Enynals, reactions

Very recently, Genet and Michelet developed a diastereoselective reaction that took place by hydroamination of an unactivated alkene followed by a cydization process under very mild conditions. This 1,6-enyne reaction was compatible with electron-poor aromatic amines, including amines bearing chloride atoms (Equation 8.73), which is very useful for further functionalization of the substituted aniline ring [164]. 

It should be noted that nonmetathetical enyne reactions to afford 1,3-dienes are known to be catalysed by low-valent transition metals for a recent review see Ref. [96]. 

Terminal enynes Reaction of aryl Grignard reagents with pyridazine 1-oxide leads exclusively to terminal (E)-enynes in 50-75% yield. Alkyl Grignard reagents lead to 1,3-dienes in rather low yield. 

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. 

SCHEME 17.17 Synthesis of substituted benzene by enyne reaction between an alkyne and a 1,3-diene. (Adapted with permission from Ref. [10]. Copyright (2009) American Chemical Society). 

Under the same mechanistic concept, when endocyclic double bonds are present, the metathesis allows the ring expansion to bridged bicycles (Reaction a Scheme 7.21) [44]. Although cyclobutane mechanistic pathway has been debated for several years, it was rarely supported by the isolation of cyclobutanes or isomerized cyclobutanes formed from the cyclization of 1,6-, 1,7-, or 1,8-enynes (Reaction b Scheme 7.21) [45,46]. 

Terminal alkynes undergo the above-mentioned substitution reaction with aryl and alkenyl groups to form arylalkynes and enynes in the presence of Cul as described in Section 1.1.2.1. In addition, the insertion of terminal alkynes also takes place in the absence of Cul, and the alkenylpalladium complex 362 is formed as an intermediate, which cannot terminate by itself and must undergo further reactions such as alkene insertion or anion capture. These reactions of terminal alkynes are also treated in this section. 

The benzene derivative 401 by the intermolecular insertion of acrylate[278], A formal [2 + 2+2] cycloaddition takes place by the reaction of 2-iodonitroben-zene with the 1,6-enyne 402. The neopentylpalladium intermediate 403 undergoes 6-endo-lrig cyclization on to the aromatic ring to give 404[279],... 

The cyclic 2,4-dienoate 184, formed by the Pd-catalyzed cyclization of the 1,6-enyne 183, reacted with 154 to form the azulene derivative 185[118], The 3-methylenepyrrolidine 188 is formed by the reaction of the Zn reagent 186 with the chiral imine 187 with high diastereomeric excess. The structure of the allylic ethers is important for obtaining high diastereoselectivity[l 19],... 

Another interesting transformation is the intramolecular metathesis reaction of 1,6-enynes. Depending on the substrates and catalytic species, very different products are formed by the intramolecular enyne metathesis reaction of l,6-enynes[41]. The cyclic 1,3-diene 71 is formed from a linear 1,6-enyne. The bridged tricyclic compound 73 with a bridgehead alkene can be prepared by the enyne metathesis of the cyclic enyne 72. The first step of... 

The Pd(0)-catalyzed addition of trimethylsilyl iodide to an alkyne, followed by capture with alkynylstannane, affords the stereo-defined enyne 186. The reaction is explained by the oxidative addition of iodosilane, the insertion of an alkyne to generate the vinylpalladium 185, and the capture of 185 with the alkynylstannane 184[102]. 

Fluonnated ylides have also been prepared in such a way that fluonne is incorporated at the carhon P to the carbamonic carbon Vanous fluoroalkyl iodides were heated with tnphenylphosphine in the absence of solvent to form the necessary phosphonium salts Direct deprotonation with butyUithium or hthium dusopropy-lamide did not lead to yhde formation, rather, deprotonation was accomparued by loss of fluonde ion Flowever deprotonation with hydrated potassium carbonate in thoxane was successful and resulted in fluoroolefin yields of45-S0% [59] (equation 54) P-Fluorinated ylides may also be prepared by the reaction of an isopropyli-denetnphenylphosphine yhde with a perfluoroalkanoyl anhydnde The intermediate acyl phosphonium salt can undergo further reaction with methylene tnphenylphosphorane and phenyUithium to form a new yhde, which can then be used in a Wittig olefination procedure [60] (equation 55) or can react with a nucleophile [6/j such as an acetyhde to form a fluonnated enyne [62] (equation 56)... 

The direction of addition, verified by acetylene oxidation into a known acid, proves that the nitiilimine carbon atom adds to the terminal atom of the enyne system, which is inconsistent with the assumed polarization of the unsaturated compound H2C=CH—C=C—R from the vinyl group towardR. The authors explain this by a possible transfer of the reaction center in nitrilimine as a particle with a nucleophilic center on a carbon Ph—C=N" —N —Ph Ph—C =N =N—Ph (63ZOB3558). 

The ease with which the dipolarophile interacts with vinylacetylenes depends mainly on a spatial factor. The study of the reactions of alkylthiobuten-3-ynones-l and their selenic and telluric analogs with DPNT shows that, in this case, nitrilimine also acts as a nucleophilic agent with a nucleophilic center on the carbon atom of the 1,3-dipole and always adds to the terminal carbon of the enyne system to form l,3-diphenyl-5-/ -2-pyrazolenines. The oxidation of the latter with chloranil leads to alkynylpyrazoles (65ZOR51). 

An example of the reaction of hydrazones with enynes is reported in a German patent (91GEP4001600). The alkynylpyrazoles were prepared by treating of RNHN=CR C02R2 with CH2=CR 0R" (R =C1, Br R = alkyl) followed by aromatization with acid (Scheme 26). 

---