A serendipitous cascade of rhodium vinylcarbenoids with aminochalcones for the synthesis of functionalized quinolines

Abstract

A serendipitous five-step cascade of rhodium vinylcarbenoids with aminochalcones enables a unique synthetic approach to highly functionalized tri- and tetra-cyclic quinolines. The cascade reaction begins with the insertion of aminochalcone nitrogen into rhodium vinylcarbenoids followed by intramolecular aldol cyclization to provide a substituted indoline intermediate that undergoes an oxy-Cope rearrangement to provide a 9-membered azacycle, which then rearranges to the functionalized quinoline through an intramolecular aldol/dehydration sequence. With a catalyst loading as low as 0.1 mol%, the cascade reaction has proven to be general with a range of aminochalcones and vinylcarbenoids.

Stereoselective Synthesis of Diverse Lactones through a Cascade Reaction of Rhodium Carbenoids with Ketoacids

“…We refluxed the insertion product in CH 2 Cl 2 with Rh 2 (TFA) 4 alone and with the addition of excess triethylamine. We did not observe any conversion of insertion product 3a to aldol product 4a , suggesting that a rhodium-bound zwitterionic intermediate is necessary for the aldol cyclization. ,, …”

“…A variety of aryl substituents on ketoacids were also tolerated, bearing electron-withdrawing and electron-donating groups ( 4g – l , Figure ). The compounds 4g – l were then subjected to the thermally induced oxy–Cope ring expansion reaction in refluxing toluene (boiling point 110 °C) as previously reported for the synthesis of medium-sized oxacycyles. , To our surprise, the reaction was found to be sluggish in refluxing toluene.…”

“…With an underlying goal of accessing medium-sized rings, we then turned our attention to vinyldiazoacetates, which will result in aldol products having the divinyl functionality necessary for the thermally induced oxy-Cope ring expansion , to provide access to 10-membered benzannulated lactones. To our delight, the cascade proceeded in good yield with high diastereoselectivity to provide the corresponding δ-lactones bearing two vinyl substituents.…”

Three-Component Approach to Pyridine-Stabilized Ketenimines for the Synthesis of Diverse Heterocycles

“…While pursuing the substrate scope of our previously developed carbene cascade, we attempted to synthesize ethyl 1-tosyl-1 H -1,2,3-triazole-4-carboxylate via the well-established click chemistry. To our surprise, instead of isolating the expected triazole, we exclusively observed a uniquely masked form of ketenimine stabilized as a zwitterionic adduct with 2,6-lutidine.…”

Synthesis of multi‐functionalized quinolines and 1,2‐dihydroquinolines through FeCl3‐mediated reactions of carbonyl compounds with 2‐vinylanilines

“…[19][20][21] Nevertheless, the majority of these methods suffer from drawbacks such as strong acidic or basic conditions, high reaction temperatures, long reaction times, excessive oxidants, low regioselectivities, and so on. In recent decades, significant progress has been made in the development of transitionmetal-catalyzed methods such those using iridium, [22] rhodium, [23][24][25][26] ruthenium, [27][28][29][30][31][32] palladium, [33][34][35][36] nickel, [37] gold, [38][39][40] silver, [41][42][43][44][45] copper, [46][47][48][49][50][51][52][53] and iron [54][55][56] because of their functional group tolerance, stero-and regioselectivity, and excellent yields under mild reaction conditions. Although these procedures provide efficient routes for assembling the quinoline skeleton, most of them use expensive and often toxic metal catalysts, which often generate heavy metal impurities in the product and limit their large-scale applications.…”