Benzylmagnesium bromide

Strecker153 reported in 1910 that the reaction of thionyl chloride with two equivalents of phenylmagnesium bromide or benzylmagnesium bromide afforded diphenyl or dibenzyl sulphoxides, respectively (equation 49 Table 8). The corresponding sulphides are formed as by-products of this reaction. Recently, other sulphoxides were prepared by this procedure154,155. It should be pointed out that this rather simple approach to the synthesis of symmetrical sulphoxides has not yet found wider application. 

Omission of the phenolic group from cyclazocine results in a molecule which retains analgesic activity. In a classical application of the Grewe synthesis,15 the methylated pyridinium salt 54 is condensed with benzylmagnesium bromide. There is thus obtained the dihydropyridine 55. Treatment of that intermediate with sodium borohydride results in reduction of the iminium function to afford the tetrahydro derivative 56. Cyclization of 56 on treatment with acid leads to the desired benzomorphan nucleus. The cis compound (57) is separated from the mixture of isomers and demethylated by the cyanogen bromide procedure (58,... 

In 1973, Taddei succeeded in preparing optically active (+)-benzyl-z-propylmethyl-phenyltin, (+)-(62), by a reaction of the optically unstable z -propylmethylphenyltin menthoxide with benzylmagnesium bromide U) (see Table 4). This asymmetric induction very probably does not yield an optically pure compound but is a very rapid and facile route to optically active organotin compounds of unknown optical purity. 

Figure 3.50. Scope of Pd/54-catalyzed asymmetric cross-coupling of vinyl bromides with a-(trimethylsilyl)benzylmagnesium bromide.

The synthetic route to clomiphene is in fact very close to that used for its nonbasic parent. The basic side chain, usually referred to as a basic ether, is incorporated in the first step by alkylation of the phenol in 4-hydroxybenzophenone (6-1) with 2-chlorotriethylamine. The addition of benzylmagnesium bromide to the product (6-2) affords the tertiary alcohol (6-3). 

Essentially the same route is followed for the synthesis of the triphenylethylene nitromifene (8-5). The sequence starts with Friedel-Crafts acylation of the alkylation product (8-1) from phenol and 1,2-dibromoethane with the acid chloride from anisic acid (8-2). The displacement of bromine in the product (8-3) with pyrrolidine leads to the formation of the basic ether and thus (8-4). Condensation of that product with benzylmagnesium bromide gives the tertiary alcohol (8-5). This product is then treated with a mixture of nitric and acetic acids. The dehydration products from the first step almost certainly consist of a mixture of the E and Z isomers for the same reasons advanced above. The olefin undergoes nitration under reaction conditions to lead to nitromifene (8-6) as a mixture of isomers [8] the separated compounds are reported to show surprisingly equivalent agonist/antagonist activities. 

Optically active allylsilanes. Optically active allysilanes have now been obtained by coupling a-(trimethylsily1)benzylmagnesium bromide with vinyl bromides, effected with PdCl2 complexed with the ferrocenylphosphine (R)-(S)-PPFA (this volume, la). The (R)-isomer is formed preferentially, usually in high optical purity. 

The synthetic drawbacks of amino-substituted reagents are not observed when using resonance stabilized carbanions such as a-deprotonated nitriles 77) and carbonyl compounds 25), or allyl-21 and benzylmagnesium bromide 77), the corresponding very reactive tris-aminotitanium reagents undergoing rapid (—78 ° to —20 °C, 0.5 h) Grignard-type addition (80-95 % yields). 

The Freund reaction of 3,4-dimethylpyridine methobromide and benzylmagnesium bromide affords a mixture of two isomeric di-hydropyridines (46a, b). The partial reduction of the latter isomer to l,3,4-trimethyl-6-benzyl-3-piperideine (47) was performed by hydrogenation (Pd/BaS04), or by the action of sodium borohydride, or on treatment of the perchlorate with lithium aluminum hydride.39... 

Benzotriazol-l-yl)-2//-azirines 847, obtained by treatment of oximes 846 with tosylchloride and aqueous KOH, were reacted with benzylmagnesium bromide or 4-methylbenzylmagnesium bromide in the presence of zinc chloride and gave 2-benzyl-2//-azirines 848. Potassium phthalimide and the sodium salt of benzenethiol converted the 2-(benzotriazol-l-yl)-2//-azirines 847 into novel 2//-azirines 849 and 850 (Scheme 211) <2003JOC9105>. 

The palladium/PPFA-catalyzed asymmetric cross-coupling of a-(trimethylsilyl)-benzylmagnesium bromide 25 has also been applied to the synthesis of optically active propargylsilane 29 (18% ee) by the use of l-bromo-2-phenylacetylene as a coupling partner (Scheme 2-18) [37]. 

To that end, the logarithms of the pseudo-first-order rate constants for reactions of 0.02 M Grignard reagent with 0.25 M benzophenone were plotted against the (corrected) voltage of an anodic process at a current density of /i, = 0.06 A cm ( o.oe) [46]- An approximate linear correlation was obtained for methyl-, ethyl-, isopropyl-, t-butyl-, and benzylmagnesium bromide, which, as the author carefully worded it,... 

Kinetic isotope effects were positive for methyl-, phenyl-, and ortho-to y Grignard reagents in diethyl ether, weak for benzylmagnesium bromide, and near zero for allyl-, crolyl-, and ffeTt-butylmagnesum halides. 

Benzylmagnesium bromide is also reported to react by an electron-transfer mechanism [70] with pyridazin however, a polar mechanism was involved in the reaction of benzylmagnesium bromide with benzil [71]. 

As expected, altering a reaction parameter, such as temperature, can facilitate nucleophilic substitution, over the other types of reactions [Eq. (12) 11]. In this example, at —50 C, nucleophilic substitution predominates, with the vinyl fluoride undergoing substitution with the benzylmagnesium bromide, instead of the competitive nucleophilic addition to the carbonyl or the olefin. 

Allylic alcohols do not react with alkyl- and aryl-Grignard reagents [90]. However, Swierezewski [91] reported that methyl-, phenyl-, and benzylmagnesium bromides reacted with allylic alcohols in the presence of a catalytic amount of NiCl2(PPh3)2 to give either a mixture of SN2/SN2 -coupled products, or when Ri or R2 is equal to phenyl, to the sole Sn2 compound [Eq. (91) and Table 23]. The same selectivity has been observed by Wenkerl in similar conditions [92]. 

Benzyldihydrothebaine results from the interaction of thebaine and benzylmagnesium bromide [2]. 

The asymmetric cross-coupling was successfully applied to the synthesis of optically active allylsilanes [50,51] (Scheme 10). The reactions of a-(trimethyl-silyl)benzylmagnesium bromide (49) with vinyl bromide (4b), (E)-bromopro-pene (( )-50), and (R)-bromostyrene E)-8) in the presence of 0.5 mol % of a palladium complex coordinated with chiral ferrocenylphosphine, (R)-(S)-PPFA (10a), gave the corresponding (R)-allylsilanes (51) with 95%, 85%, and 95% ee, respectively, which were substituted with phenyl group at the chiral carbon center bonded to the siHcon atom. These allylsilanes were used for the S. ... 

Some organoboron compounds can also be obtained by transmetallations for example, the alkyl groups of trialkylborons are replaced stepwise by benzyl groups on treatment of the compounds with benzylmagnesium bromide.228... 

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