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A One‐Pot Oxidation/Enantioselective Oxa‐Michael Cascade
Author(s) -
Willemsen Jorgen S.,
Megens Rik P.,
Roelfes Gerard,
van Hest Jan C. M.,
Rutjes Floris P. J. T.
Publication year - 2014
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201301885
Subject(s) - chemistry , enantioselective synthesis , yield (engineering) , catalysis , michael reaction , cascade reaction , copper , aqueous solution , redox , combinatorial chemistry , reaction conditions , one pot synthesis , organic chemistry , reaction mechanism , materials science , metallurgy
A laccase/(2,2,6,6‐tetramethylpiperidin‐1‐yl)oxy (TEMPO) mediated oxidation was combined with an aqueous, enantioselective copper‐catalyzed Michael addition reaction of water in one pot. The copper catalyst was also immobilized onto DNA to induce enantioselectivity in the reaction. Low conversions were observed when the reactions were performed simultaneously, caused by an undesired reaction of an oxidised TEMPO intermediate. We increased the conversions by using a stepwise approach. Thus, after completion of the oxidation, the first reaction was stopped by inhibiting the enzyme with HCO 2 K and reducing the reactive TEMPO intermediate. Next, the Michael addition reaction was started by adding the Cu catalyst. By applying this strategy, an efficient two‐step one‐pot sequence, proceeding with 20 % ee , was realized. The yield and ee of the second reaction were not affected by the oxidation reaction.