A mild and metal-free cross-dehydrogenative coupling reaction of nitrogen heteroarenes with aldehydes has been developed by the structural hybridization of promoting reagents. The procedure is environmentally benign, cost-effective and industrially scalable, which allows the direct acylation of electron-deficient nitrogen heteroarenes in moderate to good yields. Furthermore, the synthetic utility of this new method in the synthesis of a variety of pharmaceutically relevant isoquinoline alkaloids has been also demonstrated.