AgNTf2-Catalyzed Regioselective C-H Alkenylation of N,N-Dialkylanilines with Ynamides.

Regioselective C-H alkenylation of N,N-dialkylanilines with ynamides was developed using AgNTf2 as a catalyst. This approach represents a facile hydroarylation of ynamides, allowing for the introduction of an alkenyl group exclusively at the para position of aniline derivatives. As a result, a series of 4-alkenyl N,N-dialkylanilines were synthesized with excellent regioselectivities.

Cu(OTf)2 catalyzed Ugi-type reaction of N,O-acetals with isocyanides for the synthesis of pyrrolidinyl and piperidinyl 2-carboxamides.

The Cu(OTf)2 catalyzed Ugi-type reactions of N,O-acetals with isocyanides have been described for the synthesis of pyrrolidinyl and piperidinyl 2-carboxamides. 4-Hydroxy-5-substituted-prolinamides can be obtained in high diastereoselectivities (2,4-cis/trans > 19 : 1) and a stereoselective model was proposed for 2,4-cis selectivity. Moreover, 4-F-VH 032, a novel analog of the VHL ligand, was conveniently obtained by utilizing the present method.

TMSOTf-mediated synthesis of skipped dienes through the addition of olefins to imines and semicyclic N,O-acetals.

A novel approach to skipped dienes has been developed through the TMSOTf-mediated one-pot addition-substitution of olefins 2a, 2f and 2g with imines 1a-1g, and a series of aryl substituted skipped dienes 3aa-3gf were accordingly obtained in 62%-94% yields. Moreover, semicyclic N,O-acetals 5 and 7 could also undergo this transformation to produce the corresponding skipped dienes 6aa and 6af-6al and 8ba and 8bf-8bk in moderate to good yields.

Zn(OTf)2-catalyzed hydroamination of ynamides with aromatic amines.

The Zn(OTf)2-catalyzed hydroamination of ynamides 2a-2l with aromatic amines 1a-1r was developed. This protocol features broad substrate scope of aromatic amines, good functional group tolerance for ynamides, and excellent regioselectivities. As a result, a variety of substituted amidine compounds 3aa-3oa, 3ab-3al and 3pa-3rk were prepared in moderate to excellent yields and with high regioselectivities.

Synthesis of Functionalized Bicyclo[2.2.2]octan-2-ones Skeleton via Tandem Process of Amino Acid Involved Formal [4 + 2] and Decarboxylative-Mannich Sequence.

An efficient approach to a functionalized bicyclo[2.2.2]octan-2-one scaffold has been developed through a one-pot cascade process including amino acid involved successive Michael addition and decarboxylative-Mannich sequence. Starting from α,ß-unsaturated ketones and amino acids, a series of desired products 7a-7m and 8a-8o were obtained with moderate yields. In addition, the tandem process was reasonably explained by the results of DFT calculations.

Nickel-Catalyzed Regioselective Hydroamination of Ynamides with Secondary Amines.

The first Ni(OTf)2-catalyzed hydroamination of ynamides 2 was developed by reacting with secondary amines (1 and 4). This protocol features excellent regioselectivity, a broad substrate scope of secondary aryl amines, and good functional group tolerance for ynamides. Using this method, a variety of substituted ethene-1,1-diamine compounds were prepared in moderate to excellent yields with high regioselectivities.

Synthesis of a 3,4-Dihydro-1,3-oxazin-2-ones Skeleton via an Intermolecular [4 + 2] Process of N-Acyliminium Ions with Ynamides/Terminal Alkynes.

An approach to access functionalized 3,4-dihydro-1,3-oxazin-2-ones has been developed by reacting semicyclic N,O-acetals 5 and 6 with ynamides 7 or terminal alkynes 8 in a one-pot fashion. The reaction went through a formal [4 + 2] cycloaddition process to generate a number of functionalized 3,4-dihydro-1,3-oxazin-2-ones 9a-9ak and 10a-10bc in yields of 34-97%. In addition, the utility of this transformation was demonstrated by the synthesis of (±)-sedamine 13.

