Unexpected 5,6,7,8,9,10-Hexahydro-6,6-pentamethylenephenanthridines and 2,3,4,5-Tetrahydro-4,4-tetramethylene-1<i>H</i>-cyclopenta[<i>c</i>]quinolines from Skraup–Doebner–Von Miller Quinoline Synthesis and Their Implications for the Mechanism of That Reaction

The real mechanism of the Skraup–Doebner–Von Miller quinoline synthesis remains controversial and not well understood despite several mechanistic studies reported on the matter. A series of unexpected and unusual 5,6,7,8,9,10-hexahydro-6,6-pentamethylenephenanthridines and 2,3,4,5-tetrahydro-4,4-tetramethylene-1<i>H</i>-cyclopenta­[<i>c</i>]­quinolines have been obtained through the Skraup–Doebner–Von Miller quinoline synthesis. On the basis of these unexpected results and in agreement with some of the previously reported quinoline syntheses, an alternative mechanistic pathway is proposed for this variant of the reaction. It involves the formation of a Schiff base through a reaction between the ketone and the aniline derivative in the first step, followed by a cycloalkenylation at the <i>ortho</i>-position to the amine functional group of the aniline derivative, and an annulation in the final step to close the quinoline ring, leading to a dihydroquinoline derivative. To the best of our knowledge, this is the first report of such a mechanistic pathway being proposed for any variant of the Skraup–Doebner–Von Miller quinoline synthesis

Unexpected 5,6,7,8,9,10-Hexahydro-6,6-pentamethylenephenanthridines and 2,3,4,5-Tetrahydro-4,4-tetramethylene-1<i>H</i>-cyclopenta[<i>c</i>]quinolines from Skraup–Doebner–Von Miller Quinoline Synthesis and Their Implications for the Mechanism of That Reaction

The real mechanism of the Skraup–Doebner–Von Miller quinoline synthesis remains controversial and not well understood despite several mechanistic studies reported on the matter. A series of unexpected and unusual 5,6,7,8,9,10-hexahydro-6,6-pentamethylenephenanthridines and 2,3,4,5-tetrahydro-4,4-tetramethylene-1<i>H</i>-cyclopenta­[<i>c</i>]­quinolines have been obtained through the Skraup–Doebner–Von Miller quinoline synthesis. On the basis of these unexpected results and in agreement with some of the previously reported quinoline syntheses, an alternative mechanistic pathway is proposed for this variant of the reaction. It involves the formation of a Schiff base through a reaction between the ketone and the aniline derivative in the first step, followed by a cycloalkenylation at the <i>ortho</i>-position to the amine functional group of the aniline derivative, and an annulation in the final step to close the quinoline ring, leading to a dihydroquinoline derivative. To the best of our knowledge, this is the first report of such a mechanistic pathway being proposed for any variant of the Skraup–Doebner–Von Miller quinoline synthesis

Unexpected 5,6,7,8,9,10-Hexahydro-6,6-pentamethylenephenanthridines and 2,3,4,5-Tetrahydro-4,4-tetramethylene-1<i>H</i>-cyclopenta[<i>c</i>]quinolines from Skraup–Doebner–Von Miller Quinoline Synthesis and Their Implications for the Mechanism of That Reaction

The real mechanism of the Skraup–Doebner–Von Miller quinoline synthesis remains controversial and not well understood despite several mechanistic studies reported on the matter. A series of unexpected and unusual 5,6,7,8,9,10-hexahydro-6,6-pentamethylenephenanthridines and 2,3,4,5-tetrahydro-4,4-tetramethylene-1<i>H</i>-cyclopenta­[<i>c</i>]­quinolines have been obtained through the Skraup–Doebner–Von Miller quinoline synthesis. On the basis of these unexpected results and in agreement with some of the previously reported quinoline syntheses, an alternative mechanistic pathway is proposed for this variant of the reaction. It involves the formation of a Schiff base through a reaction between the ketone and the aniline derivative in the first step, followed by a cycloalkenylation at the <i>ortho</i>-position to the amine functional group of the aniline derivative, and an annulation in the final step to close the quinoline ring, leading to a dihydroquinoline derivative. To the best of our knowledge, this is the first report of such a mechanistic pathway being proposed for any variant of the Skraup–Doebner–Von Miller quinoline synthesis

Stereospecific Suzuki, Sonogashira, and Negishi Coupling Reactions of <i>N</i>‑Alkoxyimidoyl Iodides and Bromides

A high-yielding stereospecific route to the synthesis of single geometric isomers of diaryl oxime ethers through Suzuki coupling of <i>N</i>-alkoxyimidoyl iodides is described. This reaction occurs with complete retention of the imidoyl halide geometry to give single <i>E</i>- or <i>Z</i>-isomers of diaryl oxime ethers. The Sonogashira coupling of <i>N</i>-alkoxyimidoyl iodides and bromides with a wide variety of terminal alkynes to afford single geometric isomers of aryl alkynyl oxime ethers has also been developed. Several of these reactions proceed through copper-free conditions. The Negishi coupling of <i>N</i>-alkoxyimidoyl halides is introduced. The <i>E</i> and <i>Z</i> configurations of nine Suzuki-coupling products and two Sonogashira-coupling products were confirmed by X-ray crystallography

Stereospecific Suzuki, Sonogashira, and Negishi Coupling Reactions of <i>N</i>‑Alkoxyimidoyl Iodides and Bromides

A high-yielding stereospecific route to the synthesis of single geometric isomers of diaryl oxime ethers through Suzuki coupling of <i>N</i>-alkoxyimidoyl iodides is described. This reaction occurs with complete retention of the imidoyl halide geometry to give single <i>E</i>- or <i>Z</i>-isomers of diaryl oxime ethers. The Sonogashira coupling of <i>N</i>-alkoxyimidoyl iodides and bromides with a wide variety of terminal alkynes to afford single geometric isomers of aryl alkynyl oxime ethers has also been developed. Several of these reactions proceed through copper-free conditions. The Negishi coupling of <i>N</i>-alkoxyimidoyl halides is introduced. The <i>E</i> and <i>Z</i> configurations of nine Suzuki-coupling products and two Sonogashira-coupling products were confirmed by X-ray crystallography