Benzylic halides, homocoupling

Non-steroidal anti-inflammatory a-arylpropionic acids were also prepared from the corresponding benzylic chlorides and CO2 using as catalyst Ni-dppe or Ni-dppp in the presence of COD (Table 16) [103]. The use of the catalyst in this reaction is not absolutely required but its use limits the homocoupling reaction which would be the main process at high concentration of the benzylic halide and low pressure of CO2 [104]. 

We reported that smooth oxidative addition of organic halides such as aryl, benzyl, and allyl halides to metallic nickel proceeded to afford organonickel halides under mild conditions, which yielded homocoupled products [11, 41] or ketones by the reaction with acid chlorides [42] or alkyl oxalyl chlorides [43]. We describe here a new method for the preparation of 3-aryl-2-hydroxy-l-propanones (4) in good yield by the Grignard-type addition of benzyl halides to 1,2-diketones mediated by metallic nickel under neutral conditions [44]. 

In spite of the usefulness of these complexes, it is generally not possible to cause the satisfactory reaction with transition metals in the metallic state [86] under mild conditions due to their poor reactivity. We have reported that activated metallic nickel, prepared by the reduction of nickel halide with lithium, underwent oxidative addition of benzylic halides to give homocoupled products [45]. We reported that carbonylation of the oxidative adducts of benzylic halides to the nickel proceeded smoothly to afford symmetrical 1,3-diarylpro-pan-2-ones in moderate yields, in which the carbonyl groups of alkyl oxalyl chlorides served as a source of carbon monoxide [43] see Equation 7.5. 

One possible mechanistic sequence for the present reaction is shown in Scheme 7.1. The carbon monoxide insertion into the carbon-metal o bond of alkyltransition metal complexes is well known [88]. Thus, the oxidative addition of benzyl halide to metallic nickel gives benzylnickel (II) halide 4, and the insertion of carbon monoxide, which is formed by decarbonylation of alkyl oxalyl chloride into the benzyl-nickel bond of complex 4, would afford arylacetyl (II) complex 5. The metathesis of complexes 4 and 5 seems to give (arylacetyl)benzylnickel complex 6, which undergoes reductive elimination to yield l,3-diarylpropan-2-one, 3. The formation of 1,2-diarylethane may be explained by the reductive elimination of bisbenzylnickel complex 7 formed by metathesis of benzylnickel complex 4 [89]. It is also possible that the reaction of benzyl halide with complex 4 or 5 gives homocoupled product or ketone, respectively. 

Metallic nickel was easily prepared by stirring a mixture of nickel halide and lithium metal (2.3 equiv) with naphthalene (0.1 equiv) as an electron carrier at room temperature for 12 h in DME (glyme) (Equation 7.9). The resulting black powders which slowly setded in a colorless solution after stirring was stopped were used for the reductive homocoupling reaction of benzylic halides (Equation 7.10). 

The results of the reaction of benzyl and substituted benzyl halides with metallic nickel powders are summarized in Table 7.13. Benzyl chloride reacted at room temperature with metallic nickel prepared from nickel chloride to give a mixture of the coupled product bibenzyl (40%) and the reduction product toluene (60%). However, the coupled product was found to be formed mainly when the reaction was run at 70°C and when the nickel powders used were prepared from nickel iodide. Under these conditions, a yield of 86% bibenzyl was attained. The fact that iodide ion present in the system facilitates the homocoupling reaction may be ascribed to the chlorine-iodine exchange during the reaction [148]. Higher reaction temperatures such as 70°C may also accelerate the exchange reaction. 

Thus, the homocoupling reaction might be reasonably explained by the smooth oxidative addition of benzyl halide to nickel in the metallic state, which... 

The oxidative addition of Mn to benzyl halides was completed at rt in 20 min in THF (Scheme 8.1). Small amounts (3-9%) of the homocoupling product of benzyl halide were observed. This problem was improved by using more highly active manganese [16] prepared from manganese iodide. Trace amounts (<1%) of homocoupling product were formed in this case. 

The resulting benzylic manganese reagents were found to undergo a variety of cross-coupling reactions. It was also found that homocoupled products of functionalized benzyl halides could be readily prepared depending on reaction conditions. 

We examined the homocoupling of benzyl halides under the influence of active manganese in a wide variety of conditions. As shown in Table 8.15, lequiv of active manganese and 2 equiv of benzyl bromide produced 47% of homocoupling products. But the homocoupling yield was decreased to 27% by using 1 equiv of benzyl bromide. 

Best results were obtained when the active manganese was added to the neat benzyl bromide. The reaction was completed within 10 min at rt without a catalyst [39]. Several other benzyl halides produced good to excellent yields of homocoupling products, which showed a wide tolerance of functional groups such as nitrile, ester, nitro, chloro, bromo, methoxy, and methyl groups (Table 8.16). 

Functionalized organozinc halides are best prepared by direct insertion of zinc dust into alkyl iodides. The insertion reaction is usually performed by addition of a concentrated solution (approx. 3 M) of the alkyl iodide in THF to a suspension of zinc dust activated with a few mol% of 1,2-dibromoethane and MeaSiCl [7]. Primary alkyl iodides react at 40 °C under these conditions, whereas secondary alkyl iodides undergo the zinc insertion process even at room temperature, while allylic bromides and benzylic bromides react under still milder conditions (0 °C to 10 °C). The amount of Wurtz homocoupling products is usually limited, but increases with increased electron density in benzylic or allylic moieties [45]. A range of poly-functional organozinc compounds, such as 69-72, can be prepared under these conditions (Scheme 2.23) [41]. 

Kagan also showed that allylic, benzylic and propargylic halides undergo efficient reaction with ketones (Scheme 5.65).98 Importantly, in the absence of ketone, these alkyl halides react rapidly with Sml2 to yield Wurtz homocoupled products, hence the use of Barbier conditions is crucial. 

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