This chapter describes various syntheses of hamigeran B. Different methodologies were developed, and for our part, we achieved a formal synthesis of (±)-hamigeran B involving an intramolecular alkynylogous Mukaiyama aldol reaction promoted by dual Lewis acid activation as a key step. This unexpected reaction was discovered by treating a ketone with TBSOTf/NEt3 in order to obtain the corresponding silyl enol ether, which, in fact, evolves toward a new type of intramolecular aldol reaction. Fortunately, the study of the scope and limitations of this reaction allowed us to set up an original synthetic route to hamigeran B. Our results indicated clearly that serendipity plays a key role in the development of original strategies in organic synthesis.