Enantioselective Copper‐Catalyzed Quinoline Alkynylation

Abstract

Ah ighly enantioselective copper-catalyzed alkynylation of quinolinium salts is reported. The reaction employs StackPhos,an ewly developed imidazole-based chiral biaryl P, Nligand, and copper bromide to effect at hree-component reaction between aq uinoline,at erminal alkyne,a nd ethyl chloroformate.U nder the reaction conditions,t he desired products are delivered in high yields with ee values of up to 98 %. The transformation tolerates awide range of functional groups with respect to both the alkyne and the quinoline starting materials and the products are easily transformed into useful synthons.E fficient, enantioselective syntheses of the tetrahydroquinoline alkaloids (+ +)-galipinine,( + +)-angustureine,and (À)-cuspareine are reported.

Kinetic Resolution of 2‐Aryldihydroquinolines Using Lithiation – Synthesis of Chiral 1,2‐ and 1,4‐Dihydroquinolines

“…There are only a few examples of the asymmetric synthesis of 1,2-dihydroquinolines and these include the addition of a nucleophile (such as a vinylboronic acid) to C-2 of a quinolinium salt in the presence of a chiral ligand, [7][8][9][10][11][12] or conjugate addition of an aniline followed by intramolecular aldol reaction. [13] Direct addition of an organometallic species to quinoline generally gives moderate enantioselectivity with sparteine as a chiral ligand, [14] although an asymmetric Heck reaction with a 1,4-dihydroquinoline has been successful.…”

Synthesis of tetranuclear complex of Pd(II) with thiosemicarbazone ligands derived from 2‐quinolone and its catalytic evaluation in Suzuki–Miyaura‐type coupling reactions and alkoxylation of chloroquinolines

“…It has been clinically used as an antiviral (uranidine, buchapine, & virantmycin), anticancer (camptothecin, karenitecin, & quinidine), antimalarial (2‐ n ‐propylquinoline, chimanines B, & galipeine), antiparasitic (cusparine, skimmianine, & antidesmone), antibacterial and antifungal (evocarpine, flindersiamine, & haplopine), antiplatelet (simulenoline, robustine, & confusameline), and anti‐inflammatory (evolitrine & quinolactacins A1 and A2) activities. [ 1 ] Functionalization of quinolines by catalysis includes various reactions like CC, CN coupling, [ 2,3 ] CH activation, [ 4,5 ] and corresponding alkenylation, [ 6,7 ] and alkynylation, [ 8,9 ] alkoxylation, [ 10,11 ] and aryloxylation. [ 12,13 ] Traditionally, alkoxylation of aromatic compounds was achieved through nucleophilic aromatic substitution, Mitsunobu reaction, and Williamson's ether synthesis.…”

Chemoenzymatic Enantioselective Synthesis of the Hancock Alkaloids (S)- and (R)-Galipeine, (S)-Cuspareine, (S)-Galipinine, and (S)-Angustureine

“…Indeed, the great interest in the synthesis of this tetrad is evidenced by the large number of studies in the literature. 2 , 8 9 10 11 12 13 14 15 16 17 18…”