"1,4" Alkyl Migrations in Fischer Indole Cyclizations

Article abstract of DOI:10.1021/ja00534a033

The product from Fisher indole cyclization and dehydrogenation of cyclohexanone 2,4,6-trimethylphenylhydrazone (1) was determined to be 2,3,4-trimethylcarbazole (3) resulting from a formal 1,4-methyl migration, as previously proposed.To determine the destinations of migrating groups in these rearrangements, the Fischer indole cyclization and dehydrogenation of cyclohexanone 2-ethyl-6-methylphenylhydrazone (17) were studied.The products obtained were 1-ethylcarbazole, 1-methylcarbazole, 2-ethyl-1-methylcarbazole (18), and an apparent mixture of 1-ethyl-4-methylcarbazole (21) and 4-ethyl-1-methylcarbazole (22).However, no 1-ethyl-2-methylcarbazole (19), which would have been obtained by a "1,4"-methyl migration, was obtained.Analysis of the product ratios suggested that the apparent <1,4> ethyl shift in formation of 18 actually proceeded by a formal <1,5> shift of either an ethyl or a methyl group, followed by a <1,2> ethyl shift.Cyclization of 3-pentanone 2,4,6-trimethylphenylhydrazone (26) proceeded to give the product of "1,4" methyl migration, demonstrating that such reactions can occur with phenylhydrazones of ketones other than cyclohexanone.It is proposed that steric factors play a major role in determining whether migrating groups undergo <1,2> or "1,4" shifts during Fischer indole cyclizations.