Total Synthesis of Lacosamide

Total synthesis of anticonvulsant amino acid, lacosamide, is reported. The key step is stereospecific allyl cyanate-to-isocyanate rearrangement, which proceeds with chirality transfer. The enantiopure starting material for the rearrangement step was accessed from ethyl l-lactate

The synthesis of chiral branched allylamines through dual photoredox/nickel catalysis

Allylamines are versatile building blocks in the synthesis of various naturally occurring products and pharmaceuticals. In contrast to terminal allylamines, the methods of synthesis of their branched congeners with internal, stereodefined double bond are less explored. This work describes a new approach for a preparation of allylamines via cross-coupling of alkyl bromides with simple 3-bromoallylamines by merging photoredox and Ni-catalysis. The reaction proceeds under mild conditions, under blue light irradiation and in the presence of an organic dye, 4CzIPN, as a photocatalyst. The scope of suitable reaction partners is broad, including alkyl bromides bearing reactive functionalities (e.g., esters, nitriles, aldehydes, ketones, epoxides), and N-protected allylamines, as well as N-allylated secondary and tertiary amines and heterocycles. The employment of non-racemic starting mater.ials allows for rapid and easy construction of complex multifunctional allylamine derivatives without erosion of enatiomeric purit

Multifunctional Heteropentalenes: From Synthesis to Optoelectronic Applications

In the broad family of heteropentalenes, the combination of two five-membered heterocyclic rings fused in the [3,2-b] mode has attracted the most significant attention. The relatively straightforward access to these structures, being a consequence of the advances in the last two decades, combined with their physicochemical properties which match the requirements associated with many applications has led to an explosion of applied research. In this Perspective, we will discuss the recent progress of heteropentalenes’ usefulness as an active element of organic light-emitting diodes and organic field-effect transistors. Among the myriad of possible combinations for the different heteroatoms, thieno[3,2-b]thiophenes and 1,4-dihydropyrrolo[3,2-b]pyrroles are subject to the most intense studies. Together they comprise a potent optoelectronics tool resulting from the combination of appreciable photophysical properties, chemical reactivity, and straightforward synthesis

The Synthesis of 5‑Amino-dihydrobenzo[<i>b</i>]oxepines and 5‑Amino-dihydrobenzo[<i>b</i>]azepines via Ichikawa Rearrangement and Ring-Closing Metathesis

The combination of Ichikawa’s rearrangement and a ring-closing metathesis reaction of allyl carbamates is presented as a method for the preparation of 5-amino-substituted 2,5-dihydro-benzo­[<i>b</i>]­oxepines, 2,5-dihydro-benzo­[<i>b</i>]­azepines, and 2,5-dihydro-benzo­[<i>b</i>]­thiepins. It was demonstrated that the use of nonracemic allyl carbamates enables the synthesis of enantioenriched benzo-fused seven-membered heterocycles. Finally, it was shown that further functionalization of the obtained structures allows access to pharmacologically active 5-amino-substituted 2,3,4,5-tetrahydro-1-benzo­[<i>b</i>]­oxepine scaffolds

The Synthesis of α,α-Disubstituted α‑Amino Acids via Ichikawa Rearrangement

An approach to α,α-disubstituted α-amino acids is reported. The key step is allyl cyanate-to-isocyanate rearrangement. As demonstrated, the resultant allyl isocyanates can be directly trapped with various nucleophiles, for instance, alcohols, amines, and organometallic reagents, to provide a broad range of <i>N</i>-functionalized allylamines. The developed method has been successfully applied in the synthesis of two bioactive peptides: 2-aminoadamantane-2-carboxylic acid derived P2X₇-evoked glutamate release inhibitor and 4-amino-tetrahydropyranyl-4-carboxylic acid derived dipeptide GSK-2793660, which is currently in clinical trials as cathepsin C inhibitor for the treatment of cystic fibrosis, noncystic fibrosis bronchiectasis, ANCA-associated vasculitis and bronchiectasis

A DFT study of 1,3-dipolar cycloaddition reactions of 5-membered cyclic nitrones with α,β-unsaturated lactones and with cyclic vinyl ethers. Part I

International audienceThe 1,3-dipolar cycloaddition of cyclic nitrones with electron-poor and electron-rich cyclic dipolarophiles (α,β-unsaturated lactones and vinyl ethers) is studied. The energies of the cycloaddition reactions have been investigated through molecular orbital calculations at the B3LYP/6-31+G(d) level theory. Different reaction channels and reactants approaches, effective in regio- and stereochemical preferences are discussed. The results were compared with experimental data to find a good agreement

A DFT study of 1,3-dipolar cycloaddition of cyclic nitrones to unsaturated lactones. Part II

International audienceThe 1,3-dipolar cycloadditions of cyclic nitrones to five-membered unsaturated lactones are studied. Special attention was focused on a single and double asymmetric induction when one or both components were chiral. The energies of the cycloaddition reactions are investigated through application of molecular orbital calculations at the B3LYP/6-31+G(d) theory level. A study of the different reactants’ approaches and their conformational aspects revealed the stereochemical preferences of these reactions. The results of these calculations correspond well with the previously reported experimental data

Synthesis of Polyhydroxylated Piperidine and Pyrrolidine Peptidomimetics via One-Pot Sequential Lactam Reduction/Joullié–Ugi Reaction

A direct approach to the synthesis of polyhydroxylated piperidine and pyrrolidine peptidomimetics is described. The presented strategy is based on one-pot reduction of sugar-derived lactams with Schwartz’s reagent followed by a multicomponent Ugi–Joullié reaction