Synthesis of quinolines via ortho-lithiated N-acylanilines. A modified Friedlaender synthesis

Generation of oxindole-2-thiones (thiols) via dilithiatedN-tert-Boc-anilines. Synthesis of a sulfur analog of MK886

“…It has recently been alleged (6) that the degree of o-lithiation reported by us for tertBoc-aniline could not be repeated. We have reproduced the reported yields of electrophile-trapped products on numerous occasions but, as has been pointed out by us (7), it is important that the THF-pentane ratio originally reported (ca. 2: 1; tert-butyllithium is sold in pentane solution) be adhered to.…”

“…The dianion of l l d , generated in this case with LDA, was treated with thiocarbonyldiimidazole. 7 The thiol 14c was indeed obtained as the major product, but only in 35% yield. This reaction nevertheless deserves further examination.…”

Elemental fluorine

“…Similarly, using formic acid as solvent gave a complex mixture containing many fluorinated products and significant amounts of tar but, in this case, four major products 2a-d could be identified by 19 F NMR. (Scheme 1).…”

“…Although conversion of 1 was moderate, even after six equivalents of fluorine had been passed through the stirred reaction mixture, 2a-c and 2e were obtained in a total yield of 91% by 19 F NMR (Scheme 2). The reaction mixture was poured into water and neutralised (sodium bicarbonate) and, although separation of the fluorinated products was difficult, difluoro-quinoline 2c was isolated and purified by column chromatography.…”

4,4-Dialkoxybutan-2-ones as Synthons

“…The reactions of acetonitrile with ketone (E)-3a and 3-buten-2-one regioselectively give 5-acetyl-3-methyl-and 3-acetyl-4-methylisoxazoles, respectively [118]. Alkaline cleavage of 5-methylisoxazole (162) gives cyanoacetone (164) [6,14,119] which reacts with phenylhydrazine to form 5-amino-3-methyl-1-phenylpyrazole (165) [6,14,22,119,120]. Formylation of the latter according to VilsmeierHaak leads to 5-amino-3-methyl-1-phenylpyrazole-4-carbaldehyde (166) [6,121] which is used to build up fused pyrazolopyridine and pyrazolopyrimidine systems 167 and 168 [6,14,122] (Scheme 53).…”