Propiolate coupling

Apart from Cu1, Zn11 salts or Zn metal were also shown to be effective, thus bringing forward an alternative efficient protocol (36) which may be useful for the applications in which the contamination of products by Cu cannot be tolerated. Such protocols can also be advantageous in cross-coupling with acetylenes bearing electron-withdrawing substituents, such as propiolate esters,115 which usually give unsatisfactory results under the standard conditions. 

Even the three-component coupling reaction of diphenyl diselenide, ethyl propiolate, and unsaturated compounds occurs under photo-irradiation (Table 5). Alkenes,198,199 1,3-dienes,198,199 vinylcyclopropanes,200 and isocyanides199,201 serve as the unsaturated coupling partner to afford the corresponding coupling products with high regioselectivity. 

Table 5 Photo-induced three-component coupling reaction of diphenyl diselenide, ethyl propiolate, and unsaturated compounds...

Triflates also undergo Heck reactions and Gribble and Conway reported several such couplings of l-(phenylsulfonyl)indol-3-yl triflate (34) to afford 3-vinylindoles 224 [183]. Cyclohexene, allyl bromide, and methyl propiolate failed to react under these conditions, but triphenylphosphine afforded 225 in excellent yield (93%), and divinyl carbinol yielded the rearranged enal 226 (82% yield). 

Trost exploited the annulation of electron rich phenols and alkynoates to obtain coumarins in the presence of transition metal complexes. Ethyl propiolate and 3,4,5-trimethoxyphenol were coupled in formic acid in the presence of a palladium complex and sodium acetate to give 5,6,7-trimethoxycoumarin via a net C-H insertion in acceptable yield (4.42.). The coupling, characteristic of electron rich phenols, was also catalyzed by other transition metals, such as platinum or silver.56... 

The quinoline portion of the target alkaloids was prepared by condensing p-anisidine 9 with ethyl propiolate, followed by bromination. Coupling of 10 with the boronic ester 8 proceeded to give 11, the intermediate for the synthesis of both 1 and 2. Selective direct epoxidation of 11 using the usual reagents failed, but Sharpless asymmetric dihydroxylation was successful, providing the diol in > 96 4... 

In our attempt to extend the coupling reaction of arenes with alkenes to the coupling with alkynes, as shown in Scheme 4, it was found that the reaction of arenes with ethyl propiolate in TFA (trifluoroacetic acid) gave addition products instead of a coupling product [3]. This addition reaction has been extended to various alkynes and various arenes and also to intramolecular reactions for synthesis of heterocycles such as coumarins, quinolines, and thiocoumarins. 

An interesting three-component reaction occurred when a solution of diphenyl diselenide (SI), an electron-deficient alkyne (e.g., ethyl propiolate), and an excess of an isocyanide (SO) was irradiated through Pyrex with a tungsten lamp (hv > 300 nm). The reaction is based on a selective sequentially radical addition, as illustrated in Scheme 3.33, and the coupling products were formed in 58-85% yield [83], As for the example reported in Scheme 3.33, the elaboration of compound 52 yielded a precursor for the construction of the carbapenem framework. 

The Ni(dppe)Br2-catalyzed condensation of oxabenzonorbomadienes with either p-iodo-(Z)-propenoates or o-iodobenzoate provided a new synthesis of aimulated coumarins. As shown below, this reaction was also found to be regioselective <030L4903>. The same group also reported the reductive coupling of oxabenzonorbomadienes and 7-oxanorbomenes with various propiolates under similar Ni-catalyzed conditions at room temperature <03CEJ3165>. 

In the laboratory of M. Nilsson, a facile one-pot synthesis of isocumestans (6H-benzofuro[2,3-c][1]benzopyran-6-ones) was developed via a novel extension of the Castro-Stephens coupling utilizing ortho-iodophenols and ethyl propiolate. The reaction can be regarded as an extended Castro-Stephens coupling where an intermediate cuprated benzofuran couples with a second equivalent of ortho-iodophenol, and the product lactonizes to isocumestan. 

