Enynes reaction mechanisms

Although the path (a) has been verified by a stoichiometric reaction [23], the details of exact reaction mechanism remain unsettled. Triggered by this publication [and the Pd-catalyzed doublethiolation of alkynes described in Eq. (7.7) in Section 7-3], a number of transition metal-catalyzed additions of S-X or Se-X bonds to C-C unsaturated organic compounds started to be published. In 1994, BackvaU et al. applied the Pd(OAc)2-catalyzed hydrothiolation to conjugated enynes and obtained 17,... 

To probe the reaction mechanism of the silane-mediated reaction, EtjSiD was substituted for PMHS in the cyclization of 1,6-enyne 34a.5 The mono-deuterated reductive cyclization product 34b was obtained as a single diastereomer. This result is consistent with entry of palladium into the catalytic cycle as the hydride derived from its reaction with acetic acid. Alkyne hydrometallation provides intermediate A-7, which upon cw-carbopalladation gives rise to cyclic intermediate B-6. Delivery of deuterium to the palladium center provides C-2, which upon reductive elimination provides the mono-deuterated product 34b, along with palladium(O) to close the catalytic cycle. The relative stereochemistry of 34b was not determined but was inferred on the basis of the aforementioned mechanism (Scheme 24). 

Scheme 4. Reaction mechanism of enyne with Fischer carbene complex...

Trost and Tanoury found an interesting skeletal reorganization of enynes using a palladium catalyst.In this reaction, the second product is derived from a metathesis reaction (Equation (5)). It was speculated that the reaction would proceed by oxidative cyclization of enynes with the palladium complex followed by reductive elimination and then ring opening. To confirm this reaction mechanism, they obtained a compound having a cyclobutene ring, which was considered to be formed by the reductive elimination (Equation (6)). 

Shortly after the discovery of enyne metathesis, Trost began developing cycloisomerization reactions of enynes using Pd(ll) and Pt(ll) metallacyclic catalysts (429-433), which are mechanistically divergent from the metal-carbene reactions. The first of these metal catalyzed cycloisomerization reactions of 1,6-enynes appeared in 1985 (434). The reaction mechanism is proposed to involve initial enyne n complexation of the metal catalyst, which in this case is a cyclometalated Pd(II) cyclopentadiene, followed by oxidative cyclometala-tion of the enyne to form a tetradentate, putative Pd(IV) intermediate [Scheme 42(a)]. Subsequent reductive elimination of the cyclometalated catalyst releases a cyclobutene that rings opens to the 1,3-diene product. Although this scheme represents the fundamental mechanism for enyne metathesis and is useful in the synthesis of complex 1,3-cyclic dienes [Scheme 42(fe)], variations in the reaction pathway due to selective n complexation or alternative cyclobutene reactivity (e.g., isomerization, p-hydride elimination, path 2, Scheme 40) leads to variability in the reaction products. Strong evidence for intermediacy of cyclobutene species derives from the stereospecificity of the reaction. Alkene... 

The results summarized in Scheme 25 indicate the following. First, lx)th Ni and Pd catalysts can induce and catalyze the desired bicyclization. Second, the product yields observed with Pd catalysts tend to be modest and lower than those observed with Ni catalysts. Both classes of catalysts have, however, been used in subsequent studies. The comparative usefulness of Ni and Pd catalysts in a given case should probably be experimentally determined. One significant factor affecting the yield of cascade bicyclization is the stereochemistry of the initial allylmetallation. If this step leads to tra i-l,2-disubstituted cyclopentane derivatives, they would not be converted to the desired bicycles, unless the stereochemistry is corrected under the reaction conditions. This stereochemical problem does not exist in cases of the enyne reaction. Presumably for this reason, the bicyclization yields appear to be more favorable in the enyne bicyclization. The cyclic allylmetaUation-Type II acylmetallation cascade mechanism shown in Scheme 26 has been suggested and generally accepted. 

However further studying of reaction mechanism by and C-labeling experiments [47] have shown that two kinds of metathesis dienes are obtained. Treatment of labeled enyne 38 with palladacycle complex 39 led to a mixture of 1,3-dienes 40 and 41, which were designated as single cleavage and double cleavage products, respectively (Scheme 7.22). 

SCHEME 7.65 Reaction mechanism and formation of by-products in the synthesis of echinopines by Vanderwal et al. (a) for enyne 112 and (b) enyne 113. 

