Ir and NHC Dual Chiral Synergetic Catalysis: Mechanism and Stereoselectivity in γ-Butyrolactone Formation.
J Am Chem Soc
; 144(35): 16171-16183, 2022 09 07.
Article
in En
| MEDLINE
| ID: mdl-36006026
ABSTRACT
Cooperative dual catalysis is a powerful strategy for achieving unique reactivity by combining catalysts with orthogonal modes of action. This approach allows for independent control of the absolute and relative stereochemistry of the product. Despite its potential utility, the combination of N-heterocyclic carbene (NHC) organocatalysis and transition metal catalysis has remained a formidable challenge as NHCs readily coordinate metal centers. This characteristic also makes it difficult to rationalize or predict the stereochemical outcomes of these reactions. Herein, we use quantum mechanical calculations to investigate formation of γ-butyrolactones from aldehydes and allyl cyclic carbonates by means of an NHC organocatalyst and an iridium catalyst. Stereoconvergent activation of the racemic allyl cyclic carbonate forms an Ir-π-allyl intermediate and activation of an unsaturated aldehyde forms an NHC enolate, the latter of which is rate-limiting. Union of the two fragments leads to stereodetermining C-C bond formation and ultimately ring closure to generate the product lactone. Notably, CO2 loss occurs after formation of the C-C bond and Et3NH+ plays a key role in stabilizing carboxylate intermediates and in facilitating proton transfer to form the NHC enolate. The computed pathways agree with the experimental findings in terms of the absolute configuration, the enantiomer excess, and the different diastereomers seen with the (R)- and (S)-spiro-phosphoramidite combined with the NHC catalyst. Calculations reveal the lowest energy pathway includes both an NHC ligand and a phosphoramidite ligand on the iridium center. However, the stereochemical features of this Ir-bound NHC were found to not contribute to the selectivity of the process.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Heterocyclic Compounds
/
Iridium
Type of study:
Prognostic_studies
Language:
En
Journal:
J Am Chem Soc
Year:
2022
Type:
Article
Affiliation country:
United States