Ni-catalyzed direct alcoholysis of N-acylpyrrole-type tertiary amides under mild conditions

Abstract

N-Acylpyrrole-type amides are a class of versatile building blocks in asymmetric synthesis. We report that by employing Ni(COD)2/2,2′-bipyridine (5 mol%) catalytic system, the direct, catalytic alcoholysis of N-acylpyrrole-type aromatic and aliphatic amides with both primary and secondary alcohols can be achieved efficiently under very mild conditions (rt, 1 h) even at gram scale. By increasing the catalyst loading to 10 mol%, prolonging reaction time (18 h), and/or elevating reaction temperature to 50 °C/80 °C, the reaction could be extended to both complex and hindered N-acylpyrroles as well as to N-acylpyrazoles, Nacylindoles, and to other (functionalized) primary and secondary alcohols. In all cases, only 1.5 equiv. of alcohol were used. The value of the method has been demonstrated by the racemization-free, catalytic alcoholysis of chiral amides yielded from other asymmetric methodologies.