Enantioselective, Nickel-Catalyzed Suzuki Cross-Coupling of Quinolinium Ions

Abstract

Quinolinium ions are engaged in an asymmetric, Ni-catalyzed Suzuki cross-coupling to yield 2-aryl and 2-heteroaryl-1,2-dihydroquinolines. Key to the development of this method is the use of a Ni(II) pre-catalyst that activates without the need for strong reductants or high temperatures. The Ni-iminium activation mode is demonstrated as an exceptionally mild pathway to generate enantioenriched products from racemic starting materials.

Parameterization of phosphine ligands demonstrates enhancement of nickel catalysis via remote steric effects

“…Accordingly, we were able to develop an asymmetric variant of the N , O -acetal coupling using a chiral phosphonite ligand for Ni (ref. 21 ). We recently considered whether this strategy could be expanded to offer a general C sp 3 –C bond-forming approach to ether synthesis from a broad range of readily available and stable acyclic and cyclic acetals in combination with boronic acids (Fig.…”

Copper activation of boronic acids: factors affecting reactivity

“…We examined the possibility of developing a copper‐catalysed addition of boronic acids to N ‐acyl quinolinium ions. This is an attractive route for the synthesis of substituted dihydroquinolines, a commonly encountered bioactive core . A metal‐catalysed process has been developed for this reaction, and in that study it was found that a Ni(0) catalyst turned electron‐deficient aryl boronic acids – normally unreactive in Petasis‐type reactions – into viable nucleophiles (although yields were still lower than those observed for electron‐neutral or electron‐rich aryl boronic acids).…”

Organocatalytic alkylation of carbohydrate‐containing aldehydes with dihydroquinoline N,O‐acetals: Absolute configuration of 1,2‐dihydroquinolines

“…4,5 Most approaches for the preparation of chiral 2substituted dihydroquinolines in nonracemic form are able to introduce only rather simple organic frameworks making use of sophisticated metal catalysts in strictly anhydrous and/or oxygen-free reaction conditions. [6][7][8][9][10] Mannich-type reactions have recently been reported by us and other research groups using synergistic cooperative metal-organocatalysis starting from dihydroquinoline N,O-acetals as proelectrophiles [11][12][13][14] or directly from quinolines. 15 It should be noted that while there are precedents about the use of chiral aldehydes as the electrophilic acceptors in organocatalyzed reactions, 16,17 we are not aware of reactions in which chiral aldehydes, such as saccharidic aldehydes, have been used as the nucleophilic donor.…”

“…The most striking example is N ‐ethoxycarbonyl‐2‐ethoxy‐1,2‐dihydroquinoline (EEDQ), a powerful irreversible dopamine‐receptor antagonist . Most approaches for the preparation of chiral 2‐substituted dihydroquinolines in nonracemic form are able to introduce only rather simple organic frameworks making use of sophisticated metal catalysts in strictly anhydrous and/or oxygen‐free reaction conditions . Mannich‐type reactions have recently been reported by us and other research groups using synergistic cooperative metal‐organocatalysis starting from dihydroquinoline N,O‐acetals as proelectrophiles or directly from quinolines .…”