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Sterically hindered molybdenum(III) amido complexes of the general type [Mo[(tBu)(Ar)N]3] (1), upon treatment with CH2Cl2 or other halogen donors, have been converted into highly effective catalysts for all kinds of alkyne metathesis reactions. Although the actual nature of the propagating species formed in situ is still elusive, halogen transfer to the Mo center of 1 plays a decisive role in the activation of such precatalysts. It was possible to isolate and characterize by X-ray crystallography some of the resulting molybdenum halide derivatives such as 15, 16 and 20 which themselves were shown to be catalytically active. Numerous applications illustrate the performance of the catalytic system 1/CH2Cl2 which operates under mild conditions and tolerates an array of polar functional groups. The wide scope allows the method to be implemented into the total synthesis of sensitive and polyfunctional natural products. Most notable among them is a concise entry into the potent anticancer agents epothilone A (86) and C (88). The macrolide core of these targets is forged by ring closing alkyne metathesis (RCAM) of diyne 113, followed by Lindlar hydrogenation of cycloalkyne 114 thus formed. Since this strategy opens a stereoselective entry into (Z)-alkene 115, the approach is inherently more efficient than previous syntheses based on conventional RCM.

A ring closing alkyne metathesis reaction catalyzed by the molybdenum complex 26 followed by a Lindlar reduction of the resulting cycloalkyne product opens an efficient and stereoselective entry into epothilone A and C

The suitably functionalized cyclopentanone derivatives 12, 13, 19, and 37 serve as common precursors for the synthesis of various prostaglandins, prostaglandin-1,15-lactones, and unnatural analogues thereof. All of them contain a 2-butynyl entity which is elaborated into the intact α side chain of the targets either via a sequence comprising ring closing alkyne metathesis/Lindlar reduction or via alkyne cross metathesis (ACM)/Lindlar reduction. These novel approaches are distinguished by (i) the ready accessibility of the required cyclopentenone substrates via a three-component coupling reaction, (ii) the inherent flexibility which allows one to make a series of analogues starting from these common platforms, (iii) a small number of steps, and (iv) an excellent overall yield. The key alkyne metathesis reactions are efficiently catalyzed either by the tungsten alkylidyne complex (t-BuO)₃W⋮CCMe₃ or, preferentially, by a catalyst formed in situ from Mo[N(t-Bu)(Ar)]₃ and CH₂Cl₂, the reactivity of which can be fine-tuned by varying the Ar substituent on the amido ligands. These organometallic tools exhibit a remarkable application profile, tolerate an array of polar groups, rigorously distinguish between different π-electron systems, and catalyze the reactions under conditions that are sufficiently mild to preserve even highly sensitive functionalities. The structures of the macrocyclic prostaglandin lactone derivatives 22 and 32 were characterized by X-ray crystallography