2 functionalized quinolines

The synthesis of reaction intermediate is also very important and sometimes could provide a direct proof to support the mechanism. To obtain the stable intermediate of this reaction, they selected 2 functionalized quinoline Sa as the starting material (Scheme 10.18). The results showed that the steady intermediate 9b was achieved after isomerization from the intermediate 9a when Sa was treated using Pd/C with hydrogen in MeOH. After the synthesis ofthe intermediate 9b, the hydrogenation reaction was carried out, and the desired product was obtained with 96% ee [3], which was the same enantioselectivity as direct hydrogenation of compound Sa. They can also detect the existence of intermediate 9b in the direct hydrogenation of compound Sa with a low pressure of hydrogen and in a shorter reaction time in... 

Efficient synthetic methods have been developed for the synthesis of 4-functionalized quinolines mediated by triflic acid.703 Electron-rich, highly reactive ethynyl ketene-S,5-acetals react readily with arylamines and aldehydes in an aza-Diels-Alder reaction to afford the desired products [Eq. (5.256)]. Arylimines and ethynyl ketene-S,5-acetals react similarly (60-70% yields). 

Friedlander quinoline synthesis has been accomplished in ionic liquids with substoichiometric amounts of FeCl3-6H20 (Scheme 8.33) [101]. The substitution pattern of products 77 is, however, relatively limited to 2,4-diaryl-functionalized quinolines, as depicted in Scheme 8.33. 

Ila, Junjappa, and coworkers described an efficient route to highly functionalized quinolines. Their starting materials are a-oxoketene lV,5-anilinoacetals and Vilsmeier reagents <03JOC3966>. Optimized conditions require R groups to be methoxy, except for the cases where naphthylamine rather than aniline is the parent compound. In that case the yields are also excellent. 

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. 

Y. L. Zhao, W. Zhang, S. Wang, Q. Liu, J. Org. Chem. 2007, 72, 4985 988. Ethynyl ketene-5,5-acetals the highly reactive electron-rich dienophiles and applications in the synthesis of 4-functionalized quinolines via a one-pot three-component reaction. 

MahataPK, VenkateshC, Kumar U, KS, IlaH, JunjappaH (2003) Reaction of a-oxoketene-N, S-arylaminoacetals with Vilsmeier reagents an efficient route to highly functionalized quinolines and their benzo/hetero-fused analogues. J Org Chem 68 3966-3975... 

Functionalized benzofurans have been prepared from ort/io-hydroxyphenones and 1,1-dichloroethylene via a chloromethylene furan which rearranges into a benzofuran carbaldehyde under acidic conditions. A synthesis of 3-(but-2-enylidene)quinolin-4(3//)-ones has been described via a triflic acid-mediated Fries rearrangement of 3-butadienyl-2-azetidinones, a protocol that provides access to C(3)-functionalized quinolin-4(3//)-ones. °... 

In another attractive approach, P-functionalized quinoline-4-carbo)q lic acids were prepared by the Pfitzinger reaction of isatin and dialkyl- or diaryl-(2-methyl-4-oxopent-2-yl)phosphine oxides (Scheme 54). ... 

Quinoline may be prepared by heating a mixture of aniline, anhydrous glycerol and concentrated sulphuric acid with an oxidising agent, such as nitrobenzene. The reaction with nitrobenzene alone may proceed with extreme violence, but by the addition of ferrous sulphate, which appears to function as an oxygen carrier, the reaction is extended over a longer period of time and Is under complete control. 

Lindlar Catalyst ( Pd/BaS04/ quinoline)- partially poisoned to reduce activity will only reduce the most reactive functional groups. 

The presence of other functional groups ia an acetylenic molecule frequendy does not affect partial hydrogenation because many groups such as olefins are less strongly adsorbed on the catalytic site. Supported palladium catalysts deactivated with lead (such as the Liadlar catalyst), sulfur, or quinoline have been used for hydrogenation of acetylenic compound to (predominantiy) cis-olefins. 

These reactions are related to the formation of pyrroles and quinolines from aminocarbonyl compounds and acetylenes (582,583) and may be contrasted with the formation of pyran derivatives by electrophilic attack on an enamine, followed by addition of an oxygen function to the imonium carbon (584-590). 

Similarly, W-methyl-D-aspartate (NMDA) antagonists 32 with analgesic activity were prepared, again using the Meth-Cohn quinoline synthesis as the key entry reaction, subsequent functional group manipulation giving the desired target compound. 

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