Get access

Catalyzed Selective Direct α- and γ-Alkylation of Aldehydes with Cyclic Benzyl Ethers by Using T+BF4 in the Presence of an Inexpensive Organic Acid or Anhydride

Authors

  • Heinrich Richter,

    1. Organisch-Chemisches Institut, Universität Münster, Corrensstrasse 40, 48149 Münster (Germany), Fax: (+49) 251-83-33202
    Search for more papers by this author
  • Renate Rohlmann,

    1. Organisch-Chemisches Institut, Universität Münster, Corrensstrasse 40, 48149 Münster (Germany), Fax: (+49) 251-83-33202
    Search for more papers by this author
  • Dr. Olga García Mancheño

    Corresponding author
    1. Organisch-Chemisches Institut, Universität Münster, Corrensstrasse 40, 48149 Münster (Germany), Fax: (+49) 251-83-33202
    • Organisch-Chemisches Institut, Universität Münster, Corrensstrasse 40, 48149 Münster (Germany), Fax: (+49) 251-83-33202
    Search for more papers by this author

  • T+BF4: 2,2,6,6-Tetramethylpiperidine-1-oxoammonium tetrafluoroborate.

Abstract

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 Ac2O 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.

Ancillary