Many metabolites found in nature contain alkyne or enyne moieties, and therefore, the Sonogashira reaction has found frequent utility in their syntheses. Several of the most recent and promising applications of this coupling methodology toward the total synthesis of natural products exclusively employed the typical copper-cocatalyzed reaction.
An example of the coupling of an aryl iodide to an aryl acetylene can be seen in the reaction of an iodinated alcohol and tris(isopropyl)silylacetylene, which gave an alkyne, an intermediate in the total synthesis of the benzindenoazepine alkaloid bulgaramine.
There are other recent examples of the use of aryl iodides for the preparation of intermediates under typical Sonogashira conditions, which, after cyclization, yield natural products such as benzylisoquinoline  or indole alkaloids An example is the synthesis of the benzylisoquinoline alkaloids (+)-(S)-laudanosine and (–)-(S)-xylopinine. The synthesis of these natural products involved the use of Sonogashira cross-coupling to build the carbon backbone of each molecule.