Novel intramolecular cycloaddition reactions of arylamino-substituted Fischer chromium carbenes

Ring‐Closing Metathesis: Novel Routes to Aromatic Heterocycles

“…In 1993, Sçderberg and co-workers discovered that, upon heating, the N-arylamino-substituted chromium carbene 76 was converted into the corresponding indole 77 in a formal metathesis reaction (Scheme 18). [49] This represented one of only a few complexes which were shown to cyclise in this manner.…”

Solvent-Free Heck-Jeffery Reactions under Ball-Milling Conditions Applied to the Synthesis of Unnatural Amino Acids Precursors and Indoles

“…When the imino tautomer 18 obtained from the coupling between 9 and AA was subjected to cyclization conditions, in an attempt to form the corresponding benzofuran derivative, no product was formed either. The unsubstituted 2-iodoaniline (20) and the electron-donating substituted substrate 27 both gave the corresponding indole derivatives 21 and 28 in fair yields, whereas substrates 22, 29 and 30 containing mildly electron-donating substituents gave the corresponding indoles 24, 31 and 32, respectively, in more modest yields. The yield-determining process in the reaction sequence was invariably the coupling reaction as determined by the weight of the residue remaining after a short workup prior to cyclization, whereas the cyclization-elimination reaction was nearly quantitative.…”

“…The literature describes many methods to cyclize unprotected orthoethynyl anilines to 2-substituted indoles, [13][14][15][16][17][18][19] but unprotected ortho-ethenyl counterparts are somewhat more scarce. 20,21 Syntheses of methyl-1H-indole-2-carboxylate derivatives in the literature include a Fischer synthesis, reductive cyclization of methyl-2-nitro cinnamate and cyclization of azidoesters. [22][23][24] The compound itself, has been used as starting material for the synthesis of HIV-1 integrase inhibitors.…”

“…Nevertheless, 2-halo aniline substrates gave products resulting from Heck-coupling but some of the primary coupling products easily cyclized to give indole derivatives (see Table 2, products 21, 24, 28, 31 and 32). During the reaction of 2-iodoaniline (20) with the olefin TLC analysis clearly indicated the formation of only one compound, which upon chromatographic workup, was converted into two new compounds. The crude product apparently underwent a reaction in contact with the slightly acidic silica.…”

“…The indole derivative 32 has been used as starting material for Suzuki and Sonagashira coupling reactions. 30,31 Interestingly, in a further attempt to perform the coupling between 2-iodoaniline (20) and AA under conventional conditions, using N-methyl-2-pyrrolidone as solvent, no coupling product was formed after 24 hours at 80 °C. This is remarkable as the temperature attained in the ball mill after one hour of milling seldom rises above this level but it is sufficient to form product.…”