Bifunctional asymmetric catalysis: amplification of Brønsted basicity can orthogonally increase the reactivity of a chiral Brønsted acid.
The reactivity of a series of symmetrical chiral Brønsted acids (polar ionic hydrogen-bond donors) follows the counterintuitive trend wherein the more Brønsted basic member is a more effective catalyst for the aza-Henry (nitro-Mannich) reaction. This new design element leads to a substantially more reactive catalyst for the aza-Henry reaction, one that can promote the addition of a secondary nitroalkane. Additionally, when an achiral Brønsted acid (TfOH) is used in slight excess of the neutral, chiral bisamidine ligand, diastereoselection can be optimized to levels generally greater than 15:1 while the enantioselection remains unchanged at generally >90% ee.
Department of Chemistry and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37235-1822, USA.
Tyler A
TA
Davis
Jeremy C
JC
Wilt
Jeffrey N
JN
Johnston
D000143:Acids / Q000737:chemistry*; D000578:Amidines / Q000737:chemistry*; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D015394:Molecular Structure; D013237:Stereoisomerism
D000143:Acids; D000578:Amidines; D001372:Aza Compounds