Benzylmagnesium chloride, reaction with

The reaction of benzylmagnesium chlorides wnth thiophenealde-hydes and thienyl ketones has been used for the preparation of styrylthiophenes and 1,2,2-triarylethylenes, which are of biological interest. In stilbene and 1,2,2-triphenylethylene the reactivity toward electrophilic reagents is transferred with deactivation to the double bond. However, styrylthiophene is formylated and acylated... 

The stereospecific conversion of menthyl arenesulphinates into chiral aryl methyl sulphoxides may also be achieved by means of methyllithium . The reaction of methyllithium with diastereoisomerically or enantiomerically pure arenesulph-inamides 283 was found to give optically active aryl methyl sulphoxides 284 (equation 156). The preparation of optically active sulphoxides 285 and 286, which are chiral by virtue of isotopic substitution (H - D and - respectively), involves the reaction of the appropriate non-labelled menthyl sulphinates with fully deuteriated methyl magnesium iodide (equation 157) and with benzylmagnesium chloride prepared from benzyl chloride labelled with carbon (equation 158). 

The related 6-trifluoromethyl-l,3-dioxin-4-ones underwent conjugate addition reactions with Gilman reagents, or with Grignards with copper(I) catalysis (Eq. 112). The 6-substituted compounds were also available, and were used to synthesise threonine and aZZo-threonine analogues [303]. Stark contrast between the behaviour of fluorinated and non-fluorinated compounds is revealed in Eq. (113). While benzylmagnesium chloride adds smoothly to the 6-methyl... 

The carbonyl groups in 4//-thiopyrans 20a were easily reduced to diastereomeric hydroxy derivatives 606a.61,370 The reaction of 20a with benzylmagnesium chloride gave benzylidene derivatives 606b370 and with phenylhydrazine the corresponding SchifF bases 606c.61,99... 

Synthesis (Pohland, 1953 1955 1963 janssen and Karel (Janssen)1956 Sullivan et al., 1963) In the Grignard reaction of 3-dimethylamino-2-methyl-1-phenyl-propan-lone with benzylmagnesium chloride 4-dimethylamino-3-methyl-1,2-diphenyl-butan-2-ol is formed. The preferred product is the a-diastereomer(75 % a-form, 15 % p-form). The a-form crystallizes and the diastereomeric p-form remains in solution, because of its better solubility. Racemic resolution to obtain the analgetically (+) enantiomer can be achieved on the pure a-Grignard product via fractional crystallization of the salts with D-camphorsulfonic acid. Alternatively the resolution can be achieved by treating the racemic mannich product 3-dimethylamino-2-methyl-1-phenyl-propan-1-one with (-)-dibenzoyltartaric acid in acetone as solvent. 

The immonium salt (98) on reaction with numerous nucleophiles yields 9-substituted indolizidines. From the reaction with benzylmagnesium chloride, (100 R = Ph) is obtained (100 R = C02Et) results from a Reformatsky reaction. Reaction of the bridgehead substituted indolizidines (100) with methyl iodide and base results in /3-elimination with ring opening, a nine-membered heterocycle (101) being formed. This type of reaction has been varied widely. 

Depending upon the conditions, the reaction of benzylmagnesium chloride with benzal-dehyde can yield benzylphenylmethanol, dibenzoylphenylmethane and 1,3-diphenyliso-chroman. The last product arises from the acid-catalyzed dehydration of the 1,5-diol (296), which is the predominant product when the Grignard reagent is added to benzaldehyde at room temperature (Scheme 81) (51 3163). There was no evidence for the formation of o-methylbenzhydrol, consistent with the lack of this type of product with citronellal and various simple aliphatic aldehydes (44JA354,51JA3237). 

As an example, a reaction of benzylmagnesium chloride with 1-(1-isopropoxybenzyl)benzotriazole gave 1 -isopropoxy-1,2-diphenylethane, b.p. 70°/0.04 mmHg (85%). 

The reaction of aliphatic thioureas 26 with benzylmagnesium chlorides gives carbodiimides 27 (R = Me, Pr, i-Pr) in 60-72 % yields. ... 

The diols (97) from asymmetric dil droxylation are easily converted to cyclic sii e esters (98) and thence to cyclic sulfate esters (99).This two-step process, reaction of the diol (97) with thionyl chloride followed by ruthenium tetroxide catalyzed oxidation, can be done in one pot if desired and transforms the relatively unreactive diol into an epoxide mimic, ue. the 1,2-cyclic sulfate (99), which is an excellent electrophile. A survey of reactions shows that cyclic sulfates can be opened by hydride, azide, fluoride, thiocyanide, carboxylate and nitrate ions. Benzylmagnesium chloride and thie anion of dimethyl malonate can also be used to open the cyclic sulfates. Opening by a nucleophile leads to formation of an intermediate 3-sidfate aiuon (100) which is easily hydrolyzed to a -hydroxy compound (101). Conditions for cat ytic acid hydrolysis have been developed that allow for selective removal of the sulfate ester in the presence of other acid sensitive groups such as acetals, ketals and silyl ethers. 

CH2CH=CH2. M = W R = vy). With benzylmagnesium chloride under CO, this latter reaction forms the acyl... 

Dimethyl and diethyl sulfates have been widely employed in the synthesis of alkylbenzenes and alkylnaphthalenes from aryl- and benzyl-type organometallic reagents. The final methyl groups of isodu-rene and pseudocumene are introduced in this manner. The reaction is superior to the Wurtz synthesis (method 9) for the preparation of o- and -diethylbenzenes. n-Propylbenzene obtained from benzylmagnesium chloride and diethyl sulfate ° is contaminated with a "rearranged product, f -ethyltoluene. ... 

Other authors have also described copper catalysis in the Grignard reaction. In the presence of copper salt, cyclohexene oxide reacts with phenylmagnesium chloride under mild conditions to give tra s-2-phenylcyclohexanol in good yield in the absence of the catalyst, the conversion is low. At the same time, benzylmagnesium chloride led to a yield of 90% even without the catalyst. The reactions between epoxynitriles and Grignard reagents have likewise been studied in detail. ... 

Interesting publications of work undertaken in this field of reactivity by a research group in (what at that time was part of) the USSR, unfortunately, was published mainly in rather inaccessible journals. The rates of reaction of phenylacetylene with ethyl- and phenylmagnesium bromide were measured in diethyl ether and in tetrahydrofuran, respectively [32]. The results, presented in Table 8, clearly show the dramatic change in the second-order rate constants, when diethyl ether is replaced by tetrahydrofuran as the solvent. The same effect had been found in 1968 by others [33] for the reaction of benzylmagnesium chloride with phenylacetylene at 0°C the second-order rate constant (/c2 X 10 L mol sec ) was 0.008 in diethyl ether and 84 in tetrahydrofuran, a change by a factor of (more than) 10 thousand. 

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