Luca Steiner

The reported syntheses of dipyrromethanes and tetrapyrroles suffer from accompanying polymerization processes lowering yields and necessitating a laborious workup. Here we present the reaction of geminal dimethoxyethers (i.e., acetals or ketals) with pyrrolic nucleophiles under mild conditions solving those problems. The observed minimal polymerization enables greatly simplified purification procedures. This is possible, because under anhydrous, mildly acidic conditions, geminal dimethoxyethers are more reactive than their carbonyl counterparts. The reaction of geminal dimethoxyethers with pyrrolic nucleophiles proceeds smoothly and selectively at 0°C. Computational studies suggest that geminal dimethoxyethers react readily, while unfeasibly high intermediate energies hamper the reaction of carbonyl compounds under the same conditions. We demonstrate a high functional group tolerance and high yields by the preparation of 27 dipyrromethanes, one porphyrin, and 20 calix[4]pyrroles, many of which include synthetic anchor points for facile postfunctionalization. The method was scaled up to a 500 mmol scale for a dipyrromethane and a 252 mmol scale for a two‐walled calix[4]pyrrole, without loss in yield or purity.

It has been long known that hexamethylphosphoric acid triamide ( HMPA ) may cause genetic defects and cancer. Nevertheless, it is frequently used as highly polar aprotic solvent and as very strong Lewis base in synthetic organic chemistry as well as in other applications. Several attempts of replacing this hazardous compound by alternative strong Lewis bases have been reported in the literature, but the knowledge about these useful compounds and their properties does not receive the deserved attention of potential applicants. In the current computational study, we compare the Brønsted and Lewis basicity of HMPA , the already established replacement compound tripyrrolidino phosphoric acid triamide ( TPPA ) and of two conformationally restricted phosphoric acid triamides. The density functional theory study also includes N , N ′ ‐ dimethyl‐ N , N ′ ‐ propylene urea ( DMPU ) as known Lewis basic additive in a few transformations of lithium organic compounds. The Gibbs free energies of the reactions of these Lewis bases with protons, with lithium cations and with samarium(II) as well as samarium(III) species, were calculated including THF as solvent sphere. The results reveal that TPPA and one of the newly designed phosphoric acid triamides ( HAPO‐2 ) are stronger bases than HMPA in all computed reactions and are excellent substitutes of hazardous HMPA .

This study analyzes the samarium diiodide‐promoted cyclizations of 5‐arylpentan‐2‐ones to dearomatized bicyclic products utilizing density functional theory. The reaction involves a single electron transfer to the carbonyl group, which occurs synchronously with the rate determining cyclization event, and a second subsequent proton‐coupled electron transfer. These redox reactions are accurately computed employing small core pseudo potentials explicitly involving all f‐electrons of samarium. Comparison of the energies of the possible final products rules out thermodynamic control of the observed regio‐ and diastereoselectivities. Kinetic control via appropriate transition states is correctly predicted, but to obtain reasonable energy levels the influence of the co‐solvent hexamethylphosphortriamide has to be estimated by using a correction term. The steric effect of the bulky samarium ligands is decisive for the observed stereoselectivity. Carbonyl groups in para‐position of the aryl group change the regioselectivity of the cyclization and lead to spiro compounds. The computations suggest again kinetic control of this deviating outcome. However, the standard mechanism has to be modified and the involvement of a complex activated by two SmI₂ moieties is proposed in which two electrons are transferred simultaneously to form the new C−C bond. Computation of model intermediates show the feasibility of this alternative+ mechanism.

Samarium diiodide is a versatile single electron transfer (SET) agent with various applications in organic chemistry. Lewis structures regularly insinuate the existence of a ketyl radical when samarium diiodide binds a carbonyl group. The study presented here investigates this electron transfer by the means of computational chemistry. All electron CASPT2 calculations with the inclusion of scalar relativistic effects predict an endotherm electron transfer from samarium diiodide to acetone. Energies calculated with the PBE0-D3(BJ) functional and a small core pseudopotential are in good agreement with CASPT2. The calculations confirm the experimentally measured increase of the samarium diiodide reduction potential through the addition of hexamethylphosphoramide also known as HMPA.