Beyond the Limits of Atropochirality: Design of Highly Conformationally Restrained Biaryls with Bridgehead Phosphine Oxide.

In the last three decades, reacting sterically congested ortho-substituted arenes to form atropochiral biaryls is an appealing venture and a challenging subject that has garnered significant attention. Therefore, there is interest in developing methods to prepare these compounds. In this study, an efficient approach to produce a new class 2,2' disubstituted biaryls bridgehead phosphine oxides with an unusual topology and exceptional conformational stability is presented. Our methodology demonstrates that depending on the substitution pattern on the aryl moieties, the methanophosphocine backbone could be rigid enough to observe a double atropochirality, resulting in an under covered class of molecules. Notably, our studies revealed that replacing only one hydrogen at the ortho position by a fluorine atom led to sufficiently restricted rotation at temperatures below 80 °C, extending "far away" the limits of atropostability. Finally, our investigations, which employed variable-temperature NMR spectroscopy and DFT calculations, yielded unique insights into the isomerisation mechanism, indicating that the two biaryl motifs are fully independent in spite of their proximity.

New Approaches toward Building Csp -P bond: A Two-Decade Overview.

Since the review of Savignac, the past 20 years have seen significant progresses on the synthesis of alkynylphosphorus compounds considerably expanding the original and rather limited organic toolbox. This comprehensive review explores the latest and potentially greener methodologies using sustainable catalysis or direct metal-free couplings from stable and easy to handle precursors. Recent progress and mechanistic insights for metal-catalyzed reactions with a particular emphasis on copper, palladium, nickel and silver catalytic systems, photocatalytic and metal-free reactions are detailed covering most of the publications related to this field since 2000 until March 2022.

Convergent Synthesis of (R)-Silodosin via Decarboxylative Cross-Coupling.

A new approach to Silodosin capitalizing on a radical retrosynthetic strategy to dissect the molecule into two halves is reported. Using a reductive decarboxylative cross-coupling, a simple indoline can be coupled to a chiral pool-derived fragment to arrive at the target in only seven steps (LLS). This route avoids the use of resolution strategies or asymmetric hydrogenation that requires a subsequent Curtius rearrangement to install a key amino functionality.

Electroreductive Olefin-Ketone Coupling.

A user-friendly approach is presented to sidestep the venerable Grignard addition to unactivated ketones to access tertiary alcohols by reversing the polarity of the disconnection. In this work a ketone instead acts as a nucleophile when adding to simple unactivated olefins to accomplish the same overall transformation. The scope of this coupling is broad as enabled using an electrochemical approach, and the reaction is scalable, chemoselective, and requires no precaution to exclude air or water. Multiple applications demonstrate the simplifying nature of the reaction on multistep synthesis, and mechanistic studies point to an intuitive mechanism reminiscent of other chemical reductants such as SmI2 (which cannot accomplish the same reaction).