Diverted domino reactivity in tertiary skipped diynes: a convenient access to polyfunctionalized cyclohexadienones and multivalent aromatic scaffolds.

Domino reactions constitute single-operation, multi-step processes able to generate two or more bonds under a constant set of reaction conditions. Usually, they transform simple starting materials into more complex chemical entities utilizing networks of construction reactions. This property makes them excellent synthetic tools to carry out molecular construction with atom-, redoxand step-economy. The sequential order by which these multi-step processes are performed (the reaction manifold) ultimately determines the chemical outcome of the process and therefore, the topology of the final product (the skeletal connectivity). In the last years, we have focused our efforts in the use of small, readily-accessible, densely functionalized platforms for the diversity-oriented domino generation of privileged structural motives with biological relevance. Skipped diynes 1 constitute an example of such platforms (Figure 1). They are conveniently synthesized in one step and multigram scale from alkyl propiolates and acid chlorides via a triethylamine assisted multicomponent A2BB’ 4CR. [8] This modular origin ensures a convenient grade of functional diversity on the tertiary sp-center (diversity domain). The reactivity profile of the platform is defined by the two alkynoate units and the propargyl ester function (reactivity domain). Recent reports from our group have shown how these C7-units can be selectively transformed into polysubstituted pyrroles 4, 1,4-diazepane derivatives 5 or pyrazoles 6, when they are made to react with primary amines, 1,2-diamines and hydrazines respectively (Scheme 1). Figure 1. Synthesis and properties of skipped diynes 1.