Second-generation chiral-substituted poly-N-vinylpyrrolidinones (CSPVPs) (−)-1R and (+)-1S were synthesized by free-radical polymerization of (3aR,6aR)-and (3aS,6aS)-5-ethenyltetrahydro-2,2-dimethyl-4H-1,3-dioxolo [4,5-c]pyrrol-4-one, respectively, using thermal and photochemical reactions. They were produced from respective D-isoascorbic acid and D-ribose. In addition, chiral polymer (−)-2 was also synthesized from the polymerization of (S)-3-(methoxymethoxy)-1-vinylpyrrolidin-2one. Molecular weights of these chiral polymers were measured using HRMS, and the polymer chain tacticity was studied using 13 C NMR spectroscopy. Chiral polymers (−)-1R, (+)-1S, and (−)-2 along with poly-N-vinylpyrrolidinone (PVP, MW 40K) were separately used in the stabilization of Cu/Au or Pd/Au nanoclusters. CD spectra of the bimetallic nanoclusters stabilized by (−)-1R and (+)-1S showed close to mirror-imaged CD absorption bands at wavelengths 200−300 nm, revealing that bimetallic nanoclusters' chiroptical responses are derived from chiral polymer-encapsulated nanomaterials. Chemo-, regio-, and stereoselectivity was found in the catalytic C−H group oxidation reactions of complex bioactive natural products, such as ambroxide, menthofuran, boldine, estrone, dehydroabietylamine, 9-allogibberic acid, and sclareolide, and substituted adamantane molecules, when catalyst Cu/Au (3:1) or Pd/Au (3:1) stabilized by CSPVPs or PVP and oxidant H 2 O 2 or t-BuOOH were applied. Oxidation of (+)-boldine N-oxide 23 using NMO as an oxidant yielded 4,5-dehydroboldine 27, and oxidation of (−)-9-allogibberic acid yielded C6,15 lactone 47 and C6-ketone 48.

Catalytic oxidations of tricyclic endo-norbornene-fused tetrahydrofuran with bimetallic nanoclusters Cu/Au-PVP and H2O2 or t-BuOOH as an oxidant provided C-H bond oxidation adjacent to the ether function and 4-oxa-tricyclo[5.2.1.0]-8,9-exo-epoxydecane (4), however, oxidation with Pd/Au-PVP took place at the C=C function giving epoxide 4 and oxidative three-bond forming dimeric product, dodecahydro-1,4:6,9-dimethanodibenzofurano[2,3-b:7,8-b']bisoxolane (5). Formation of the latter suggests the involvement of a reactive Pd-C intermediate. Similarly, oxidative C-C bond forming reactions were found in cycloaddition reactions of N2-Boc-1,2,3,4-tetrahydro-γ-carbolines and 2,3-dihydroxybenzoic acid with 2 - 5 mol% Cu/Au-PVP and H2O2 at 25 oC, providing two-bond-forming [4+2] cycloadducts. Under similar reaction conditions, Pd/Au-PVP did not produce the cycloadduct, indicating a need of complexation between Cu with the carboxylic acid group of 2,3-dihydroxybenzoic acid and allylic amine function of γ-carbolines in the cyclization reaction. The reported intermolecular coupling reactions using Pd/Au-PVP or Cu/Au-PVP nanocluster catalysts under oxidative conditions at 25 oC are unprecedented.

Tricyclic pyrone (TP) molecules have shown protection of MC65 neuroblastoma cells death induced by amyloid‐β proteins through SβC gene, a decrease of amyloid‐β peptide levels, and improvement of motor functions and memory in Alzheimer's disease mouse and rat models. Mechanistic studies suggest TP molecules modulate N‐methyl‐D‐aspartate receptor. A short synthesis of chiral TP analogs was sought using a Pd(0)‐catalyzed displacement of TP allylic acetate intermediate with sodium azide or substituted benzylamines. A three‐step sequence of reactions by the treatment of 2‐{(5aS,7S)‐3‐methyl‐1‐oxo‐1,5a,6,7,8,9‐hexahydropyrano[4,3‐b]chromen‐7‐yl}allyl acetate (9) with (Ph3P)4Pd and sodium azide, followed by reduction with Zn‐NH4OCHO and coupling with 3‐fluoro‐4‐hydroxybenzaldehyde and NaCNBH3 was found to give TP coupling molecule, (5aS,7S)‐7‐(1‐(3‐fluoro‐4‐hydroxybenzylamino)prop‐2‐en‐2‐yl)‐3‐methyl‐6,7,8,9‐tetrahydropyrano[4,3‐b]chromen‐1(5aH)‐one (2), in a good yield. An alternative shorter pathway – a two‐step sequence of reactions – by the displacement of 9 by 4‐(t‐butyldimethylsilyloxy)‐3‐fluoro‐benzylamine with a catalytic amount of (Ph3P)4Pd in THF followed by removal of the silyl ether protecting group gave 2, albeit in a lower chemical yield. The described syntheses should provide general procedures for the synthesis of a library of TP molecules for the discovery of anti‐Alzheimer drugs.