RESUMEN
Continuous flow synthetic technologies had been widely applied in the total synthesis in the past few decades. Fully continuous flow synthesis is still extremely focused on multi-step synthesis of complex natural pharmaceutical molecules. Thus, the development of fully continuous flow total synthesis of natural products is in demand but challenging. Herein, we demonstrated the first fully continuous flow approach towards asymmetric total synthesis of natural tetrahydroprotoberberine alkaloids, (-)-isocanadine, (-)-tetrahydropseudocoptisine, (-)-stylopine and (-)-nandinine. This method features a concise linear sequence involving four chemical transformations and three on-line work-up processing in an integrated flow platform, without any intermediate purification. The overall yield and enantioselectivity of this four-step continuous flow chemistry were up to 50 % and 92 %ee, respectively, in a total residence time of 32.5â min, corresponding to a throughput of 145â mg/h.
Asunto(s)
Alcaloides , Productos Biológicos , Alcaloides/química , Alcaloides de Berberina , Productos Biológicos/química , Ciclización , EstereoisomerismoRESUMEN
An efficient asymmetric Mannich/cyclization cascade strategy was established from 2-benzothiazolimines with N-acylpyrazoles to provide optical active benzothiazolopyrimidine derivatives using a copper-based complex. The mild cascade process constructed various structurally diverse products with broad scope of substrates together with excellent enantioselectivities (up to 99 % ee) and diastereoselectivities (up to 99:1 d.r.).
RESUMEN
A unified strategy for an efficient and high diastereo- and enantioselective synthesis of (-)-chloramphenicol, (-)-azidamphenicol, (+)-thiamphenicol, and (+)-florfenicol based on a key catalytic syn-selective Henry reaction is reported. The stereochemistry of the ligand-enabled copper(II)-catalyzed aryl aldehyde Henry reaction of nitroethanol was first explored to forge a challenging syn-2-amino-1,3-diol structure unit with vicinal stereocenters with excellent stereocontrol. Multistep continuous flow manipulations were carried out to achieve the efficient asymmetric synthesis of this family of amphenicol antibiotics.
Asunto(s)
Tianfenicol , Antibacterianos , Catálisis , Cloranfenicol/análogos & derivados , Compuestos Heterocíclicos con 3 Anillos , Nitrocompuestos , Tianfenicol/análogos & derivadosRESUMEN
Versatile reactive activities of allyl alcohols with free indoles in C-H functionalization reactions were investigated. Direct alkylation or cascade cyclization reactions could be selectively controlled based on the catalyst system: Ru(PPh3 )3 Cl2 provided C3-substituted ß-ketone indoles whereas [Ru(p-cymene)Cl2 ]2 yielded cyclized indoles.
RESUMEN
Rhodium(iii)-catalyzed N-directed ortho C-H activation and subsequent roll-over C-H activation represents an important strategy to synthesize fused polycyclic compounds. Herein, the novel methodology broadens the scope of the coupling partner to alkenes, which working smoothly with 7-azaindoles has been proven to be an efficient and atom-economical strategy to access complex π-conjugated 7-azaindole derivatives.
RESUMEN
A novel one-pot synthesis of π-conjugated polycyclic compounds, which could undergo further facile transformation to form complex polycyclic heteroarene compounds, has been realized between 7-azaindoles and α,ß-unsaturated ketones. This distinctive cascade process proceeds via a rhodium(iii)-catalyzed alkylation/copper-catalyzed radical annulation-aromatization pathway.
RESUMEN
A novel RuII-catalyzed tandem C-H bond activation tool has been successfully developed involving allylation and oxidative cyclization of 2-phenyl indoles with allyl carbonates. This one-pot reaction is a new way to synthesize indolo[2,1-a]isoquinoline units via a simple and efficient process.
RESUMEN
A convenient rhodium(III)-catalyzed cascade reaction of 7-azaindoles and alkynes through multiple C-H bond activation for the synthesis of unique [5]azahelicenes has been developed. The optical property of these screw-shaped helicene derivatives could be further utilized in electronic devices to recognize mercury ions.
RESUMEN
A highly efficient IrIII -catalyzed cascade cyclization of indoles and diazoes giving access to unique pentacyclic-fused carbazoles has been developed. This novel strategy expanded the application scope of coupling partners to take diazo compounds as a C2 source, and two new cycles, three new C-C and one new C-N bonds were formed in one-pot.