Benzyl reagent

A three-necked, round-bottomed flask equipped with a thermometer, reflux conductor, N, inlet and an overhead mechanical stirrer was charged sequentially with H O (5 mL), 50% NaOH (2 mL. 39 mmol), and adenine (2 g, 15 mmol). After the adenine had dissolved, a solution of benzylating reagent (16 mmol) and phase-transfer catalyst (5 mol%) in organic solvent (30-40 mL) was added. The system was stirred under reflux and then cooled to rt. The precipitated solids were filtered, washed with lIjO (2x10 mL), and dried in vacuo to give the crude bcnzylated adenine mixtures. For separation see ref 82. 

C-Alkylations of hindered aldehyde enamines can be effected with a variety of alkylating agents, but only allylic and benzylic reagents are useful for alkylations of unhindered systems.Acyclic, homoan-nular and heteroannular dienamines undergo alkylation primarily at the a-positions. ° As discussed above, reactions of enamines with electrophiles containing sp -hybridized carbon atoms have numerous limitations. On the other hand, enamine reactions with electrophilic alkenes are highly useful and have received wide coverage in the literature. 

Cyclobutanols. Grignard reagents induce rearrangement of oxaspiropentanes to cyclobutanones which react further. Benzylic reagents provide some cyclopropanols. 

The reactivity of the dialkyl complexes TiR2(LL)2 (LL = N,N -dimethylaminotroponiminato) has been widely studied. Reactions with CO and aldehydes or ketones afford unsymmetrical diolato complexes that convert to the corresponding vicinal diols after hydrolysis. CO and acetylene react to form the oxametallacyclopentene complex. Treatment with RNC yields the free imine and low-valent titanium species (Scheme 131). In the reaction with BucNC, free ButN=CMe2 is formed and the addition of benzaldehyde or benzyl reagents affords titanium diolato or enediolato complexes. Thiolato-alkoxo or amido-alkoxo titanium complexes can also be similarly prepared (Scheme 132).123-125... 

Lemieux and Kondo have prepared this ester by the reaction of benzyl alcohol, 2,4,6-trimethylpyridine or pyridine in CH2CI2, and triflic anhydride at -60°. It was shown to be a very powerful benzylating reagent, particularly for preparation of 2-O-benzyl derivatives of sugars. 

TABLE 6. Some Fundamental Features of the Benzylic Reagents in Pd-Catalyzed Cross-Coupling... 

Benzylation of a monoacetylated diol is shown in Example 1. The Dudley benzyl reagent was uniquely effeetive for protection of the free alcohol without loss and/or migration of the labile acetyl group. 

Example 4, In j//M-formation of the Dudley benzyl reagent is achieved by treating a mixture of an alcohol and 2-benzyloxypyridine with CHsOTf ... 

The Dudley reagents are employed for the protection of alcohols as benzyl or PMB ethers, respectively, under mild conditions. Carboxylic acids are readily protected as well. Activation of the appropriate Dudley reagent in the presence of an alcohol furnishes the desired aiylmethyl ether. The benzyl reagent is activated upon warming to approximately 80-85 °C, whereas activation of the PMB reagent occurs at room temperature upon treatment with methyl triflate (CHsOTf) or protic acid." Aromatic solvents, most commonly trifluorotoluene, often provide the best results. Magnesium oxide (MgO) is typically included in the reaction mixture as an acid scavenger. For benzylation of carboxylic acids, triethylamine (EtsN) is used in place of MgO. ... 

Zhang and co-workers reported the preparation of the two C2-dipho-sphine boranes 92 by nucleophilic attack of the carbanion derived from K)-PAMP to ftis(benzylic) reagents 91 (Scheme 4.42). 

Pd-catalyzed benzylation shares some fundamental features with Pd-catalyzed allylation. However, it is less complicated and generally more favorable than allylation, even though oxidative addition of benzylic electrophiles with Pd is kinetically less favorable than that of allylic electrophiles. Much of these differences between benzyl and allyl may be attributable to the fact that the li,y rr-bond in benzyl is part of an aromatic ring system and is hence less reactive toward Pd than that in allyl. Some fundamental features of the benzylic reagents in Pd-catalyzed cross-coupling are summarized in Table 6. 

Actually the first />-alkylation to be effected involved the benzyl reagent the yield of -benzylphenyl duryl ketone was only 22%, however 36.)... 

The benzyl reagent and quinoline have been reported to give a mixture of the 4-benzyl and the 2,4-dibenzyl derivatives (51). 

Of particular interest here is the behavior of pyridine toward the benzyl reagent since the principal product was 4-benzylpyridine (54). 

After a Michael addition, the expected conjugated addition product 14a is formed in 92% yield. The corresponding benzylic chloride (12b) requires a reaction time of 48 h leading to the benzylic zinc chloride (13b). Allylation of 13b provides the aromatic benzoate 14b in 87% yield (Scheme 7.6). The use of DMSO/ THF mixture has a favorable effect allowing the synthesis of substituted benzylic reagents such as 3 [9]. Similarly, the preparation of alkylzinc iodides is facilitated... 

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