Palladium-copper-catalyzed Sonogashira

Starting from the related o-iodohydroxycoumarin 9 and trimethylsilylacetylene, the disubstituted psoralen 10 was obtained in high yield by Aquila through a palladium-copper-catalyzed Sonogashira/annulation reaction (Scheme 3) [60]. A variety of new psoralen derivatives were subsequently synthesized from 10 by substitution of the reactive trimethylsilyl group. 

Scheme 14 illustrates Linstrumelle s synthesis of (9Z,11 )-9,11,13-tetradeca-trienyl acetate (8), the pheromone of the pyralid moth, Stenoma cecropia [25]. The key steps were palladium and copper-catalyzed Sonogashira couplings (A+B and C+D). Another noteworthy feature in this synthesis was the use of activated zinc dust in aqueous methanol for the reduction of the triple bonds of E to give two double bonds of 8. 

Generally, the Sonogashira coupling reaction is achieved by a palladium-copper catalyzed reaction of aryl or vinyl halide and terminal alkyne [70-72], The presence of the copper co-catalyst is an obstacle, however, towards the metallodendritic approach of the system. In this context, only a few examples of copper-free procedures have been reported [73-77], involving for instance, in situ Pd(0) complex formation with bulky phosphines [78]. 

Bohm, V. P. W., Herrmann, W. A. Coordination chemistry and mechanisms of metal-catalyzed C-C coupling reactions, 13 a copper-free procedure for the palladium-catalyzed Sonogashira reaction of aryl bromides with terminal alkynes at room temperature. Eur. J. Org. Chem. 2000,3679-3681. 

The palladium-catalyzed arylation and alkenylation of terminal alkynes with aryl or alkenyl hahdes in presence of a copper(l) co-catalyst is called Sonogashira reaction. In the same way as in the other cross-coupling reactions described before, it is possible to immobihze the alkyne or the aromatic bromides, iodides or triflates on sohd supports (Scheme 3.15). 

Pd/Cu-catalyzed cross-coupling of organohalides with terminal alkynes. Cf. Cadiot-Chodkiewicz coupling and Castro-Stephens reaction. The Castro-Stephens coupling uses stoichiometric copper, whereas the Sonogashira variant uses catalytic palladium and copper. 

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