Regioselective Syntheses of 2,3‐Substituted Pyridines by Orthogonal Cross‐Coupling Strategies

Abstract 2‐Aryl/alkylamino‐3‐aryl I and 3‐aryl/alkylamino‐2‐aryl pyridines II , as important potentially bioactive compounds, were synthesized by applying orthogonal cross‐coupling strategies. Combinations of the Suzuki–Miyaura, Liebeskind–Srogl, and Buchwald–Hartwig protocols gave access to the title compounds in a straightforward and operationally simple manner. Full control over the regioselectivity at the 2‐ and 3‐positions was achieved by using 2,3‐dichloropyridine or 3‐iodo‐2‐(methylthio)pyridine as simple, commercially available starting materials. Within this contribution, efficient and high yielding conditions were developed for the Suzuki–Miyaura cross‐coupling reaction of 2‐substituted 3‐chloropyridines, a transformation formerly underrepresented in the literature. For the synthesis of 3‐alkyl/arylamino‐2‐aryl pyridines, the stability of the methylthio group was exploited under Pd‐catalysis in the absence of a copper source. This even enabled the development of an operationally highly facile (semi)‐one‐pot protocol to access the aforementioned compound class that avoided one purification step. A series of products I and II was prepared by using the developed protocols with excellent regioselectivity and good yields.