Abstract:A catalytic enantioselective synthesis of a new class of quinolizidines and indolizidines is presented. An asymmetric Brøn-sted acid catalyzed hydrogenation cascade as well as a sequential Brønsted acid/metal catalyzed hydrogenation protocol of 2-substituted quinolines yields benzofused quinolizidines and indolizidines in good yields with high diastereo-and enantioselectivities.
“…Later, Glorius and co‐workers reported the ruthenium‐catalyzed asymmetric hydrogenation of indolizines followed by diastereoselective heterogeneous reduction, providing a direct access to indolizidine alkaloids . Alternatively, a sequential chiral Brønsted acid‐ and supported‐metal‐nanoparticle‐catalyzed transfer hydrogenation/hydrogenation protocol of 2‐substituted quinolines has been described by Rueping and co‐workers . This method realized the two‐step enantioselective synthesis of several benzo‐fused quinolizidines, but the scope has proven very limited.…”
Ar apid construction of enantioenriched benzofused quinolizidines,i ndolizidines,a nd their analogues by ruthenium-catalyzed asymmetric cascade hydrogenation/ reductive amination of quinolinyl-and quinoxalinyl-containing ketones has been developed. This reaction proceeds under mild reaction conditions,a ffording chiral benzo-fused aliphatic N-heterocyclic compounds with structural diversity in good yields (up to 95 %) with excellent diastereoselectivity (up to > 20:1 dr) and enantioselectivity (up to > 99 %e e). Furthermore,t his catalytic protocol is applicable to the formal synthesis of (+ +)-gephyrotoxin.Scheme 1. Synthesis of quinolizidines, indolizidines, and their analogues via chemoselective asymmetric hydrogenation/intramolecular asymmetric reductive amination cascade process.
“…Later, Glorius and co‐workers reported the ruthenium‐catalyzed asymmetric hydrogenation of indolizines followed by diastereoselective heterogeneous reduction, providing a direct access to indolizidine alkaloids . Alternatively, a sequential chiral Brønsted acid‐ and supported‐metal‐nanoparticle‐catalyzed transfer hydrogenation/hydrogenation protocol of 2‐substituted quinolines has been described by Rueping and co‐workers . This method realized the two‐step enantioselective synthesis of several benzo‐fused quinolizidines, but the scope has proven very limited.…”
Ar apid construction of enantioenriched benzofused quinolizidines,i ndolizidines,a nd their analogues by ruthenium-catalyzed asymmetric cascade hydrogenation/ reductive amination of quinolinyl-and quinoxalinyl-containing ketones has been developed. This reaction proceeds under mild reaction conditions,a ffording chiral benzo-fused aliphatic N-heterocyclic compounds with structural diversity in good yields (up to 95 %) with excellent diastereoselectivity (up to > 20:1 dr) and enantioselectivity (up to > 99 %e e). Furthermore,t his catalytic protocol is applicable to the formal synthesis of (+ +)-gephyrotoxin.Scheme 1. Synthesis of quinolizidines, indolizidines, and their analogues via chemoselective asymmetric hydrogenation/intramolecular asymmetric reductive amination cascade process.
The construction of an aryl ketone structural unit by means of catalytic carbon–carbon coupling reactions represents the state-of-the-art in organic chemistry. Herein we achieved the direct deoxygenative ketone synthesis in aqueous solution from readily available aromatic carboxylic acids and alkenes, affording structurally diverse ketones in moderate to good yields. Visible-light photoredox catalysis enables the direct deoxygenation of acids as acyl sources with triphenylphosphine and represents a distinct perspective on activation. The synthetic robustness is supported by the late-stage modification of several pharmaceutical compounds and complex molecules. This ketone synthetic strategy is further applied to the synthesis of the drug zolpidem in three steps with 50% total yield and a concise construction of cyclophane-braced 18–20 membered macrocycloketones. It represents not only the advancement for the streamlined synthesis of aromatic ketones from feedstock chemicals, but also a photoredox radical activation mode beyond the redox potential of carboxylic acids.
“…The residue was purified by flash chromatography on silica gel prewashed with Et 3 N using ethyl acetate/hexane (1:4) and 5% Et 3 N as eluent to give product 6 (75 mg, 61%). Colorless oil; Trans-6-propyl-2-(phenylthio) -1,6,7,8,9,9a-hexahydro-4-quinolizinone (7). To a solution of compound 5 (112 mg, 0.37 mmol) in 1,2-dichloroethane (3 mL) under nitrogen was added dropwise PBr 3 (0.21 mL, 2.22 mmol) at reflux for 3 h. The mixture was cooled in an ice bath, and saturated NaHCO 3 solution was then slowly added.…”
Section: Generalmentioning
confidence: 99%
“…Among the piperidine natural products are the bicyclic indolizidines and quinolizidines [5][6][7][8][9][10][11][12][13][14][15][16]. Imino-Diels-Alder reactions are very useful for the synthesis of tetrahydropyridines [17][18][19].…”
Abstract:Starting from a thio-substituted 4-quinolizidinone, a series of C-6 alkylated derivatives with a trans C-6, C-9a relationship was synthesized. Further transformations led to the first stereoselective total synthesis of the structure proposed for (±)-quinolizidine 195C, the major alkaloid isolated from the skin extracts of the Madagascan frog Mantella betsileo. Since the spectral data of the synthetic and natural products differed significantly, the true structure of (±)-quinolizidine 195C remains uncertain.
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