Butylmagnesium chloride

Solutions of tert.-butylmagnesium chloride and cyclopentylmagnesium chloride in diethyl ether can be prepared in the same way. In these cases also the purity of the chlorides Is of great importance for a successful and smooth conversion into the Grignard reagent. 

The crude tosylate obtained after evaporation of the diethyl ether was dissolved In 150 ml of THF. After addition of 1 g of CuBr the solution was cooled to -10°C and a solution of tert.-butylmagnesium chloride in 250 ml of THF, prepared from 0.40 mol of -butyl chloride and magnesium (see Chapter II, Exp. 4) was added... 

The actual mechanism by which a particular reaction proceeds strongly depends on the nature of the organomagnesium reagent. For instance benzophenone reacts with methylmagnesium bromide by a polar mechanism, while the reaction with t-butylmagnesium chloride proceeds for steric reasons by a SET-mechanism. 

The yield of w-butylmagnesium chloride is increased to 80% (analyzed by evolution of w-butanc) if twice the stated amount of magnesium is used. 

Merck s thienamycin synthesis commences with mono (V-silylation of dibenzyl aspartate (13, Scheme 2), the bis(benzyl) ester of aspartic acid (12). Thus, treatment of a cooled (0°C) solution of 13 in ether with trimethylsilyl chloride and triethylamine, followed by filtration to remove the triethylamine hydrochloride by-product, provides 11. When 11 is exposed to the action of one equivalent of tm-butylmagnesium chloride, the active hydrogen attached to nitrogen is removed, and the resultant anion spontaneously condenses with the electrophilic ester carbonyl four atoms away. After hydrolysis of the reaction mixture with 2 n HC1 saturated with ammonium chloride, enantiomerically pure azetidinone ester 10 is formed in 65-70% yield from 13. Although it is conceivable that... 

Polarization also occurs in coupling and disproportionation reactions of Grignard reagents with alkyl halides. The vinyl protons of isobutene produced in the reaction of t-butylmagnesium chloride with t-butyl bromide show A/E polarization as do the methyl protons of isobutane (Ward et al., 1970). Similar results arise in the reaction of diethyl-magnesium with organic halides (Kasukhin et al., 1972). 

Mikolajczyk and coworkers have summarized other methods which lead to the desired sulfmate esters These are asymmetric oxidation of sulfenamides, kinetic resolution of racemic sulfmates in transesterification with chiral alcohols, kinetic resolution of racemic sulfinates upon treatment with chiral Grignard reagents, optical resolution via cyclodextrin complexes, and esterification of sulfinyl chlorides with chiral alcohols in the presence of optically active amines. None of these methods is very satisfactory since the esters produced are of low enantiomeric purity. However, the reaction of dialkyl sulfites (33) with t-butylmagnesium chloride in the presence of quinine gave the corresponding methyl, ethyl, n-propyl, isopropyl and n-butyl 2,2-dimethylpropane-l-yl sulfinates (34) of 43 to 73% enantiomeric purity in 50 to 84% yield. This made available sulfinate esters for the synthesis of t-butyl sulfoxides (35). 

In this series, too, replacement of the N-methyl by a group such as cyclopropylmethyl leads to a compound with reduced abuse potential by virtue of mixed agonist-antagonist action. To accomplish this, reduction of 24 followed by reaction with tertiary butylmagnesium chloride gives the tertiary carbinol 27. The N-methyl group is then removed by the classic von Braun procedure. Thus, reaction with cyanogen bromide leads to the N-cyano derivative (28) hydrolysis affords the secondary amine 29. (One of the more efficient demethylation procedures, such as reaction with ethyl chloroformate would presumably be used today.) Acylation with cyclopropylcarbonyl chloride then leads to the amide 30. Reduction with lithium aluminum hydride (31) followed by demethylation of the phenolic ether affords buprenorphine (32).9... 

With f-butylmagnesium chloride the substitution of only one chlorine atom of the phosphorus trichloride is possible, giving dichloro-t-butylphosphine (65-70%). 

An interesting application of a 1,2-disubstituted cyclopropanol in a seven-membered ring-annelation methodology has been developed by Cha et al. [82], The cyclopropanol 124, obtained from methyl 1-cyclopentenecarboxylate (123) and 4-(triisopropylsilyloxy)-butylmagnesium chloride, was converted to a 1,2-dialkenylcyclopropanol bis-silyl ether, which, by a subsequent facile Cope rearrangement, afforded the cycloheptadiene-anne-lated cyclopentane derivative 125 in 32% overall yield (Scheme 11.32). 

To a solution of phosphorus trichloride (6.4 g) in dry tetrahydrofuran (20 mL) was added tert-butylmagnesium chloride (1.0 M THF solution, 52 mL) at —78°C under an argon atmosphere over a period of 2 hours. 

Addition of RMgBr to nitriles. Grignard reagents react with nitriles slowly if at all, but even r-butylmagnesium chloride will add to nitriles in refluxing THF when catalyzed by a copper(I) salt. The adduct can be converted to a ketimine by anhydrous protonation, to a primary amine by reduction (Li/NH,), or to a ketone by hydrolysis. The actual reagent may be a cuprate such as R3Cu(MgX)2. 

Dichlorobis(cyclopentadienyl)titanium-sec-Butylmagnesium chloride, Cp2TiCl2-sec-BuMgCl (1). 

Bouveault reactionDMF is recommended for formylation of tertiary Grig-nard reagents. Thus pivaldehyde can be obtained in 57-61% yield by reaction of r-butylmagnesium chloride with twofold excess of DMF in ether. 

Butyltin trichloride reacts with the sodium salt of 2-mercaptoethanol to give a trinuclear oxathiastannolane, which, with butylmagnesium chloride, gives an oxathiaststannolane dimer, which can be prepared also from the reaction of butanestannonic acid with 2-mercaptoethanol (Equation (172)).s... 

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