A novel method for the construction of 1-azaspirocycles from 5-alkyl-/-arylamine furylcarbinols though intramolecular aza-Piancatelli rearrangement was developed. By using PPh3/diethyl azodicarboxylate instead of a Lewis acid, 1-azaspirocyclic compounds were obtained in good yields and the reaction temperature was reduced to room temperature. In addition, substrates with groups that are sensitive to high temperatures or Lewis acids are tolerated under these reaction conditions. This is the first method that is applicable not only to 5-(N-arylaminoalkyl)furylcarbinols with better yields but also to 5-(N-alkylaminoalkyl)furylcarbinols.

•First report to prepare ROCH2OR from DCM with alcohols using Cu(NHC) as catalyst.•The reaction conditions are mild and the yields are excellent.•The unsymmetrical ethers are also obtained using the similar method.A facile, rapid and efficient method for the preparation of dialkoxymethanes from dichloromethane with alcohols catalyzed by a Cu-NHC complex is reported. A variety of symmetrical dialkoxymethanes can be prepared under mild condition in excellent yields (up to 98%). The unsymmetrical ether is also obtained in 89% yield from the etherification of p-tolylmethanol and n-butyl chloride catalyzed by ICyCuCl complex at 80 °C. The reaction provides a new method for the preparation of dialkoxymethanes under mild conditions in excellent yields.

A new one-pot route to azabicycles involving the [3,3]-sigmatropic rearrangement of dehydration product from allylic alcohol carbamate and base promoted twofold cyclization was described.

Copper N-heterocyclic carbene complexes can be readily used as catalysts for both aerobic oxidation of alcohols to aldehydes and reduction of imines to amines. Our methodology is universal for aromatic substrates and shows versatile tolerance to potential cascade reactions. A one-pot tandem synthetic strategy could afford useful imines and secondary amines via an oxidation–reduction strategy.

A novel series of trifluoromethyl indole derivatives have been designed, synthesized and evaluated for anti-HIV-1 activities in MT-2 cells. The hydrophobic constant, acute toxicity, carcinogenicity and mutagenicity were predicted. Trifluoromethyl indoles 10i and 10k showed extremely promising activities against WT HIV-1 with IC50 values at the low nanomolar level, similar to efavirenz, better than nevirapine, and also possessed higher potency towards the drug-resistant mutant strain Y181C than nevirapine. Preliminary SAR and docking studies of detailed binding mode provided some insights for discovery of more potent NNRTIs.

Co2(CO)8 was found to be effective for cycloisomerization reaction of arylene 1,7-enynes to form 2,3-dihydroindene derivatives, and a catalytic version assisted by different Lewis base ligands was also studied.

To better use gossypol to find promising anticancer compounds, a series of new and known bis-Schiff base analogs of chiral gossypol were synthesized, and their anticancer activity on HeLa, U87 and M85 cells was tested. The results showed that through a simple chemical modification, less active (+)-gossypol could be converted into more active derivatives. When compared with (−)-gossypol, many more potent compounds that could be the promising anticancer agents were found, and some of them were more potent than the anticancer drug Cisplatin against all three cancer cell lines. By eliminating target functional groups, we observed that the major contributor to the anticancer activity of chiral gossypol seemed to be the phenolic groups, and not the aldehyde groups. Through comprehensive analysis of chiral gossypol analogs, the structure–activity relationships were elaborated.Synthesis of chiral gossypol analogs and their anticancer activity on HeLa, U87 and M85 cells as well as structure–activity relationships were elaborated.