The reaction between secondary enediamines and propiolic acid esters has been studied in detaiP. In aprotic solvents such as benzene and dioxane, 8 adds to methyl propiolate at ambient temperature to give almost quantitatively product 118 with a tron -configuration of the new double bond, as indicated by a Jhh coupling constant of around 16 Hz in the NMR spectrum. It appears that the reaction proceeds via an ene-addition mechanism. In refluxing ethanol, the C-adducts 118 are converted to the heterocyclic compounds 119. The direct transformation of 8 to 119 is easily achieved in alcoholic solvents. 1,1-Enediamines with jS-nitro, ester and acetyl substituents undergo analogous addition and cyclocondensation reactions to give heterocyclic compounds jj5(39,i2o A -Ethynylcarbonyl imidazole behaves similarly to propiolic acid esters ° (equation 41). 

The procedure outlined above describes the selective, retentive, p-coupling of (Z)-2,3-dibromopropenoic acid ethyl ester with (trimethylsilyl)acetylene employing the palladium-modified version of the Castro-Stephens reaction.4 5 The dibromide starting material is readily available by bromination of ethyl propiolate (Procedure A), as described by Trippett and Hall.2 The coupling product has been shown to be a versatile precursor for the synthesis of variously substituted enynes and enediynes. For example, a second acetylene may be introduced into the a-position under modified coupling conditions. Alternatively, reduction of the ester with diisobutylaluminum hydride and protection of the resultant alcohol with tert-butyldiphenylsilyl chloride affords a vinyl bromide that can be metalated and trapped with various electrophiles. These procedures have been used on the gram and multigram scale.5... 

Reaction with unsaturated acids and derivatives. Propiolic acids undergo halodecarboxylation at room temperature with NXS in the presence of a quaternary ammonium salt. Analogous Hunsdiecker reaction products from alkenoic acids can be used in situ for Heck coupling. ... 

Coupling reaction. Photoinduced three-component coupling combines an alkene (enol ether, silyl enol ether, 1,3-diene, etc.) and ethyl propiolate to form a carbon chain in which the two PhSe groups from PhSeSePh are separately located. The reaction starts from p-addition of PhSe radical to the ester. 

The five-coordinate hydride-dihydrogen complex [OsH(T)2-H2) (CO)(P Pr3)2]BF4 acting as a template for the carbon-carbon coupling between methyl propiolate and 1,1-diphenyl-2-propyn-l-ol... 

THE FIVE-COORDINATE HYDRIDE-DIHYDROGEN COMPLEX [OsH(ri2-H2)(CO)(PiPr3)2 BF4 ACTING AS A TEMPLATE FOR THE CARBON-CARBON COUPLING BETWEEN METHYL PROPIOLATE AND I,l-DIPHENYL-2-PROPYN-l-OL... 

In contrast to the reaction with phenylacetylene, the treatment of 190 with 2 equiv of methyl propiolate leads to the alkenyl-alkynyl compound 200 (Scheme 55). The use of a 1 1 molar ratio of alkyne to osmium complex gives the same product along with unreacted dihydride-dihydrogen complex [79]. The addition of a toluene solution of HCl to a toluene solution of 200 produces the carbon-carbon coupling of the alkynyl and alkenyl fragments to give selectively the... 

C (10 mmHg). In CeD, the PNMR shift was <5 +159, entirely consistent with the presence of a C=P double bond, and this was confirmed by the C NMR spectrum, which showed phosphorus to be directly coupled to an sp carbon (<5 194.7, Jfc 68.7 Hz) and to an sp carbon 37.1, /pc 51.4 Hz). The 27f-phospholes where the 2-phenyl was replaced by 2,4,6-trimethylphenyl, 2,4,6-trimethoxyphenyl, and methyl were also made in good yield by this method. These 2 -phospholes are thermally stable but very sensitive to water and were hydrated on attempted chromatography on Kieselgel to form the phospholanone (204). Other reactions observed (Scheme 46) included a Diels-Alder cycloaddition with methyl propiolate (giving (205)), and a 1,3-dipolar cycloaddition with mesityl nitrile oxide that formed (206). 

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