Pentanidium–Catalyzed Enantioselective α-Hydroxylation of Oxindoles Using Molecular Oxygen

Chen

Chemistry An Asian Journal

et al. 2013

Self Cite

Improving the selectivity of anticancer drugs towards cancer cells is one of the main goals of drug optimization; the prodrug strategy has been one of the most promising. A light‐triggered prodrug strategy is presented as an efficient approach for controlling cytotoxicity of the substitutionally inert cytotoxic complex [Ru(dppz)2(CppH)](PF6)2 (C1; CppH=2‐(2‐pyridyl)pyrimidine‐4‐carboxylic acid; dppz=dipyrido[3,2‐a:2′,3′‐c]phenazine). Attachment of a photolabile 3‐(4,5‐dimethoxy‐2‐nitrophenyl)‐2‐butyl (DMNPB) ester (“photocaging”) makes the otherwise active complex C1 innocuous to both cancerous (HeLa and U2OS) and non‐cancerous (MRC‐5) cells. The cytotoxic action can be successfully unleashed in living cells upon light illumination (350 nm), reaching similar level of activity as the parent cytotoxic compound C1. This is the first substitutionally inert cytotoxic metal complex to be used as a light‐triggered prodrug candidate.

Section: Methodsmentioning

confidence: 99%

Bicyclic‐Guanidine‐Catalyzed Asymmetric Michael Addition of 3‐Substituted Oxindoles to 2‐Cyclopentenone

Chen

Chemistry An Asian Journal

et al. 2013

Self Cite

“…20 Jiang and Tan have also reported the molecular oxygen oxidation of oxindoles employing a stoichieometric base and a chiral pentadinium salt, but the substrate screen was narrow with the only group at nitrogen studied being p-methoxybenzyl. 21 Our procedure appears quite general with the protecting group on nitrogen having little influence on the reaction, however, a group at nitrogen is essential for the reaction to occur (see 4b, Table 1 for example, this is presumably due to deprotonation of the nitrogen in preference to enolate formation). Intrigued by these findings we also carried out a competition experiment through the addition of an electrophile to the reaction.…”

Section: Graphical Abstractmentioning

confidence: 96%

A catalytic, mild and efficient protocol for the C-3 aerial hydroxylation of oxindoles

Buckley

D.‐R.

2013

Tetrahedron Letters

A catalytic, mild and efficient protocol for the C-3 aerial hydroxylation of oxindoles his item ws sumitted to voughorough niversity9s snstitutionl epository y theGn uthorF Citation: fguviD fFF nd pix ¡ exhi hFEFD fFD PHIQF e tlytiD mild nd effiient protool for the gEQ eril hydroxyltion of oxindolesF etrE hedron vettersD SR @VAD ppFVRQEVRTF Additional Information:• xysgiX this is the uthor9s version of work tht ws epted for pulition in etrhedron vettersF ghnges resulting from the pulishE ing proessD suh s peer reviewD editingD orretionsD struturl formtE tingD nd other qulity ontrol mehnisms my not e refleted in this doumentF ghnges my hve een mde to this work sine it ws suE mitted for pulitionF e definitive version ws susequently pulished tX httpXGGdxFdoiForgGIHFIHITGjFtetletFPHIPFIIFHVQ Methods for functionalization of the oxindole nucleus are of significant value in medicinal chemistry and natural product synthesis.1 Due to their unprecedented structural diversity, biological activity and structural challenge, oxindoles continue to attract the interest of chemists and biologists alike. For example, the convolutamydines, 2 and the 3-hydroxywelwitindolinones are part of a growing list of biologically active 3-hydroxyoxindoles (Figure 1).3 3-Hydroxyoxindoles with a quaternary benzylic centre are a useful class of compounds also found in several drug candidates, including the potent, orally active growth hormone There are a number of reports on the enantioselective formation of quaternary carbon centers at the 3-position of oxindoles.6 For example, Hartwig first reported the palladiumcatalysed synthesis of oxindoles by amide α-arylation with ees of up to 67%; 7 This was later improved upon by Kündig using modified N-heterocyclic carbenes 8 and Marsden has reported several methods for the synthesis of 3-hydroxy-and 3-aminooxindoles. 9Copper-mediated processes have also recently been employed to prepare quaternary C-3 oxindoles by both the Kündig 10 and Taylor groups.11 Also of note are the recent reports by Franz,12 who has reported the asymmetric direct addition of nucleophiles to isatins using chiral Lewis acids, and Shibata and Toru who have reported the asymmetric C-3 hydroxylation of oxindoles also using chiral Lewis acids, with an oxaziridine as the stoicheiometric oxidant. 13 Thus owing to the significance of the oxindole structural motif, the development of catalytic methods for the synthesis of oxindoles bearing a C-3 hydroxy quaternary centre is highly desirable.Gassman and Halweg reported the air oxidation of oxindoles to isatins (Scheme 1) through treatment of 3-methylthiooxindoles with a strong stoicheiometric base and air; strict anhydrous conditions were required in order to prevent degradation of the isatin to the corresponding anthranilic acid.14 We also noted the recent report from Curran and co-workers, 15 where the attempted removal of the trimethylsilyl (TMS) group from 1 resulted in 3-hydroxy-1,3-dihydroindol-2-one 2 being the sole product of the reaction (Scheme 2). Careful investigation of...

“…There are few methodologies for the synthesis of chiral 3-hydroxy-3-methyl-2-oxindoles in the literature, and the number of catalytic enantioselective examples is scarce. For example, the asymmetric oxidation of 3-methylindolin-2-one has been described for the synthesis of such compounds [25][26][27]. However, the most direct and versatile methodology is the enantioselective nucleophilic addition of organometallic reagents to isatins (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

Catalytic Enantioselective Addition of Me2Zn to Isatins

et al. 2017