Manganese‐Catalyzed Dehydrogenative [4+2] Annulation of N?H Imines and Alkynes by C?H/N?H Activation

Described herein is a manganese‐catalyzed dehydrogenative [4+2] annulation of N H imines and alkynes, a reaction providing highly atom‐economical access to diverse isoquinolines. This transformation represents the first example of manganese‐catalyzed C H activation of imines; the stoichiometric variant of the cyclomanganation was reported in 1971. The redox neutral reaction produces H₂ as the major byproduct and eliminates the need for any oxidants, external ligands, or additives, thus standing out from known isoquinoline synthesis by transition‐metal‐catalyzed C H activation. Mechanistic studies revealed the five‐membered manganacycle and manganese hydride species as key reaction intermediates in the catalytic cycle.     

The photoisomerization of 11‐cis‐retinal protonated schiff base in gas phase: Insight from spin‐flip density functional theory

This extensive theoretical study employed the spin‐flip density functional theory (SFDFT) method to investigate the photoisomerization of 11‐cis‐retinal protonated Schiff base (PSB11) and its minimal model tZt‐penta‐3,5‐dieniminium cation (PSB3). Our calculated results indicate that SFDFT can perform very well in describing the ground‐ and excited‐state geometries of PSB3 and PSB11. We located the conical intersection (CI) point and constructed the photoisomerization reaction path of PSB3 and PSB11 by using the SFDFT method. To further verify the SFDFT results, we computed the energy profiles along the constructed linearly interpolated internal coordinate (LIIC) pathways by using high‐level theoretical methods, such as the EOM‐CCSD, CR‐EOM‐CCSD(T), CASPT2, NEVPT2, and XMCQDPT2 methods. The SFDFT method predicts that the photoisomerization of PSB3 is barrierless, in accordance with previous complete‐active‐space self‐consistent‐field (CASSCF) results. However, an energy barrier is predicted along the LIIC pathways of PSB11. This finding is different from previous CASSCF results and may indicate that the photoisomerization of PSB11 in gas phase is similar to that in solution. However, the higher spin contamination of the SFDFT method in the vicinity of the CI point caused the located CI geometry to deviate from that of the real CI. In addition, the LIIC pathways are only approximations to the minimum energy path (MEP). Thus, further experimental and theoretical studies are needed to verify the existence of an energy barrier along the photoisomerization reaction path of PSB11 in gas phase. © 2013 Wiley Periodicals, Inc.     

Novel cytotoxic nine-membered macrocyclic polysulfur cembranoid lactones from the soft coral Sinularia sp.

One novel nine-membered macrocyclic polysulfur cembranoid lactone, sinulariaoid A (1); three new multioxygenated cembranoids, sinulariaoid B (2), sinulariaoid C (3), sinulariaoid D (4); and four known cembranoids, capilloloid (5), dihydrosinularin (6), sinularin (7), and dihydrosinuflexolide (8) were isolated from the soft coral Sinularia sp. collected off of Sanya Bay in the South China Sea. Their stereochemical structures were determined on the basis of extensive spectroscopic methods, including single crystal X-ray diffraction analysis. Sinulariaoid A (1) is the first reported nine-membered macrocyclic polysulfur cembranoid from soft coral. The cytotoxic activities of compounds 1–8 were determined in four human cancer cell lines (HepG2, HepG2/ADM, MCF-7, and MCF-7/ADM). Of these, sinulariaoid A (1) exhibited the most potent anticancer activity in vitro, and its cytotoxicity in HepG2/ADM was more potent than in the other three cell lines. Furthermore, it was found that sinulariaoid A (1) induced apoptosis, and its selective toxicity toward HepG2/ADM cells was not related to P-glycoproteins.     

Total synthesis of fuzinoside

The first total syntheses of fuzinoside (1b) were achieved from d-galactose through two strategies (BCA and ABC) in 11 (total yield: 5.0%) and 15 (total yield: 3.7%) steps, respectively. Comparison of NMR data of synthetic compound 1b and those of the fuzinoside isolated from the lateral roots of Aconitum carmicaelii suggests that the structure reported in the literature ^1 and 2 might not be accurate. The synthetic fuzinoside (1b) exhibited moderate cardiac activity in the isolated bullfrog heart assay.     

Transition-metal-free synthesis of (Z)-3-ylidenephthalides from 2-acyl-benzoic acids

We report a highly efficient method for the synthesis of (Z)-3-ylidenephthalides via intramolecular cyclization of readily available 2-acyl-benzoic acids mediated by TSTU at room temperature. Using this method, diversely substituted (Z)-3-ylidenephthalides have been generated in good to excellent yields. The application of the method is highlighted by gram-scale preparation of the antiplatelet drug n-butylphthalide.     

Isoquinoline skeleton synthesis via chelation-assisted C−H activation

Transition-metal-catalyzed isoquinoline synthesis that profits from the strategy of chelation-assisted C−H activation has flourished over the past decade. By virtue of the directed C−H bond cleavage of imines, amines, amidines, oximes, hydroximoyl halides, hydrazones, or azines, diverse isoquinoline derivatives have been accessed from alkynes, conjugated dienes, or diazo compounds under the catalysis of rhodium, ruthenium, palladium, nickel, or manganese. This digest summarizes the annulation reactions via chelation-assisted C−H activation leading to isoquinolines, isoquinolinium salts, or isoquinoline N-oxides.     

A pair of unprecedented cyclohexylethanoid enantiomers containing unusual trioxabicyclo[4.2.1]nonane ring from Clerodendrum bungei

A pair of unprecedented enantiomers (1a/1b) of cyclohexylethanoid bearing an unusual trioxabicyclo[4.2.1]nonane ring, along with two known structurally related cyclohexylethanoids, (+)-rengyolone (2) and cleroindicin E (3), were isolated from the aerial parts of Clerodendrum bungei. The structures and absolute configurations of the enantiomers were determined by comprehensive spectroscopic analysis, single-crystal X-ray diffraction, and quantum mechanical calculation of the electronic circular dichroic (ECD) spectra. The postulated biogenetic pathway of 1a/1b was also discussed.     

Phosphonium salt induced stereoselective allylic rearrangement during chlorination of α-hydroxyallylphosphinates

α-Hydroxyallylphosphinates were stereoselectively converted to γ-chloro allylphosphinates when treated with Ph₃P and CCl₄, via substitution of hydroxyl and migration of double bond. The reaction was promoted by phosphonium cation that acted as Lewis acid.     

Synthesis of structurally diverse diarylketones through the diarylmethyl sp CH oxidation

Under open-flask conditions, an efficient method to assemble a series of diversely functionalized diarylketones in the presence of commercially available NBS has been developed. Yields of up to 99% have been achieved employing diarylmethanes as starting material. Based on ¹⁸O-labeled experiment, the addition of stoichiometric water eventually leads to excellent yields in all carbonylation cases.     

Syntheses of 4′-spirocyclic phosphono-nucleosides as potential inhibitors of hepatitis C virus NS5B polymerase

To discover novel nucleosides as potential antiviral agents, 4′-spirocyclic phosphono-nucleosides were designed to mimic the monophosphate of R-1479, a known nucleoside inhibitor of HCV NS5B. Bypassing the first kinase step to nucleoside monophosphate is viewed as advantageous since this phosphorylation is often observed as the rate-limiting transformation to the active NTP for many nucleosides. Efficient synthetic routes were developed with a triphenylphosphine–iodine cyclization reaction as the key step to form the tetrahydrofuran 4′-spirocycle. The desired 4′-spirocyclic phosphono-cytidine analogs 12a, 12b, and 16 were prepared in 11 steps.