in vivo evaluations of dihydroquinoline- and dihydroisoquinoline-based targetor moieties for brain-specific chemical delivery systems. J Drug Target 10 63. 

Benzannelation results in an attenuation of aromaticity effects in 4n + 2rc-systems.255 The base-catalyzed hydrogen isotope exchange and isomerization reactions of isomeric dihydrobenzazocines 135 and 136 show these compounds have moderately enhanced kinetic acidity as compared with dihydroquinoline models and is attributable to a small degree of aromatic stabilization in the incipient 1()n electron benzazocinyl anions.255... 

Condensation of 5,6-dihydroquinolin-8(7//)-ones, such as 93, with 2-aminoaromatic aldehydes, such as 94, afforded dihydrobenzo[h][l,10]phe-nanthrolines, such as 95 (Scheme 17), as precursors of a number of interesting compounds (88JA3673 90AGE923 93JOC1666). Condensation of 5,6-dihydroquinolin-8(7//)-one 93 with ternary iminium perchlorates, for example, 96, in the presence of ammonium acetate has been reported to give compounds such as 97 that contain the benzo[h][l,10]phenanthroline ring system (Scheme 18) (93TL1775). 

Lithium in liquid ammonia conditions can produce l,4-dihydroquinoline" and 3,4-dihydroisoquinoline." Conversely, lithium aluminium hydride reduces generating l,2-dihydroquinoline" and 1,2-dihydroisoquinoline. These dihydro-heterocycles can be easily oxidised back to the fully aromatic systems, or disproportionate, especially in acid solution, to give a mixture of tetrahydro and re-aromatised compounds. Stable dihydro-derivatives (see also 9.13) can be obtained by trapping following reduction, as a urethane, by reaction with a chloroformate. Quaternary salts of quinoline and isoquinoline are particularly easily reduced, either catalyticaUy or with a borohydride in protic solution, giving... 

The sequence of this reaction was established by the isolation of intermediates, the distribution of substituents in the products and C-labeling. The first step is the Michael addition of the amine to the enone system 80 with formation of P-amino ketones 81. They cyclize to give 82 with intramolecular hydroxyalkylation via the protonated C=0 group. Dehydration leads to 1,2-dihydroquinoline 83, which on dehydrogenation affords quinoline 84. 

The mechanism postulated for this reaction involves 67T-electrocyclization of the 2-azahexatriene system in 97. This is followed by a [1,5] sigmatropic hydrogen shift in the quinonoid intermediate 99. Finally aromatization and oxidation of the 1,2-dihydroquinoline 100 [106] occurs. 

The mild conditions under which DDQ effects dehydrogenation of dihydroquinoline compounds has proved useful for activating a resin bound safety-catch linker for cleavage by aminol-ysis (eq 24). The excess DDQ and DDQH are easily removed by filtration after the activation step, effectively purging the system of these potential impurities. Conversely, removal of DDQ and DDQH with polymer-bound scavenger resins has also proven valuable in solution phase applications. ... 

The SnCl2-reduction system has also been apphed in the reduetion of S 2 nucleophilic substitution products 583, alfording more functional quinolines, 4-(substituted vinyl)-quinolines 584, in moderate yields, with several exclusions of the formation of dihydroquinoline derivative 585 (Scheme 4.174). However, using compounds 586 as substrates without a ketone moiety, the ester group can also participate in the intramolecular cychzation, but the subsequent dehydrogenation does not occur and, therefore, tetrahydroquinolin-2-ones 587 were obtained in 51-62% yields (frans form only). From this study, the preference of the activated carbonyl group COR for cychzation has the order R = Me > Ph > O-alkyl. 

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