Quinolines spiro annulated at heterocyclic fragment: Synthesis and properties

Abstract

Chemical information of the quinolines spiro annulated at heterocyclic fragment with cycloalkanes or heterocycles is reviewed. Synthetic approaches to three possible spiro-2(1H)-, spiro-3(4H)-and spiro-4(1H)quinoline core derivatives are analysed. Their syntheses are divided into three groups: a) chemical transformations of the substituted quinoline ring, b) construction of spiro structure from the alicyclic precursors, mainly, amine derivatives or imines preformed from cyclic ketones; c) rearrangements of more complex heterocycles leading to the spiro quinolines. Special attention is paid to spiro quinolines that display pharmacological properties. Synthetic routes to the discorhabdin alkaloids are also briefly discussed on in this review.

Discorhabdins and Pyrroloiminoquinone-Related Alkaloids

“…Because of their unusual highly fused structures and prominent biological properties but mass-limited samples in natural sources, the discorhabdins and related alkaloids have attracted great interest for organic synthesis over the past 20 years. So far, several groups have accomplished the total syntheses of the natural discorhabdins A 1 , ,,− ,,,,,, C 3 , ,,− ,,− E 5 , and prianosin B 54 (Table ), while extensive synthetic studies were focused on the syntheses of the key intermediates of discorhabdins and related alkaloids. − ,− ,,,,, The key structure of discorhabdin D 4 with a characteristic C 2 –N 18 bond, was synthesized by Heathcock et al in 1999 . Synthetic studies toward the simple marine pyrroloiminoquinone-related alkaloids ( 59 – 119 ) have also been investigated (Table ), − and some approaches have already been reviewed. ,, Herein, we only focus on the strategies toward the total or semisyntheses of discorhabdin-type alkaloids.…”

Rhodium(I)-Catalyzed Synthesis of Indoles: Amino-Claisen Rearrangement of N-Propargylanilines

“…N -Propargylanilines are alternative candidates for the preparation of heterocycles, since regioselective intramolecular hydroarylation reactions of N -propargylanilines are considered to be divergent methods for the preparation of quinoline or indole frameworks (6- endo or 5- exo ). Intramolecular hydroarylation reactions have been achieved by various metal catalysts, , and the reactions of N -propargylanilines have been known to proceed via the 6- endo mode to give 1,2-dihydroquinolines (path b , Scheme ). , On the other hand, amino-Claisen rearrangements , of N -propargylaniline derivatives, which could be considered to be an alternative route to the quinoline ring system, have been reported to proceed through o -allenylaniline under the thermal or Cu-promoted conditions , (path a′ ). Although a few examples of the thermal rearrangements of N -propargylanilines brought about the formation of indoles (path a ), the reactions required extremely high temperatures (240−260 °C) and the products were obtained in low yields .…”

Regiospecific β-lactam ring-opening/recyclization reactions of N-aryl-3-spirocyclic-β-lactams catalyzed by a Lewis–Brønsted acids combined superacid catalyst system: a new entry to 3-spirocyclicquinolin-4(1H)-ones

“…5c-e On the other hand, the exploration of the synthetic and medicinal utility of 3-spirocyclicquinolines, an interesting class of quinoline derivatives, was restrained by the lack of efficient synthetic methods. 6 Herein, we wish to report the first superacid-catalyzed chemoselelctive b-lactam ringopening/recyclization of N-aryl-3-spirocyclic-b-lactams, 7 which were prepared by a one-pot cyclization reaction of readily available acetoacetanilide derivatives, thus providing a new atom economic approach to 3-spirocyclicquinolin-4(1H)-ones.…”

“…Superacid can be prepared in situ by the combination of two components, a strong Lewis acid and a strong Brønsted acid. 6 The combination of FeCl 3 and HOTf is necessary for the chemoselective b-lactam ring-opening of N-aryl-3-spirocyclicb-lactams, therefore, a possible reaction mechanism involving a superacid species like H[Fe(OTf)Cl 3 ] is proposed (Scheme 2). The superacid H[Fe(OTf)Cl 3 ] is first formed and then reacts with substrate 2a to give protonated intermediates I-III.…”