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Catalyzed Selective Direct α‐ and γ‐Alkylation of Aldehydes with Cyclic Benzyl Ethers by Using T + BF 4 − in the Presence of an Inexpensive Organic Acid or Anhydride
Author(s) -
Richter Heinrich,
Rohlmann Renate,
García Mancheño Olga
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201101786
Subject(s) - alkylation , chemistry , catalysis , trifluoroacetic acid , selectivity , organic chemistry , trifluoroacetic anhydride , salt (chemistry) , medicinal chemistry
The cross dehydrogenative coupling (CDC) of cyclic benzyl ethers with aliphatic and α,β‐unsaturated aldehydes has been developed. The mild reaction conditions, in which an N‐oxoammonium salt derived from TEMPO (2,2,6,6‐tetramethyl‐1‐piperidinoxyl) is employed as the oxidant in combination with a Cu catalyst, allow the use of relatively redox‐unstable aldehydes under oxidative CDC conditions. The addition of a catalytic amount of trifluoroacetic acid (TFA) or Ac 2 O facilitates the reaction and increases the efficiency and selectivity. In contrast to the expected α‐alkylation obtained with aliphatic aldehydes, α,β‐unsaturated aldehydes led preferentially to the more challenging γ‐alkylated products. The utility of the developed methodology was demonstrated by the synthesis of isochromane‐derived bioactive compounds, such as the dopamine antagonist sonepiprazole.