Marc Magre

Filling the Gaps in the Challenging Asymmetric Hydroboration of 1,1‐Disubstituted Alkenes with Simple Phosphite‐Based Phosphinooxazoline Iridium Catalysts

We have identified a readily accessible phosphinooxazoline‐based phosphite‐oxazoline catalytic system, (S)‐4‐isopropyl‐2‐{2‐[(3,3′,5,5′‐tetra‐tert‐butyl‐1,1′‐biphenyl‐2,2′‐diyl)phosphite]phenyl}‐2‐oxazoline (L1 a), that can hydroborate a range of 1,1‐disubstituted aryl olefins with high enantioselectivity (up to 94 %), excellent yields and perfect regioselectivity. The new phosphite‐oxazoline ligands efficiently hydroborate a broader range of olefins than previous phosphinooxazoline ligands. In particular, a wide range of α‐tert‐butylstyrenes can be hydroborated that bear aryl substituents with different electronic and steric properties, which complements previous results with N‐heterocyclic copper catalysts, the only other system reported to date that has achieved these reactions.

Extending the Substrate Scope for the Asymmetric Iridium-Catalyzed Hydrogenation of Minimally Functionalized Olefins by Using Biaryl Phosphite-Based Modular Ligand Libraries

Asymmetric hydrogenation is one of the most efficient and atom-economical tools to prepare chiral molecules. However, the enantiodiscrimination of simple, minimally functionalized olefins is still challenging and requires more sophisticated ligand design. Herein, we discuss our progress in the successful development of ligand design for the iridium-catalyzed asymmetric hydrogenation of minimally functionalized olefins.

Theoretical and Experimental Optimization of a New Amino Phosphite Ligand Library for Asymmetric Palladium‐Catalyzed Allylic Substitution

A new library of modular amino phosphite ligands obtained in a few synthetic steps from enantiopure amino alcohols has been tested in asymmetric Pd‐catalyzed allylic substitution. The modular ligand design is crucial to find highly selective catalysts for each substrate type using a wide range of C‐, N‐, and O‐nucleophiles. A DFT study of the species responsible for the enantiocontrol was used to optimize the ligand structure. By selecting the ligand components, we were able to identify unprecedented catalytic systems that can create new chiral C−C, C−N, and C−O bonds in a variety of substrate types (hindered and unhindered) in high yields and enantioselectivities (ee values up to 99 %). Further studies on the Pd‐π‐allyl intermediates provided a deep understanding of the effect of ligand structure in the origin of enantioselectivity. Potential applications of the new Pd/amino phosphite catalysts were demonstrated by the practical synthesis of a range of chiral carbocycles by simple tandem reactions, with no loss of enantioselectivity.

Enantioselective synthesis of 6,6-disubstituted pentafulvenes containing a chiral pendant hydroxy group

Simple enantioselective synthesis of 6,6-disubstituted pentafulvenes bearing chiral pendant hydroxy groups are attained by cascade reactivity using commercially available proline-based organocatalysts. Condensation of cyclopentadiene with the acetyl function of a 1,2-formylacetophenone, followed by cyclization of a resulting fulvene-stabilized carbanion with the formyl group, generates bicyclic chiral alcohols with initial er values up to 94:6. Exceptional enantio-enrichment of the resultant alcohols results upon crystallization-even near racemic samples spontaneously de-racemize. This enables new families of substituted cyclopentadienes that are both enantiomerically and diastereomerically pure to be rapidly attained.