Approach to Tertiary-Type ß-Hydroxyl Carboxamides Through Sc(OTf)3-Catalyzed Addition of Ynamides and Ketones.

An efficient approach to access functionalized tertiary-type ß-hydroxyl carboxamides has been developed through Sc(OTf)3-catalyzed addition of ynamides and substituted ketones. Water was found to be an important reaction substrate, and the solvent was not needed in this process. A broad range of substituted ynamides and ketones was well applicable to the reaction with excellent chemical selectivities. Moreover, several chiral ß-hydroxyl carboxamides 3j-3r were prepared with excellent regioselectivities and outstanding diastereoselectivities.

Antifungal Activity of Griseofulvin Derivatives against Phytopathogenic Fungi in Vitro and in Vivo and Three-Dimensional Quantitative Structure-Activity Relationship Analysis.

With environmental pollution, residual hazards accumulate and severe drug resistance and many other problems appear; some highly toxic drugs have been banned, and antifungal agents are far from satisfactory. Natural products play an important role in the discovery and development of new pesticides. The natural product griseofulvin (1) has been known as an antifungal agent in the treatment of dermatomycoses for decades. In this study, a series of new griseofulvin derivatives were synthesized with good yields. Their structures were characterized by 1H and 13C nuclear magnetic resonance and high-resolution mass spectrometry (electrospray ionization). The antifungal activities of griseofulvin analogues were first evaluated against five phytopathogenic fungi ( Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani, and Fusarium solani) in vitro. Of significance is that most of them showed excellent antifungal activities against C. gloeosporioides. The antifungal activities of the four best compounds (6a, 6c, 6e, and 6f) against C. gloeosporioides were further investigated in vivo using infected apples. The results suggested that compounds 6c, 6e, and 6f [half-maximal inhibitory concentration (IC50) = 47.25 ± 1.46, 49.44 ± 1.50, and 53.63 ± 1.74 µg/mL, respectively] were better than thiophanate-methyl (IC50 = 69.66 ± 6.07 µg/mL). Furthermore, comparative molecular field analysis was performed on the basis of the antifungal activity results of all 22 of the compounds against C. gloeosporioides in vitro. The three-dimensional coefficient contour plots revealed that the suitable bulky and electronegative acyl-substituted groups seem to be more favorable for increasing activity at the 4' position of griseofulvin. The structure-activity relationships were also discussed. Griseofulvin derivatives can be used for the development of highly effective and safe agricultural fungicides.

Approach to Chiral 1-Substituted Isoquinolone and 3-Substituted Isoindolin-1-one by Addition-Cyclization Process.

An approach to access 1-substituted isoquinolones has been developed through the addition-cyclization of imines with Grignard reagents in the presence of 2,2'-dipyridyl. A number of substituted aromatic magnesium reagents were amenable to this process, and the desired products were obtained with excellent yields and outstanding diastereoselectivities ( dr > 99:1). The utility of this convenient approach is demonstrated by the formal synthesis of ( S)-cryptostyline II. Moreover, N-methylmorpholine (NMM) was found to be an effective additive for the formation of 3-substituted isoindolin-1-ones using one-pot addition-cyclization-deprotection of imine with Grignard reagents.

A practical approach to asymmetric synthesis of dolastatin 10.

Dolastatin 10, an antineoplastic agent for cancer chemotherapy, is a linear peptide possessing N,N-dimethyl Val-OH, l-valine, (3R,4S,5S)-dolaisoleucine, (2R,3R,4S)-dolaproine and (S)-dolaphenine. Our efficient synthesis includes the following three key features: (1) SmI2-induced cross-coupling was employed to couple aldehyde 11 with (S)-N-tert-butanesulfinyl imine 12 to generate the required stereocenters of Dap (7); (2) asymmetric addition of chiral N-sulfinyl imine 10 provided a straightforward approach to the synthesis of the protected Doe ((S,S)-8); (3) a practical method to the key subunit Val-Dil (24a) has been established as an alternative synthetic route for the synthesis of this challenging chemical structure.