Mild Divergent Semireductive Transformations of Secondary and Tertiary Amides via Zirconocene Hydride Catalysis.

The mild catalytic partial reduction of amides to imines has proven to be a challenging synthetic transformation, with many transition metals directly reducing these substrates to amines. Herein, we report a mild, catalytic method for the semireduction of both secondary and tertiary amides via zirconocene hydride catalysis. Utilizing just 5 mol % of Cp2ZrCl2, the reductive deoxygenation of secondary amides is demonstrated to furnish a diverse array of imines in up to 94% yield with excellent chemoselectivity and without the need for glovebox handling. Moreover, a novel reductive transamination of tertiary amides is also achievable when the catalytic protocol is carried out in the presence of a primary amine at room temperature, providing access to an expanded assortment of imines in up to 98% yield. Through slight procedural tuning, the single-flask conversion of amides to imines, aldehydes, amines or enamines is feasible, including multicomponent syntheses.

Catalytic Chemo-, Regio-, Diastereo-, and Enantioselective Bromochlorination of Unsaturated Systems Enabled by Lewis Base-Controlled Chloride Release.

A new strategy is described for the Lewis base-catalyzed bromochlorination of unsaturated systems that is mechanistically distinct from prior methodologies. The novelty of this method hinges on the utilization of thionyl chloride as a latent chloride source in combination with as little as 1 mol % of triphenylphosphine or triphenylphosphine oxide as Lewis basic activators. This metal-free, catalytic chemo-, regio-, and diastereoselective bromochlorination of alkenes and alkynes exhibits excellent site selectivity in polyunsaturated systems and provides access to a wide variety of vicinal bromochlorides with up to >20:1 regio- and diastereoselectivity. The precision installation of Br, Cl, and I in various combinations is also demonstrated by simply varying the commercial halogenating reagents employed. Notably, when a chiral Lewis base promoter is employed, an enantioselective bromochlorination of chalcones is possible with up to a 92:8 enantiomeric ratio when utilizing only 1-3 mol % of (DHQD)2PHAL.

Expanding Zirconocene Hydride Catalysis: In Situ Generation and Turnover of ZrH Catalysts Enabling Catalytic Carbonyl Reductions.

Despite the wide use and popularity of metal hydride catalysis, methods utilizing zirconium hydride catalysts remain underexplored. Here, we report the development of a mild method for the in situ preparation and use of zirconium hydride catalysts. This robust method requires only 2.5-5 mol % of zirconocene dichloride in combination with a hydrosilane as the stoichiometric reductant and does not require careful air- or moisture-free techniques. A key finding of this study concerns an amine-mediated ligand exchange en route to the active zirconocene hydride catalyst. A mechanistic investigation supports the intermediacy of an oxo-bridged dimer precatalyst. The application of this method to the reduction of a wide variety of carbonyl-containing substrates, including ketones, aldehydes, enones, ynones, and lactones, is demonstrated with up to 92% yield and exhibits broad functional group tolerability. These findings open up alternative avenues for the catalytic application of chlorozirconocenes, potentially serving as the foundation for broader applications of zirconium hydride catalysis.

Copper Hydride Catalyzed Enantioselective Synthesis of Axially Chiral 1,3-Disubstituted Allenes.

The general enantioselective synthesis of axially chiral disubstituted allenes from prochiral starting materials remains a long-standing challenge in organic synthesis. Here, we report an efficient enantio- and chemoselective copper hydride catalyzed semireduction of conjugated enynes to furnish 1,3-disubstituted allenes using water as the proton source. This protocol is sufficiently mild to accommodate an assortment of functional groups including keto, ester, amino, halo, and hydroxyl groups. Additionally, applications of this method for the selective synthesis of monodeuterated allenes and chiral 2,5-dihydropyrroles are described.