Alkynylzinc coupling

The cross-coupling reactions of allenes with components containing sp-carbon atoms are useful synthetic transformations since they provide yne-allenes and enyne-allenes, respectively. Due to the synthetic potential of these classes of carbon-rich unsaturated compounds, the scope and limitations were systematically investigated [1, 16-18]. The first synthetic application was reported in 1981, describing the preparation of alkynyl-substituted allenes by coupling of alkynylzinc chlorides with allenyl halides (Scheme 14.8) [11]. 

The cross-coupling reaction of vinylic tellurides with dialkylzinc or alkynylzinc reagents under Pd(PPh3)4-CuI catalyst was established as a useful method to synthesize different types of dienes, enynes or enediynes. ... 

Alkynylzinc chlorides are useful imermedtates in Pd°-catalysed couplings with vinyl, heteroaryl [56) and acyl halides [89] tsee Chaps. V and X). The conversion of lithium alkyn-vlides into alkynylzinc halides with anhydrous zinc chloride in THF proceeds smoothly and quantitatively under mild conditions. 

As usual, the reactivity order with respect to halogen in C=C-X is I > Br > Q. The organic halide in the couplings with alkynylzinc halides is usnaily an iodide, though also activated vinylic bromides (e.g. BrCH=CHCOOC2H5) have been found to react smoothly. We... 

The cross-coupling of alkynylzinc halides or fluorinated alkenylzinc halides with fluori-nated alkenyl iodides allows the preparation of a range of fluorinated dienes or enynes - Functionalized allylic boronic esters can be prepared by the cross-coupling of (dialkylbo-ryl)methylzinc iodide 428 with functionalized alkenyl iodides. The intramolecular reaction provides cyclized products, such as 429 (Scheme 109) ° °. In some cases, reduction reactions or halogen-zinc exchange reactions are observed. 

In summary, the Pd-catalyzed alkynylation with alkynylzincs has finally become generally applicable with the exception of the alkynyl-alkyl coupling and often capricious... 

SCHEME 49. Pd-catalyzed cross-coupling of alkynylzincs with (S)-ICH=CHC1 and (/t)-ICH= CHBr... 

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... 

Pd°-Catalysed Coupling of Alkynylzinc Chlorides with Acvl Halides... 

Alkyl-2//-pyran-2-ones are formed when (Z)-5-alkyl-2-en-4-ynoic acids, available by a Pd-catalysed coupling of alkynylzinc compounds with (Z)-3-iodopropenoic acid, are treated with ZnBr2. When cyclisation is effected by Ag2C03, 5-alkylidenefuran-2(5f/)-ones are produced selectively <02TL5673>. 

Haloboration of terminal alkynes yielded stereodefined (Z)-2-halo-l-alkenylboron compounds e.g., 114, 115 that allowed further functionalization of the resulting C-Br or G-B bond. 2,2-Disubstituted-l-alkenylboronic esters were stereoselectively obtained when the haloboration was followed by cross-coupling with 1-alkynylzinc chlorides (Equation (18)).192 The iodoboration-conjugate addition sequence gave alkenyl iodides that were used as intermediate for the total synthesis of deoxyepothilone derivatives (Equation (19)).193-195... 

The use of alkynylzinc reagents instead of alkynes and the use of Pd(PPh3)4 as the catalyst also promotes the coupling reaction leading to enynes 230 and enediynes 231 in good yields and with retention of the double-bond... 

Diynes. A general method for preparation of 1,3-diynes, particularly terminal ones, involves palladium-catalyzed coupling of alkynylzinc derivatives with (E)-l-iodo-2-chloroethylene. This alkene is obtained in 83% yield by reaction of acetylene with iodine monochloride in 6 A HCI. Coupling results in a l -chloro-1,3-cnync (1), which is converted into a l-sodio-l,3-diyne (2), which in turn can be reduced or alkylated to give a 1,3-diyne. 

An alternative method involves coupling the alkynylzinc derivative with vinyl bromide to give a l-en-3-yne, which is converted into a terminal 1,3-diyne selectively by brom-ination of the double bond followed by debromination (equation I). 

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