Benzyl migration

A second, and more chemical, verification is due to Finke et al.,21 who also invented the descriptive phrase persistent radical effect and gave a prototype example to the extreme. The thermal reversible 1,3-benzyl migration in a coenzyme B12 model complex leads to the equilibrium of Scheme 9. Earlier work had shown that the reaction involves freely diffusing benzyl and persistent cobalt macrocycle radicals, but the expected self-termination product bibenzyl of benzyl was missing. Extending the detection limits, the authors found traces of bibenzyl and deduced a selectivity for the formation of the cross-products to the self-termination products of 100 000 1 or 99.999%. Kinetic modeling further showed that over a time of 1000 years only 0.18% of bibenzyl would be formed, and this stresses the long-time duration of the phenomenon. 

A more flexible approach to pyrroles has been developed (Tetrahedron Lett. 2004,45,9315) by Keiji Maruoka of Kyoto University. Rearrangement of 5 by the A1 complex 6 leads, by preferential benzyl migration, to the trisubstituted pyrrole 7. 

In an effort to define the scope of the benzyl migration reaction, and to elucidate its mechanism, Knabe et al.1 have treated a series of 1-substituted 1,2-dihydroisoquinolines with acids. The following reactions have been observed (a) rearrangement, (b) elimination of the C-l substituent, (c) disproportionation without rearrangement, (d) disproportionation after rearrangement, and (e) recovery of starting material (Scheme VIII). The results are summarized in... 

Some benzyl migrations have been observed in simple enamines,3,149 e.g., (144) (145) -y (146) allyl migrations have also been observed,3 e.g., (147) (148). 

It is interesting to note that Ph2MeSiH is the major monosilane from the disproportionation of PhMeSiH2 but that BzMe iH is the major monosilane from BzMeSiH2. It therefore appears that phenyl migration is more facile than methyl migration, but methyl is more facile than benzyl migration in these disproportionations. 

Fused bicyclic morpholones 145 and 146 have been synthesized in good yields but with modest diastereoselectivity from 1,3-oxazolidines 144 via reaction of the nitrogen of the oxazolidine with a metallocarbene intermediate followed by a benzyl migration (Scheme 37) <2003TA917>. 

Suzuki, Y., Takemura, Y., Iwamoto, K.-i., Higashino, T., Miyashita, A. Carbon-carbon bond cleavage of a-hydroxybenzylheteroarenes catalyzed by cyanide ion retro-benzoin condensation affords ketones and heteroarenes and benzyl migration affords benzylheteroarenes and arenecarbaldehydes. Chem. Pharm. Bull. 1998, 46,199-206. 

The reaction of benzylideneacetophenone oxide (37) with aqueous sodium hydroxide in ethanol at reflux for 1.5 h affords, on work-up, a 72% yield of the acid (38). The reaction proceeds via benzyl phenyl diketone, and isotopic labeling indicates that exclusive benzyl migration occurs. Benzyl 2-hyc oxyphe-... 

A solution to this problem was the introduction of a methyl group ortho to the imine group, as in complex 149, that sterically protects the complex from benzyl migration. The MAO-activated 149 is remarkably stable, and overall activity is moderate (about 50gPE (mmol M)-1 h-1 bar-1).1188... 

The cobalt—hydride intermediate has not been isolated and is virtually undetected. Cobalt hydride reaction with an olefin by first migrating the hydrogen atom from cobalt to a porphyrin nitrogen atom (78) or carbon atom (79) is precedented by the isomerization of a benzylcobalt chelate. In that case, the benzyl migrates reversibly from the cobalt to the carbon atom of the equatorial ligand.253... 

The existence of the methyl ylid under these experimental conditions receives support from the formation of 9 which was characterized by the g.c. peak enhancement technique 83>. The precursor of 9 must have been <5 m which undergoes a Stevens rearrangement with benzyl migration to give 9. The absence of 9 under Lepley and Becker s conditions 95> was one of the reasons that they ruled out the existence of the free ylid. It is unfortunate that neither the methyl ylid nor its lithio derivative could be trapped. It is also worth noting that in this formulation of the ylid, the anion is not included as it is throughout the discussion of trimethyl-ammoniummethylide. 

The reaction of carbene (from diazomethane) with N-methyl pyrrolidine gives products resulting from insertion into all of the C-H bonds but no N-methyl piperidine was formed by a Stevens rearrangement of the methyl ylid. However, when phenyl diazoacetate was treated with benzyldimethylamine, benzyl migration occurs presumably via an intermediate ylid 45>. 

Further work exploring the migratory aptitude of different substituents has been described [91l Phenylacetone is converted into benzyl acetate, showing exclusive benzyl migration in accordance with the chemical reaction achieved with tri-fluoroacetic acid. Different results were observed with phenacetaldehyde, where an inverted preference is seen as compared with the peracidic reactions. 

Scheme 16.34 Effective [l,2]-shift of oxonium ylides bearing benzylic migrating groups.

Fig. 27 Reaction of an imidazolium salt bearing phenol N-substituents with Zr(CH2Ph)4 in toluene and in THF, with the latter resulting in benzyl migration. ...

PPh3 concentrations a limiting rate is reached that presumably represents rate-determining benzyl migration to give the usual acyl type intermediate that is then trapped by nucleophile. The limiting rate constant increases... 

Scheme 1-280. Predominant inversion upon benzyl migration and almost exclusive retention upon trimethylsilyl migration to the lithiated centers of 361 and 362.

Upon prolonged standing or, more rapidly, upon refluxing for 4-18 hours, the sodium atom migrates and benzyl-sodium is formed, as is proved by the production of phenylacetic acid in good yield upon carbonation. 

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