Davide Audisio

Catalytic Asymmetric Diastereodivergent Deracemization

Your wish is my command: Deracemization is a powerful strategy wherein a racemate is converted into a 100 % yield of a single enantiopure product. A new concept in catalytic deracemization is presented, in which a racemate with n stereogenic elements can be selectively converted into each one of 2(m) (m = number of chiral centers of the product) different enantiopure products, by simple tuning of the reaction conditions.

Diastereodivergent De-epimerization in Catalytic Asymmetric Allylic Alkylation

Diastereomers made to order: In an unprecedented ligand-controlled process a racemic mixture of four stereoisomers can be converted with high selectivity into each one of the diastereomers of the product, at will (see scheme). The mechanism of this deracemization of epimers, that is, a de-epimerization, was also studied.

Stereoselective Synthesis of Dienyl-Carboxylate Building Blocks: Formal Synthesis of Inthomycin C

A direct synthesis of stereodefined halodienes is reported. Those key building blocks enable a concise access to polyenic products, as demonstrated in a modular synthesis of Inthomycin C.

Copper(I)-Catalyzed Cycloaddition of 4-Bromosydnones and Alkynes for the Regioselective Synthesis of 1,4,5-Trisubstituted Pyrazoles

Copper-catalyzed cycloaddition of alkynes with 4-bromosydnones provides a convenient, mild, and regioselective method for the synthesis of a wide range of bromopyrazoles. The broad functional group tolerance of the cycloaddition reaction and further palladium-catalyzed cross-coupling reactions allowed the preparation of polyfunctionalized 1,4,5-pyrazoles that are otherwise difficult to obtain by conventional methods.

An Atom-Economical and Stereoselective Domino Synthesis of Functionalised Dienes

Open sesame: A direct synthesis of functionalised and stereodefined dienes, relying on a domino allylic alkylation/electrocyclic ring-opening sequence, is reported. This method allows concise access to doubly vinylogous esters. A further systematic study of ring-opening rates of carbon-substituted cyclobutenes allowed the design of substrates amenable to sequential pericyclic reactions (see scheme).

Regio- and Enantioselective Cyclobutene Allylations

Catalytic asymmetric allylation of lactone 1 with allyl boronates leads to functionalized cyclobutenes in high regio- and stereoselectivity.

Diastereodivergent Processes in Palladium-Catalyzed Allylic Alkylation

Dynamic deracemizations are robust strategies wherein a racemate is converted into a single enantiopure product in 100 % yield. A process can be defined as diastereodivergent if multiple diastereomers of the product are possible and if a specific process offers the ability to generate each and every one of them by fine‐tuning the reaction conditions. Palladium‐catalyzed asymmetric allylic alkylation with stabilized nucleophiles is a versatile strategy that can be used to achieve this goal. In this concept, we summarize the advances that have been made in this field. We also introduce and develop the novel concepts of diastereodivergent deracemization and diastereodivergent de‐epimerization.

Bioorthogonal Click and Release Reaction of Iminosydnones with Cycloalkynes

We report the discovery of a new bioorthogonal click-and-release reaction involving iminosydnones and strained alkynes. This transformation leads to two products resulting from the ligation and fragmentation of iminosydnones under physiological conditions. Optimized iminosydnones were successfully used to design innovative cleavable linkers for protein modification, thus opening up new areas in the fields of drug release and target-fishing applications. This click-and-release technology offers the possibility of exchanging tags on proteins for functionalized cyclooctynes under mild and bioorthogonal conditions.

Palladium-catalyzed decarboxylative cyanation of aromatic carboxylic acids using [13C] and [14C]-KCN

The development of robust and straightforward methods to efficiently label aromatic moieties starting from simple and convenient radio-synthetic sources still represents a considerable challenge. In this report, a new palladium-catalyzed decarboxylative cyanation protocol has been described. This procedure utilizes [(14)C]-labeled potassium cyanide, one of the simplest and commercially available sources of carbon-14. Under the optimized reaction conditions, a series of [(13)C] and [(14)C]-aromatic nitriles were easily prepared (12-74% yield starting from potassium cyanide). The usefulness of this methodology is highlighted by a rare example of a formal two-step [(12)C]-[(14)C] carbon isotope exchange. The current synthetic approach may represent a promising alternative to traditional preparations of relevant building blocks such as labeled aromatic nitriles.

Design and Synthesis of Iminosydnones for Fast Click and Release Reactions with Cycloalkynes

Emerging applications in the field of chemical biology are currently limited by the lack of bioorthogonal reactions allowing both removal and linkage of chemical entities on complex biomolecules. We recently discovered a novel reaction between iminosydnones and strained alkynes leading to two products resulting from ligation and fragmentation of iminosydnones under physiological conditions. We now report the synthesis of a panel of substituted iminosydnones and the structure reactivity relationship between these compounds and strained alkyne partners. This study identified the most relevant substituents, which allow to increase the rate of the transformation and to develop a bifunctional cleavable linker with improved kinetics.