Quinoline reaction with organometallics

On the basis of considerable documentation regarding the reactions of quinolines with organometallics, the aminoquinolines were expected to... 

The preparation of hydroquinoline derivatives is of great interest owing to their biological activity but, in many cases, their preparation has involved the tedious use of chiral auxiliaries and organometallic reagents.AgOTf has been used to activate phenyl chloroformate toward condensation with quinoline, as well as isoquinoline, for subsequent reaction with chiral allylsilanes, to give 2-allylated derivatives (eq 15). ... 

Quinoline and isoquinoline react with organometallic reagents exactly as pyridine does (Section 25-6). Give the products of their reaction with 2-propenylmagnesium bromide (allylmag-nesium bromide). 

In summary, palladium-mediated reactions, especially cross-coupling reactions have found many applications in quinoline synthesis. It is noteworthy that due to the a and S activation for the C(2) and C(4) positions, even 2-chloro- and 4-chloro-quinolines are viable substrates for palladium-catalyzed reactions under standard conditions. With the advent of the palladium chemistry and more commercially available organometallic substrates, more palladium-mediated quinoline syntheses are to be added to the repertoire of quinoline chemistry. 

An initial step of orthometallation probably also occurs when aniline is allowed to react with ethylene in the presence of a rhodium(I) catalyst. 2-Methylquinoline (10 turnovers relative to the metal) and JV-ethylaniline (30 turnovers) are formed after 72 h in what are probably two independent reaction pathways (Scheme 144).216 It is interesting to note that the intramolecular cyclization step in the proposed216 mechanism (Scheme 144) has precedent in the palladium-promoted quinoline synthesis reported by Hegedus et al.16 (see Scheme 142), but the transformation 118->119 is unusual in the chemistry of organometallic insertion reactions.106... 

To obtain quinolines bearing fluorine atoms in the pyridine ring, cyclizations of fluorinated ortho-vinylphenylnitriles and isonitriles proved to be an effective approach. Indeed, 3-fluoroquinolines 48a-d have been obtained by cyclocondensation of organometallic reagents with 2-(2,2-difluorovinyl)phenyl substituted isonitriles 47 (Scheme 17). 2-(2,2-Difluorovinyl)anilines 45, derived from the reaction of 2,2,2-trifluoroethyl tosylate, butyl magnesium salt of 2-iodoaniline, butyl lithium and triaUcylborane, have been transformed into isonitriles 47 [27, 28]. 

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