High Rotational Barrier Atropisomers.

Atropisomers have attracted a great deal of attention lately due to their numerous applications in organic synthesis and to their employment in drug discovery. However, the synthetic arsenal at our disposal with which to access them remains limited. The research described herein is two-pronged; we both demonstrate the use of MCR chemistry as a synthetic strategy for the de novo synthesis of a class of atropisomers having high barriers to rotation with the simultaneous insertion of multiple chiral elements and we study these unprecedented molecular systems by employing a combination of crystallography, NMR and DFT calculations. By fully exploiting the synthetic capabilities of our chemistry, we have been able to monitor a range of different types of interaction, i. e. π-π, CH-π, heteroatom-π and CD-π, in order to conduct structure-property studies. The results could be applied both to atroposelective synthesis and in drug discovery.

C1 functionalization of imidazo heterocycles via carbon dioxide fixation.

Utilizing CO2 as a one-carbon building block in the preparation of high-value chemical entities is a cornerstone of modern organic synthesis. Herein, we exemplify this strategy through a mild, one-pot methodology that gives rapid access to N-heteroaryl substituted 6-, 8- and 9-membered carbamates via CO2 fixation.

Instant Macrocyclizations via Multicomponent Reactions.

Macrocycles fascinate chemists due to both their structure and their applications. However, we still lack efficient and sustainable synthetic methods, giving us straightforward access to them. Herein, a rapid macrocyclization utilizing a two-step, one-pot approach based on orthogonal multicomponent reaction (MCR) tactics is introduced. This synthetic protocol, which is based on Ugi and Groebke-Blackburn-Bienaymé reactions with isocyanides tethered to alkyl tosylates, yields medium sized macrocycles that are otherwise difficult to achieve. Single crystal structures reveal conformational reorganization via intramolecular hydrogen bonding, and modeling studies profile the synthesized libraries.

New oxacycles on the block: benzodioxepinones via a Passerini reaction.

Oxacycles and benzoxepanes are privileged motifs present in a variety of natural products and functional molecules. However, their synthetic access is limited. Here, we demonstrate a rapid synthesis of unprecedented benzoxepanes from readily available starting materials in one step via a Passerini multicomponent reaction. The reaction proceeds smoothly under mild reaction conditions. We have obtained a single-crystal X-ray structure, revealing a butterfly conformation, combined with useful structural features. In addition, we have performed both a full interaction map on the X-ray structure and a profile analysis of a virtual library based on the proposed scaffold with a special focus on certain physicochemical parameters to demonstrate their potential usage in drug discovery.

ß-Borylation of conjugated carbonyl compounds with silylborane or bis(pinacolato)diboron catalyzed by Au nanoparticles.

Conjugated aldehydes and ketones undergo reaction with Me2PhSiBpin (pin: pinacolato) catalyzed by Au nanoparticles supported on TiO2 forming exclusively the ß-borylation products, via the intermediate formation of the labile silaboration adducts. This chemoselectivity pathway is complementary to the so far known analogous reaction catalyzed by other metals, where ß-silylation occurs instead. ß-Borylation also occurs with pinBBpin under identical reaction conditions in a variety of conjugated carbonyl compounds, including esters and amides which are unreactive in their attempted Au-catalyzed silaboration.