Isopropylmagnesium

The conjugate addition of trichloromethylmagnesium chloride, prepared from 2.7 equivalents of isopropylmagnesium chloride and one equivalent of carbon tetrachloride at 110 C, to 8 (R1 = CH3) gave 9 with overall selectivity of 98 2 in 99% yield31. 

The procedure described is essentially that of Lawesson and Frisell.4 2-Hydroxythiophene has been prepared in low yields by Hurd and Kreuz 5 from 2-thienylmagnesium bromide and oxygen in the presence of excess isopropylmagnesium bromide. 

Aziridines have been opened by organometallic reagents to give amines. Although less reactive than epoxides, it is also possible to open aziridines with organometallic reagents. Isopropylmagnesium chloride reacts with A-tosyl 2-... 

The magnesium enolates are prepared by treatment of malonic acid half ester either with magnesium ethylate[24],[32] or with isopropylmagnesium bromide[24] or chloride.t26] Ref. [23] describes the synthesis of a 13C-labelled ethyl acetoacetate. Concerning the synthesis of porphyrin / -ketoesters,[3 1 it was noticed that the method via imidazolides is more efficient than the other approach via acid chlorides and sodiomalonic esters. 

A trapping experiment of the optically active triorganotin chloride (5) with isopropylmagnesium bromide did give the expected methylneophylphenylisopropyltin (9) in a 20% yield but unfortunately, this tetraorganotin compound, which is optically stable (see Table 1), was obtained as a racemic mixture. 

The second cycloaddition substrate took to form of 91 (Scheme 1.9b), incorporating a vinyl sulfone dipolarophile. Beginning with cyano ketone 84, which was readily prepared from 1,5-dicyanopentane via a previously reported three-step sequence [45], condensation with thiophenol produced vinyl sulfide 85 in 84 % yield. Vinyl sulfide 85 underwent bromination in acetonitrile to afford bromo-vinyl sulfide 86 (86 %), which was then treated with isopropylmagnesium chloride [46] to effect metal-halogen exchange affording an intermediate vinyl magnesium bromide species. Subsequent alkylation with Mel in the presence of catalytic CuCN provided the alkylated vinyl sulfide 87 in 93 % yield. The nitrile within vinyl... 

A 500-ml., four-necked, round-bottomed flask is equipped with an efficient stirrer, a reflux condenser, a 250-ml. dropping funnel, and a low-temperature thermometer (Note 2). In the flask are placed 34.4 g. (21.8 ml., 0.25 mole) of phosphorus trichloride (Note 3) and 150 ml. of anhydrous ether. A solution of 0.50 mole of isopropylmagnesium chloride in about 150 ml. of ether (Notes 4 and 5) is placed in the dropping funnel. 

Chlorodiisopropylsilane, Cl(i-Pr)2SiH (1). The silane is prepared in 76% yield by reaction of isopropylmagnesium chloride with trichlorosilane. 

In situ magnesiation of an allenyl iodide with isopropylmagnesium bromide gives rise to a transient allenyl Grignard reagent, which adds to aldehydes and ketones to afford mainly homopropargylic alcohol adducts (Table 9.8) [18]. The anti diastereo-mers are favored, especially with sterically demanding aldehydes. Additions to ketones are less selective. 

Cyclopentolate Cyclopentolate, 2-(dimethylamino)ethylic ester of 1-hydroxycyclopentane-a-phenylacetic acid (14.1.39), is synthesized by the esterification of a-(l- droxycylopentyl) phenylacetic acid (14.1.38) using 2-dimethylaminoethylchloride, a-(l- Hydroxycyclopentyl) phenylacetic acid (14.1.38) is synthesized by reacting the sodium salt of phenylacetic acid with cyclopentanone in the presence of isopropylmagnesium bromide [30]. 

With unsubstituted 5-iodouracil 336, a trimagnesiated species 337 can be formed by sequential treatment with methylmagnesium chloride and isopropylmagnesium chloride, and reaction with various electrophiles then selectively gives 5-functionalized uracil derivatives 338 <20070L1639>. The same procedure was also successfully applied to the functionalization of 6-iodouracils, including the synthesis of Emivirine and l-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (ElEPT) precursors <20070L1639>. 

In a related organometallic approach, treatment of the diiodoarylformamidine 878 with isopropylmagnesium bromide gave an organomagnesium intermediate which reacted with a variety of alkyl, allyl, and aryl isocyanates to give 3-substituted-8-iodo-4(37/)-quinazolinones 879 <20020L1819>. 

Since the first reports23 in 1963 on metalation of imines, a number of bases such as ethyl-1 or isopropylmagnesium bromide1 24, lithium9 and potassium diethylamide13, lithium diisopropyl-amide (LDA), lithium 2,2,6,6-tetramethylpiperidide (LTMP)9 10,13, and lithium bis(trimethylsi-lyl)amide13 have been successfully applied in the preparation of imine-derived azaenolates. The most common of these reagents is LDA which has been applied in deprotonation reactions of the whole palette of different imines. 

Alternatively, metalation of cyclohexanone imines can be performed with isopropylmagnesium bromide by refluxing in THF for 2 hours1,24. Alkylation of the magnesium azaenolate of the (E)-2-amino butyl ether derivative at —78 °C provides (E)-2-methylcyclohexanone in an overall yield of 52% and 81% enantiomeric excess24. 

From the reaction of the radical anion of l,2-bis[(2,6-diisopropylphenyl)imino]acen-aphthene (dpp-bian) with i -PrMgCl, the persistent radical complex isopropylmagnesium dpp-bian (253) was isolated in yields up to 60% (equation 20). An X-ray crystal-structure determination of 253 showed that the magnesium atom has distorted tetrahedral coordination geometry as the result of the cr-bonded isopropyl group, one coordinate-bonded diethyl ether molecule and A, A -chelate bonding of the dpp-bian radical anion. The radical anionic character of the dpp-bian moiety is indicated by the relatively long Mg—N bond distances [Mg-N 2.120(2) and 2.103(2) A]. 

It should be noted that the sequence deprotonation/reverse Brook rearrangement between the triisopropylsilyloxy allene and isopropylmagnesium chloride in THE does not provide the magnesium enolate. 

In 2002, Figad re and coworkers reported the mono-reduction of 2-aryl (or heteroaryl)-1,1-dibromo-l-alkenes (Scheme 23). The reaction is achieved with one equivalent of isopropylmagnesium chloride in the presence of iron(III) acetylacetonate. Pure ( )-alkenyl bromides are obtained. With two equivalents of alkyl Grignard reagent, the mono-substituted product is obtained in moderate yield. 

The protocol is used for the preparation of 25 kg of the aldehyde in Banyu, and applied to the synthesis of a muscarinic receptor agonist. It is noteworthy that halogen-metal exchange reactions with other metal reagents such as butyllithium or isopropylmagnesium bromide led to more complex mixtures. The Banyu protocol was applicable to similar monoformylation reactions of dibromoheteroarenes (Table 12). 

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