The Stereoselective Total Synthesis of the Elusive Cephalosporolide F.

Here we report a seven-step protecting-group-free stereoselective total synthesis of the elusive (+)-cephalosporolide F from d-glucose. A microwave-assisted reaction between the Meldrum's acid and the d-glucose to the respective octono-1,4-lactone derivative, and a low temperature visible-light photoredox spirocyclization of a chiral N-alkoxyphthalimide to ceph F, are the two key chemical reactions that allowed the accomplishment of this unprecedented feat under an environmentally friendly processes.

Multinuclear mesoionic 1,2,3-triazolylidene complexes: design, synthesis, and applications.

The chemistry of multinuclear metal complexes bearing by N-heterocyclic carbene (NHC) ligands, is an area of fast growing interest in modern organometallic chemistry. In particular, complexes supported by mesoionic (MIC) 1,2,3-triazolylidenes are attracting a great deal attention due to their postulated superior donor capacity compared to classical NHC ligands. Despite the readily available synthetic routes to MIC-based ligand platforms featuring several substitution levels, most of the coordination chemistry of triazolylidenes is still dominated by mononuclear complexes. In this short review article, recent progress on the design and synthesis of multinuclear triazolylidene complexes (ranging from di- to tetranuclear species) is discussed. Special emphasis is placed on their structural features, electronic properties and catalytic applications.

Can an n(O) → π* Interaction Provide Thermodynamic Stability to Naturally Occurring Cephalosporolides?

The stereocontrolled synthesis of naturally occurring products containing a 5,5-spiroketal molecular structure represents a major synthetic problem. Moreover, in a previous work, the stereocontrolled synthesis of cephalosporolide E (ceph E), which presumably was obtained from its epimer congener (ceph F) through an acid-mediated equilibration process, was reported. Consequently, we performed a theoretical investigation to provide relevant information regarding the title question, and it was found that the higher thermodynamic stability of ceph E, relative to ceph F, is caused by an n → π* interaction between a lone electron pair of the oxygen atom of the spiroketal ring (nO) and the antibonding orbital of the carbonyl group (π*C=O). Although similar stereoelectronic interactions have been disclosed in other molecular structures, its presence in ceph E, and very likely in other related naturally occurring products, represents a novel nonanomeric stabilizing effect that should be introduced into the chemical literature.

Total synthesis of cephalosporolide E via a tandem radical/polar crossover reaction. The use of the radical cations under nonoxidative conditions in total synthesis.

The present work reports the first example of the use of the chemistry of radical cations under nonoxidative conditions in total synthesis. Using a late-stage tandem radical/polar crossover reaction, a highly stereoselective total synthesis of cephalosporolide E (which is typically obtained admixed with cephalosporolide F) was accomplished. The reaction of a phthalimido derivative with triphenyltin radical in refluxing toluene engenders a contact ion-pair (radical cation) that leads, in the first instance, to the cephalosporolide F, which is transformed into the cephalosporolide E via a stereocontrolled spiroketal isomerization promoted by the diphenylphosphate acid that is formed during the tandem transformation.

Stereoselective C-glycosidation of D-fucose derivatives directed by the protective groups.

Stereoselectivity in the C-glycosidation of lactones derived from D-fucose by following Kishi's method, which involves the addition of a nucleophile onto a carbohydrate-derived lactone and subsequent reduction of the lactol, was found to be reliant on the nature of the C2 and C3 protective groups. Lactones bearing TBDMS protecting groups selectively afford 1,3-trans products (α anomer), in which the stereoselective outcome is in apparent concordance with Woerpel's model. On the other hand, their benzylated congeners produce the 1,3-cis products (ß anomer) as the major diastereoisomers. The latter results suggest an abnormal behavior during the stereoselective nucleophilic substitution at the anomeric position of the benzylated lactones.