Organic co-solvents in aqueous DNA-based asymmetric catalysis

Abstract

Water-miscible organic co-solvents can be used in DNA-based catalytic asymmetric reactions at appreciable concentration without a negative effect on enantioselectivity. While the rate of the copper(II) Diels–Alder reaction is affected negatively by the presence of organic co-solvents, the copper(II) catalyzed Michael addition and Friedel–Crafts alkylation reaction are significantly faster. Additionally, the presence of organic co-solvents allows for reaction temperatures <0 °C, which results in higher ee's. This is used to perform enantioselective Michael additions and Friedel–Crafts alkylations at gram scale, using catalyst loadings as low as 0.75 mol%. These results are an important step towards application of the DNA-based catalysis concept in organic synthesis