Conjugate Addition with Terminal Alkynes

The addition of terminal alkynes to carbon-carbon double bonds has not been explored until recently, possibly because C=C double bonds are not as good electrophiles as C=N or C=0. In 2003, Carreira et al. reported the first conjugate addition reaction of terminal alkynes to C=C catalyzed by copper in water. The reaction proceeded with derivatives of Meldmm s acid in water in the presence of Cu(OAc)2 and sodium ascorbate (Eq. 4.35). However, this method was hmited to C=C double bonds with two electron withdrawing groups. 

On the other hand, Li et al. reported the first palladium-catalyzed 

4-addition of terminal alkynes to vinyl ketones in water with high yields (Eq. 4.36). At nearly the same time, Chisholm et al. reported such a reaction catalyzed by Rh(acac)(CO)2 (acac = acetylacetonoate) in the presence of tra(o-methoxyphenyl)phosphine in aqueous dioxane 

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Scheme 2.26 Enantioselective conjugate addition of terminal alkynes to a,p-unsaturated thioamides with the use of chiral Cu(i) complex, Li(OC6H4- 3-OMe), and chiral phosphoric acid.

Conia-ene reactions [24], respectively (Scheme 26.3a and b), while DBU has been used to generate enamines for palladium-mediated allylation with allylic carbamates [25] (Scheme 26.3c). More recently, Shibasaki s group studied the cooperation of Cu(CH3CN) (soft Lewis acid) and Li(OC5H4-p-OMe) (hard Brpnsted base) in the conjugate addition of terminal alkynes... 

Zinc The conjugate addition of terminal alkynes ArC=CH to 2-arylidene-1,3-diketones RCH=C(COMe)2, catalysed by Et2Zn in the presence of (/ )-VANOL (523), has been reported to proceed readily in a mixture of toluene and EtN02 at room temperature, giving the products with <91%... 

Success was obtained with Ru3(CO)i2 as catalyst precursor [6], but the most efficient catalysts were found in the RuCl2(arene)(phosphine) series. These complexes are known to produce ruthenium vinylidene spedes upon reaction with terminal alkynes under stoichiometric conditions, and thus are able to generate potential catalysts active for anti-Markovnikov addition [7]. Similar results were obtained by using Ru(r]" -cyclooctadiene)(ri -cyclooctatriene)/PR3 as catalyst precursor [8]. (Z)-Dienylcarba-mates were also regio- and stereo-selectively prepared from conjugated enynes and secondary aliphatic amines (diethylamine, piperidine, morpholine, pyrrolidine) but, in this case, RuCl2(arene) (phosphine) complexes were not very efficient and the best catalyst precursor was Ru(methallyl)2(diphenylphosphinoethane) [9] (Scheme 10.1). 

Additions. Allyl sulfonates result from the Pd-catalyzed reaction of allenes with sulfonylhydrazines. The enyne formation by the addition of terminal alkynes to those conjugated to electron-withdrawing substituents is a synthetically significant process. 

Conjugated dienes undergo hydroperfluoroalkylation with perfluoroalkyl iodides and zinc in the presence of titanium catalysts 02 Yields are moderate to good (52-74%) but stereoselectivity is low. From allylic halides functionalized on the a-vinylic position (TMS, carboxylate, phosphonate), additions to terminal alkynes provide functional dienes, used in further synthetic reactions leading to lactones and carboxylic or phosphonic esters.228... 

Other examples reported with a terminal and an internal alkyne as in 50, which do not like 49 have an additional possibility for conjugation, show that then the terminal alkyne isomerizes [62, 87, 88] (Scheme 1.21). 

Suitably protected amino acids (112) (cysteine, serine, and lysine) have been added via the side-chain heteroatom (S, O, and N, respectively) to conjugated alkynones, alkynoic ester and alkynoic amide (113). The expected heterosubstituted vinyl product (114) was formed in each case, mainly as the ii-isomer. In an accompanying paper, this type of addition was applied to the derivatives of fluorescein, 7-hydroxycoumarin, Sudan 1, and dansyl chloride with linker arms containing a conjugated terminal alkyne. 

A copper-catalysed, enantioselective, conjugate addition of a terminal alkyne, which undergoes an in situ metallation, has been reported. The addition of phenylacetylene to Meldrum s acid-derived acceptors (196) takes place in aqueous medium, without recourse to an inert atmosphere. The success of the enantioselective reaction was made possible by the use of PINAP (198), a new class of P,IV-ligands (cf. QUINAP), which have the advantage of easier resolution. Furthermore, these modular ligands are responsive to numerous electronic and steric modifications that permit optimization of the reaction. The products (197) were obtained in good yields and with 82-97% ee.235... 

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