Conformational Control of Chiral Amido-Thiourea Catalysts Enables Improved Activity and Enantioselectivity.
While aryl pyrrolidinoamido-thioureas derived from α-amino acids are effective catalysts in a number of asymmetric transformations, they exist as mixtures of slowly interconverting amide rotamers. Herein, the compromising role of amide bond isomerism is analyzed experimentally and computationally. A modified catalyst structure that exists almost exclusively as a single amide rotamer is introduced. This modification is shown to result in improved reactivity and enantioselectivity by minimizing competing reaction pathways.
Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
Dan
D
Lehnherr
Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
David D
DD
Ford
Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
Andrew J
AJ
Bendelsmith
Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
C Rose
CR
Kennedy
Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
Eric N
EN
Jacobsen
D002384:Catalysis; D006860:Hydrogen Bonding; D012996:Solutions; D013237:Stereoisomerism; D013890:Thiourea / Q000737:chemistry*
D012996:Solutions; D013890:Thiourea