Triple bond formation oxygen nucleophiles

On the other hand, when the oxidative carbonylation of a ,a -disubstituted propynylamines was carried out in the presence of an excess of CO2, the intermediate carbamate species could undergo cyclization with incorporation of CO2 into the five-membered cycle, either by direct nucleophilic attack of the carbamate oxygen to the triple bond coordinated to Pd(II) (Scheme 33, path a) or through the intermediate formation of a palladium carbamate complex followed by triple bond insertion (Scheme 33, path b). Carbon monoxide insertion into the Pd - C bond of the resulting stereoisomeric vinylpalladium intermediates then led to the final oxazolidi-none derivatives. 

This is further indicated in the reactions of 3-butyn-l-ol with [Fe( /2-CH2=CMe2)(CO)2( -C5H5)]+, which afford a mixture of dihydrofuran complex (64) and the oxacyclopentylidene complex (65) (84). The formation of these two derivatives involves a common tp-alkyne intermediate, which either forms 64 directly by internal nucleophilic attack of the oxygen on the complexed C=C triple bond, or rearranges to the vinylidene. This forms 65 by a similar attack of the hydroxy group on the a-carbon, followed... 

On the basis of the same principle, we developed a three-component synthesis of macrocycles starting from azido amide (46), aldehyde (47) and a-isocyanoaceta-mide (48) (the cx-isocyanoacetamides are easily available, see [84—86]) bearing a terminal triple bond (Scheme 11) [87]. The sequence is initiated by a nucleophilic addition of isonitrile carbon to the in situ generated imine 50 led to the nitrilium intermediate 51, which was in turn trapped by the amide oxygen to afford oxazole 52 (selected examples [88-94]). The oxazole 52, although isolable, was in situ converted to macrocycle 51 by an intramolecular [3+2] cycloaddition upon addition of Cul and diisopropylethylamine (DIPEA). In this MCR, the azido and alkyne functions were not directly involved in the three-component construction of oxazole, but reacted intramolecularly leading to macrocycle once the oxazole (52) was built up. The reaction created five chemical bonds with concurrent formation of one macrocycle, one oxazole and one triazole (Scheme 15). 

The formation of acyl halide-Lewis acid complexes can be demonstrated readily. Acetyl chloride, for example, forms both 1 1 and 1 2 complexes with AICI3 which can be observed by NMR. The existence of acylium ions has been demonstrated by X-ray diffraction studies on crystalline salts. For example, crystal structure determinations have been reported for p-methylphenylacylium and methyl-acylium " (acetylium) ions as SbF salts. There is also a good deal of evidence from NMR measurements which demonstrates that acylium ions can exist in non-nucleophilic solvents. The positive charge on acylium ions is delocalized onto the oxygen atom. This delocalization is demonstrated in particular by the short O—C bond lengths in acylium ions, which imply a major contribution from the structure having a triple bond ... 

The oxidation of terminal acetylenes, like that of monosubstituted olefins, often results in inactivation of the P450 enzyme involved in the oxidation. In some instances, this inactivation involves reaction of the ketene metabolite with nucleophilic residues on the protein [196, 197], but in other instances it involves alkylation of the prosthetic heme group (Fig. 4.31). Again, as found for heme alkylation in the oxidation of olefins, the terminal carbon of the acetylene binds to a pyrrole nitrogen of the heme and a hydroxyl is attached to the internal carbon of the triple bond. Of course, as one of the two m-bonds of the acetylene remains in the adduct, keto-enol equilibration yields a final adduct structure with a carbonyl on the original internal carbon of the triple bond [182, 198]. It is to be noted that the oxidation of terminal triple bonds that produces ketene metabohtes requires addition of the ferryl oxygen to the imsubstituted, terminal carbon, whereas the oxidation that results in heme alkylation requires its addition to the internal carbon. As a rale, the ratios of metabolite formation to heme alkylation are much smaller for terminal acetylenes than for olefins. 

Heterocyclization based on simple acetylenes requires a catalyst to be present [33, 447-449]. Haloacetylenes with alkyl or aryl substituents also undergo heterocyclization but less effectively. However, activated electron-deficient haloacetylenes readily react with nucleophiles. With binucleophiles, this reaction often leads to the formation of heterocycles. Haloacetylene often reacts in a similar manner to acetyl chloride, differing from the latter by the absence of released water. However, sometimes an unusual reaction occurs, as was shown by the reaction of dialkyl l-chloroacetylene-2-phosphonates with specific binucleophiles. l-Chloro-2-dialkoxyphorylacetylenes 4.981 react readily with diethyl acetamidomalonate in acetonitrile in the presence of potassium carbonate as a base, to form oxazoline derivatives 4.991. The reaction has two steps nucleophilic substitution of the acetylenic chlorine atom followed by attack of the amide oxygen atom on the triple bond activated by... 

Abstract The formation of carbon-oxygen bond upon addition of O-nucleophUes to unsaturated molecules is very attractive as it represents an atom economical strategy to prepare a variety of saturated compounds from olefins and vinylic derivatives from aUcynes. Group 8 metals, especially ruthenium have provided an important contribution in this field. We report here on iron- and ruthenium-catalyzed addition of nucleophiles to unsaturated systems. As additions to alkenes are still scarce with these metals and the use of iron catalysts is limited, the main part of the chapter is dedicated to addition of carbamates, carboxylic acids, alcohols and water to triple bonds with ruthenium catalysts. 

The proposed mechanism hypothesized the nucleophilic attack of the oxygen to the Pd-complexed C-C triple bond, through the enol amide form, producing the oxazole skeleton by formation of the c-alkenylpalladium complex. The intervention of water provided, through its enol form, the 4,5-dihydrooxazole-5-carbaldehyde. The oxidizing system also promoted the dehydrogenation step (Scheme 54). 

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