Angel Vidal

Microbial oxidation in synthesis: Preparation of 6-deoxy cyclitol analogues of myo-inositol 1,4,5-trisphosphate from benzene

Abstract The novel 6-deoxy, 6-deoxy-6-fluoro and 6-deoxy-6-methyl myo-inositol 1,4,5-trisphosphate derivatives (4), (5) and (6) were derived from benzene via microbial oxidation to cis-1,2-dihydroxycyclohexa-3,5-diene (2) and conversion through to the key epoxyacetonide (7).

Tandem 1,5-Hydride Shift/1,5-S,N-Cyclization with Ethylene Extrusion of 1,3-Oxathiolane-Substituted Ketenimines and Carbodiimides. An Experimental and Computational Study†

Under thermal activation in solution, N-[2-(1,3-oxathiolan-2-yl)]phenyl ketenimines and carbodiimides were converted into 2,1-benzisothiazol-3-ones bearing a pendant N-styryl or imidoyl fragment, respectively. These processes should occur with the concomitant formation of ethylene as result of the fragmentation of the 1,3-oxathiolane ring. The conversions of ketenimines took place under softer thermal conditions, toluene 110 degrees C, than those of carbodiimides, o-xylene 160 degrees C. A computational DFT study unveiled the mechanistic course of these transformations, rare tandem processes consisting of an initial 1,5-hydride shift of the acetalic hydrogen atom to the central carbon atom of the heterocumulene function leading to the respective o-azaxylylene. This transient intermediate then converts, in a single step, into ethylene and the experimentally isolated benzisothiazolone. This latter stage of the mechanism is rather peculiar, combining a 1,5-cyclization by S-N bond formation, aromaticity recovery at the benzene nucleus, and the fragmentation of the oxathiolane framework originating a new carbonyl group. It can be related with a vinylogous retro-ene reaction and shows pseudopericyclic characteristics. The computations also revealed that the alternative 6pi electrocyclization of the transient o-azaxylylenes cannot compete, on kinetic and thermodynamic grounds, with the experimentally observed reaction channel. The two alternative reaction paths of a number of ketenimines and carbodiimides were computationally scrutinized, the results being in accord with the experimental outcomes. In addition, sulfur extrusion from the benzisothiazolones by the action of triphenylphosphine under two different reaction conditions led to three different types of heterocyclic products, 4(3H)-quinolones, quinolino[2,1-b]quinazolin-5,12-diones, and dibenzo[b,f][1,5]diazocin-6,12-diones, whose formation is explained by the initial formation of an intermediate imidoylketene. This reactive species could be trapped by a nucleophilic solvent, ethanol.

Heterocyclic synthesis via a tandem aza-Wittig reaction/heterocumulene-mediated annulation reaction. New methodology for the preparation of quinazoline derivatives.

Abstract The aza-Wittig reaction of iminophosphoranes derived fromN-substituted o-azidobenzamides or 2-(o-azido) phenyl benzimidazolewith isocyanates, carbon dioxide or carbon disulphide, lead tofunctionalized 4(3H)-quinazolinones and benzimidazo [1,2-c]quinazolines respectively.

Unexpected formation of 2,1-benzisothiazol-3-ones from oxathiolano ketenimines: a rare tandem process.

A rare one-pot reaction, a tandem [1,5]-H shift/1,5 electrocyclization/[3 + 2] cycloreversion process, leading from N-[2-(1,3-oxathiolan-2-yl)]phenyl ketenimines to 1-(beta-styryl)-2,1-benzisothiazol-3-ones and ethylene, is disclosed and mechanistically unraveled by means of a computational DFT study. The two latter stages of the tandem process are calculated to occur in a single mechanistic step via a transition structure of pseudopericyclic characteristics.

[4 + 2] Cycloaddition Reaction of C-Aryl Ketenimines with PTAD as a Synthetic Equivalent of Dinitrogen. Synthesis of Triazolocinnolines and Cinnolines

C,C,N-Triaryl ketenimines and C-alkyl-C,N-diaryl ketenimines react with 2 equiv of PTAD to provide 1,2,4-triazolo[1,2-a]cinnolines with a pendant triazolidindione group by means of a Diels-Alder/ene sequence. The treatment of such adducts with potassium hydroxide affords 3-aminocinnolines.

Cycloaddition reactions of carbodiimides. The first example of an intramolecular Diels–Alder reaction of CC-conjugated carbodiimides

An one-pot preparation of α-carbolines and quinindolines from conjugated carbodiimides based on a tandem Intramolecular Diels–Alder cycloaddition/oxidative aromatization is described.

One-pot Preparation of Derivatives of the Unknown Fluoreno[2,3,4-i,J]isoquinoline Ring From Conjugated Ketenimines By a Consecutive Electrocyclic Ring-closure Claisen Rearrangement Intramolecular Diels-alder Cycloaddition Double Aromatization Process

A short synthesis of fluoreno[2,3,4-i,j]isoquinoline derivatives (8) based on a new method of three consecutive annelations which involves thermal cyclization of conjugated ketenimines is described; the crystal structure of (8) has been determined.

One-pot preparation of derivatives of the unknown 1,9-diazaphenalene ring by a consecutive electrocyclic ring-closure/Claisen rearrangement/intramolecular amination process

A short synthesis of 1,9-diazaphenalene derivatives (8) based on a new method of two consecutive pyridine annelations which involves cyclization of conjugated carbodiimides (5) is described.

Iminophosphorane-substituted proton sponges. Part 5. Structures in the solid state. Correlation between solid state 31P MAS NMR spectra and crystal structures

The 31P NMR spectra of protonated Iminophosphorane-substituted proton sponges of known crystal structure have been recorded in the solid state under the conditions of magic angle spinning (MAS) and 1H-decoupling. Variable temperature experiments and a comparison with the averaged 31P chemical shifts in solution show that no proton transfer occurs in the crystal, even when strong intramolecular hydrogen bonds are present. Good agreement between the NMR results and the X-ray structures gives weight to structural predictions based on solid state 31P MAS NMR spectroscopy, for compounds which do not yield suitable monocrystals.

One-pot preparation of rigid bicyclic guanidines from bis(iminophosphoranes) by a consecutive five-step process

A one-pot synthesis of bicyclic guandines based on a new method of dihydropyrimido annelation, which involves reaction of bis(iminophosphoranes) with aromatic isocyanates, is described.