Nickelacycle alkylation

Nickelacycle 66 also reacts with aliphatic halides. Usually, allq lation reactions were carried without isolating any intermediate by treating anhydride 63 with 1.5 equiv each of Ni(COD)2 and ligand in THE at 23 °C for 5 h, followed by addition of excess alkyl halides (10-20 equiv)... 

The alkylation reactions proceed with moderate to good yields with primary iodides (Entries 1,3,6, and 7) or bromides (Entries 2,4, and 5) in the absence of additives or polar solvents. The only byproducts detected were small amounts of ( )-a- and P-A -phthaloyl alanines and ( )-A -phthaloyl aspartic acid. In a few instances, small amounts of A Vinylphthalimide, resulting from double decarboxylation, were also detected. Shorter reaction times were required when the reaction was performed at 40 °C. Secondary iodides also gave alkylated derivatives (Entries 8 and 9). However, no alkylation was observed when more hindered substrates, such as a-cholestanyl iodide and menthyl iodide or bromide were used. These halides were recovered unchanged or suffered elimination to afford mixtures of alkenes after several days at room temperature. On the other hand, no alkylation took place with methyl p-toluenesulfonate, ethyl triflate, and propylene oxide under the same reaction conditions. Similarly, alkenyl and aiyl halides were unreactive with nickelacycles. 

In contrast with the results obtained with simple allqfl halides, benzyl bromide leads to the formation of 77 and the ketone 78 in variable ratios (Scheme 26). A similar result has been reported in the reactions between the oxidative addition product of Ni(COD)bpy or Ni(COD)TMEDA with cw-4-cyclohexen-l,2-dicarboxylic anhydride and alkyl iodidesWith allyl bromide as the electrophile, ketone 79 is the only product isolated. However, when the reaction is performed with isolated nickelacycle 66 in the absence of Ni(CO)2Me2Phen, allylated alanine 80 is formed exclusively (60% yield) (Scheme 26). These results show that the carbonyl nickel complex is not inert because with certain reagents it transfers CO to the nickeMactone 66. Alternatively, the formation of ketones in these reactions could be explained by alkylation of the primary oxidative addition product or by carbonylation of allyl or benzyl bromide to give acyl bromides which react with 66 to give the observed products. However, this last reaction pathway seems unlikely because acetyl or benzoyl chloride do not react with in situ generated nickelacycle 66. 

As shown throughout this article, nickelacycles of general structure 1 can be prepared in a number of ways, mainly by oxidative addition to cyclic anhydrides followed by decarbonylation and by oxidative coupling of CO2/RNCO with alkenes and alkynes. These oxa- and azanickelacycles react by -elimination, oxidation, insertion, and alkylation reactions. Although most of the chemistry uncovered so far requires stoichiometric... 

Under milder conditions, and with the right choice of ligands, nickelacycles 4,288 can be isolated that may correspond to intermediates in the decarbonylation-decarboxylation reaction, and are related to carboxylation products (see Scheme 4.93). The alkyl carbon-nickel bond in these complexes can be intercepted by both alkyl halides (Scheme 4.100)," and organometallic species (Scheme 4.101). ... 

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