Quinoline-4-carbaldehyde

A combination of a reductive amination and a Michael addition has been used to synthesize the anticancer alkaloid camptothecin (2-955) via 2-954, starting from the quinoline carbaldehyde 2-953 and benzylamine (Scheme 2.214) [487]. 

The presence of N-atoms in the aromatic part of the aldehyde appears essential for chiral amplification. With only one nitrogen, such as in the case of 3-pyridine carbaldehyde, autocatalytic kinetics but no chiral amplification effect has been observed [24,25]. In the case of 3-quinoline carbaldehyde, i.e., in the presence of two nucleophilic centers, autocatalysis as well as moderate chiral amplification were reported [26,27]. Highest amplification capacity is observed in the presence of two N-atoms in the aromatic part of the aldehyde, where for the substituent at the 2-position the amplification capacity increases H < CH3 < f- Bu - C=C -, i.e., with the size and rigidity of this group. So far, detailed studies that could relate the given observations to the possible mechanism of chiral amplification in Soai s reaction are still to be carried out. 

A four-step synthesis of 8-amino-7-quinoline carbaldehyde (87) from 8-hydroxyquinoline (88) has been disclosed (Scheme 48) (94T(50) 10685). Major steps involved a Bucherer reaction followed by Claisen type rearrangement, isomerization and ozonolysis. Amino aldehyde (87) underwent Friedlander condensation with 2-acetylpyridine to form 2-pyridyl-l,10-phenanthroline (89). 

An interesting intermediate 30 was proposed to result from the sequential addition of pyridine to tetrachlorocyclopropene (31). Compound 30 represents an alkyl nitrogen ylide with two 1-chloroalkyl pyridinium moieties in the same molecule. Pyridines with electron-withdrawing groups and heterocycles with an electron-deficient nitrogen, for example, pyridine-3-carbaldehyde or quinoline, react with 31 to yield the corresponding mono-substituted products 32a and 32b (83JOC2629) (Scheme 8). 

The zinc alkoxide of 2-methyl-l-(3-quinolyl)propan-l-ol was used in a catalytic amount to give ee up to 94% in the enantioselective alkylation of quinoline-3-carbaldehyde by diisopropyl-... 

Methyl groups at positions 2 and 4 in quinoline are selectively oxidized by selenium dioxide (76BSF789). For example, 2,3,8-trimethylquinoline gives 3,8-dimethylquinoline-2-carbaldehyde (Scheme 61). 

Thieno[3,2- ][l]benzofuran 61 was synthesized on a preparative scale starting with benzo[/ ]furan-2-carbaldehyde 344. Condensation of aldehyde 344 with 2-thioxothiazolidin-4-one in the presence of sodium acetate in acetic acid afforded 345, which by base-catalyzed hydrolysis gave 346 in good yield. Upon treatment with bromine, acid 346 was cyclized to give acid 347, which on standard decarboxylation by treatment with copper in quinoline afforded 61 in high yield (Scheme 35) <1997CCC1468>. 

On the other hand, (,S )-3-quinolyl alkanol 84 with 94% catalyzes enantioselective isopropylation of quinoline-3-carbaldehyde to give the (,S )-3-quinolyl alkanol 84 itself with 94% 166. The substituent at the 7-position increases the enantiomeric excess to 97% 167. 

Soai et al. established highly enantioselective asymmetric autocatalysis in the asymmetric isopropylation of pyrimidine-5-carbaldehyde 27 (Scheme 14) [44], quinoline-3-carbaldehyde [45], and 5-carbamoylpyridine-3-carbaldehyde [46]. Among these, 2-alkynyl-5-pyrimidyl alkanol is a practically perfect asymmetric autocatalysis [47]. When 0.2 equivalents of 2-alkynyl-5-pyrimidyl alkanol 28b with >99.5% ee was employed as an asymmetric autocatalyst in the isopropylation of 2-alkynylpyrimidine-5-carbaldehyde 27b, it automultiplies in a yield of >99% without any loss of ee (>99.5% ee). When the product was used as an asymmetric autocatalyst for the next run, pyrimidyl alkanol 28b with >99.5% ee was obtained in >99%. Even after tenth round, pyrimidyl alkanol 28b with >99.5% ee was formed in a yield of >99% [47]. 

Chiral 3-quinolyl alkanol acts as a highly enantioselective asymmetric autocatalyst. Chiral (S)-59 with 94% ee catalyzes the enantioselective addition of i-Pr2Zn to quinoline-3-carbaldehyde (58) to... 

After studying various nitrogen-containing compounds, we found that the zinc alkoxide of 2-methyl-l-(3-quinolyl)propan-l-ol 5 (Fig. 1) catalyzes the enantioselective formation of itself with the same configuration in the reaction between quinoline-3-carbaldehyde and z-P Zn to produce the product 5 in high ee (up to 94% ee) [58]. In addition, the 5-carbamoyl-3-pyridyl alkanol 6 (Fig. 1) can act as an efficient autocatalyst to catalyze its own production in a highly enantioselective manner (up to 86% ee) [59]. 

The 3-(2-furoyl)quinoline-2-carbaldehyde has been used as a fluorogenic reagent for the analysis of primary amines by liquid chromatography with laser-induced fluorescence detection [10,11]. 

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