Alkenyl chlorides, Negishi coupling

Peyrat, J.-F., Thomas, E., L Hermite, N., Alami, M., Brian, J.-D. Versatile palladium(ll)-catalyzed Negishi coupling reactions with functionalized conjugated alkenyl chlorides. Tetrahedron Lett. 2003,44, 6703-6707. 

Total synthesis of (+)-pumiliotoxin A (39) has been achieved based on the Negishi coupling of the alkylzinc chloride 37, derived from the alkyl iodide, with the alkenyl iodide 38 at room temperature, and subsequent deprotection [58], The alkylzinc reagent 41 was prepared conveniently by the reaction of the alkyl iodide 40 with Zn/Cu couple, and treated with 2-iodoimidazole 42 to afford the adduct 43 [47],... 

Chen and Wang described a nickel-catalyzed carbonylative Negishi coupling reactions [82]. In the presence of a catalytic amount of nickel chloride and 4,4 -dimethoxyl-2,2 -bypyridyl under carbon monoxide atmosphere, various enones were produced from enol triflates and diorganozinc reagents (Scheme 4.44). They demonstrate that the rate of CO insertion is increased by the addition of lithium or magnesium halides and the use of polar solvents. Alkenyl iodides can also be used instead of enol triflates. 

Dienes and l -enynes. Negishi et al have extended the synthesis of 1,3-enynes by palladium-catalyzed cross-coupling of alkynylzinc chlorides with an alkenyl halide (8, 472) to a similar stcrcospccific synthesis of 1,5-dienes or 1,5-enynes by coupling an alkenyl halide with a homoallyl- or homopropargylzinc chloride. An example is the synthesis of the 1,5-cnync I (equation 1). This reaction... 

Alkenyl-alkenyl cross-coupling. Baba and Negishi have prepared a catalyst from this Pd(II) complex and 2 equiv. of diisobutylaluminum hydride that promotes this coupling reaction. Tetrakis(triphenylphosphine)palladium(0) is inactive, as is material prepared in situ from palladium chloride, triphenylphos-phine and HAKr-CtHg) . A nickel catalyst prepared from Ni(acac)2, PfCnHsja, and diisobutylaluminum hydride is somewhat less efficient. The coupling Involves (E)-alkenylalanes (4, 158, 159) and alkenyl halides. The products are (E,E)- and (E,Z)-dienes. 

The Negishi alkynylation reactions are most efficient in the context of C(sp)-C(sp ) cross-couplings. Reactive aryl or alkenyl iodides and chlorides are suitable electrophilic partners, as well as other related electrophiles such as triflates, acetates, or tosylates. Notably, 2-methylthiooxazole (302) is also a suitable partner that can be converted, for instance, into the corresponding 2-ethynyloxazole 303 in the presence of Pd(PPh3)4 in THF at 60 °C (Scheme 4.68) [202]. 

In general, alkenyl tosylates displayed enhanced reactivity compared to the corresponding phosphates in the Negishi cross couplings. However, decomposition of the aryl vinyl tosylates required the employment of the more stable aryl vinyl phosphates. Due to the weak coordinating abilities of the phosphate an alkenylpal-ladium(II) chloride complex is presumably formed after the oxidative addition similarly to the complex generated from the corresponding tosylate electrophiles [4]. 

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