The reaction mechanism of arylacetylene thermal polymerization has been studied on 4-(l-hexyloxy)-phenylacetylene i, used as a monofunctional model compound. Its linear dimers 2-5 [a diyne and 3 enyne isomers] were also synthetized and their thermal behavior investigated. Reaction products were analyzed by chromatography (HPLC, SEC), spectroscopy ( H and NMR) and spectrometry (SIMS) techniques. 

This type of cyclopropanation reaction catalyzed by a gold(I) complex produced cyclopropylmethyl carbene complex 321, which is reactive toward external alkenes or nucleophiles. The reaction depended on the ligand of the gold complex as well as the substituted patterns of enyne compounds. Echavarren and coworkers reported a cyclopropanation reaction mechanism. The cyclopropane gold complex intermediates 322 and 323 were trapped by external alkenes to give cyclopropanes 324 and 325, respectively (Scheme 1.157) [227]. 

The nonlinearity of the correlation between log k/ko) and Hammett (Tp constant at the cyclization of compounds 3.971 suggests that there is a change in reaction mechanism of C -C cyclization of the enyne carbodiimide, possibly from carbene to polar intermediates. Electron donor substituents X and Y increase probability of formation of the high polar zwitterionic carbene intermediate (Scheme 3.147, structures B and C), whereas electron-withdrawing substituents lead to a less polar carbenes (Scheme 3.147, structure A). The mechanism of polar intermediate is supported by a noticeable increase of the reaction rate with increasing the donor properties of the solvent that was observed for carbodiimide 3.971a. However, more detailed study of conditions of the... 

The key steps of the reaction mechanism (Scheme 15) follow those proposed for carbometallation of alkenes. It is noteworthy that the transmetallation with EtMgBr proceeds at the Zr-sp C bond, which is a rare phenomenon, and at the end of the catalytic cycle vinylmagnesium bromide 35 is obtained, which after hydrolysis affords the enyne 34. 

Interesting carbometallation was reported for the vanadocene rf-C5H5)2VCl2 36 catalyzed addition of trimethylaluminium to bis(trimethylsi-lyl)butadiyne. The reaction resulted in the formation of the dimethylated enyne 37 (Scheme 16) [23]. Although, the reaction itself was unprecedented and afforded purely the Z-isomer, its synthetic applicability at the present state is negligible because of the low overall yield of the product (27%) and its limited scope. No reasoning for a possible reaction mechanism was given. 

Recently, it has been shown that the titanocene dicarbonyl (rj -C5H5)2Ti(CO)2 113 is a convenient complex that catalyzes a number of cyclization reactions. Among suitable substrates are enynes that can be easily cyclized into the corresponding vinylmethylenecycloalkanes 114 (Scheme 48) in the presence of this compound. Representative examples are shown in Table 21 [62]. The reaction mechanism is outlined in Scheme 49 and proceeds through the formation of the titanacyclopentene 115, which is followed by j3-hydrogen elimination to 116 and, finally, by reductive elimination to 114. Formally, it resembles cyclization of dienes via metallacycle formation. 

The same reaction can be carried out under catalysis of the ruthenium complex 53. The reaction mechanism is identical with the one depicted in Scheme 49. The advantage of ruthenium catalysis is that enynes with various degree of the substitution of the double bond can be used for the construction of both five- and six-membered rings, and strikingly mild reaction conditions (in many cases the reaction proceeds at room temperature). Also, a number of functional groups are tolerated. Some typical examples are given in Table 22 [63]. 

While diene metathesis or diyne metathesis are driven by the loss of a (volatile) alkene or alkyne by-product, enyne metathesis (Fig. 2) cannot benefit from this contributing feature to the AS term of the reaction, since the event is entirely atom economic. Instead, the reaction is driven by the formation of conjugated dienes, which ensures that once these dienes have been formed, the process is no longer a reversible one. Enyne metathesis can also be considered as an alkylidene migration reaction, because the alkylidene unit migrates from the alkene part to one of the alkyne carbons. The mechanism of enyne metathesis is not well described, as two possible complexation sites (alkene or alkyne) exist for the ruthenium carbene, leading to different reaction pathways, and the situation is further complicated when the reaction is conducted under an atmosphere of ethylene. Despite its enormous potential to form mul-... 

With regard to the mechanism of the cycloisomerization, Fiirstner et al. found strong evidence of a metallacyclic intermediate. By labeling the allylic position of enynes 46 and 48, they showed that reactions yielding traws-annulated rings 47 transferred the deuterium atom to the exocychc double bond (eq. 1 in Scheme 10), whereas c -annulated rings 49 formed with complete preservation of the position of the deuterium atom (eq. 2 in Scheme 10). This corresponds well to a metallacycUc... 

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