Isoquinoline, deprotonative metalation

Fig. 20 Homologation reaction after deprotonative metalation of isoquinoline by using TMP-zincate...

The iodination of pyridine, quinoline, and isoquinoline via a-metalation using lithium di-fert-butyltetramethylpi-peridinozincate (TMP-zincate) proceeds smoothly at room temperature using iodine as the electrophile. The chemoselective deprotonative zincation generated 2-iodopyridine 70 and 1-iodoisoquinoline 71 in 76% and 93% yield, respectively. Quinoline metalated preferentially at the 8-position to give 61% yield of the 8-iodo derivative 72 and 26% yield of 2-iodoisoquinoline 73 (Equations 25-27) <1999JA3539>. 

Direct deprotonation of quinolines or isoquinolines can only be succeeded via directed ort/io-metalation. Metal-halogen exchange can be used to produce organometallic nucleophiles from the halides located either on the benzene or the pyridine ring. ... 

Reactions with aikynes may aiso result in the formation of cyclized products. Thus a ruthenium-catalysed reaction with aromatic amides has been used to give isoquinoline derivatives. On the basis of values of the kinetic isotope effect, A h/ d> proposed that the rate-determining step is a concerted acetate-assisted metalation-deprotonation process to yield the intermediate (30), followed by aikyne insertion and ring closure. The reaction of arylketones with alkynes may yield indenols when catalysed by rhodium cyclopentadienyl in the presence of silver and copper salts. The reaction proceeds regioselectively, so that reaction of acetophenone with 1-phenyl-1-propene... 

Various heteroaromatic compounds were similarly deprotonated (Fig. 19) [28]. Among electron-rich cases, thiophene- and furan-carboxylate provided the iodo derivatives after treatment of the intermediate zincates with iodine. Interestingly, bare jt-deficient heteroaromatic compounds were also readily deprotonated. With TMP-zincaie as a base and conducting the reactions at room temperature followed by addition of iodine, pyridine, quinoline, and isoquinoline could be efficiently metalated-iodinated. Under the same conditions, quinoline was deprotonated at both C2 and C8 in a 7 3 ratio, whereas isoquinoline was deprotonated specifically at Cl. 

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