Several NPN-type ligands bearing two chiral pyrrolidinyl groups derived from N-phenyl-(S)-prolinol were prepared by two synthetic methods. Their palladium-complex-catalyzed asymmetric allylic alkylation of malonates with 1,3-diphenyl 2-propenyl acetate delivered the products with good to high enantioselectivities (84–97% ee), including an optically active fluorine-containing compound.Bis[2-(S)-(2-methoxylmethylpyrrolidinyl)phenyl]phenyl phosphine oxideC30H37N2O3P[α]D20=+43 (c 1.00, CHCl3)Source of chirality:(S)-2-methoxylmethylpyrrolidineAbsolute configuration:2S,2′Stert-Butyl bis[2-(S)-(2-methoxylmethylpyrrolidinyl)phenyl]phosphine oxideC28H41N2O3P[α]D20=+143 (c 1.02, CHCl3)Source of chirality:(S)-2-methoxylmethylpyrrolidineAbsolute configuration:2S,2′SBis[2-(S)-(2-methoxylmethylpyrrolidinyl)phenyl]phenyl phosphineC30H37N2O2P[α]D20=-165 (c 1.05, CHCl3)Source of chirality:(S)-2-methoxylmethylpyrrolidineAbsolute configuration:2S,2′S(Sp)-[2-(S)-(2-Methoxylmethylpyrrolidinyl)phenyl] (2-methoxyl-phenyl)phenyl phosphine oxideC25H28NO3P[α]D20=+146 (c 1.05, CHCl3)Source of chirality:(S)-2-methoxylmethylpyrrolidineAbsolute configuration:S,Sp(Rp)-[2-(S)-(2-Methoxylmethylpyrrolidinyl)phenyl] (2-methoxyl-phenyl)phenyl phosphine oxideC25H28NO3P[α]D20=-5 (c 1.00, CHCl3)Source of chirality:(S)-2-methoxylmethylpyrrolidineAbsolute configuration:S,Rp(Rp)-[2-(S)-(2-Methoxylmethylpyrrolidinyl)phenyl] (2-methoxyl-phenyl)phenyl phosphine oxideC25H28NO2P[α]D20=-43 (c 0.84, CHCl3)Source of chirality:(S)-2-methoxylmethylpyrrolidineAbsolute configuration:S,Rp(Sp)-[2-(S)-(2-Methoxylmethylpyrrolidinyl)phenyl] (2-methoxyl-phenyl)phenyl phosphine oxideC25H28NO2P[α]D20=-105 (c 0.94, CHCl3)Source of chirality: (S)-2-methoxylmethylpyrrolidineAbsolute configuration: S,Sp(S)-(1-Phenylpyrrolidin-2-yl)methanolC11H15NO>99.8% ee[α]D20=-119 (c 1.15, CHCl3)Source of chirality: (S)-prolineAbsolute configuration: S(S)-2-(Methoxymethyl)-1-phenylpyrrolidineC12H17NO[α]D20=-155 (c 1.04, CHCl3)Source of chirality: (S)-prolineAbsolute configuration: S(S)-[1-(2-Diphenylphosphanylphenyl)pyrrolidin-2-yl]methanolC23H24NOP[α]D20=+3.4 (c 1.05, CHCl3)Source of chirality: (S)-prolineAbsolute configuration: S(S)-(1-(2-Bromophenyl)pyrrolidin-2-yl)methanolC11H14BrNO[α]D20=+51 (c 1.16, CHCl3)Source of chirality: (S)-proline or (S)-prolinolAbsolute configuration: S(S)-(1-(4-Bromophenyl)pyrrolidin-2-yl)methanolC11H14BrNO[α]D20=-79 (c 0.98, CHCl3)Source of chirality: (S)-prolineAbsolute configuration: S(3aS)-2,3,3a,4-Tetrahydro-1H-5-oxa-9b-aza-cyclopenta[a]naphthaleneC11H13NO[α]D20=+46 (c 1.19, CHCl3)Source of chirality: (S)-proline or (S)-prolinolAbsolute configuration: S(S)-1-(2-Bromophenyl)-2-(methoxymethyl)pyrrolidineC12H16BrNO[α]D20=+23 (c 1.30, CHCl3)Source of chirality: (S)-proline or (S)-prolinolAbsolute configuration: S(S)-2-(Benzyloxymethyl)-1-(2-bromophenyl)pyrrolidineC18H20BrNO[α]D20=+3.8 (c 1.01, CHCl3)Source of chirality: (S)-prolineAbsolute configuration: Stert-Butyl bis[2-(S)-(2-methoxylmethylpyrrolidinyl)phenyl]phosphineC28H41N2O2P[α]D20=-125 (c 1.10, CHCl3)Source of chirality: (S)-proline or (S)-prolinolAbsolute configuration: 2S,2′SBis-[2-(S)-(2-benzoxymethylpyrrolidinyl)phenyl]phenyl phosphineC42H45N2O2P[α]D20=-78 (c 0.90, CHCl3)Source of chirality: (S)-prolinolAbsolute configuration: 2S,2′S(R,E)-Dimethyl 2-(1,3-diphenylallyl)-2-fluoromalonateC20H19FO484% ee[α]D20=+35 (c 0.22, CHCl3)Absolute configuration: R

The resolution of (±)-[2.2]paracyclophane-4,12-dicarboxylic acid (±)-1 has been realized through the diastereomeric esters of (1S)-hydroxymethyl-4,7,7-trimethyl-2-oxabicyclo-[2.2.1]heptan-3-one, simply separated by flash chromatography and hydrolyzed with tBuOK/H2O. (R)-(−)-1 and (S)-(+)-1 were obtained in high enantiomeric excesses (>97%) while the determinations of the absolute configurations of (R)-1 and (S)-1 were carried out by X-ray diffraction.(Rρ,S)-(−)-Bis((4,7,7-trimethyl-2-oxabicyclo-[2.2.1]heptan-3-one-1-yl)methyl)-[2.2]paracyclophane-4,12-dicarboxylateC38H44O8De > 99% (by NMR)[α]D20=-39.6 (c 3.25, CHCl3)Source of chirality: synthesisAbsolute configuration: Rρ,S(Sρ,S)-(+)-Bis((4,7,7-trimethyl-2-oxabicyclo-[2.2.1]heptan-3-one-1-yl)methyl)-[2.2]paracyclophane-4,12-dicarboxylateC38H44O8De > 99% (by NMR)[α]D20=+81.3 (c 1.00, CHCl3)Source of chirality: synthesisAbsolute configuration: Sρ,S(Rρ)-(−)-[2.2]Paracyclophane-4,12-dicarboxylic acidC18H16O4Ee > 97% (by HPLC)[α]D20=-156 (c 0.25, EtOH)Source of chirality: synthesisAbsolute configuration: Rρ

A novel series of trifluoromethyl indole derivatives have been designed, synthesized and evaluated for anti-HIV-1 activities in MT-2 cells. The hydrophobic constant, acute toxicity, carcinogenicity and mutagenicity were predicted. Trifluoromethyl indoles 10i and 10k showed extremely promising activities against WT HIV-1 with IC50 values at the low nanomolar level, similar to efavirenz, better than nevirapine, and also possessed higher potency towards the drug-resistant mutant strain Y181C than nevirapine. Preliminary SAR and docking studies of detailed binding mode provided some insights for discovery of more potent NNRTIs.