Enantioselective Hydrosilylation of β,β‐Disubstituted Enamides to Construct α‐Aminosilanes with Vicinal Stereocenters

Abstract

Despite the advances in the area of catalytic alkene hydrosilylation, the enantioselective hydrosilylation of alkenes bearing a heteroatom substituent is scarce. Here we report a rhodium‐catalyzed hydrosilylation of β,β‐disubstituted enamides to directly afford valuable α‐aminosilanes in a highly regio‐, diastereo‐, and enantioselective manner. Stereodivergent synthesis could be achieved by regulating substrate geometry and ligand configuration to generate all the possible stereoisomers in high enantio‐purity.

Coordination Assistance: A Powerful Strategy for Metal-Catalyzed Regio- and Enantioselective Hydroalkynylation of Internal Alkenes

“…This strategy is also applicable to other types of hydrofunctionalization. For example, we have developed a series of enantioselective hydroborations and hydrosilylations of alkenes bearing a polar functional group. These enantioselective carbon–carbon and carbon–heteroatom bond formation reactions provided expedited access to diverse useful building blocks with complete atom economy and minimal waste generation.…”

“…The intermediate diverges at this point depending on the subsequent migratory insertion event. Migration insertion of the alkene into the metal−hydride bond (41) followed by C− C-forming reductive elimination furnishes propargyl amide 37 (Chalk−Harrod mechanism). Alternatively, migration insertion of the alkene into the metal−carbon bond occurs first (42), followed by C−H-forming reductive elimination to deliver the homopropargyl amide product 38 (modified Chalk−Harrod mechanism).…”

Stereodivergent Synthesis of All Stereoisomers of 2,3-Disubstituted δ-Lactam Derivatives via Organocatalytic Cascade Reactions and Base-Induced Epimerization

“…Our group has previously employed a dual catalytic strategy, utilizing two distinct organocatalysts, to selectively synthesize diastereomers of multiple substituted hexanes. In addition to these approaches, stereodivergent synthesis has been achieved by employing various types of chiral catalysts or different configurations of starting materials . Despite some advancements in strategies for stereodivergent synthesis, the application of these methods to δ-lactam synthesis remains challenging due to the reliance on chiral metal complexes as catalysts in reported stereodivergent approaches with reactions primarily limited to allylation or propargylation.…”

Expanding Biocatalysis for Organosilane Functionalization: Enantioselective Nitrene Transfer to Benzylic Si–C–H Bonds

“…Functionalized organosilicon compounds are valuable chemical reagents and intermediates that have a wide range of applications in material science, − medicinal chemistry, − and organic synthesis. − One particularly useful subclass is chiral α-aminosilanes, which can serve as mimics for amino acids − and structural motifs in peptide isosteres and protease inhibitors. − Significant advances have been made in the synthesis of α-aminosilanes through chemical methods; − however, these methods are limited in scope due to the use of air-sensitive reagents, precious metal catalysts, or the need for prefunctionalized substrates. Direct enzymatic installation of the nitrogen functionality via Si–C–H bond activation could overcome these limitations.…”