Synthesis of quinoline-3-carboxylates by a Rh(II)-catalyzed cyclopropanation-ring expansion reaction of indoles with halodiazoacetates

Abstract

SummaryIn this letter, we report a novel synthesis of ethyl quinoline-3-carboxylates from reactions between a series of indoles and halodiazoacetates. The formation of the quinoline structure is probably the result of a cyclopropanation at the 2- and 3-positions of the indole followed by ring-opening of the cyclopropane and elimination of H–X.

Carbon Atom Insertion into Pyrroles and Indoles Promoted by Chlorodiazirines

“…Though benzal halides have been employed toward this purpose, the procedures are typically low yielding . α-halo diazoalkanes have similarly been reported, but their intrinsic instability has limited their use. − Suero has recently reported the related α-iodonium diazo compounds as surprisingly stable, isolable carbynyl cation equivalents, though despite increased stability relative to the parent α-halo compounds, Suero reagents retain the requirement of a stabilizing electron-withdrawing group. − Moreover, the associated oxidizing capacity of iodine­(III) limits their application to reducing substrates such as pyrroles and indoles.…”

Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin

“…The choice of reaction conditions for the cyclopropanation–ring expansion of 3-chloroindole ( 3 ) with X-EDA was based on our previous work (Scheme 1) [15]. During our investigation of the cyclopropanation–ring expansion of indoles with halodiazoacetates, we identified Rh 2 (esp) 2 (1 mol %) as the optimal catalyst.…”

“…We recently discovered that Rh carbenes derived from ethyl α-halodiazoacetates (X-EDA) react readily with unprotected indoles to form ethyl 3-carboxyquinoline structures (Scheme 1) [15].…”

“…The effect of indole substituents on the yields of ethyl quinoline-3-carboxylates [15]. Green = good, orange = medium, red = poor.…”

On the cause of low thermal stability of ethyl halodiazoacetates

“…We later developed a rapid and efficient synthetic procedure for the synthesis of ethyl halodiazoacetates 2a – c ( Scheme 1 ) from 1 and studied their reactivity in Rh(II)-catalyzed reactions [ 11 ]. In the presence of Rh(II) catalysts the halodiazoacetates extrude N 2 and form the corresponding Rh–carbenes which undergo typical carbenoid reactions such as cyclopropanation [ 11 ], cyclopropanation–ring expansion [ 12 ], and C–H insertion and Si–H insertion reactions [ 13 ].…”