2.2.4- Substituted 1,2-dihydroquinolines formation

An efficient high yielding synthesis of 3-substituted 2,3-dihydroquinolin-4-ones 90 was developed by using a one-pot sequential multi-catalytic process <06TL4365>. The scheme below shows the one-pot sequential multi-catalytic Stetter reaction of aldehyde 91 and a, (3-unsaturated esters 92, resulting in the formation of the desired dihydroquinolines 90. 

Reduction of quinolines in acid solution at a lead cathode or by dissolving zinc leads to attack on the heterocyclic ring with the formation of 4,4-coupled products, together with the tetrahydroquinoline [82,83]. In the case of 2- and 4-methyl substituted quinolines, dimeric products are obtained in 10 90 % yields. In these processes, dimerization of the one-electron addition product is in competition with further reduction to give the 1,4-dihydroquinoline, The latter is an enamine and it... 

Acylation of quinoline with methylchloroformate (Scheme 5.2.69) generates the A-acyliminium ion in situ, which is efficiently trapped by allenyltri-n-butylstannane to give the 1,2-dihydroquinoline 322 in excellent yield. A potentially important Se substitution is illustrated by the reaction of 4-acetoxy-2-azetidinone 323 with the mixture of diastereomers 324 (Scheme 5.2.69) in the presence of BFj OEt2. Generation of the reactive A-acyliminium species leads to formation of jS-lactam 325 with moderate diastereoselection.ioo... 

The reverse process, the electrocyclic ring cleavage of azacyclohexadienes, can also be effected photochemically. Evidence that ring opening of N-substituted 1,2-dihydroquinolines proceeds from the lowest triplet excited state has been published.The formation of homoadamantano[4,5-d]imidazoles (29) to (31) from the homoadamantano[4,5-b]-5, 6 -dihydropyrazines (32)... 

Heterocycles with a similar 1,4-dihydropyridine ring, such as TV-substituted 1,4-dihydroquinolines (39), have also been allowed to react with dimethyl acetylenedicarboxylate. Depending on the substituent at the ring, a (2 + 2)-cycloadduct (40)60 or a linear Michael adduct (41)59 was formed. The (2 + 2)-cycloadducts (43) of l,2-dihydropyridines(42) with dimethyl acetylenedicarboxylate are far less stable. Only NMR spectroscopy at —10° to 0° has provided evidence for the formation of 43. At room temperature the (2 + 2)-cycloaddition was followed by isomerization to the corresponding 1,2-dihydroazocine (44).15>6 The reaction took a different course when other dienophiles were employed for instance, with iV-phenylmaleimide or maleic anhydride, Diels-Alder-type adducts were formed. Reaction of a 1,2-dihydropyrazine (45) with dimethyl acetylenedicarboxylate yielded a bicyclic compound, which was shown to be not the expected (2 + 2)-cycloadduct 46, but the isomeric 2,7-diazabicyclo(4.2.0]octa-2,4-diene (47). This compound was claimed to result from initial (2 + 2)-cycloaddition, ring opening, and subsequent m/ramolecular (2 + 2) cycloaddition [Eq. (9)1.62... 

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. 

The standard Chichibabin amination of quinoline with sodium amide in DMA gives 2-aminoquinoline in a low 7% yield and 2-amino-3,4-dihydroquinoline in a 24% yield. Not until the introduction of the Chichibabin oxidative amination variant (e.g., in the presence of KMn04) were these yields improved. Regio-chemical outcome depends on reaction temperature (kinetic or thermodynamic control). 2-aminoquinoline (39) forms at -65 °C, i.e., the kinetic adduct, and is isolated in a 50-55% yield with no evidence of 4-amino adduct formation, whereas 4-aminoquinoline (40) forms in 60-65% yield at 15 °C, i.e., the thermodynamic adduct (oxidant added at -45 C), with 6-7% of 39. Substituted quinolines give various... 

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