Visible light-promoted and gold-photoredox catalyzed reactions of heteroatom(N, S, Se, O)-tethered alkynes with arenediazonium salts selectively reacted to build vicinal diaryl-substituted 2H-benzo[e][1,2]thiazine 1,1-dioxides (benzosultams), benzoselenophenes, benzothiophenes, 4H-chromen-4-ones (flavones), 3H-indoles, 1H-isochromen-1-ones (isocoumarins), and 4H-thiochromen-4-ones (thioflavones). Moreover, the utility of functionalized 3H-indoles as precursors for further elaboration has been demonstrated with the switchable and facile preparation of 1H-indoles, 2-oxindoles, and 3-oxindolines.
A selective and convenient synthesis of tri- and tetrasubstituted α,β-unsaturated ketones, as well as 2,3-diarylbenzofurans has been developed with the aid of light and taking advantage of a cooperative gold/photoredox-catalyzed 2-fold arylation reaction of TMS-terminated alkynols. The reaction of 3-(trimethylsilyl)prop-2-yn-1-ols was competent to generate diarylated α,β-unsaturated ketones; whereas the photoredox sequence involving 2-[(trimethylsilyl)ethynyl]phenol exclusively afforded 2,3-diarylbenzofurans. The reaction of terminal alkynes proceeded in poor yields while the use of bulkier silyl groups, such as TIPS, resulted unproductive. Apparently, the C(sp) arylation reaction is the first event on the domino bis-arylative sequence. These results could be explained through the intermediation of arylgold(III) species and several single electron transfer processes.
2-(Pyridinium-1-yl)-1,1-bis(triflyl)ethanides have been used as 1,2-dipole precursors in a metal-free direct [2+2] cycloaddition reaction of alkynes. Remarkably, this mild and facile uncatalyzed protocol requires neither irradiation nor heating.
1,2-Dipole Tf2CCH2 is generated in situ from 2-(2-fluoro-pyridin-1-ium-1-yl)-1,1-bis[(trifluoromethyl)-sulfonyl]ethan-1-ide and immediately reacted at room temperature with azides to afford previously unknown 4-trifluoromethanesulfonyl 1,2,3-triazoles in a highly regio- and chemoselective fashion.
Ther oom temperature radical cycloetherification/arylation cascade of allenols andd iazonium salts hasb een accomplished via ac ombination of gold and photoredox catalysis to provide 2,3,4-trisubstituted-2,5-dihydrofurans.T he functionalized oxacycle formation sequence is chemo-andr egioselective for the cycloetherification and for the position that bears the aryl moiety after the cross-coupling. Mechanistici nvestigationsr evealed that this transforma-tion proceeds through an initial oxidation of gold(I) to ap henyl gold(III) complex, which,u pon coordination to the allene,c atalyzes its cyclization and leads to the coupling product after ar eductive elimination regenerating Au(I).Scheme 5. Gold-photoredox-cocatalyzed reaction of allenols 5a-e with aryldiazonium salts 2.C ontrolled synthesis of oxaspirooxindoles 6aa-6ee.Scheme6.Gold-photoredox-cocatalyzed reaction of allenols 7 with aryldiazonium salts 2.C ontrolled synthesis of oxaspiro-b-lactams 8.Scheme9.Alternative mechanistice xplanation for the goldphotoredox-cocatalyzed preparation of oxacycles 3, 6, 8,a nd 10 from allenols 1, 5, 7,and 9 and diazonium salts 2.Scheme 10. Oxidationo ft he original Au(I) complex by addition of aP hr adical and single electron transfer from Ru(bipy) 3 . [3] Theb arrier for the reductive eliminationoni ntermediate VI is low (2.2 kcal mol À1 )a nd explains the presence of the aryl-phospine couplingproduct amongt he reaction products.
Multidrug resistance of cancer cells to cytotoxic drugs still remains a major obstacle to the success of chemotherapy in cancer treatment. The development of new drug candidates which may serve as P-glycoprotein (P-gp) efflux pump inhibitors is a promising strategy. Selenium analogues of natural products, such as flavonoids, offer an interesting motif from the perspective of drug design. Herein, we report the biological evaluation of novel hybrid compounds, bearing both the flavone core (compounds 1–3) or a bioisosteric analogue core (compounds 4–6) and the triflyl functional group against Gram-positive and Gram-negative bacteria, yeasts, nematodes, and human colonic adenocarcinoma cells. Results show that these flavones and analogues of flavones inhibited the activity of multidrug resistance (MDR) efflux pump ABCB1 (P-glycoprotein, P-gp). Moreover, the results of the rhodamine 123 accumulation assay demonstrated a dose-dependent inhibition of the abovementioned efflux pump. Three compounds (4, 5, and 6) exhibited potent inhibitory activity, much stronger than the positive control, verapamil. Thus, these chalcogen bioisosteric analogues of flavones become an interesting class of compounds which could be considered as P-gp efflux pump inhibitors in the therapy of MDR cancer. Moreover, all the compounds served as promising adjuvants in the cancer treatment, since they exhibited the P-gp efflux pump modulating activity.
The [2+2] cycloaddition of ynamides with the highly polarized reagent Tf2 C=CH2 has been developed to regioselectively afford bis(triflyl)aminocyclobutenes in the absence of catalyst under mild conditions. Incidentally, with the ynamides bearing electron-rich aromatic rings at the C-terminal, an interesting reactivity switch was observed; a cyclization/hydroxylation sequence yielded 2-amino-3-(triflyl)cyclobut-2-enols. Aminocyclobutene construction with addition of alcohols resulted in the formation of aminocyclobutenyl ethers through a cyclization/hydroalkoxylation process. Moreover, the utility of functionalized aminocyclobutenes as precursors for further elaboration was demonstrated with the preparation of α-amino-β,γ-unsaturated ketones and 3-(triflyl)buta-1,3-dien-2-amines through 4 π-electrocyclic ring opening.
A regioselective synthesis of general applicability has been designed for the one‐pot preparation of 2,3‐disubstituted‐cyclobutenones from iodoalkynes through cyclobutenylation, Suzuki CC coupling, and ketone formation. This one‐pot methodology has been applied to the selective synthesis of an orally active cyclooxygenase II inhibitor. Furthermore, the obtained cyclobut‐2‐en‐1‐ones were used as synthons in several transformations, such as, the preparation of β‐lactams, phthalazines, cyclohexa‐2,5‐dien‐1‐ones, and cyclopent‐3‐en‐1‐ones.
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