Alkynylzinc reagents

The Pd-catalyzed reactions of alkynylzinc chlorides 22, which are readily obtainable in situ from anhydrous zinc chloride and alkynyllithium or -magnesium, with alkenyl iodides or bromides 21 provide the corresponding terminal or internal enynes 23 in high yield and with high ( 97%) stereospecificity [Eq. (9)] [16]. Aryl bromides or iodides can also be used to produce arylalkynes [17]. 

The interesting stereospecific Pd-catalyzed cross-coupling reactions of 1-alkynylzinc chlorides 25 with a diastereoisomeric mixture of alkenyl halides (E)- or (Z)- 24, have been described. The ( )-bromoalkene reacts preferentially in these reactions to afford good yields of (E)-enynes 26 of very high stereoisomeric purity [Eq. (10)] [18], The enyne can easily be selectively transformed into the corresponding dienes, which may be used to prepare stereodefined polyunsaturated natural products. 

Several fluorinated enynes have been prepared by reacting combinations of alkynylzinc chlorides with fluoroalkenyl iodides, or perfluoroalkynylzinc chlorides with alkenyl iodides [20]. 

A general and convenient route to conjugated diynes, especially terminal diynes from the corresponding chloroenynes, has been developed [21], Thus, readily available (E)-iodochloroethylene was first reacted with alkynylzinc derivatives in the presence of a Pd-phosphine complex catalyst to produce ( )-chloroenynes 30 in high yield. The chloroenynes 30 could then be readily converted into the corresponding terminal diynes 31 [Eq. (12)]. 

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Similar observations have been made with the addition of alkynylzinc reagents to aldehydes in the presence of the lithium salt of Wmethylephedrine (26)28. Whereas addition of 2-phenyl-ethynylzinc bromide to an aromatic aldehyde led to the chiral alcohol in 88% ee, addition of ethyl(2-phenylcthynyl)zinc afforded the same alcohol with only 42% ee. 

Addition of Aryl-, Alkenyl- and Alkynylzinc Reagents to Aldehydes... 

Asymmetrical addition of alkynylzinc reagents to nitrones has been achieved in the presence of L-tartaric acid ester as a chiral additive (665). 

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. ... 

Sonogashira protocol.The alkynylzinc reagent can also be prepared in situ form terminal alkynes by addition of ZnCl2 as a co-catalyst. ... 

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... 

Negishi and co-workers also reported in 1978 Pd-catalyzed alkynylation reactions with alkynylmetals containing Mg, B, A1 and Sn. But B and Sn versions have sometimes been known as the Suzuki and Stille alkynylation reactions, respectively. Negishi and co-workers during 1977-1978 reported the Pd-catalyzed alkynylation reactions of alkynylzinc reagents with 1-halo-l-alkynes and aryl halides. 

Optically active aliphatic propargylic alcohols are converted to corticoids (90% ee) via biomimetic polyene cyclization, and to 5-octyl-2(5ii)-furanone. The ee s of propargylic alcohols obtained by this method are comparable with those of the enantioselective reduction of alkynyl ketones with metal hydrides, catalytic enantioselective alkylation of alkynyl aldehydes with dialkyIzincs using a chiral catalyst ((S)-Diphenyl(l-methylpyrrolidin-2-yl)methanol) (DPMPM), and the enantioselective alkynylation of aldehydes with alkynylzinc reagents using A(A-dialkylnorephedrines. °... 

The use of organozinc substrates in coupling reactions is often supported by PdCl2(dppf). On the other hand, the use of the PPhj derivative does not always give the desired products [115]. This is best illustrated in the coupling between 1,2-dihaloalkenes and 1-alkynylzinc reagents (Scheme 1-7), in which Pd(PPh3)4... 

King, A. O., Negishi, E., Villani, F. J., Jr., Silveira, A., Jr. A general synthesis of terminal and internal arylalkynes by the palladium-catalyzed reaction of alkynylzinc reagents with aryl halides. J. Org. Chem. 1978, 43, 358-360. 

Asymmetric additions of alkynylzinc reagents (pyridines and alkaloids as N-containing ligands) to aldehydes and ketones 03T9873. 

Hoveyda and Snapper reported that the addition of mixed alkynylzinc reagents to various aryl imines can be catalyzed by Schiff base ligand 52 and zirconium tetraisopropoxide to afford the protected propargylamines in good yields and enantioselectivities [130]. The oxidative removal of the o anisidyl group affords the propargylamine without any racemization (Scheme 1.40). 

Methylmagnesium bromide modified by ZnCl2 reacts with aldehydes in the presence of the Ti alkoxide derived from 51. It leads to chiral 2-alkanols. A Ti(IV) complex of the C2-symmetric isophthalamide 52 and a diastereomer of 42 catalyze the addition of alkynylzinc reagents to aldehydes, whereas the polymer-linked hydroxy-imine 53 alone is used for the same purpose. ... 

Alkynylzinc reagents. The direct alkynylation of aldehydes is subject to asymmetric induction in the presence of a chiral base such as (-l-)-Af-methylephedrine. Addition to the C=N bond of A-tosylimines and nitrones by this procedure is also successful. ... 

Asymmetric addition of alkynylzinc reagents to aldehydes has been developed with A-methylephedrine (or other chiral amino alcohol) as the chiral ligand. The alkynylzinc reagent is prepared in situ from the terminal alkyne and this allows use of the metal salt (zinc triflate) as a catalyst in substoichiometric amount (1.145). 

BINOL is an effective ligand in the titanium-catalysed asymmetric addition of alkynylzinc reagents to aldehydes. Aromatic, aliphatic and a,P-unsaturated aldehydes such as (6.35) are converted into the propargylic alcohol with 91-99% ee using the alkynylzinc, generated from phenylacetylene and diethylzinc. Carriera and coworkers have developed an enantioselective alkynylzinc addition that is also... 

King, A.O., Okukado, N., Negishi, E.-I., 1977. Efighly general stereo-, regio-, and chemo-selective synthesis of terminal and internal conjugated enynes by the Pd-catalysed reaction of alkynylzinc reagents with alkenyl haUdes. J. Chem. Soc., Chem. Commun. 19,683-684. 

It should also be mentioned that an analogous cross-coupling reaction between vinybc teUurides and alkynylzinc reagents is also possible using 5mol% of NiCl2(dppe) (dppe, l,4-bis(diphenylphosphino)ethane) in refluxing THF [224], The formation of 310 showcases this reaction (Scheme 4.71). 

This reaction provides a satisfactory route to 1,4-enynes, and alkynylzinc reagents containing various types of substituents (alkyl, phenyl, silyl, or alkoxy) can be adequately used. Synthetically important, under such conditions, y.y-disubstituted allyl derivatives such as neryl acetate (313) can be converted into the corresponding cross-coupling adducts such as 314 (Scheme 4.73). 

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